SUBSTITUTED ISOQUINOLINE-1,3(2H,4H)-DIONES, 1-THIOXO-1.4-DIHYDRO-2H-ISOQUINOLINE-3-ONES AND 1.4-DIHYDRO-3(2H)-ISOQUINCLONES AND METHODS OF USE THEREOF FIELD OF THE INVENTION The present invention relates to isoquinoline-1,3(2H,4H)-dione derivatives. 1-thioxo-1,4-dihydro-2H-isoquinoline-3-one derivatives and 1,4-dihydro-3(2H)-isoquinolone derivatives, methods of making thereof, compositions comprising an effective amount of a isoquinoline-1,3(2H,4H)-dione derivative, 1-thioxo-1.4-dihydro-2H-isoquinoline-3-one derivative or a 1,4-dihydro-3(2H)-isoquinolone derivative and methods for treating or preventing cancer, comprising administering to a subject in need thereof an effective amount of a isoquinoline-1,3(2H,4H)-dione derivative, 1 -thioxo-1,4-dihydro-2H-isoquinoline-3-one derivative or a 1,4-dihydro-3(2H)-isoquinolone derivative. BACKGROUND OF THE INVENTION Protein kinases are a family of enzymes that catalyze the transfer of the terminal phosphate of ATP the hydroxyl group of specific tyrosine, serine, threonine, or histidine residues in protein. It is known that such phosphorylation plays a fundamental role in essentially all molecular aspects of cell life including metabolism, cell proliferation, cell differentiation, cell migration, and cell survival, and that protein kinases constitute major pharmacological targets [Schlessinger and Ullrich, Neuron, 9, 383 (1992); Cohen, P. Nat. Rev. Drug Discov. 1, 309-315 (2002); Scapin G., Drug Discovery Today 7(11): 601-611 (2002)]. Of the many different cellular functions in which the activity of protein kinases is known to be required, some processes represent attractive targets for therapeutic intervention for certain disease states. For example, specific protein kinases have been implicated as targets in cancer [Traxler, P. M., Exp. Opin. Ther. Patents, 8, 1599 (1998); Bridges, A. J., Emerging Drugs, 3, 279 (1998)], restenosis [Mattsson, E., Trends Cardiovas. Med. 5, 200 (1995); Shaw, Trends Pharmacol. Sci. 16, 401 (1995)1, atherosclerosis [Raines, E. W., Bioessays, 18, 271 (1996)], blood vessel proliferative disorders such as angiogenesis [Shawver, L. K., Drug Discovery Today, 2, 50 (1997); Jackson et al J. Pharm. Exp. Ther. 284, 687 (1998); Folkman, J., Nature Medicine, 1, 27 (1995)], chronic obstructive pulmonary disease, bone disease such as osteoporosis [Boyce, J. Clin. Invest, 90, 1622 (1992), Tanaka et at, Nature, 383, 528 (1996)], psoriasis [(Dvir, et al. J. Cell Biol. 113, 857 (1991)], inflammatory disorders such as arthritis [(Badger, J. Pharm. Exp. Ther. 279, 1453 (1996)], central nervous system disorders such as Alzheimer's [(Mandelkow, E. M., et al, FEBS Lett, 314, 315 (1992); Sengupta, A. et al, Mol Cell. Biochem. 167, 99 (1997)], pain sesation [Yashpal, K.. J. Neurosci. 15, 3263-72 (1995)], autoimmune diseases and transplant rejection [Bolen and Brugge, Ann. Rev. tmmunol. 15, 371 (1997)], thrombosis [Salari, FEBS, 263, 104 (1990)], metabolic disorders such as diabetes [Borthwick, A. C. et al, Biochem. Biopys. Res. Commun. 210, 738 (1995)], and infectious diseases (Lum, R. T. PCT Int. Appl., WO 9805335A1 980212), and viral infections [Littler, E. Nature, 160, 358 (1992)]. A partial, non-limiting, list of such kinases includes CDK1, CDK2, CDK3, CDK4, CDK5. CDK6. CDK7, CDK8, CDK9, CDK11, PDK1, PDK2, cRafl, c-src, abl, Araf, ATK, bcr-abl, Blk, Braf, Brk. Btk, cfrns, c-fms, c-kit, c-met, CSF1 R, CSK, EGFR, ErbB2, ErbB3, ErbB4,ERK, ERK1, ERK2, Fak, fes, FGFR1, FGFR2, EGFR3, EGFR4, EGFR5, Fgr. FLK-4, Fps, Frk, Fyn. GSK, gskSa, gsk3b, Hck, IGF-1R, IKK1, IKK2, IKK3, INS-R, integrin-linked kinase, Jak, JAK1, JAK2, JAK3. JNK, Lck, Lyn, MEK, MEK1, MEK2, p38, PDGFR, PIK, PKB1, PKB2. PKB3, PKC, PLK1. Polo-like kinase, PYK2, tiel. tie2. TrkA, TrkB, TrkC, UL13, UL97, VEGF-R1, VEGF-R2, Yes, AKT. and Zap70. In addition to tyrosine kinases, there are serine/threonine protein kinases, that phosphorylate serine and/or threonineresidues on proteins. Among them, cyclin-dependent kinases (CDKs) play a key role in regulating the cell cycle machinery. These complexes consist of two components: a catalytic subunit (the kinase) and a regulatory subunit (the cyclin). To date, 13 CDKs have been identified along with 25 cyclin-box-containing proteins [Knockaert, M.; Greengard, P.; Meijer L. Trends in Pharmacological Sciences 23(9): 417-425.] Each kinase associates with a specific regulatory partner and together make up the active catalytic moiety. Each transition of the cell cycle is regulated by a particular CDK compiex: G1/S by CDK2/cydin E, CDK4/cyclin D1 and CDK6/cyclln D2; S/G2 by CDK2/cyciin A and CDK1/cyclin A; G2/M by CDK1/cyclin B, the coordinated activity of these kinases guides the individual cells through the replication process and ensures the vitality of each subsequent generation [Science, 274,1643-1677 (1996); Ann. Rev. Cell. Dev. Biol., 13, 261-291 (1997); Fischer, P. M. Current Opinion in Drug Discovery and Development, 4(5), 623-634 (2001); Draetta, Trends Biochem. Set. 15:378-382 (1990); Sherr. Cell 73:1059-1065 (1993)]. An increasing body of evidence has shown a link between tumor development and CDK related malfunctions. Over-expression of the cyclin regulatory proteins and subsequent kinase hyperactivity have been linked to several types of human cancers [Senderowica, A. M., and Sausvilte, E. A., J. Nat. Acad. Sci., U.S.A. 96, 376-387 (2000); Garrett, M. D., Current Opin. Genetics Devel., 9, 104 (1999); Webster, K. R., Exp. Opin. Invest. Drugs, 7, 865-887 (1998); Jiang, Proc. Natl. Acad. Sci. USA 90:9026-9030 (1993); Wang, Nature 343:555-557 (1990)]. More recently, endogenous, highly specific protein inhibitors of CDKs were found to have a major affect on cellular proliferation [Sherr, C. J., Roberts, J. M. Genes Dev. 13, 1501-1512 (1999); Kamb et al. Science 264:436-440; Beach Nature 336:701-704 (1993)]. These inhibitors include p16 (an inhibitor of CDK4/cyclin D1), p21 (a general CDK inhibitor) and p27 (an inhibitor of CDK2/cydin E). A recent crystal structure of p27 bound to CDK2/cyclin A showed how these proteins effectively inhibit the kinase activity through multiple interactions with the CDK complex [Pavletich, Nature 382:325-331 (1996)J. These proteins help to regulate the ceil cycle through specific interactions with their corresponding CDK complexes. Cells deficient in these inhibibors are prone to unregulated growth and tumor formation. In addition to treating human cancers, CDK inhibitors could be useful in the treatment of other cell proliferative disorders such as familial adenomatosis polyposis, psoriasis, neuro-fibromatosis, fungal infections, endotoxic shock, vescular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, glomerulonephritis, and post-surgical stenosis and testenosis [U.S. Patent 6,114,365]. CDKs are also know to play an important role in apoptosis. Therefore, CDK inhibitors, could be useful in the prevention of AIDS development in HIV-infected patients; inflammatory bowel disease, and diabetes mellitus, dementia, Parkinson's disease, amyotrophic lateral sclerosis, retinitis pigmentosa, spinal muscular atrophy and cerebellar degeneration; myelodysplastic syndromes, aplastic anemia, ischernic injury associated with myocardial infarctions, stroke and reperfusion injury, arrhythmia, atherosclerosis, toxin-induced or alcohol related liver diseases, hematological diseases, for example, chronice anemia; degenerative diseases of the musculoskeletal system, for example, osteoporosis, aspirin-sensentive rhinosinusitis, cystic fibrosis, multiple sclerosis, kidney diseases and pain [U.S. Patent 6,107,305].. Also, it has been discovered that some CDK inhibitors can be used in combination therapy with some other anticancer agents. For example, the cytotoxic activity of the CDK inhibitor, Flavopiridol. has been used with other anticancer agents in cancer combination therapy [Cancer Research 57:3375 (1997)]. In addition, a recent report showed that CDK5 is involved in the phosphorylation of tau protein, and therefore, CDK inhibitors may be useful in the treatment of Alzheimer's disease [J. Biochem., 117: 741-749 (1995)]. This increasing body of evidence has led to intense discovery efforts to search for small molecule inhibitors of the CDK family and their associated regulatory molecules (cyclins) as an approach to cancer chemotherapy [Sausville, E. A., Trends in Molecular Medicine 8(4), S32-S37 (2002); Malumbres. M. and Barbacid, M. A/at Rev. Cancer 1, 222-231 (2001)]. More than 50 small molecule inhibitors of cydin-dependent kinases have been Identified. These CDK inhibitors all target the ATP-binding pocket of the catalytic site of the kinases. The effects of CDK inhibitors on the cell cycle and their potential value for the treatment of cancer, alopecia, neurodegenerative disorders (e.g. Alzheimer's disease, amyotrophic lateral sclerosis and stroke), cardiovascular disorders (e.g. atherosclerosis and restenosis), glomeruionephritis, viral infections (e.g. HCMV, HIV and HSV) and parasitic protozoa (Plasmodium sp. and Leishmania sp.) has been, extensively studied [Knockaert, M. Greengard, P. Meijer L.. Trends in Pharmacological Sciences 23 (9), 417-425 (20O2); Malumbres, M, and Barbacid, M. Nat. Rev. Cancer 1, 222-231 (2001), Slelecki. T. M. J. Med. Chem. 43, 1-18 (200O)]. Three properties make CDK inhibitors attrctive as potential anti-tumor agents. First, they are potent anti-proliferative agents, arresting cells in G1 [Soni, R. J. Nail. Cancer Inst. 21, 436-446 (2001)] or G2/M [Damiens, E. et at. Oncogens 20, 3786-3797 (2001)]. Second, they trigger apoptosis, alone or in combination with other treatments [Edamatsu, H. et al. Oncogens 19, 3059-3068 (20OO)]. Third, in some instances, inhibition of CDKs contributes to cell differentiation [Matushansky, I. Et al. Proc. Nail. Acad. Sci. U.S.A. 97, 14317-14322 (2000)J. Despite the significant research efforts and resources which have been directed towards the development of novel anticancer agents and improved methods for treating cancer there remains a need in the art for novel compounds, compositions, and methods that are useful for treating cancer with improved therapeutic indices. BRIEF SUMMARY OF THE INVENTION This invention relates to isoquinoline-1,3(2H,4H)-diones, 1-thioxo-1,4-dihydro-2H-isoquinoline-3-ones, and 1,4-dihydro-3(2H)-isoquinolones containing compounds as well as their phamnaceutically acceptable salts having the structure of Formula I, wherein: G3 (Formula Removed)or a pharmaceutically acceptable salt thereof, A1 is CO, C(S), NCOR100, NH, or C(R,XR2); A2 is H, OH, CH2OH, C1-6 alkyl, alkoxy, benzyloxy, arylaikyl, benzyl, aryl, acyl, -C(O)R, -OC(O)O-PEG, -CH2OC(O)0-PEG, -OC(O)NH-PEG, OC(0)OH, CH2O(C(0)OH, OC(O)halogen, CH2OC(O)halogen, OC(O)CH2halogen, OC(O)CH2S(CH2)mO-PEG wherein the aryl or benzyl is optionally substituted with PEG is Y1 is CRg or N, provided that when Y1 is N, then Y2 is NR1 Y2 is NR,, NIR1N(R1), NHC(O) or NHNHC(O); L1 is C(R7)(R8); R1 and R2are each independently H, C1-6 alkyl, aryl, or benzyl, or R1 and R2when taken together with the carbon atom to which they are attached form a 3-6 membered spirocyclic ring; R is C1-6 alkyl, aryl, or pyridyl; R3 is H, aryl, C1-6 alkyl. OR, NR10R11, or -O-, provided that when R3 is OR or -NR10R11, that e and f are 0 when Z is H; R4, is selected from the group consisting of H, aryl, or C1-8 alkyl, halogen, -CN, -OCF3, -NO2, -COOH, -CF3, OH, SH, N3, -C(O)H, heteroaryl, C1-6alkoxy, heterocycloalkyi, C2-6 alkenyl, C2-8 alkynyl, -COR100, -Oaryl, -OR100, -NHaryt, -S(O)mR100, -C(O)Q, C(O)OR100, -NR100aryl. -OR100aryl. -SR100aryl, - NHR102OH, -NHR102OR100, -NHR102NHR100, -NR100R102OH, -NHR102Q, -NR100R102NH2. -NR100R102NHR100, -NR100R102OR100. -NR100R102Q. -OR102OH, -OR102OR100. -OR102NH2, -OR102NHR100, -OR102Q, -OCOR100, -OR100COR100. -NHCOR100, -NHCONH2, -NHCONHR100, -NHR10oCOR100, -NHR102NH2, -NHOH, -NHOR100, -CONR10R11, -NHSO2R100,, NR10.R11. -NHC(O)-heteroaryl,-NHC(O)R102-heteroaryl. OC(O)CH2halogen, -OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG, -N(R10)(R11). -NHC(O)R102-aryI, and -NHC(O)NH-heterocycloalky) that is optionally substituted with up to three C1-3 alkyl groups; wherein said aryl, said heteroaryl. and said heterocydoalkyl are each optionally substituted with up to four independently selected R12 groups; wherein said C2-6 alkenyl, said C1-6 alkyl, C1-6alkoxy, and said C2-6 alkynyl are each optionally substituted with up to three independently selected R13 groups; R5 is selected from the group consisting of C1-8 alkyl or alkenyl, wherein the alkyl or alkenyl are optionally- substituted with OH, OR. NR10R11, C1-6 alkyl; R7 and RB are selected from the group consisting of H, C1-6 alkyt, OR100, OH, C(O)H or COOH; R10 and R11 are selected from the group consisting of H, C1-6 alkyl, C2-6alkenyl, C1-6 acyl, -S(O)2aryI, -C(O)C2-6 alkenyl, C2-6 alkynyl, aryl or heteroaryl, wherein said C1-6 acyl is optionally substituted with a heteroaryl, wherein said C1-6 alkyl is optionally substituted with up to three halogen atoms, wherein said aryl and said heteroaryl are optionally substituted with up to three R12 groups, wherein R10 and Rn may be taken together with the N to which they are attached to form a 3-8 membered heterocylic ring, wherein said heterocyclic ring may contain additional atoms selected from the group N, O, and -S(O)m and said heterocyclic ring may be additionally substituted with 1 to 4 substituents selected from the group consisting of C1-6alkyl, OH, -OC1-6alkyl, -OC3-6cycloalkyl, -(CH2)nOH, -(CH2)nOC1-6alkyl, -(CH2)nOC3-6cycloalkyl, -NR10Rn, -(CH2)nNR10R11. and =O; R12 is independently selected from the group consisting of aryloxy, halogen. OH, -COOH, -C(O)H. -C(O)R, -C1-3 perhaloalkyl, -OCF3, C1-6 acyl, -CN, -NO2, aryl, heteroaryl, -S-C1-6 alkyl, -NHCOd-aalkyl, -N(R15)(R16), C1-3 perhaloalkoxy, C1-6 alkyl, C2-6 alkenyl, -CONH2. -CF3. SH, N3, heterocycloalkyi, -C(O)R100, -OR100. -NHaryl, -S(O)mR100-C(O)Q, C(O)OR100. -C{O)NHR100. -NR100aryl, -N(R100) R102aryl, - OR102aryl, - SR102aryl, -NHS(O)R100, - NHR102OH, -NHR102OR100. -NHR102NHR100. -N(R100)R102OH, -NHR102Q, -N(R100}R102NH2 -N(R100)R102NHR100. -N(R100)R102OR100. -N{R100)R102Q, -OR102OH. -OR102OR100, -OR102NHz, -OR102NHR100, -OR102Q, -OC(O)R100, - OR102C(O)R100. -NHC(O)R100. -NHCONH2, -NHCONHR100, - IMHR102tC(O)R100, -NHR102NH2, -NHS(O)2-aryl, -NHOH, -NHC(O)aryl, -NHOR100, -NHC(O)-heteroaryl, -NHC(O)R102-heteroaryl, -C(O)N(R10)(R11), -N(R10)(R11), NHC(O)R102aryl, and NHC(O)NH-heterocycloalkyl that is optionally substituted with up to three C1-3 alkyl groups, wherein said C2-6 alkenyl, said d^ alkyl, and said C2-6 alkynyl are each optionally substituted with up to three independently selected R13 groups and -N(R15)(R16); R13 is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, d-e alkyl, C3-6 cycloalkyi, heterocycle, heterocycloalkyi, heterocycloalkyloxy, CN, OH, C1-6 alkoxy, halogen and -COOH, -SH, -COM, -COR100, -CONH2, -CONHR100, -COQ, -OCOR100, -OCONH2, -OCONHR100, -OCOQ, -OR102OH, -OR102NR15R16, and wherein said aryl, heteroaryl, and heterocycloalkyl are optionally substituted with up to three independently selected R18 groups; R15 and R16 are selected from the group consisting of H, C1-6 alkyl, and C1-6 acyl; and wherein said R15 and R16 groups taken together with the nitrogen to which they are attached may form a heterocylic ring of 3 to 8 atoms with 1 or 2 additional heteroatoms selected from the group N, O, and -S(O)m, the heterocyclic ring may be substituted with groups consisting of OH, -OC3-6cycloalkyl. -OC1-6 alkyl, -(CH2)nOH, -(CH2)nOC1-6alkyl, -NR10R11, -(CH2)nNR10R11, and -(CH2)nOC3-6cycloalkyl; R18 is independently selected from the group consisting of OH, halogen, -NO2, dialkylamino, -N(R15)(R18), -COOH, -S(O)2NH2, C1-3 perhatoalkyl, -OCF3, C1-3 alkoxy, C,^ alkyl, CN, C1-8 cyanoalkyi and C4-8 cycloalkenyl, wherein said cycloalkenyl is optionally substituted with up to three groups independently selected from OH and C1-3 alkoxy, and wherein said C1-6 alkyl is optionally substituted with -N(R15){R16); R20 is selected from the group consisting of C1-6 alkyl, C3-6 cycloalkyl and alkeny), wherein said C1-6 alkyl is optionally substituted with up to three halogen atoms or a group of Formula -C(CH2)(Q")]k'CH3; R21 is selected from the group consisting of C1-6 alkyl and cycloalkyl; RZJ is selected from the group consisting of heteroaryl, aryl, arylalkyl and C1-6 alkyl, wherein said C14 alkyl is optionally substituted up to three halogen atoms; is selected from the group consisting of aryl, heteroaryl and C1-6 alkyl, wherein said aryl and said heteroaryl is optionally substituted with up to three C1-3 alkyl groups, and said C1-6 alkyl is optionally substituted with up to three halogen atoms; R24 is selected from the group consisting of H, -COOH, C3-6 cycloalkyl, -OCHF2, -OCHCI2, C1-3 perhaloalkyl, C1-6 alkoxy, heteroaryl, heterocycloalkyl, C2-6 alkynyl, C1-8 alkyl, C2-6 alkenyl, and aryl, wherein said C1-6 alkyl is optionally substituted with up to three groups independently selected from halogen and C3-6 cycloalkyl, said C2-6 alkenyl optionally substituted with up to three groups independently selected from halogen and N(R27)(R28). said aryl is optionally substituted with up to three OH groups, and said heterocydoalkyl is optionally substituted with up to three independently selected C1-6 alkyl groups, -(CH2)mcycloalkyl, -(CH2)nOH, -(CH2)nOR, -(CH)2NR10Rn, -COR5, and Q; R25 is OH, or NR10R11; R27 and R28 are independently selected from the group consisting of C1-6 alkyl, C3-6 cycloalkyl. heterocydoalkyl. C2-8 alkenyl. H. aryl. Q, -C(O) C3-6 alkyl(cycloalkyl), -COalkyl. -COalkenyl. -COalkynyl, -COaryl. -COheteroaryl, -COcycloalkyl, C1-6 acyl, -C(O)C(O)OH, halogen, -COC1-6halogen, C1-3alkoxy, and arylalkyl, wherein said C1-6 alkyl, aryl, acyl, and heterocydoalkyl are optionally substituted with up to three R52 groups; or R27 and R28 together with the nitrogen atom to which they are attached can form a 5 or 6 membered saturated heterocyclic ring that can include one additional O. N, or S ring atom, said saturated heterocyclic ring optionally substituted with a carboxylate or C1-3 alkyl groups; R31 is selected from the group consisting of trialkylsilyl, C1-6 alkoxycarbonyl. C1-6 alkyl, C2-6 alkenyl, heteroarylalkyl, heterocydoalkyl and arylalkyl, wherein said C1-6 alkyl, said arylalkyl and said heteroarylalkyl are each optionally substituted with up to three independently selected R53 groups, and said heterocydoalkyl is optionally substituted with up to three C1-6 alkyl groups; is selected from the group consisting of H, C1-6 acyl, heteroaryl and C1-6 alkyl, wherein said heteroaryl is optionally substituted with up to three C1-3 alkyl groups, and said C1-6 alkyl is optionally substituted with up to three heteroaryl or R52 groups; is selected from the group consisting of heterocycloaikyl. aryl, C1-3 perhaloalkyl, -N(R27)(R28) and C1-6 alkyl, wherein said aryl, C1-6 alkyl, heterocycloaikyl, are optionally- substituted with up to three groups selected from halogen, C1-6 alkyl, aryl, OH and - is selected from the group consisting of aryloxy, C1-6 alkyl, aryl and alkoxy, wherein said aryl is optionally substituted with COOH, and said alkoxy is optionally substituted with -N(R27)(R28); R35 is selected from the group consisting of dialkylamino, or C14 alkyl that is optionally substituted with -COOH or with - is selected from the group consisting of -R100, -R102R100, -R102OR100, -R102OH, and -R102Q; R50 is selected from the group consisting of heterocydoalkyl, (N=H), NH2, -NHCOC1-3 alkyl, C1-3 alkyl. -NHCOC1-3 cycloalkyl, -NHCO1-3 heterocydoalkyl. -OH, -CN, -COOH. -N(R27)(R2s). -SO2N(R27)(R28). halogen, heteroaryl and aryl, wherein said aryl, heteroaryl. or heterocycloalkyl are optionally substituted with a group selected from C1-3 alkyl, C(O)H, C1-4 alkoxy, and -CONHN(R21)2, and up to three groups selected from halogen, and NH2; is independently selected from the group consisting of COH, OH, CN, NH2, . -N(R21)2, C1-6 alkyl. aryl. -COaryl, heterocycloalkyi, halogen. C1-3 perhaloalkyl, and -C3-6 cycloalkyl. wherein the aryl can be substituted with COOH; is selected from the group consisting of OH, C1-6 alkyl, arylalkyloxy, heterocydoalkyl, C1-3 alkoxy, halogen and C3-6 cydoalky!; RIM is selected from the group consisting of C1-12alkyl, C3-8 cyctoalkyl aryl, heteroaryl, C2-6alkenyl, and C2-6alkynyl; R102 is a divalent C1-8alkyl; R200 is selected from the group consisting of — (CR201 R201)qR203 , N(R201){CH2)qR203 and -NHC(O)NH-R203; R201 is selected from the group consisting of H and C1-6 alkyl; is selected from the group consisting of dialkylamino and a 5-7 membered heterocydoalkyl ring having up to three ring hetero atoms selected from O, N and S, said heterocydoalkyl ring being optionally substituted with up to three independently selected R204 groups; R204 is selected from the group consisting of OH, COOH, C1-6 alkyl, alkoxycarbonyl, arylalkyl, heteroarylalkyl, C2-8 alkenyl, C3-6 cycloalkyl, aryl, C1-6 alkoxy, C2-6 acyl, heterocycloalkyl, -C(O)N(R300)(R300), -NHC(O)R300, -NtR201)(R201), and -NHC(=0)N(R201)(R201), wherein said c1-6 alkyl is optionally substituted with up to three independently selected R207 groups, wherein said arylalkyl and said heteroarylalkyl are each optionally substituted with up to three independently selected R208 groups, wherein said C2-6 acyl may optionally contain one double bond, and may optionally be substituted with -NR10R11, wherein said heterocycloalkyl is optionally substituted with up to three independently selected C1-6 alkyl groups; R206 is independently C1-6 alkyl or C(O)NH2; R207 is independently selected from the group consisting of CN,. heterocycloalkyl, C1-3 alkoxy, OH, N{R27)(R28) and C3-6l cycloalkyl; R209 is R211. R212-C=C-. or (R212)2C=C(R212)- ; R210 is C1-6 alkyl, or C1-6 alkoxy; R211 is aryl and heteroaryl wherein said aryl and said heteroaryl, are each optionally substituted with up to four independently selected R12 groups; R212 is C1-6 alkyl, aryl, and heteroaryl, wherein said C1-6 alkyl is optionally substituted with up to three independently selected R13 groups wherein said aryl and said heteroaryl, are each optionally substituted with up to four independently selected R12 groups; R214 is R41, or R211; is selected from the group consisting of H, C1-3 alkoxy and C1-6 alkyl wherein said C1-6 alkyl Is optionally substituted with a dialkylamino group; e is 0 or 1 provided that when R3 is OR or NRR then e is 0; f is 0-5; k' is 1-6; m is 0, 1 , or 2; n is 1-4; q is 1-3; r is 2-1 800; v is 1 or 2; G1, G2, G3 and G4 are each independently selected from the group consisting of H, halogen, -CN, -OCF3, -NO2, -COOH, -CONH2, -CF3. OH, SH. N3. -C(O)H. heteroaryl, C1-6alkoxy, heterocydoalkyl, aryl, C3-10cycloalkyl, C1-12 alkyl, C2-6 alkenyl, C2-6 alkynyl, -COR100, -OC3-10Cycloalkyl, -Oaryl, -OR100, R209 R211, Q, -OS(0)2NH2, OS(0)2R22, -S(0)mR100. -C(O)Q, C(OPR100, -NHR100, -NR100aryl, -OR102aryl. -SRiozaryl, - NHR102OH, -NHR102OR100, -NHR102NHR100, , -OR102OH, -OR102R100, -OR102NH2, -OR102NHR100, -OR102Q, -OCOR100, -OR102COR100, -NHCOR100, -NHCONH2, -NHCONHR100, -NHR102COR100, -NHR102NH2, -NHOH, -NHOR100 -CONR10Rn, -NHSO2R100, -NHC(0)-heteroaryl, -NHC(O)R102-heteroaryl. OC(O)CH2halogen. OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG, v, NHC(O)R102-aryl. and NHC(O)NH-heterocydoalkyl optionally substituted with up to three C1-3 alkyl groups; wherein said aryl, said heteroaryl, and said heterocydoalkyl are each optionally substituted with up to four independently selected R12 groups; wherein said C2-8 alkenyl, said C1-6 alkyl, C1-6alkoxy, and said C2-6 alkynyl are each optionally substituted with up to three independently selected R13 groups; Q is -NR100R100 optionally the R100 groups taken together with the nitrogen to which they are attached form a heterocylic ring of 3 to 8 atoms with 1 or 2 additional heteroatoms selected from the group N, O, and S, said heterocyclic ring may optionally be substituted with groups consisting of OH, OC1-6 alkyl, (CH2)nOH, (CH2)nOC1-6alkyl, NR10Rn, (CH2)nNR10Rn, and C1-6 alkyl; Q" is selected from the group consisting of O, S, and NH; Z may be absent or is selected from the group consisting of H, aryl, heteroaryl, cycloalkyl, dialkylamino, COOH, heterocycle, pyridone. C1-12 alkyl, wherein said alkyl is optionally substituted with up to 3 groups selected from an OH group, Q, NHQ, COOH, and a 5-10 member heteroaryl ring system having one or two rings with up to four ring heteroatoms independently selected from O, N and S, wherein said aryl, said pyridone, said cycloalkyl, said heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of R210, R41. R209, R211. R214. OR41, (=O), OH, COOR100. C1-8 alkyl, C1-6 alkoxy, C-K, perhaloalkyi, halogen, C1-6 perhaloalkoxy, (=NH), NH2,-NO2, C(O)H, -C(O)OH,-C(O)NH2, CN. Q, heterocycle. heteroaryt. S-C1-3 alkyl, S-CV 3 perhaloalkyi, S-heteroaryl, aryl, C2-8 alkynyl, C(NH)NH2, heterocydoalkyl, C2-8 alkenyl, - O-CC(O)-R20, -O-C(O)OR21. -NHS(O)2R22, -R102NHS(O)2R23. -NHC(O)R24, R102NHC(0)R24, -NHC(OXCH2)mR25, -CH2N(R27)(R28,), -OC(O)N(R27)(R28). -N(R28)(R28), - OR31 -S(O)2NHR32, -S(O)2R33, -C(O)R34, -CH2C(O)OH, -C(O)NHR35. R200, - CH2NHS(O)2R21, OC(O)CH2hatogen. OC(O)R100, -OC(O)CH2S(CH2)mO-PEG, - OC(O)NH-PEG, H, -CN, -OCF3, -CF3.SH, N3. -C(O)H, -COR100. -OR100, -Saryl, -C(O)Q, C(O)OR100, -C(O)NHR100. -NR100aryl, -OR102aryl, -SR102aryl, -NHS(O)-R100, - NHR102OH, -NHR102OR100. -NHR102NHR100, -NR100R102OH, -NHR102Q, -NR100R102NH2. NR100R102NHR100. -NR100R102OR100. -NR100R102Q. -OR102OH, -OR102OR100. -OR102NH2, - OR102NHR100. -OR102Q, -OCOR100, -OR102COR102OR102COR100, OR^^ORto^R^zOR^. -NHCOR100. -NHCONH2, -NHCONHR100, -NHRM2COR100, -NHR102NH2. -NHS(O)2-aryl. -NHOH, -NHC(O)aryl. - -NHOR100, -NHC(O)-heteroaryl, - NHC(0)R102-heteroaryl, OC(O)CH2halogen, OC(O)CH2S(CH)mO-PEG. OC(O)NH-PEG, OS(O)2NH2, OS(O)2R22, -N(R10)(Rn), NHC(O)R102-aryl, and NHC(O)NH-heterocycIe that is optionally substituted with up to three C1-6 alkyl groups, wherein said C2-6 alkenyl, said C1-6 alkyl, and said C2-8 alkynyl are each optionally substituted with up to three independently selected R13 groups, wherein said d.e alkyi, said -S-C-1-8 alkyl, and C1-6 alkoxy are each optionally substituted with up to three independently selected R50 groups, wherein said aryl is optionally substituted with up to three groups independently selected from OH and NH2, wherein said heteroaryl and said S-heteroaryl, heterocycle, and said heterocycloalkyl, are each optionally substituted with up to three independently selected R51 groups, wherein said C2-6 alkenyl is optionally substituted with COOH, wherein any two adjacent carbon atoms of said aryl, heteroaryl or heterocycloalkyl can optionally be joined together by a group of the Formula -O-C(Ra)(Rb)-O- where, Ra and Rb are independently H, C1-3 alkyl, phenyl or alkoxycarbonyl; and C1-3 alkoxy and C1-3 pemaloalkyl, wherein said aryl can be substituted with COOH. Among the embodiments of compounds of Formula (I) of this invention including pharmaceutically acceptable salts thereof are those in the embodiments below, wherein the other variables of Formula (I) in the embodiments are as defined above wherein: In one embodiment, A1 is CO or C(R1)(R2). In another embodiment, e is 1 ; f is 0; Y1 is CR3 ; Y2 is NR1 Z is selected from the group consisting of aryl, heteroaryl, bicydic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of -CH2N(r27)(r28), -NHR102NHR100. -NHR102Q, -NR100R102NH2. -NR100R102NHR100. -NR100R102Q, -OR102NH2, -OR102NHR100. -OR102Q, and -NHR102NH2. In another embodiment, e is 1 ; f is 0; A1 is C=O; A2 is H; Y1 is CR3 ; Y2 is Nr,; Z is selected from the group consisting of aryl. heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-1 0 member heteroaryl ring system having one OR two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of -CH2N(r27)(r28), -NHR102NHR100. -NHR102Q, -NR100R102NH2. -NR100R102NHR100, -NR100R102Q, -OR102NH2, -OR102NHR100 -OR102Q. and -NHR102NH2. In one embodiment, e is 1 ; f is 0; A1 is CH2; A2 is H; Y1 is CR3 ; Y2 is Nr,; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl. bicyclic heteroaryl, heterocycle, and a 5-1 0 member heteroaryl ring system having one OR two rings, having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of -CH2N(r27)(r2a), -NHR102NHR100. -NHR102Q, -NR100R102NH2, -NR100R102NHR100, -NR100R102Q, -OR102NH2, -OR102NHR100, -OR102Q. and -NHR102NH2. In another embodiment, e is 1; f is 0; A1 is CR1R2; A2 is H; Y1 is CR3 ; Y2 is NR1, Z is selected from the group consisting of aryl, heteroaryl, bicydic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one OR two rings, having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicydic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of -CH2N(r27)(R28), -NHR102NHR100. -NHR102Q, -NR100RioZNH2, -NR100R102NHR100. -NR100R102Q. -OR102NH2, -ORi02NHR,oo, -OR102Q, and -NHR102NH2. In further embodiments, Z is selected from a six membered aryl, heteroaryl OR heterocyclic ring and further providing that the independently selected substituent on Z is at the para position of said six membered ring. In one embodiment, e is 1; Y1 is CR3; Y2 is NRi; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one OR two rings, having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkynyl, and C2-6 alkenyl wherein said alkyl is substituted with OR102NR15R16. NH2 OR NfrzrXraO. alkenyl and alkynyl are substituted with OR102NR15rte and wherein said S-alkyl and alkoxy are substituted with NH2 OR In another embodiment, e is 1; A1 is C=O; A2 is H; Y1 is CRa ; Y2 is NR,; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one OR two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl. said bicyclic heteroaryl. and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, S-C1-3 alkyl, C2-6 alkynyl. and C2-6 alkenyl wherein said alkyl is substituted with -OR102NR15R16, NH2 OR -N(R27)(R28), alkenyl and alkynyl are substituted with -OR102NR-15R16and wherein said S-alkyl and alkoxy are substituted with NH2 OR -N(R27)(R28). In one embodiment, e is 1; A1 is CH2; A2 is H; Y1 is CR3; Y2 is NR-,; Z is selected from the group consisting of aryl, heteroaryl, bicycllc aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one OR two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-8 alkynyl, and C2-8 alkenyl wherein said alkyl is substituted with -OR102NR15R16. NH2 OR -N(R27)(R28), alkenyl and alkynyl are substituted with -OR102NR15R16and wherein said S-alkyl and alkoxy are substituted with NH2 OR -N(R27)(R28)- In an embodiment of the invention, e is 1; A1 is CR1R2; A2 is H; Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one OR two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl. said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of C14 alkyl, C1-6 alkoxy, S-C1-3 alkyl, C2-6 alkynyl, and C2-6 alkenyl wherein said alkyl is substituted with OR102NR15R16, NH2 OR N(R27)(R28), alkenyl and alkynyl are substituted with OR102NR15R16and wherein said S-alkyl and alkoxy are substituted with NH2 OR N(R27)(R28). In a further embodiment, e is 1; f is 0; Y1 is N; Y2 is NR1 Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic and heteroaryl, and a 5-10 member heteroaryl ring system having one OR two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, and said bicyclic heteroaryl, are each optionally substituted with up to five substituents independently selected from the group consisting of -CH2N(R27)(R28), -NHR102NHR100, -NHR102Q. -NR100R102NH2, - R102Q,-OR102NH2, -OR102NHR100, -OR102Q. and -NHR102NH2. In another embodiment, e is 1; f is 0; A1 Is C=O; A2 is H; Y1 is N ; Y2 is NR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, and bicyclic heteroaryl, and a 5-10 member heteroaryl ring system having one OR two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, and said bicydic heteroaryl, are each optionally substituted with up to five substituents independently selected from the group consisting of -NHR102NHR100. -NHR102Q. -NR100R102NH2, -NRiopr102NHR100. -NR100R102Q. -OR102NH2, -OR102NHR100, -OR102Q, and -NHR102NH2. In an embodiment, e is 1; f is 0; A1 is CH2; A2 is H; Y1 is N ; Y2 is NR1 Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, and bicyclic heteroaryl, and a 5-10 member heteroaryl ring system having one OR two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicydic aryl, and said bicydic heteroaryl, are each optionally substituted with up to five substituents independently selected from the group consisting of -NHR102NHR100. -NHR102Q, -NR100R102NH2. -NR100R102NHR100. , -OR102NH2, -OR102NHR100, -OR102Q, and -NHR102NH2. In another embodiment, e is 1 ; f is 0; A1 is CR1; A2 is H; Y1 is N ; Y2 is NRr. Z is selected from the group consisting of aryl, heteroaryl, bicydic aryl, and bicydic heteroaryl, and a 5-10 member heteroaryl ring system having one OR two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicydic aryl. and said bicyclic heteroaryl, are each optionally substituted with up to five substituents independently selected from the group consisting of -NHR102NHR100. -NHR102Q. -NR100R102NH2, -NR100R102NHR100. -, -OR102NH2, -OR102NHR100, -OR102Q, and -NHR102NH2. In one embodiment, e is 1 ; f is 0; Y1 is CR3 ; Y2 is Z is selected from the group consisting of aryl, OR heteroaryl wherein said aryl, and said heteroaryl, are each optionally substituted with up to three substituents independently selected from the group consisting of R210, R41, R209, r211. r214. OR41. OH. C1-6 alkyl, C1-6 alkoxy, C1-3 perhaloalkyl, halogen, C1-3 perhaloalkoxy, NH2. Q, heterocycle, heteroaryl, S-C1-3 alkyl, S-C1-3 perhaloalkyl, S-heteroaryl, aryl, -O-C(O)-R20, -NHC{O)R24, -NHC(O)(CH2)mR25, -OC(O)N(R27)(R28), -N(R27)(R28). -OR31. R200. OC(O)R100. -OCC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -CF3, SH, -OR100, -Saryl, NR100aryl, -OR102aryl, -Sr102aryl, -NHR102OH, - NHR102OR100, -NR100R102OH, -NHR102Q, -NR100R102OR100, -NR100RiozQ, -ORiozOH, -OR102OR100, -OR102Q, -OCOR100. OR102COR102OR102OR100, -NHC(O)aryl, -NHC(0)-heteroaryi, -NHC(O)r102-heteroaryl, OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG, ), and NHC{O)r102-aryl. In an embodiment, e is 1; f is 0; A1 is C=O; A2 is H; Y1 is CR3 ; Y2 is NR,; Z is selected from the group consisting of aryl, OR heteroaryl wherein said aryl, and said heteroaryl, are each optionally substituted with up to three substituents independently selected from the group consisting of R210. R41, R209, R211. R214 OR41, OH. C1-6 alkyl, C1-6 alkoxy, C1-3 perhaloalkyl, halogen, C1-6 perhaloalkoxy, NH2, Q, heterocycle, heteroaryl, S-C1-3 alkyl, S-C1-3 perhaloalkyl. S-heteroaryl, aryl, -O-C(O)-r20, -NHC(O)r24, -NHC1-6XCHaXNRas. -OC(0)N(r27)(R28), -N(R27)(R28), -OR31,, R200. OC(O)R100, -OC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -CF3, SH. -OR100, -Saryl, NR100aryl, -OR102aryl, -Sr102aryl, -NHR102OH. - NHR102OR100, -NR100 R102 OH, -NHR102 Q. -NR100 R102 OR100. -NR100R102Q. -OR102aOH, -OR102OR100. -OR102Q, -OCOR100, OR102COR102 OR102 OR100, -NHC(O)aryl, -NHC(O)-heteroaryl, -NHC(O)R102-heteroaryl, OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG, ). and NHC(O)R102-aryl. In another embodiment, e is 1; f is 0; A1 is CH2; A2 is H; Y1 is CR3 ;Y2 is NR1; Z is selected from the group consisting of aryl, OR heteroaryl wherein said aryl, and said heteroaryl, are each optionally substituted with up to three substituents independently selected from the group consisting of R210 R41, R209, R211. R214, OR41, OH, C1-6 alkyl, C1-6 alkoxy, C1-6 perhaloalkyl. halogen, C1-3 perhaloalkoxy, NH2, Q, heteracycle, heteroaryl, S-C1-3 alkyl, S-C1-3 perhaloalkyl, S-heteroaryl, aryl, -O-C(O)-R20, -NHC(O)R24, -NHC(O)(CH2)mR25, -OC(0)N(R27)(R28). -N(R27)(R28). -OR31 R200, OC(O)R100. -OC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -CF3, SH, -OR100, -Saryl. NR100aryl, -OR102aryl, -SR102aryl, -NHR102OH, - NHR102OR100, -NR100OR102OH, -NHR102Q. -NR100R102OR100. -NR100R102Q, -OR102OH. -OR102OR100, -OR102Q, -OCOR100. OR102COR102OR102OR100, -NHC(O)aryl, -NHC(O)-heteroaryl, -NHC(O)R102-heteroaryl, OC(O)CH2S(CH)mO-PEG. OC(O)NH-PEG, -N(R10)(R11), and NHC(O)R102-aryl. In one embodiment, e is 1 ; f is 0; A1 is CR1R2; A2 is H; Y1 is CR3 ; Y2 is NR,; Z is selected from the group consisting of aryl, OR heteroaryl wherein said aryl, and said heteroaryl, are each optionally substituted with up to three substituents independently selected from the group consisting of R210, R41, R209. R211.R214, OR41, OH, C1-6 alkyl, C1-6 alkoxy, C1-6 perhaloalkyl, halogen, C1-3 perhaloalkoxy, NH2, Q, heterocycle, heteroaryl, S-C1-3 alkyl, perhaloalkyl, S-heteroaryl, aryl. -O-C(O)R20, -NHC(O)R24. -NHC(O)(CH2)mR25 OC(O)N(R27)(R28), -N(R27)(R28). -OR31, R200, OC(O)R100, -OC(O)CH2S(CH2)mO-PEG. -OC(O)NH-PEG, -OCF3, -CF3, SH, -OR100. -Saryl, NR100aryl, -OR102aryl. -Sr102aryl, -NHR102OH, - NHR102OR100. -NR100R102OH, -NHR102Q, -NR100R102OR100, -NR100R102Q, -OR102OH, -OR102OR100, -OR102Q, -OCOR100, OR102COR102OR102OR100, -NHC(O)aryl, -NHC(O)-heteroaryl, -NHC(O)r102-heteroaryl, OC(O)CH2S(CH)m,O-PEG, OC(O)NH-PEG, -N(R10)(rn), and NHC(O)r102-aryl. In one embodiment, Z is selected from moieties of the Formulae (Formula Removed)ptionally substituted with up to 3 independently selected substituents. In an embodiment, e is 1; f is 1; Y1 is CR3; Y2 is NR,; Z is selected from a moiety of the Formula (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R41, R211, R214, C1-6 alkyl, C1-3 perhaloalkyl, heterocycte, heteroaryl. aryl, and heterocycloalkyl. (Formula Removed)In one embodiment, e is 1; f is 1; A1 is C=O; A2 is H; Y1 is CR3; Y2 is Z is selected from a moiety of the Formula (Formula Removed) wherein said Z is optionally substituted with a 'substituent selected from the group consisting of R41 R211 R214, C1-6 alkyl, C1-3 perhaloalkyl, heterocycle, heteroaryi, aryl, and heterocydoalkyl. In another embodiment, e is 1; f is 1; A1 is CH2; A2 is H; Y1 is CRg; Y2 is Z is selected from a moiety of the Formula (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R41, R211, R214, C1-6 alkyl, C1-6 perhaloalkyl, heterocycle, heteroaryi, aryl, and heterocydoalkyl. In another embodiment, e is 1; f is 1; A is CR1;R2 A2 is H; Y is CR3; Y is NR,; Z is selected from a moiety of the Formula (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R210, R41, R211. R214. C1-6 alkyl, C1-3 perhaloalkyl, heterocycle, heteroaryl. aryl, and heterocycloalkyl. In one embodiment, e is 1; f is 1; Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R211, OR41, OH, C1-6 alkoxy, C1-3 perhaloalkoxy, heteroaryl, S-C1-3 alkyl, perhaloalkyl, S-heteroaryl, aryl, -O-C(O)-R20, -O-C(O)OR21 OC(O)N(R27)(R28),-OR3 OC(O)R100, -OC(O)CH2S(CH2)mO-PEG. -OC(O)NH-PEG, -OCF3, -OR100, -Saryl, OR102aryl, -SR102aryl, -OR102OH, -OR102OR100, -OR102Q, -OCOR100> OR102COR102OR102OR100, OC(O)CH2S(CH)mO-PEG, and OC(O)NH-PEG. In another embodiment, e is 1; f is 1; A is C=O; A2 is H; Y is CR3; Y2 is NR1 Z is selected from the group consisting of (Formula Removed) herein said Z is optionally substituted with a substituent selected from the group consisting of - R211. OR41, OH, C1-6 alkoxy, C1-6 perhaloalkoxy, heteroaryl, S-C1-3 alkyl, perhaloalkyl. S-heteroaryl. aryl, -O-C(O)-R20. -O-C(O)OR21, OC(O)N(r27)(R28). - OC(O)R100, -OC(O)CH2S(CH2)mO-PEG, OC(O)NH-PEG, -OCF3, -OR100, -Saryl, OR102aryl, -Sr102aryl -OR102OH. -OR102OR100, -OR102Q, -OCOR100 OR102 COR102 OR102 OR102 OC(O)CH2S(CH)mO-PEG, and OC(O)NH-PEG. In another embodiment, e is 1 ; f is 1 ; A1 is CH2; A2 is H; Y1 is CRs ; Y2 is Z is selected from the group consisting of (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R211, OR41 OH, C1-6 alkoxy, C1-3 perhaloalkoxy, heteroaryl. S-C1-6 alky), perhaloalkyl. S-heteroaryl, aryl, -O-C(O)-R20, -O-C(O)OR21, OC(O)N(R27)(R28), -OR31, OC(O)R100, -OC(O)CH2S(CH2)mO-PEG. -OC(O)NH-PEG, -OCF3, -OR100. -Saryl, - OR102aryl, -SR102aryl, -OR102OH. -OR102OR100. -OR102Q. -OCOR100, OR102COR102OR102OR100, OC(O)CH2S(CH)mO-PEG, and OC(O)NH-PEG. In one embodiment, e is 1; f is 1; A1 is CR,R2; A2 is H; Y1 is CR3 : Y2 is NRr, Z is selected from the group consisting of (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R211, OR41, OH, C1-6 alkoxy, C1-3 perhaloalkoxy, heteroaryl, S-C1-3 alkyl, perhaloalkyl, S-heteroaryl, aryl, -O-C(O)-R20, -O-C(O}OR21, OC(O)N(R27)(R28), -OR31, OC(O)R100, -OC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -OR100, -Saryl, - OR102aryl, -SR102aryl, -OR102OH, -OR102OR100, -OR102Q, -OCOR100, OR102COR102OR102OR100. OC(O)CH2-S(CH)mO-PEG. and OC(O)NH-PEG. In another embodiment, G1, G3, and G4 = H; G2 is selected from the group consisting of halogen, heteroaryl, heterocycloalkyl, aryl, C1-10cycloalkyl, C1-12 alkyl, alkenyl, C2-6 alkynyl, -Oaryl, NHaryl, and In a further embodiment, are illustrative examples OR pharmaceuttcally acceptable salts thereof of Formula (I) which include: (4Z)-4-{{(4-Methoxyphenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[4-(4-Methy1-1 -piperaanyt)phenyl]amino}rnethylene)-1,4-dihydro-3(2H)-isoquinolinone; (4Z)-4-{{[4-(1 H-lmidazol-4-yl)phenyl]amino}methylene)-1,4-dihydro-3(2H)-isoquinolinone; (4Z)-4-{{[4-(4-Methylpiperazin-1 -yl)phenyl]amino}rnethylene)isoq uinoline 1,3(2H,4H)-dione; (4Z)-4-({[4-(2-Pyrrolidin-1 -ylethyl)phenyl]amino}methylene)isc5quinoline- 1,3(2H,4/-/}~ dione; (4Z)-4-(4-MOrpholin-4-ylphenyl)arnino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[(1 H-lndazol-6-ylamino)methytene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[(Quinolin-6-ylamino)methylene]isoquinoline-1,3(2H,4H)-dione; (4E)-4-[4-(dimethylamino)benzylidene]isoquinoline-1,3(2H,4H)-dione - (4Z)-4-[4-(dimethylamino)benzylidene]isoquinoline-1,3(2H,4H)-dione (1:1); (4E)-4-(4-hydroxybenzylidene)isoqurnoline-1,3(2H,4H)-dione; (4Z)4-({[4-(Piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z-4-[{3-Chloro-4[(1 -methyl-1 H-imidazole-2-uy)thio]phenyl}amio)methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[3-Chloro-4-{(4chlorobenzyi)oxy]phenyl}amino)methylene]isoquinoline-1,3(2H,4H-dione; (4Z)-4-({[[3-(Piperidin-1-ylmethyl)phenyr|amino}methylene)isoquinoline-1,3(2H,4H)-dione) (4Z)-4-({[3-(Azepan-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-clione; t (4Z)-4-({[3-{Pyrrolidin-1-ylmethyl)phenyl]amino}methytene)isoquinoline-1,3(2H.4H)-dione) (1c); (4Z)-4-({[4-{MORhpolin-4-ylnnethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (3); (4Z)-4-[({[4-[(4-Methylpipera2in-1-yl)methyl]phenylamino)nnathylene]isoquilin-1,3(2H,4H}-dione (4); (4Z)-4-[(1 ,1 '-Biphenyl-4-ylamino)methylene]isoquinoline-1 ,3(2H, 4H)-dione; (4Z)-4-{{[3-(2-Pyrfolidin-1 -ylethy1)phenyqamino}methylene)isoquinolfne-1 ,3(2H, 4H)-dione; (4Z)-4-{({[4-[(4-Hydroxypiperidin-1-yl)methyllphenyl}amino)methylene]isoquinolin-1,3(2H.4H)-dione; (4Z>6-Bromo-4-{[(4-piperidin-1-ylrnethyl)phenyl]amino}rnethyleneisoquinoline-1,3(2H, (4Z)-4-[({[4[(Dimethylamino)methyl Jphenyl}amino)methylene] isoquinolin-1 ,3(2H ,4H )-dione; (4Z)-4-({[[4-(A2epan-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione) (id); (4Z)-6-Bromo-4-({[[4-(4-methylpiperazin-1-yl)phenyl}amino}methylene)Jsoquinoline-1,3(2H, 4H)-dione; (4Z)-6-Bromo-4-{[(4-hydroxy-3-methoxyben2yl)aniino]rnethylene}isoquinoline-1,3(2H.4H)-dione(3a); ,3-Dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amlno}phenyl)-1 ,3(2H, 4H)-dione N-Methyl-2-piperidin-1 -ylacetamide; (4Z)-Bromo-4-{[(pyridinT3-ylmethyl)amino]methylene}isoqoinoIine-1.3(2H,4H)-dione; (4Z)-6-Bromo-44I(pyndin-4-ylrnethy1)amino]methylene}isoquinoIine-1,3(2H,4H)-dione; (4Z)-6-Nitro4-({[[4-(4-methylpiperazin-1-yl)phenyl}amino}rnethylene)isoquinoline-1,3(2H, 4H)-dione; tert-Butyl 4-(4-{[(Z)-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}piperazine-1-carboxylate; (4Z)-6,7-Dimethoxy-4-({[[4-(-methylpiperazin-1 -yl) phenyl}amino)methylene] isoquinolin-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-{[(2s)-2-(methoxymethy1}pyrrolidin-1-yl]methyl}phenyl)amlno)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-6-Bromo-4-{[(4-{I(2r)-2-(methoxymethyI)pyrrolidin-1-yl]methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-6-Bromo-4-{I(3,4-dihydroxybenzyl)amino]rnethylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[2-(piperidin-1-ylmethyl)phenyl}arnino)methylene]isoquinolin-1,3(2H,4H)-dione; (4Z)-6-Nitro-4-{[(4-piperidin-1 -ylmethyl)phenyl]amino}methyleneisoquinoline-1,3(2H, 4H)-dione; (4Z)-6-Bromo-4-({[[2-(1H-indol-3-yl)ethyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-7-Bromo-4-({[[4-(Piperidin-1-ylmethyl)phenyl]armino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-7-Bromo-4-({[[4-(4-methylPiperzin-1-yl)phenyl]arnino}rnethylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(3-hydroxyben3ryl)amino)methylene}isoquinoline-1,3(2H,4-dk3ne; 2-(AcetyIoxy)-4-({[[(ZH1.3-dioxo-2t3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}-methyl)phenyl acetate; N-[(4Z)-1,3-Dioxo-4-({[[4-piperidin-1-ylmethyl)phenyl]amino}methylene)-1,2.3,4-tetrahydroisoquinolin-6-yl]acetamide; (4Z)-2-Methyl-4-{[(4-plperidin-1-ylmethyl)phenyl]amino}methyleneisoqulnoline-1,3(2H, 4H)-dione; (4Z)-^BromcMH[(3-hydroxy-4-methoxyben2yl)arnino)methylene}isc>quinoline-1,3(2H,4H-dione; (4Z)-4-{{[4-{4-Methylpiperazln-1-yl)phenyl]amino}methylene)-1,3-d»oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid; (4Z)-([(3-Aminobenzyl)arnino]methylene}-6-brORnoisoquinol»ne-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-chlORobenzyl)amino)methylene}isoquinoline-1,3(2H,4H)-dione; 2-(Acetyloxy)-4-({[[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]-amino}methyl)phenyl acetate; (4Z)-6-Chloro-4-({[[4-(piperidin-1-ylrnethyl)phenyriamino}methylene)isoquinoline-1.3(2H,4H)-dione; 4-({[[(Z)-(6-Bromo-1,3-dioxo-2,3-didroisoquinoIin-4(1 H)-ylidene)methyl]amino)methyl)benzenesulfonamide; 5-({[(Z)-(6-Bromo-1-61.3-dioxo-2,3dlihydroisoquinolin-4(1HVylidene)methyl]arnino}rnethyl)-2-methoxyphenyl acetate; 5-{[(Z)-6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}-2-hydroxybenzoic acid; (4Z)-6-Bromo-4-({[4-(pyirrolidin-1-ylmethy1)phenyl]armino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(4-Methylp iperazin-1 -yi)phenyl]amino}methylene)-6- 1 H-pyrrol-1 -yl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-{I(4-Hydroxyben2yl)amino)methylene}isoquinoline-1.3(2H ,4H-dione; (4Z)-6-Bromo-4-{[(4-hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-4-{[{3-Hydroxybenzyf)amino)methylene}isoquinoline-1,3(2H ,4H-dione; (4Z)-6-Bromo-4[(3,5-dihydroxybenzyl)arnino)rnethylene}isoquinoline-1,3(2H.4H-dione; (4Z)-N,N-Dimethyl-4-({[[4-(4-methylpiperazin-1 -yl)phenyl]amino)methylene)-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-6-carboxamide; (4Z)-N,N-Dimethyl-1.3-dioxo-4-({[[4-(piperidinylmethyl)phenyl]annino}methylene)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide; (4Z)-6-ChtORo-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}isoquinoline-1.3(2H,4H)-dione; (4Z)-6-Fluoro-4-(3-hydroxy-4-methoxybenzyl)amino)methylene}isoquinoline-1,3(2H ,4H-dione; Acetic acid 3-acetoxy-5-{[(6-bromo-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-aminol-methyl}-phenyl ester; (4Z)-6-Fluoro-4-({[[4-(4-rnethylPiperzin-1-yl)phenyl]arnino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Fluoro-4-{[(3-hydroxy-4-methoxybenzyl)amino)methylene}-6-{1 H-pyrrol-1-yl)isoquinoline-1,3(2H ,4H-dione; (4Z)-4-({[[4-Pyrrolidin-1-ylmethyl)phenyl]amino}methylene)}-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[{4-{[(4-[(dimethylamino)methyl)methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-4-({[[4 -Piperidin-1 -ylmethyl)phenyl]amino}methylene)}-6-(1 H-pyrrol-1 -yl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{t(4-[(4-hydroxypiperidin-1-yl)methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; Carbonic add 5-{[(6-bromo-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-2-methoxycarbonyloxy-phenyl ester methyl ester, 5-({[(Z)-(6-Bromo-1,3nlioxo-2,3-dihydroisoquInpl!n-4(1H)-ylidene)methyl]amino)rnethyl)-2,3-dimethoxyphenyf acetate; (4Z)^Bromo-4-[(3-hydroxy-4,5-dimethoxybenzyl)arnino)methylene}isoquinoline-1,3(2H.4H-dione; (4Z)-6-Bromo-4-{[(3,4,5-trihydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-6-lodo-4{[(3-hydroxy-4-rnethoxybenzyl)arnino]rnethylene}isoquinoline-1,3(2H,4H)-dione (5c); (4Z)-6-lodo-4-({[I4-(4-methylpiperazin-1-yl)phenyl]amlno}methylene)isoquinoline-1,3(2H,4H)-dione(11c; (4Z)-6-lodo-4-({[[4-(piperidin-1-ylmethyl)phenyl]amino}rnethylene)isoquinoline-1,3(2H ,4H)-dione (11 a); 5-({[[(Z)(6-Brornc-1.3-dioxo-2,3-dihydroisoquJnolin-4( 1 H)-yIidene)methyl]amino}methyl)-2-methoxyphenyl methyl carbonate (8b); (4Z)-5-Bromo-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}isoquinoline-1, 3(2H, 4H)-dione; (4Z)-4-{[{3-Hydroxy-4,5-dimethoxybenzyl)amino)methylene}-6-thien-3-ylisoquinoline-1,3(2H,4H-dione; (4Z)-4-{[(3-Hydroxy-4,5-dimethoxybenzyl)amino)methylene}-6-phenytisoquinoline-1,3{2H,4H-dione; (4Z)-6-(3-Furyl)-4-{[(3-hydroxy-4,5-dimethoxybenzyl)amino)methylene}isoquinoline-1.3(2H,4H-dione; (4Z)-4-{[(3-Hydroxy-4-methoxybenzyl)amino]methylene}-6-thien-3-ylisoqulnoline-1,3(2H,4H)-dione (5b); (4Z)-6-lodo-4-{[(3-hydroxy-4,5-dimethoxybenzyl)amino)methylene}isoquinoline-1.3(2H.4H)-dione; 4-[(3-Hydroxy-4-methoxy-benzylarmino)-rnethylenel-6-methoxy-4H-isoquino!ine-1,3-dione; 6-Methoxy-4-[(4-piperidpn-1-ylmethyl-phenylamino)-methylene]-4H-isoqulnoline-1,3-dione; (42)-6-(3-Furyl)-4-{[(3-hydroxy-4-methoxybenzyl)amino)methylene}isoquinolIne-1,3(2H.4H-dione; (4Z)-6-(3-Furyl)-4-({[[4-piperidin-1-ylmethyl)phenyl]amino}methylene)}isoquinoline-1.3(2H,4H)-dione; (4Z)-6-Bromo-4-(3,5-dibromo-4-hydroxybenzylidene)isoquinoline-1,3{2H,4H)-dione; (4Z)-6-Phenyl-4-({[[4-piperidin-1-ylmethyl)phenyl]amino}methylene)}lscxjuinoline-1.3(2H,4H)-dione; (4Z)-6-(3-Hydroxyphenyl)-4-({[[4-piperidin-1-ylmethyl)phenyl]amJno}methylene)}isoquinoline-1,3(2H,4H)-dione; 3-[(4Z)-1,3-Dioxo-4-({[[4-piperidin-1 -ylmethyl)phenyl]amino}methytene)-1,2,3,4-tetrahydroisoquinoline-6-yl]thiophene-2-carbaldehyde; (4Z)-4-{[(3-Hydroxy-4-methoxybenzyl)aniino]rnethylene}isoquinoline-1,3(2H,4H)-dione (3d); 5-({[[(Z)(6-lodo-1.3-dioxo2,3-dihydroisoquJnolin-4(1H)-ylidene)methyl]arnino}methyl)-2-methoxyphenyl diethylcarbamate; (4Z)-6-(4-Phenoxyphenyl)-4-{[(3-hydroxy-4,5-dimethoxyben2yl)amino]methyiene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(4-Phenoxyphenyl)-4-({[I4-Pipericlin-1 -ylmethyl)phenyl]amino}methylene)}isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-Piperldln-1-ylmethyl)phenyl]amino}methylene)-6-pyridin-3-ylisoquinoline-1,3(2H,4H}-dione; (4Z)-6-{4-Hydroxyphenyl)"4-({[[4-piperidin-1-ylmethyl)phenyl]amino}methylene)}isoquinoline-1.3(2H,4H)-d»one; (4Z)-4-({[I4-(Piperidin-1-ylmethyl)phenyl]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H.4H)-dione; (4Z)-6-Bromo-4-{[4-(2-morpholin-4-ylethyl)piperazin-1-yI]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[4-[2-(dimethylamino)ethyGpiperazin-1-yl}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(4-Methylpiperazin-1-yl)phenyl]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(4-Methylpiperaan-1-yl)phenyl]amino}methylBne)-6-thien-3-ylisoquinoIine-1,3(2H,4H)-dione; (4Z)-4-{[(1,3-Benzodioxol-5-ylrnethyl)amino]rnethylene}-6-brORnoisoquinoline-1,3(2H>4H)- dione; (4Z)-1, 3-Dioxo-4-({[[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)1. 2, 3,4-tetrahydroisoquinoline-6-carbonitrile; (4Z)-6-(4-ChlORophenylM-({[[4-(piperidin-1-ylmethyl)phenyI]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-[(1 E)-5-ChtORopent-1 -enyl]-4-({[[4-(pJperidin-1 -yimethyl)phenylJamino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-{4-ChlORophenyl)-4-{l(3-hydroxy-4,5-dimethoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(4-methoxyphenyl)-4-{[4-(4-methylpiperazln-1-yl)phenyl]arnino}rnethylene)-isoquinoline-1,3(2H,4H)-dione 4-[(4Z)-4-({[[4-{4-Methylpiperazln-1 -yl)phenyl]amino}methylene)-1,3-dioxo-1,2,3,4-tetra-hydroisoquinolin-6-yl]benzaldehyde; (4Z)(4-Methoxyphenyl)-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)-isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-Methoxyphenyl)-4-({[[4-(piperidin-1-ylmethyl)phenyl]amino}rnethylene)-Isoquinoline-1,3(2H,4H)-dlone; (4Z}-6-Piperidin-1-yl-4-({[[4-(piperidin-1-ylmethyl)phenyl]amino}rnethylene)isoquinoline-1,3(2H,4H>-dione; (4Z)-6-Piperidin-1-yl-4-(fl4-(methylPiperzin-1-y1)phenyOamino}methylene)isoquinoline-1,3{2H,4H)-dione; (4Z)-6-MORpholin-4-yl-4-({[[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-[(2r)-2-(Methoxymethyl)pyrrolidin-1-ylH-({[[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1>3(2H,4H)-dFone; (4Z)-4-{[(4TAmino-3-hydroxybenzyl)amino]mBthylene}-6-iodoisoquinoIine- 1,3(2H,4H)-dione; (4Z)-6-[(4-Methyl-piperizin-1 -yl]-4-({[[4-(piperidin-1 -ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; 5-[(4Z)-4-({[[4-(4-Methylpiperaz!n-1 -yl)phenyl]amino}methylene)-1,3-dioxo-1,2.3,4-tetradydroisoquinonlin-6-yl]-2-furaldehyde; 4Z)-6-lodo-4-({[[4-(pyrrolidin-1 -ylmethyl) phenyl}amino)methylene] isoquinolin-1,3(2H,4H)-dione; (4Z)-6-(4-FluORophenyl)-4-({[[4-(pyrrolidin-1-ylmethyl)phenyl]amino}methylene)isoquinoIine-1.3(2H,4H)-dione; (4Z)-6-Anilino-4-({[[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[(1H-indoI-6-ylmethyl)amino]rr)ethylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(3-hydroxy-4-propoxyben2yl)amino]rnethyIene}Jsoquinoline- 1,3(2H,4H)-dione; (3Z)-3-(1-{[4-(4-Methylpiperazin-1-yl)phenyl]amino}ethylidene)piperidine-2,6-dione; (4Z)-4-{[{4-Amino-3-hydroxybenzyl)amino]methylene}-6-(4 fluorophenyl)isoquinoline-1,3(2H.4H)-dione; (4Z)-7-Bromo-4-{[(3-hydroxy-4-rnethoxybenzyl)arnino]rnethylene}isoquinolirie-1,3(2H,4H)-dione; (4Z)-4-{[(3-Hydroxy-4-nTethoxybenzyl)aminolmethylene}-6-{1HH3yrazo!-4-yl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(3-hydroxy-4-isopropoxybenzyl)amino]NRiethylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[({[4-[(2-methylpyrrolidin-1-yl)rnethyl]phenyl}amino)rnethylene]isoquinoline-1,3(2H.4H)-dione; (4Z)-6-Bromo-4-({[[3-hydroxy-4-(2-hydroxyethoxy)benzyl]amlno}methylene)isoquinoline- 1,3(2H,4H)-dione; (3Z)-3-{1-[(3-hydroxy-4-methoxybenzyl)amino]ethylidene}-4-phenylpiperidine-2,6-dione; 2-(Acetylamino)-5-({[[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinblin-4(1 H)-'ylidene)methyt]amino}nnethyl)phenyl acetate; N-[4-({[[(Z)-(6-Bromo-1,3-draxo-2,3-dihydroisoquinolin-4(1 H)-rylidene)methyl]amino}nnethyl)-2-hydroxyphenyl]acetamide; (4Z)-6-Bromo-4-({[[3-hydroxy-4-(2-pyiTolidin-1-ylethoxy)benzyl]amino}methylene) isoquinoline-1,3(2H,4H)-dione; 6-Bromo-4-[(4-pipericlin-1-ylmethyl-phenyl)-hydrazono]-4H-isoquino!ine-1,3-dione HydrochlORide; N-[4-({[[(ZM1,3-Dioxo-6-thien-3-yl-2,3-dihydroisoquinolin-4(1 H)-'ylidene)methyl]amino}methyl)-2-hydroxyphenyflacetamide; 2-{Acetylamino)-5-({[[(Z)-(6-iodo-1,3-dioxo-2,3-dinydroisoquinolin-4(1 H)-'ylidene)methyf|amino}methyl)phehyl acetate; (4Z)-4-({[{4-(Benzyloxy)-3-hydroxybenzyl]amino}methylene)-6-bromoisoquinoline-1.3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-butoxy-3-hydroxybenzyI)amino]rnethylene}isoquinoline-1,3{2H,4H)-dione; (4Z)-4-({[[4-(Allyloxy)-3-hydroxybenzyf|amino}methylene)-6-bromoisoquinoline-1,3(2H.4H)-dione; (4Z)-6-Bromo-4-({[[4-(hexyloxy)-3-hydroxybenzyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; N-[2-Hydroxy-4-({[[(Z)-(6-iodo-1,3-dloxo-2,3-dihydroisoquinolin-^(1 H)-'ylidene)methyl]amino}methyl)phenyl]acetamide; 4-[(4-Piperidin-1-yImethyl-phenyl)-hydrazono]-6-thiophen-3-yl-4H-iscxjuinoline-1,3-dione; 4-(4-{[4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzonitrile; 6-(3-Fluoroc-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methyfene}-4H-isoquinoline-1,3-dione; 4-[4-(4-Methyl-piperaan-1-yl)-phenylamino]-methylene}-6-(2-mORpholin-4-yl-ethoxy)-4H-isoquinoline-1,3-dione; 6-Furan-3-yl-4-[(4-piperidin-1-ylmethyl-phenyl)-yldrazono]-4H-isoquinoline-1.3-dione; (4Z)-4-{[(4-Methyl-3-hydroxybenzyI)aminolmethylene}-6-iodoisoquinoline-'1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[3-hydroxy-4-(2-ethoxyethoxy)benzyl]amino}methylene)isoquino!Jne-1,3(2H,4H)-dione; (42)-4-[({[4-[2-(BenzyIoxy)ethoxy]-4-hydroxybenzyl}amino)methyteneJ-6-bromoisoquinoline-1 ,3(2H,4H)-dione; 4-[{3-Hydroxy-4-methoxy-benzylamino)-methylene]-1,4-dihydro-2H-isoquinoline-3-one; (4Z)^({[I4-(4-Methylpiperazin-1-yI)phenyQamino}methytene)-6-[3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyQisoquinoline-1 ,3(2H,4H)-dione (7); 4-[(4-Piperid in- 1 -ylmethyl-phenylamino)-methylene]-1 ,4-dihydro-2H-isoquinolin-3-one; (4Z)-6-Bromo-4-{[(3-hydroxy-4-rnethoxyben2yl)(methyl)amino]methylene}isoquinoline- 6-Bromo-4[4-(1H-irnidazol-4-yl)-phenylamino]-methylene}-4H-isoqulnolin-1,3-dione; (4Z)-4-{[(Chloro-hydroxybenzyl)arnino]rnethylene}-6-iodoisoquinoline-,1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-ethoxy-3-hydroxybenzyl)amino]methylene}isoquinoline-1 ,3(2H ,4H)- dione; (4Z)-1 ,2-Diacetyl-4-{[(3-hydroxy-4-methoxybenzyl)aminoJmethylene}-1 ,4-dihydrocinnolin- 3(2H)-one; 6-Furan-2-yl-[(4-pyrrolidin-1-ylmiethyl-phenylam!no)-methylene]-4H-isoquinoline-1,3-dione; 4{[4-(2-pyrrolidin-1-yl-ethyl)-phenylanfiino]-methy1ene}-1.4-dihydro-2H-isoquinolin-3-one; (4Z)-4-({[[4-{4-Methylpiperazin- 1 -yl)phenyllamino}methylene)-6-(phenylethynyl)-isoquinoline-1 ,3(2H,4H)-dione; (4Z)-6-{(4-Methoxyphenyl)ethynyl]-4-({[I4-(4-methylplperazin-1-yl)phenyl]amino}-methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{I(2,5-dihydroxybenzyl)aminoJmethylene}isoquinoline-1 ,3 (2H,4H)-dlone; (4Z)-6-BTORho-4-{[(2-hydroxybenzyl)aminoJrnethylene}isoquinoHne-1 ,3 (2H,4H>-dione; (4Z) }-6-Bromo-4-{[(2,3.4-trihydroxybenzyl)amino]methylene}iscxiuinoline-1,3 (2H.4H)-dione; 6-Bromo-4-{[4--2-pyrro)idin-1 -yl-ethyl)-phenylamino]-methylene}-4H-isoquinolin-1 ,3- dione; (4Z)-6-(3-Methoxyprop-1 -ynyl)-4-({[[4-(4-methylpiperazin-1 -yl)phenyl]amino}-methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-{[(3-Hydroxy-4-propoxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-4-{[(3-Hydroxy-4-propoxybenzyl)amino]methylene}-6-iodoisoquinoline-1>3(2H,4H>-dione; (Z)-Diethyl 5-(((6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methylamino)methyl)ben2o[d][1,3]dioxote-2,2-dicarboxylate; (4Z)-6-Bromo-4-{I(4-difluORORnethoxy-3-hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H.4-dione; (4Z)-6-Bromo-4-{[(3-fluORo-4-methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(2,2'-Bithien-5-yl)-4-({[[4-(4-methylpiprazin-1-yl)phenyl]annino}nnethyIene)-isoquinoline-1,3(2H,4H)-dione; (4Z)-4-{[(3-Hydroxy-4-propoxybenzyl)amino}methylene }-6-thiene-3-ylisoquinoline-,3(2H, 4H)-dione; 5-{{[(Z)-(6-Bronno-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- 'ylidene)methyl]amino}methyl)-2-[(methoxycarbonyl)amino]phenyl methyl carbonate; 5-({[[(Z)-(6-Bromo-1,3-dioxo-2.3-dihydroisoqulnolin-4(1 H)- 'cyclopropanecarboxylate 'ylidene)methyl]amino}methyl)-2-[(cyclopropylcarbonyl)amino]phenyl; N-[(4Z)-4-({[[4-{4-Methylpiperazin-1 -yl)phenyl]amino}methylene)-1,3-dioxo-1,2.3.4-tetrahydroisoquinolin-6-yl]acetannide; (4Z)-4-({[[4-(4-Methylpipera2in-1-yl)phenyl]amino}methylene)-6-(thien-3-ylethynyl)-isoquinoline-1,3(2H,4H)-dione; 1,2,3,4-TetrahydroSsoquinolin-6-yl]benzenesulfonarnide'N-[(4Z)-4-({[[4-(4-methylpiperazin-1 -yJ)phenyQamino}methytene)-1,3-dioxo; (4Z}-6-Bromo-4-({[[1-(3-hydroxy-4-rnethoxyphenyl)ethyl]amino}methylene)lsoquinoline- 1,3(2H,4H)dione; 5-({[[{Z)-(6-Bromo-1,3-dioxo-2.3-dihydroisoquinolin-4( 1 H)-ylidene)methyl]amino}-methyl)-2-propoxyphenyl propionate; 5-({[[{Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methy1]amino}-methyl)-2-propoxyphenyl methyl carbonate; (4Z)-6-(4-FIuORophenyl)-4-{[(3-hydroxy-4-propoxybenzyl)amino]methylene}-isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-FluORophenyI)-4-{[(3-hyclroxy-4-propoxybenzyl)amino]methylene}-isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3,4-DifluORophenyl)-4-{[(3-hydroxy-4-piropoxybenzyl)amino]methylene}-isoquinoline-1,3(2H,4H)-dione; (4Z)}-6-Bromo-4-{[(3-hydroxy-5-propoxybenzyl)amino]methylene}isoquinoline-1,3 (2H,4H)-dione; N-((4Z)-4-{[(3-Hydroxy-4-methoxybenzyl)amino]methylene}-1,3-dioxo-1.2,3,4-'tetrahydroisoquinolin-6-yl)benzenesulfonamide; N-((4Z)-4-{[(3-Hydroxy-4-propoxybenzyl)amino]methylene}-1,3-dioxo-1,2,3,4- 1,2,3,4-tetrahydroisoquinolin-6-yl]-2-thien-2-ylacetamide14; 1,2,3,4-Tetrahydroisoquinolin-6-yl]-2-thien-2-ylacetamidelN-[(4Z)-4-({[l4-(4-methylpiperazin-1 -yl)phenyl]amino}methytene}-1,3-dioxo; (4Z)-4-({[[4-(Difluoromethoxy)-3-hydroxybenzyl]arnino}methylene)-6-(3-furyl) isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[I4-(Difluoromethoxy)-3-hydroxybenzyl]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; 4Z)-6-Bromo-4-({[[4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}methytene)isoquinoline- 1.3(2H,4H)-dione; N'-[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]-3-hydroxy-4- methoxybenzohydrazide; N-(4-Methylpiperazin-1-yl)-N'-[(4Z)-4-({[[4-(4-methylpiperazln-1-'yl)phenyqamlno}mBthylene)-1,3-dioxo-1,2.3,4-tetrahydroisoquinolin-6-yl]urea; (4Z) -4-{[(3-Arnino-4,5-dihydroxybenzyl)arnino]methylene}-6-brornoisoquinoline-1,3 (2H,4H)-dione; (4Z)-4-{[4-(3,5-Dimethylpiperazln-1-yI)phenyl]amino}methylene)-6-(4-fluORophenyl)-isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(3,5-Dimethylplperazin-1-yi)phenyr)amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(3,5-Dimethylpiperazin-1-yl)phenyl]amino}methylene)-6-(3-furyl)iso-quinoline-1,3(2H,4H)-dione; (4Z)-6-(4-Fluorophenyl)-4-[(3-hydroxy-4-methoxybenzyl)arnino]methylene}iso-quinORtne-1,3(2H.4H)-dione; (4Z)-6-(3-FluORophenyl)-4-{{(3-hydroxy-4-methoxybenzyl)amino]methylene}iso-quinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(3,5-dihydroxy-4-methoxyben2yl)amino3methylene}isoquinoIine-1,3 (2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-hydroxybutyl)amino]methylene}isoquinoline-1,3 (2H,4H)-dione; (4Z)-6-Bromo-4-{[(3-hydroxy-4,5-dipropoxybenzyl)amino]methylene}isoquinoline-1,3 (2H, 4H)-dione; N-[5-({[[(ZH6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyI]-2,3-dihydroxyphenyl]acetamide; (4Z)-6-Bromo-4-[(2,3-dihydro-1H-indol-5-ylamino)methylene] isoquinoline-1.3 (2H, 4H)-dione; N-(4-{[(Z)-(6-Bronno-1,3-dioxo-2,3-dihydroisoquinolin-4{1 H)-'ylidene)methyl]amino}phenyl)-4-methylplpera2ine-1-carboxannide; (4Z)-4-({[{4-(3,5-Dimethylpiperazin-1-yl)phenyl]amino}methyIene)-6-iodoisoquirK)line-1.3(2H.4H)-dione(30); N-(4-{[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-Vlidene)methyl]amino}phenyl)-N'-(4-methylpiperazin-l-yl)urea; N-[4-({[[(Z)-(6-Bromo-1.3-dioxo-2,3-dihydroisoquinolin-4(1 H)-'ylidene)methyl]annino}methyl)-2-hydroxyphenyl]-2,2,2-trifluoroacetamide; (4Z)-6-Bromo-4-({[[4-(cycJopropylmethoxy)-3-'hydroxybenzyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-2-(hydroxymethy1)-4-({[[4-(4-rnethylpipera2dn-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H ,4H)-dicxie; 6-lodo-4-{[4-(5-methyl-2,5-diaza-bicyclot2.2.1]hept-2-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; (4Z)-6-Bromo-4({[[(2-methoxypyridin-4-yl)rnethyllamino}NRiethylene)isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[4-(4-rnethylpiperazin-1 -yl)phenyl]amino}methylene)-1,4- dihydroisoquinolin-3(2H)-one; (4Z)-6-Bromo-4-({[[(7-hydroxy-2,2-dimethyl-1,3-ben2odioxol-5- yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)6-Bromo-4-({[[(2-oxo-1,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-(2,5-Dimethyl-1H-pyrro)-1-yI)-4-({[[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-{[(4-Amino-3-hydroxybenzyl)amino]methylene}-6-bromoisoquinoline- 1,3(2H,4H)-dione; PEG5000thio-acetic acid 5-{[(6-bromo-1,3.-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-2-propoxy-phenyl ester, (4Z)-6-Bromo-4-([(4-{[2-(dirnethylamino)ethyI]thio}phenyl)arnino]rnethylene}isoquinoline-1,3(2H,4H)-dione; 2-Hydroxy-4-[(3-hydroxy-4-propoxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; (4Z)-6-Bromo-4-[({[4-{[2- (dimethylamino)ethyl](methyl)amino]phenyl}amino)nnethylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[4-(4-methyl-1,4-diazepan-1-yl)phenylJamino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[({[4-({[2S,5R)-2,4,5-trirnethylpiperazin-1-yl]phenyl}amlno)methylene]-isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[({[4H[(3r,5S)-3,4,5-trimethylpiperazJn-1-yl]phenyI}arnino)methylene]-isoquinoline-1,3(2H.4H)-dione; (4Z)-4-{{[4-(3,5-Dimethytpiperazin-1-yl)phenyl]amino}methylene)-6-nitroisoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-Fuiyl)-4-({[[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (42); (4Z)-6-lodo4-({[[6-(4-methylpiperazin-1-yl)pyridin-3-'yl]arnino}rnethytene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[(2S,5r)-2,4,5-trimethylpiperazin-1-yl]phenyl}aNRiino)methylene]-isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-({[[4-(1-NRjethylpiperidin-4-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-BrORno-4-[({[4-[(3r,5S)-3,4,5-trimethylpipera2in-1-yl]phenyl}amino)methylene]-isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-Furyl)-4-[({[4-[(3r,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H ,4H)-dione; 6-Bromo-7H7iethoxy-4-{[4-(4-niethyl-piperazin-1-yl)-phenylarnino]-methylene}-4H-isoquinoline-1,3-dione; (4Z)-6-Bromo-4-{[(4-{[2- (dimethylamino)ethyl]sulfonyl}phenyI)aminoJmethylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[(2- hydroxyethyl)(methyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-n{4-{meihyl(1-methylpyrrolidin-3- yl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; 6-Bromo-4-[(3-hydroxy-4-propoxy-benzylamino)-methylene]-7-methoxy-4H-isoquinoline-1,3-dione; (4Z)-6-lodo-4-({[I4-(pyridin-2-ylmethoxy)phenyrjamin 'methylene)isoquinoline1,3(2H ,4H>-dione; (4Z)-4-({[[4-(3,4-Dimethylpiperazin-1-yl)phenyl]amino}m6thylene)-6-iodoisoquinolin6-1,3(2H,4H)-dione; (4Z)-6-(3-Furyl)-4-({[[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[6-(4-methylpiperazin-1-yl)pyridin-3- 'yl]amini}methylene)isex|uinoline-1,3(2H,4H)-dione; (4Z)-6-(4-FluORophenyl)-4-({[[4-{piperidin-1 -ylmethyl)phenyliamino}methylene)isoquinoline-1,3(2H,4H)-drone; 6-Bromo-7-methoxy-4-[(4-p?peridin-1-ylrnethyI-phenylaimino)-rnethylene]-4H-isoquinoiine-1,3-dione; 6-(4-FluORC1-6pheriyl)-7-meethoxy-44(4-pipertdin-1-ylmethyl-phenylarnino)-methylene]-4H-isoquinoline-1,3-dione; 6-Furan-3-yI-7-methoxy-4-{I4-(4-methyl-piperazin-1-yl)-phenylamino]-methytene}-4H-isoquinoline-1,3-dione; (4Z)-6-Bromo-4-[{{4-[methyl(2-pyrrolidin-1- ylethyl)amino]phenyl}amino)nnethy)ene]isoquinoline-1,3(2H,4H)-dione; (42}-6-Bromo-4-[({[4-[nnethyl(2-piperidin-1- ylethyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-diorie; (4Z)-6-Bromo-4-[({[4-[{2- [butyl(methyl)amino]ethyl}(methyl)amino}phenyl}amino)methylene]isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[2-(dimethylamino)ethoxy]phenyl}amino)methylene]isoquinoline- 1,3(2H,4H)-dione; (42)-6-Bromo-4-{[(2-hriethyl-2,3-dihydro-1H-isoindol-5-yl)arnino]methytene}isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[4-(1 H-imidazoH -yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H> dione; (4Z)-6-Bromo-4-{[(4-{methyl[2-(4-methylpiperazin-1- yl)ethyl]amino}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[methyl(2-mORpholin-4- ylethyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; .(4Z)-6-(4-FluORophenyl)-4-({[[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)-isoquinoline-1,3(2H,4H-dione; (4Z)-6-lodo-4-{[(4-{I(3r)-3-methoxypyiTolidin-1-yl]methyl}phenyl)aminojmethylene}iscxiuinoline-1,3(2H,4H)-dione; (4Z)-6-(4-FluORophenyl)-4-{[(4-{I(3S)-3-methoxypyrrolidin-1-yl]methyl}phenyl)amino}methytene}isoquinoline-1,3(2H.4H)-dione; (4Z)-6-Bromo-4-{I(4-{[{3R)-3-methoxypyrrolidin-1-yl]methyl}phenyl)amino]methyIene}istxiuinoine-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[(4-difluORomethoxy-3-hydroxybenzyl)arnino)rnethylene}isoquinoline- 1.3(2H.4-dione; 6-({[[(Z)-(6-Brc>mo-1.3-dioxo-2,3dihydroisoquirlin-4(1H)-yliclene)methyl]arnino}methyl)- 2,2-dtmethyl-1,3-benzodioxoI-4-yl acetate; 6-({[(Z)-(6-Bromo-1,3-dloxo-2,3-dihydroisoquinolin-4( 1 H)-y1idene)methyl]amino}methyl)- 2,2-dimethyl-1,3-benzodioxol-4-yl cyclopropanecarboxylate; (4Z)-6-Bromo-4-{({[4-[3-(dimethyIamino)propyl]phenyl}amino)methylene]isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[(quinoIin-6-ylamino)methylene]isoqutnoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[(quinolin-6-ylamino)methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-( 1 H-lmidazol-1 -ylmethyl)phenyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)6-Bromo-4-[({[4-[3-{NRiethoxyamino)propyrjphenyl}arnino)rnethylene]isoquinoline- 1.3{2W,4H)-dione; (4Z)6-Bromo-4-[({[4-p- (dimethylamino)propytI(rnethyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)- dione; (4Z)-6-Bromo[({[4-[(1-inethylpyrrolidin-3-yl)oxy]phenyl}amino)methylene]isoquinoline- 1,3(2H,4H)-dione; 2-amino-2-{4-[(6-bromono-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-arnino]-phenyl}-propionic acid; 4-[(3-Hydroxy-4-propoxy-benzylamino)-methylene]-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione; 4-[3-4-Methyl-piperazin-1-yl)-propylamino]-rnethylene}-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione; dimethylbenzohydrazide; (4Z)-6-Bromo-4-({[{4-{1,3-thiazolidin-3-ylmethyl)phenyl]arnino}methylene)isoquinoHne-1.3(2H.4H)-dione; (4Z)-4-({[[4-(Pyrrolidin-1-ylmethyl)phenyl]amino}methylene)-6-[4-(trifluoromethyl)phenyl]isoquinoline-1,3{2H,4H]hdione; 2-(4-{[(Z)-(6-Bromo-1 ,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- ylidene)methyl]amino}phenyl)-N,N-dimethylacetohydrazide; Diethyl {(4Z)-4-({[[4-(4-methyIpiperazin-1-yl)phenyl]amino}methylene)-1 ,3-dioxo-1 ,2,3,4- tetrahydroisoq uinolin-6-yl]phosphonate; (4Z)-6-lod6-4-{[(4-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino]methylBne}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[4-(motpho}in-4-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[(2-methylpyrrolidin-1-yl)methyl]phenyl}arnino)methylene]-isoquinoline-1,3(2H,4H)-dione (60); (4Z)-6-Bromo-4-({[[3-f luORo-4-(4-methylpiperazin-1 - yl)phenyl]amino}methylene)-isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(4-FluORophenyl)-4-[({[4-[(2-methylpyrrolidin-1-yl)methyI]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[3-Fluoro-4-(4-rnettiylpiperazin-1-yl)phenyl]arnino}methyIene)-6-(4-fluORophenyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-Furyl)-4-[({[4-[(2-methylpyrrolidin-1-yl)methyl]phenyl}amino)methy)ene]-isoquinoline-1,3(2H,4H)-dione; PEG5000thio-acetic acid 5-{[(6-iodo-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-2-propoxy-phenyl esten 5-({[[(Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)-2-propoxyphenyl chloroacetate; tert-Butyl 4-(4-{[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyi]amino}phenyl)piperazine-1-carboxylate; (4Z)-4-({[[3-FluORo-4-(4-methylpiperazin-1-yl)phenyl]annino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-({[[4-(mORpholin-4-ylmethyI)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)4-({[[3-Fluoro-4-(4-methylpiperazin-1-yl)phenyllamino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(4-Methylplperazin-1-yl)phenyl]amino}methylene)-6-[4-(trifluoromethoxy)phenyqisoquinol!ne-1,3(2H,4H)-dione; (4Z)-6-(4-FluORophenyi)-4-{[(4-{[(2S)-2-{methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H.4H)-dione; (4Z)-6-(4-lsopropoxyphenyl)4-{[(4-(2R)-2-(meththoxymethyl)pyrrolidin-1-yl]methyl}phenyl)aminolmethylene}isoquinoline-1,3(2H,4 H)-dione; N-[4-({((Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoq uinolin-4( 1H)-ylidene)methyl]amino}methyl)-2-hydroxyphenyl]acrylamide; N-[4-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2,2-dichloroacetamide; (4Z)-4-[({[4-Amino-3-(triisopropylsllyl)oxy]benzyl}amino)methylene]-6-bromoisoquinoIine-1,3(2H,4H)-dione; (Z)-6-Bromo-4-((5-(dimethylamino)pentylamino)rnethylene)isoquinoline-1,3(2H,4H)-dione; (Z)-6-Bromo-4-((4-(dimethylaniino)butylamino)rnethylene)isoquinoline-1.3(2H,4H)-dione; (Z)-6-Bromo-4-((3-(dimethylamino)propylamino)methylene)isoquinoline-1,3(2H,4H)-dione; (Z)-6-Bromo-4-((2-(piperazin-1-yt)ethylamino)methylene)isoquinoline-1,3(2H,4H)-dione; (Z)-6-Bromo-4-((4-(diethylamino)butylamino)methylene)lsoquinoline-1,3(2H,4H)-dione; (Z)-6-Bromo-4-((3-(pyrrolidin-1-yl)propylarnino)methylene)isoquinoline-1,3(2H,4H)-dione; (Z)-6-Bromo-4-((3-mORpholinopropylarnino)methylene)isoquinoline-1,3(2H,4H)-dione; (Z)-6-Bromo-4-((3-(2-oxopyrrolidin-1-yl)propylamino)methylene)isoquinoline-1,3(2H,4H)-dione; 4-{[(5-Hydroxy-4-oxo-4H-pyran-2-ylmethyl)-amino]-methylene}-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione; 6-Bromo-4-[(5-hydroxy-4-oxo-4H-pyran-2-ylrnethyl)-arnino]-rnethylene}-4H-isoquinoline-1,3-dione; (Z)-4-((6-Bromo-1,3-dioxo-2,3-dthydroisoquinolin-4(1H)-ylidene)methylamino)butanoic acid; (Z)4-((1,3-Dioxo-6-(1 H-pyrrol-1-yl)-2.3-dihydroisoquinolin-4(1 H)-ylidene)methylamino)butanoic acid; 6-Bromo-4-{[(5-methoxy-4-oxo-4H-pyran-2-ylmethyl)-amino}-methylene}-4H-isoquinoline-1,3-dione; 4-{[(5-Methoxy-4-oxo-4H-pyran-2-ylmethyl)-amino]-methylene}-6-pyrrol-1 -yl-4H-isoquinoline-1,3-dione; (4Z)-6-Bromo-4-[({[4-[(3r,5S)-3,5-dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene]isoquinoline-1,3{2H,4H)-dione; (4Z)-4-[({[4-[(3r,5S)-3,5-Dimethytpiperazin-1-yl]-3-fluorophenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (75); N-[4-({[[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylldene)methyl]amIno}methyl)-2-hydroxyphenyl]-2,2-dichloroacetamide; N-[4-({[[(Z)-(6-Bromo-1,3-dioxo-2.3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]propanamide; N4-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]aCRylamide; (4Z)-4-[({[4-Amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methyIene]-6-iodoisoquinoline-1,3(2H.4H)-dione; (4Z)-4-[({[4-[(3r,5S)-3,5-Dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene]-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[(3r,5S)-3.5-Dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[(3r,5S)-3,5-Dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene]-6-{4-fluORophenyl)isoquinoline-1,3(2H,4H)-dione (78); (4Z)-4-({[[4-{1-Methylpiperidin-4-yl)phenyl]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[13-Fluoro-4-(4-methylpiperazin-1 -yl)phenyl]amino}methylene)-6-(1 H- pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione; 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; (4Z)-6-(3-Furyl)-4-{[(4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amlno)methylene}lsoquinoline-1,3(2H,4H)-dione; (4Z)-4-{[(4-{[(2R)-2-(Methoxymethyl)pyrrolidin-1 - yl]methyl}phenyl)amino]methylene}-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; 6-Bromo-4-[(4-hydroxy-5-methoxy-pyridin-2-ylrnethyl)-amino]-methylene}-4H-isoquinoline-1,3-dione; 4-t(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-pyrrol-1 -yl-4H-isoquinoline-1,3-dione; N-[2-Hydroxy-4-({[[(Z)-(6-iodo ,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-yljdene)methyl]amino}methyl)phenyl]benzamlde; N-[2-Hydroxy-4-({[[(Z)-(6-iodo-1,3-dioxo-2,3-dihydrolsoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyr)-2-methylpropanamide; (2E)-N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl)-2-methylbut-2-enamide; (2Z)-3-Chloro-AH2-hydroxy-4-{{[(Z)6-iodo-1,3-dfoxo-2.3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]aCRylamide; 2-[(Dimethylamino)methyl]-N-[2-hydroxy-4-({[[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyriamino}methyl)phenyl]arylamide; N-[2-Hydroxy-4-({[[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolfn-4(1 H)-yIidene)methyl]amino}rnethyl)phenyl]but-2-ynamide; N-[2-Hydroxy-4-({[[(Z)-(6-ipdo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]prop-2-ynamide; 46 N-[2-Hydroxy-4-({[[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]propanamide; N-[2-Hydroxy-4-({[[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]acrylamide; 2-[(2E)-But-2-enoylamino]-5-({[Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyf)phenyl (2E)-but-2-enoate; (4Z)-6-Bromo-4-({[[4-(1-methylpiperidin-4-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[(3r,5S)-3,5-Dimethylpiperazin-1-yI]-3- fluorophenyl}amino)methylene]-6-(4-methoxyphenyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[5-[(3r,5S)-3,5-Dimethylpipera2in-1-yl]pyridin-3-yl}amino)methylene]-6- (3- furyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(Dimethylamino)-3-hydroxybenzyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione; 6-Bromo-4-{[4-(4-chloro-3,5-dimethyl-pyrazol-1-yl)-phenylamino]-imethylene}-4H-isoquinoline-1,3-dione; 6-Bromo-4-[(4-pyridin-3-yl-phenylamino)-methylens]-4H-isoquinoline-1,3-dione:(4Z)-6-bromo-4-(3-hydroxy-4propoxybenzyl)amino]methylene}isoquinoline-1,3{2H,4H)-dione; (4Z)-6-Bromo-4-[({[6-[(2r,6S)-2,6-dimethylpiperidin-4-yl]-5-methylpyridin-3-yl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(1-Acetylpiperidin-4-yl)phenyl]amino}methylene}-6-(3-furyl)isoquinoline-1.3(2H.4H)-dione; 5-{[(ZH6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)miethyl]ramino}methyI)-2-propoxybenzoic acid; 5-({[[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)rnethyl]amino}rnethyl)-2-propoxybenzamide; 6-lodo-4-{I4-(1 -pyrrolidin-1 -yl-ethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; (4Z)r4-[({[6-[(3r.5S)-3,5-Dimethylpipera2in-1-yl]-5-methylpyridin-3- yl}amino)methylene]-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[6-[(3r, 5S)-3.5-Dimethylpiperazin-1 -yl]-5-methyipyridin-3- yl}amino)methylenel-6-thlerv3-ylisoquinoJine-1,3(2H,4H)-dione; (4Z)-4-[({[6-[(3r,5S)-3,5-Dimethylpiperazin-1-yl]-5-methylpyridin-3-yl}amino)methylene]-6-(4-methoxyphenyl)isoquinolrne-1,3(2H,4H)-dione; (4Z)-6-(4-Methoxyphenyl)-4-[({[4-{(2-methyIpyrrolidin-1-yl)methyl]phenyl}amino)-methylene]-isoquinoline-1,3(2H ,4H)-dione; (2E)-4-(pimethylamino)-N-[2-hydroxy-4-({[[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4( 1 H)-ylidene)methyl]amino}methyl)phenyl]but-2-enamide; 6-lodo-4-{[4-(4-rnethyl-piperazin-1-yl)-cyclohexylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-lodo-4-{[4-(1-methyl-pyrrolidin-2-yl)-phenylamino]-methyl€ne}-4H-isoquinoline-1,3-dione; 6-lodo-4-{(4-hydroxy-5-methoxy-pyridin-2-ylrnethyl)-arnino3-methylene}-4H-isoquinoline-1,3-dione; 4-{[(4-Hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino]-methylene}-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione; 4-{[(4-Hydroxy-5-propoxy-pyridin-2-ylmethyl)-annino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; 44[(4-Hydroxy-5-propoxy-pyridin-2-ylmethyl)-arnino]-methylene}-6-bromo-4H-isoqulnoline-1,3-dione; (4Z)-4-{{[3-Hydroxy-4-(propylamino)benzyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione; D-1-{4-[(6-lodo-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-benzyl}-pyrrolidine-2-carboxylic acid methyl ester, D-4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylarnino]-methylene}-6-iodo-4H-isoquinoline-1,3-dkane; D-4-({[4-[2-(1-Hydroxy-1-methyl-ethyl)-pyrrolidin-1-ylmethyl]-phenylamino}-methylene)-6-iodo-4H-lsoquinollne-1,3-dione; (4Z)-6-Bromo-4-[({[3.5-difluoro-4-[(8as)-hexahydropyrrolo[1,2-a]pyrazin-2(1 H)-yl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[3,5-Difluoro-4-[(8aS)-hexahydropyrrolo{1,2-a]pyrazin-2(1H)-yllphenyl}amino)-methytene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[I4-[(3r,5S)-3,5-diNRiethylpiperazin-1-yl]-3-(trifluoromethyl)phenyl]amino}methy1ene)isoquinoline-1,3(2H,4H)-dionei (4Z)-4-[({[4-[(3r,5S)-4-(N,N-Dimethylglycyl)-3,5-dmnethylpiperazin-1-yl]phenyl)amino)methylene]-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione; 4-({[4-[2-(1-Hydroxy-ethyl)-pyrrolidin-1-ylmethyri-phenylarnino}-methylene)-6-iodo-4H-isoquinoline-1,3-dione; 6-lodo-4-({[4-[2-(1-methoxy-ethyl)-pyrrolidin-1-ylmethyl]-phenylamino}-methylene)-4H-isoquinoline-1,3-dione; L-4-{[4-(2-Hydroxyrnethyl-pyrrolidin-1-ylmethyl)-phenylarnino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; tert-Butyl 4-(4-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoqutnolin-4(1 H)-ylidene)methyl]amino}phenyl)piperazine-1-carboxylate; (4Z)-6-lodo-4-{[(4-piperazin-1 -ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione; (Z)-4-(((6-Brorno-5-propoxypyridin-2-yl)methylamino)methy1ene)-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[(3r,5S)-4-{N,N-Dimethylglycyl)-3,5-dimethylprperazin-1-yl]phenyl}amino)methylene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{({[4-[(3R,5S)-3.5-dirnethylpipera23n-1-yll-3,5-difluorophenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[3-Fluoro-4-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1 H)- yl)phenytyamino)-methylene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[(3r,5S)-3,5-Dimethylpiperazin-1-yl]-3,5-dlfluorophenyl}amino)methylene]-6-thien-3-ylisoquinoline-1,3(2H4H)-dione (83); N-[(4Z)-4-{{I4-(4-Methylpiperazin-1 -yl)phenyl]amino}methylene)-1,3-dioxo-1,2,3,4-tetrahydrdisoquinolin-6-yl]acrytamide; (4Z)-6-lodo-({[[4-(4-isopropylpiperazin-1-yl)phenyliamino}rnethylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[({[4-[4-(1 -methylpiperidin-4-yl)piperazin-1 -yl]phenyl}amino)methylene]isoquinorne-1,3(2H,4H)-dione; (4Z)-6-lodo-4-({[[4-(4-propylpiperazin-1-yl)phenyl]arnino}NRiethyIene)isoquinoline-1,3(2H.4H)-dione; (4Z)-4-[({[4-[4-(2-Furylmethyl)piperazin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H.4H)-dione; (4Z)-4-[({[4-[4-(3-Furylmethyl)piperazin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3{2H,4H)-dione; (4Z)-4-[({[4-[4-(Cyclopropylmethyl)piperazin-1-yl]phenyl}amino)methylene]-6-iodoisoquino!ine-1,3(2H,4H)-dione; (4Z)-4-({[[4-(4-Cyclobutylpiperazin-1-yl)phenyl]amino}methylene)-6- iodoisoquinoline-1.3(2H,4H)-dione; (4Z)-4-({[[4-(4-Ethylpiperazin-1-yl)phenyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-t({[4-[(4-methoxypiperidin-1 -yl)methyl]phenyl}arnino)methylene]isoquinoline-1,3(2H.4H)-dione; (4Z)-6-(4-Fluorophenyl)-4-[({[4-t(4-methoxypiperidin-1-yl)methyl]phenyl}amino)methylene]isoquinoline-1.3(2H,4H)-dione; (4Z)-4-({[[6-(4-Methylpiperazin-1-yl]pyridin-3-yl]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[(4-methoxypiperidin-1 -yl)methyl3phenyl}amino)methytene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[4-(2-Hydroxy-1-methyiethyl)piperazin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[4-(4-ethylpiperazln-1 -yl)phenyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[({[4-[4-(2-methoxy-1 -methylethyl)piperazin-1 -yl]phenyl}amino)methylene]isoquinoline-1,3(2H.4H)-dione; (4Z)-4-{[(4-{4-[2-(Dimethylamino)-1-methylethy1]piperazln-1-yl}phenyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[4-(2-Hydroxyethyl)plperazln-1-ylJphenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione; 4-({[4-[1-(4-Dimethylamino-but-2-enoyl)-pyrrolidin-2-yl]-phenylamino}-NRiethylene)-6-iodc)-4H-isoquinoline-1,3-dione; 4-{[4-(4,5-Dihydro-3H-pyrrol-2-yl)-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; 4-{[4-(1,2,3,6-Tetrahydro-pyridin-2-yl)-phenylamino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione; (4Z)-6-Bromo-4-({[[3-fluoro-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]amino}-methylene)-isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[3-Fluoro-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]amino}methylene}-6- thien-3-ylisoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[6-(4-pyrrolidin-1 -ylpiperidin-1 -yl)pyridin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[(3R,5S)-4-(N,N-Dimethylglycyl)-3,5-dimethylpiperazin-1-yl]pheny)}amino)methylene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione; tert-Butyl 4-(5-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoqiiinolin-4(1 H)-ylidene)methyl]amino}pyridin-2-yl)piperazine-1-carboxylate; (4Z)-6-lodo-4-([(6-piperazin-1-ylpyrldin-3-yl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione; 4-{[4-(2-Ethoxymethyl-pyrroKdin-1-ylmethyl)-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; 4-[4-{24)imethylaminomethyl-pyrrolidin-1-yl)-3-fluoro-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; (4Z)-6-lodo-4-({[[6-(4-lsopropylpiperazin-1-yl)pyridin-3-yl]amino}methylene)isoquinoline-1,3{2H.4H)-dione; (4Z)-4-({[6-(4-Ethylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6- iodoisoquinoline-1.3(2H,4H)-dione; (4Z)-4-[({[6-[4-(Cydopropylmethyl)piperazin-1-yl]pyrldin-3-yl}amino)methytene]-6-iodoisoquinoline-1,3(2H ,4H)-dione; (4Z)-4-({[[6-(4-Ethylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H.4H)-dione; (4Z)-4-(fl6-{4-lsopropylpjperazin-1-yl)pyrldin-3-yl]amino}methylene)-6-(3-thienyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[6-[4-(Cyclopropylmethyl)piperazin-1-yl]pyridin-3-yl}amino)methylene]-6-(3-thienyl)isoquinoline-1,3(2H,4H)-dione; 4-{[4-(1-Allyl-pyrrolidin-2-yl)-phenylamino]-methyIene}-6-iodo-4H-isoquinoline-1,3-dione; 4-{[4-(1-Allyl-pyrrolidin-2-yl)-phenylamino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione; 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethy|)-phenylamino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1 ,3-dione; (4Z)-4-{[(4-{[3-(Dimethylamino)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}-6-iodoisoquinoline-1.3(2H.4H)-dione; (4Z)-4-{[(4-{[3-(Dimethylamlno)pyNRolidin-1-yl]methyl}phenyl)amino]methylene)-6-iodoisoquinoline-1 ,3(2H,4H)-dione; 44[(5-Amino-4-hydroxy-pyridin-2-ylmethyl)-arnino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; (4Z)-4-{[(4-{1-[3-(Dimethylamino)propyl)piperidin-4-yl}phenyl)amino]methylene}-6-iodoisoquinoline-1 ,3(2H,4H)-dione; 4-{[3-Fluoro-4-(2-hydroxymethyi-pyrrolidin-1-yI)-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1 ,3-dione; 6-lodo-4-{I(5-oxo-pyrrolidin-2-ylmethyl)-amino}-rnethylene}-4H-isoquinoline-1 ,3-dione; N-(4-Hydroxy-6-{[(6-iodo-1.3-dioxo-2,3-dihydro-1H-isoquinoiin-4-ylidenemethyl)-arninol-methyl}-pyridin-3-yl)-acrylamide; 1-(4--{[(Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}phenyl)-N,N-dimethylpiperidine-4-carboxamide; ,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}phenyl)piperidine-4-carboxamide; ,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methylJamino}phenyl)piperidine-4-carboxylicacid; (4-{[(Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinolin-4( 1 H)-ylidene)methyl]amino}phenyl}-N-methoxy-N-methylplperidine-4-carboxamide; N-[2-(Dimethylamino)ethyl]-1 -(4-{[(Z)-(6-iodo-1 ,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}phenyl)piperidine-4-carboxamide; (4Z)-4-[({[4-[4-(Hydroxymethyl)piperidin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H.4H)-dione; (4Z)-6-lodo-4-[({[4-[4-(methoxymethyl)piperidin-1-yl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; 4-{[4-(2-Ethyl-pyrroIidin-1-ylmethyl)-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; 6-BromcM-{[4-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 4-[4-(2-Hydroxymethyl-pyrrolidin-1-ylrnethyl)-phenylamino]-rnethylene}-6-thiophen-2-yl-4H-isoquinoline-1,3-dione; (4Z)-4-{[(4-{[2-(Hydroxymethyl)prperidin-1-yl]methyl}phenyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dlone; (4Z)-4-[({[4-[(4-Hydroxypiperidin-1-yl)methyl]phenyl}amino)methylene]-6-iodoisoquinoline-1.3(2H,4H)-dione; 6-(5-Chloro-thiophen-2-yl)-4-{[4-(2-hydroxyrnethyl-pyrrolidin-1-yImethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; (4Z)-6-Bromo-4-({[[5-(4-methyIpiperazin-1-yl)pyridin-2-yllamino}methylene)isoquinoline-1,3(2H.4H)-diqne; (4Z)-6-(3-Furyl)-4-{{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (Z)-4-((5-Brornopyridin-2-ylamino)methylene)-6-(1H-pyrrol-1-yl)isoquinoline-1.3(2H,4H)-dione; (4Z)-4-{{[2-Fluoro-6-(4-meWiylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[4-[4-({[[2-(Dimethylamino)ethyl]amino}methyl)piperldin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[[2-Hydroxy-6-(4-methyIpiperazin-1-yl)pyridin-3-yI]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione; 4-[(4Z)-4-({[[5-(4-Methylpiperazin-1 -yI)pyridin-2-yl]amino}methylene)-1,3-dioxo- 1,2,3,4-tetrahydroisoquinolin-6-yl]-2-furaldehyde; (4Z)-4-{{[5-(4-Methylpiperazin-1-yl)pyridin-2-yr|amino}methylene)-6-[5-(pyrro!idin-1-ylmethyl)-3-furyl]isoquinoline-1,3(2H.4H)-dione; 4-{[4-(1-Methyl-pyrro1idin-2-yl)-phenylamino]-methylene}-6-thtophen-2-yl-4H-isoquinoline-1,3-dione; 6-Furan-3-yW-{[4-(1-methyl-pyrrolidin-2-yl)-phenylamino]-rnethyIene}-4H-isoquinoline-1,3-dione; 6-Bromo-1,1 -dimethyl-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,4-dihydro-2H-isoquinolin-3-one; (4Z)-6-lodo4-{{I(1 -methyl-2-oxo-1,2-dinydropyridin-4-yI)methyl]arrHno}fnethylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-{[(4-{4-[(Dimethylamino)!n8thyl]piperidin-1-yl}phenyl)amino]methytene}-6-iodoisoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-({[I4-(4-{methyl(1 -methylpyrrolidin-3-yl)amJno]methyl}piperidin-1 -yl)phenyl]annino}methylene)iscxjuinoline-1,3(2H,4H)-dione; (4Z)-4-{[(4-{4-[(Ethylamino)methyl]piperidin-1-yl}phenyl)amino]methytene}-6-iodoisoquinoline-1,3(2H,4H)-dione; (42)-4-({[[2-Fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione; 6-Furan-3-yl-1,1-dimethyl-4-{[4-(4-methyI-piperazin-1-yl)-phenylamino]-methylene}-1,4-dihydro-2H-isoquinolin-3-one; (Z)-4-((5-Bromopyridin-2-ylamino)nnethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H>-dione; (Z)-6-lodo-4-((5-(1-methylpyrrolidin-2-yl)pyridin-2-ylannino)methylene)isoquinoline-1,3(2H,4H)-dione; 2-{4-[(6-lodo-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-pyrrolidine-1-carboxylic acid tert-butyl ester, 6-Iodo-4-[(4-pyrrolidin-2-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; 6-Furan-3-yl-{[[4-(2-hydroxymethyl-pyrroIidin-1-ylrnethyl)-phenylamino]-rnethylene}-4H-isoquinoline-1,3-dione; 4-({[4-[1-(2-Hydroxy-ethyl)-pyrrolid!n-2-yl]-pheny!annino}-methylene)-6-iodo-4H-isoquinoline-1,3-dione; 4-{[4-(1-Ethyl-pyrrolidin-2-yl)-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; 6-Furan-2-yl-{[4-(2-hydroxymethyl-pyrroIidin-1-ylrnethyl)-phenytarnino]-rnethylene}-4H-isoquinoline-1,3-dione; (4Z)-6-(2-Furyl)-4-{[(4-{[(2S)-2-(methoxymethyi)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[5-[(3r,5S)-3,5-Dimethylpiperazin-1-yl]pyridin-2-yl}amino)methylene]-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-t({[5-[(3r.5S)-3,5-dimethylpiperazln-1-yl]pyridin-2-yl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; N-(4-Hydroxy-6-{[(6-iodo-1,3-dioxo-2,3-dihydro-1H-lsoquinolin-4-ylidenemethyl)-arnino]-methyl}-pyridin-3-yl)-propionamide; 6-lodo-4-{[(1-methyl-4-oxo-5-propoxy-1,4-dihydro-pyridin-2-ylmethyl)-arnino]-methylene}-4H-isoquinoline-1,3-dione; 4-[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-6-thiazol-2-yl-4H-isoquinoline-1,3-dione; 4-{[4-(1-Ethyl-pyrrolidin-2-yl)-phenylamino]-methylene}-6-furan-3-yl-4H-isoquinoline-1,3-dione; (4Z)-4-({[[6-(4-Methylpiperazin-1-yl)pyridin-3-yl]amino}methy!ene)-6-(1 -methyi- 1 H-pyrrol-2-yl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-({[[2-(4-methylpiperazin-1-yl)pyrimidin-5-y1]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-Furyl)-4-({[[6-(4-methylpiperazin-1-yl)pyridazin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dlone; (4Z)-6-Bromo-4-({[[6-(4-methylpiperazin-1-yl)pyridazin-3-yl]amino}methytene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[(5-{[(2S)-2-(methoxymelhyl)pyrrolidin-1-yl]methyl}pyridin-2-yl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; 4-{[(4-Hydroxy-5-methoxy-pyrimidin-2-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1 ,3-dione; {4Z)-4-{[(4-{[4-(2-Hydroxyethyl)piperidin-1-yl]methyl}phenyl)amino]methylene}-6-iodoisoquinoline-1 ,3(2H,4H)-dione; (4Z)-4-({[[5-(4-Ethylpiperazin-1-yl)pyridin-2-yr|amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(4-Fluorophenyl)-4-{[(4-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; 44[4-(1,1-Dioxo-1-thiomorpholin-4-ylrnethyl)-phenylamino]-methylene}-6-iodo)-4H-isoquinoline-1 ,3-dione; (4Z)-6-(3-Furyl)-4-({[l2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-Furyl)-4-{[(3-hydroxy-4-propoxybenzyl)amino}methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[5-(4-isopropylpiperazin-1-yl)pyridin-2-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({[6-[(3r,5S)-3,5-Dimethylpiperazin-1-yl)pyridin-3-yl}amino)methylene]-6-[5-(hydroxymethyl)-2-furyI]isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-Furyl)-4-({[I5-(4-isopropylpipera2in-1-yl)pyridin-2-yl]amino}methylene)isoquinoline-1 ,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-{{4-(2-hydroxyethyl)piperidin-1-yl]methy5phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-arriino]-rnethylene}-6-iodo-4H-isoquinoline-1,3-dione; (4Z)-6-(3-Fury1)-4-{[(4-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; ,3-Dioxo-4-({[{4-{piperidin-1 -ylmethyl)phenyl]amino}methylene)-1 ,2,3,4-tetrahydroisoquinolin-6-yl]-2-furaldehyde; (Z)-4-(((6-Bromo-5-propoxypyridin-2-yl)methylamino)methylene)-6-iodoisoquinoline-1,3(2H.4H)-dione; 6-Furan-3-yl-4-{[(2-hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-4H-isoquinoline-1,3-dione; 4-[(4-Butyl-3-hydroxy-benzylamino)-methylene]-6-iodo-4H-isoquinoline-1,3-dione; 4-[(5-Hydroxy-2-iodo-benzylamino)-methylene]-6-lodo-4H-isoquinoline-1,3-dione; (4Z)-4-({[I2-Fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-(3-furyl)isoquinoline-1.3(2H,4H)-dione; 4-[(2-Furan-2-yl-5-hydroxy-benzylamino)-methylene]-6-iodo-4H-isoquinoline-1,3-dione; 4-{[(4'-Fluoro-2-hydroxy-biphenyl-4-ylmethyl)-amino]-rnethylene}-6-iodo-4H-isoquinoline-1,3-dione; 4-{[(4'-Fluoro-2-hydroxy-biphenyl-4-ylmethyl)-amino]-rnethylene}-6-furan-2-yl-4H-isoquinoline-1,3-dione; 6-Furan-2-yl-4-{[(4-hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino]-methylene}-4H-isoquinoline-1,3-dione; 6-Furan-2-yI-4-[(5-hydroxy-2-iodo-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-[(3-Hydroxy-4-iodo-benzyiarnino)-methytene]-6-iodo-4H-isoquinoline-1,3-dione; 4-[(4-Furan-2-yl-3-hydroxy-benzylamino)-methylene]-6-iodo-4H-isoquinoline-1,3-dione; 4-[(4-Furan-3-yl-3-hydroxy-benzylamino)-methylene]-6-iodo-4H-isoquinoline-1,3-dione; (4Z)-6-lodo-4-({[[5-(4-NRiethylpipera2in-1-yl)pyrazin-2-yl]arnmo}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(3-Furyl)-4-({[[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; 4-[(3-Hydroxy-4-pyridin-2-yI-benzylamino)-methyleneJ-6-iodo-4H-isoquinoline~1,3-dione; 4-{[(6-Hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione; 4-[(3-Hydroxy-4-pyridin-4-yl-benzylamino)-methylenel-6-iodo-4H-isoquinoline-1,3-dione; (4Z)-4-{[(4-{[3-(Dimethylamino)pyrrolidin-1-yr]methyl}phenyl)amino]methylene}-6- (4-fluorophenyl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-{{('H[3-(Dimethylamino)pyirroiidin-1-yl]methyl}phenyl)amino]methylene}-6-(3-furyl)isoquino!ine-1 ,3(2H,4H)-dione; (4Z)-4-({[[3-Hydroxy-4-(1H-pyrrol-1-yl)benzyl]amino}methi'lene)-6-iodoisoquinoline-1,3(2H,4H)-dione; 4-[(3-Hydroxy-4-pyridin-3-yl-benzylamino)-methylene]-6-iodo-4H-isoquinoIIne-1,3-dione; N-[2-Hydroxy-4-({[[(Z)-(6-iodo-1 ,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)pheny|]-2-furamide; (4Z)-6-lodo-4-({[[(2-oxo-1 -phenyl-1 ,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-({[(2-oxo-1 -phenyl-1 ,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; 4-{[(3'-Dimethylaminomethyl-2-hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1 ,3-dione; 4-[(2-Fluoro-4-furan-3-y!-5-hydroxy-benzyIamino)-rnethylene]-6-iodo-4H-isoquinoline-1.3-dione; (4Z)-4-({[{3-Hydroxy-4-(4-methylpiperazin- 1 -yl)benzyl]amino}methylene)-6-iodoisoquinoline-1 ,3(2H,4H)-dione; 4-({[I4-Hydroxy-5-(2-pyrrolidin-1-yl-ethoxy)-pyridin-2-ylmethyl]-amino}-methylene)-6-iodo-4H-isoquinoline-1 ,3-dione; (4Z)-4-[({[3-Hydroxy-4-[(2S)-2-{methoxymethyl)pyirrolidir-1-yl]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dlone; (4ZH[(4-Hydroxy-5-phenyl-pyridin-2-ylmethyl)-amino]-nnethylene}-6-iodo-4H-isoquinoline-1 ,3-dione; -(3-Furyl)-2-oxo-1 ,2-dihydropyridin-4-yl]methyl}amino)methylene]-6-iodoisoquinoline-1 ,3(2H4H)-dione; ,3-dioxo-2.3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]-N2,N2-dimethylglycinamide; (4Z)-([( 5-Furan-3-yl-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1 ,3-dione; 6-tert-Butyl-4-[(2-furan-3-yl-5-hydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 6-tert-Butyl-4-[(4-furan-3-yl-3-hydroxy-benzylamino)-methylene]-4H-isoquinoIine-1,3-dione; (42)-6-lodo-4-({[[(1-butyl-2-oxo-1,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline- 1 ,3(2H,4H)-dione; 6-tert-Butyl-4-{[(4-hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino]-methylene}-4H-isoquinoline-1 ,3-dione; 6-tert-Butyl-4-{[(4-hydroxy-5-phenyl-pyridin-2-ylmethyl)-amino]-methylene}-4H-isoquinoline-1 ,3-dione; 6-tert-Butyl-4-{[(5-furarv3-yl-4-hydroxy-pyridin-2-ylNRiethyl)-arnino]-methylene}-4H-isoquinoline-1 ,3-dione; (4Z)-6-tert-Butyl-4-I({[[1 -(3-furyl)-2-oxo-1 ,2-dihydropyridin-4-yl]methyl}amino)methylene]isoquinoline-1.3(2H,4H)-dione; 6-tert-Butyl-4-[(2-fluoro-4-furan-3-yl-5-hydroxy-benzylamino)-metnylene]-4H-isoquinoline-1 ,3-dione; 6-tert-Butyl-4-[(4-furan-3-yl-3-hydroxy-benzylannino)-methylene]-4H-isoquinoline-1,3-dione; 6-Cyclopentyl-4-[(4-furah-3-yl-3-hydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; B-Cyclopentyl-4-{[(5-furan-3-yl-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}-4H-isoquinoline-1 ,3-dione; 6-(Cyclopentyl-4-{t(4-hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino]-methylene}-4H-isoquinoline-1 ,3-dione; (4Z)-6-lodo-4-{({[2-oxo-1-(3-thienyl)-1,2-dihydropyridin-4-yl]methyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-6-lodo-4-[({[[2-oxo-1 -(3-thienyl)-1 ,2-dihydropyridin-4-yl]methyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; ,3-Dioxo-2,3-dihydro-1 H-isoquinolin-4-yfidenemethyl)-amino]-methyl}-benzenesulfonamide; 4-[(2-Trifluoromethoxy-phenylamino)-methylene]-4H-isoquinoline-1 ,3-dione; 3-[(1 ,3-Dioxb-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-benzoic acid; N-(2-Diethylamino-ethyl)-4-[(1,3-dioxo-2,3-dihydro-1H-tsoquinolin-4-ylidenemethyl)-aminoj-benzamide; 4-{{2-(3,4-Dihydroxy-phenyl)-ethylamino]-methylene}-4H-isoquinoline-1,3-dione; 4-[(4-Aminophenylamino)-methylene]-4H-isoquinoline-1,3-dione; N-{4-[(1.3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-oxalamic acid; 4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-benzamidine; {4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenylsulfanyl}-acetic acid; 4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-N-(5-methy1-[1,3,4]thiadiazol-2-yl)-benzenesulfonamide; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-{[2-(1H-Benzoimidazol-2-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 3-[N'-(1,3-Dioxo-2,3-dihydro-1 H-isoquindlin-4-ylidenemethyl)-hydrazJno]-benzoic acid; N-(4,5-Dimethyl-oxazol-2-yl)-[(1.3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-aminoj-benzenesulfonamide; N-{4-[(1,3-Dioxo-2.3-dihydro-1H-isoquinolin-4-ylrdenemethyl)-amino]-phenyl}-N-mettiyl-acetamide; {4-[(1,3-Dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-acetonitrile; 4-[(1,3-Dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-N-(5-methyl-isoxazol-3-yl)-benzenesulfonamide; 3-{4-[(1,3-Dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-acTy}ic acid; 4-{4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenenriethyl)-amino]-phenyl}-butyric acid; 4-[(4-Hydroxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-[(1.3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-2-hydroxy-benzoic acid; 4-[(3-Hydroxy-4-methoxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; 2-[(1,3-Dioxo-2,3-dihydrc-1H-isoquinolin-4-ylidenemetf)yl)-amino3-5-hydroxy-benzoic acid; 5-[(1,3-Dioxo-2,3-dihydro-1H-isoquinoIin-4-ylidenernethyl)-amino]-2-hydroxy-ben2K>ic acid; 4-{[2-(3,4-Dihydroxy-phenyl)-2-hydroxy-ethylamino]-methylene}-4H-isoquinoline-1,3- dione; 4-[(2,6-Dihydroxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; 3-(3,4-Dihydroxy-phenyl)-2-[( 1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-propionic acid; 3-(3,4-Dihydroxy-phenyl)-2-[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-propionic acid; 4-[(2,4-Dihydroxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-[(8-Hydroxy-quinolin-5-ylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-{(5-Chloro-2-hydroxy-4-nitro-phenylamino)-methylene]-4H-isoquinoline-1.3-dione; 4-({[4-I4-(2-Morpholin-4-yl-ethyl)-pipera2in-1-yl]-phenylamino}-methylene)-4H-isoquinoline-1,3-dione; 4-({[4-[4-(2-Pyrrolidin-1-yl-ethyl)-piperazin-1-yl]-phenylamino}-methylene)-4H-isoquinoline-1,3-dione; 4-[(3-Aminobenzylamino)-methylene]-4H-isoquinoline-1.3-dione; 4-[(4-Diethylaminomethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-({[4-[(Cyclopropylmethyl-propy!-amino)-methyrj-phenylamino}-methylene)-4H-isoquinoline-1,3-dione; 4-[(4-Pyrrolidin-1-ylNRjethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-({4-[(Cyclohexyl-methyl-amino)-methyl]-phenylamino}-methylene)-4H-isoquinoline-l,3-dione; 4-[(3-Aminomethyl-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; Thiophene-2-sulfonic acid (3-{[(1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide; Propane-2-sulfonic acid (3-{[(1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-afnide; N-(3-{[(1,3-Dioxo-2,3-dihydro-1H-isoquinoiin-4-ylidenemethyl)-arninol-rnethyl}-phenyl)-methanesulfonamide; 2,2,2-Trifluoro-ethanesulfbnlc acid (3-{t(1,3-dioxo-2,3-dihydro-1 H-isoquinoIin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide; Ethanesulfonic acid (3-{[(1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide; Propane- 1-sutfonic acid (3-[[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide; N-(3-([(1,3-Dioxo-2,3-dihydro-1H-iscxiuinolin-4-ylidenemethyl)-arnino]-methyl}-phenyl)-acetamide; Cyclopropanecarboxylic acid (3-{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide; Cyclobutanecarboxylic add (3-{[(1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide; Thiophene-2-sulfonic acid (4-{[(1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide; N-(4[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-methanesulfonamide; N-(4{K1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-C-phenyl-methanesulfonamide; 2,2,2-Trifluoro-ethanesulfonic acid (4{[(1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-annide; Propane-1-sulfonic add (4{[(1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide; N-(4{[(1,3-Dioxo-2,3-dihydro-1H-iscxjuinoIin-4-ylidenemethyl)-amino]-methyl}-phenyi)-3-methyl-butyramide; 4-[(3,4-Dihydroxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-{[4-(4-Ethyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoHne-1,3-dione; (444-[(1.3-Dioxo-2,3-dihydro-1H-isoquJnolin-4-ylidenerTiethyl)-amino]-phenyl}-piperazin-1 -yl)-acetonitrile; 4-{[4-(4-AIIyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 4-({[4-[4-<2-Hydroxy-ethyl)-piperaan-1-yr|-phenylamino}-methylene)-4H-isoquinoline-1,3-dione; 4-({[4-[4-(2-Diethylamino-ethyl)-piperazin-1-ylJ-phenylamino}-methylene)-4H-isoquinoline-1 ,3-dione; 4_{[4-(4-lsopropyl-piperazin-1-yl)-phenylaNRiino]-methylene}-4H-isoquinoline-1,3-dione; 4-{[4-(4-Cyclopentyl-piperazin-1-yl)-phenyfamino]-methylene}-4H-isoquinoline-1 ,3-dione; 4-[4-(4-CycJobutytmethyl-piperaao-1-yl)-phenylarTiino]-rnethylene}-4H-isoquinoline-1,3-dicne; 4-{[3-(2,2,2-Trifluoro-ethylamino)-benzyfannino]-methylene}-4H-isoquinoJine-1 ,3-dione; 4-[(4-Methylamino-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 2,2,2-Trifluoro-ethanesulfonic acid 4-[(1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-benzylamide; 4-{[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-N-ethyl-benzenesulfonamide; ,3-Dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-N-pyridin-3-ylmetnyl-benzen'esulfonamide; 6-DiethyIamino-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 6-(1.3-Dihydro-isoindol-2-yl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1 ,3-dione; 6-[Bis-(3,3,3-trifluoro-propyl)-amino]-4-[(3.4-dihydroxy-benzylamino)-methytene]-4H-isoquinoline-1 ,3-dione; N-{4-[(1,3-Dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-benzyl}-methanesulfonamide; Ethanesulfonic acid 4-[(1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]- benzylamide; 4-[(4-DipropyIaminomethyl-phenylamino)-methylene]-4H-isoquinoline-1 ,3-dione; 4-{[4-(3-Hydroxy-piperidin-1-yImethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 4-[(4-{[(2-Methoxy-ethyl)-methyl-amino]-methyI}-phenylamino)-methylene]-4H-20 isoquinoline-1 ,3-dione; 4-{I4-(2-Methyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 4-(Pyridin-4-ylaminomethylene)-4H-isoquinoline-1 ,3-dione; 4-[(5-Hydroxy-naphthalen-1 -ylamino)-nnethyIenel-4H-isoquinoline-1 ,3-dione; 25 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-phenyl-4H-isoquinoline-1 ,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-furan-2-yl-4H-isoquinoIine-1 ,3-dione; 6-(3-Phenyl-propenyl)-4-[(4-pyrrolidin-1-ylmethyl-phenylamino)-methylene}-4H-isoquinoline-1 ,3-dione; -[(6-Naphthalen-1 -yl-1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-yIidenemethyl)-amino]-30 phenyl}-acetonitrile; {4-[(6-Naphthalen-2-yl-1 ,3-dioxo-2,3-dihydro- 1 H-isoquinolin-4-ylideneimethyl)-amino]-phenyl}-acetonitrile; {4-[(1,3-Dioxo-6-quinolin-8-yl-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-acetonitrile; {4-[(6-Benzofuran-2-yl-1,3-dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-acetonitrile; {4-[(6-Benzo[b]thiophen-2-yl-1,3-dioxo-2.3-dihydro-1H-isoquinolin-4-yIidenemethyl)-amino]-phenyl}-acetonitrile; {4-[(6-Benzo[b]thtophen-3-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-acetonitrile; (4-{[6-(1 H-lndol-5-yl)-1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; 4-{[1,3-Dioxo-6-(1 H-pyrrol-2-yl)-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; (4-{[1 ,3-Dioxo6-(1 H-pyrro(-3-yl)-2, 3-dihydro-1 H-isoquinolin-4-ylidenernethyl]-amino}-phenyl)-acetonitr1le; 4-fl(6-Naphthalen-2-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-benzenesulfonamide; 4-{[(1,3-Dioxo-6-quinolin-8-y!-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyi}-ben2enesulfonamide; 4-{[(6-Benzofuran-2-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-benzenesutfonam!de; 4-{[(6-Benzo[b]thiophen-2-yl-1,3-dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl]-aminoj-methyl}benzenesulfonamide; 4-{[(6-Benzo[b]thiophen-3-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-rnethyl)-benzenesulfonamide; 4-({[[6-(1 H-lndol-5-yl)-1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide; 4-{[(1,3-Dioxo-6-(1 H-pyrrol-2-yl)-2,3-djhydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide; 4-{[(1,3-Dioxo-6-(1 H-pyrrol-3-yl)-2,3-dihydro-1 H-isoquinolin-4-yfidenemethyl]-amino}-methyl)-benzenesulfonamide; 4-[(3,4-Dihydroxy-benzylamino)methylene]-6-naphthalen-1-yl-4H-isoquinoline-1,3-dione; 4-[{3,4-Dihydroxy-benzyIamlno)-methylene]-6-naphthalen-2-yl-4H-iscx|uinoline-1,3-dione; 4-{(3,4-Dihydroxy-benzylamino)-methylene]-6-quinolin-8-yl-4H-fsoquinoline-1,3-dione; 6-Benzofuran-2-yl-4-[(3,4-dihydroxy-benzylamino)-methytene]-4H-isoquinoline-1,3-dione; 6-Ben2O[bJthiophen-2-yl-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 6-Benzo[b]thiophen-3-yl-4-[(3,4-dihydroxy-ben2ylamino)-methytene]-4H-isoquinoline-1l3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(1 B-indol-5-yl)-4H-isoquinoline-1 , 3-dione; 4-[(3.4-Dihydroxy-benzylamino)-methylene]-6-(1H-pyrrol-2-yl)-4H-isoquinoline-1,3-dione; (4-{[1,3-Dioxo-6-(2-pyridin-2-yl-vinyl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitri]e; (4-{[1,3-Dioxo-6-(2-pyridin-4-yl-vinyl)-2,3-dihydro-1H-ispquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; {4-[(1,3-Dioxo-6-styryl-2.3-dihydro-1H-iscxiuinolin-4-ylidenemethyl)-amino]-phenyl}-acetonitrile; (4-{[6-(2-Imidazol-1-yl-vinyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; 4-({[[1,3-Dioxo-6-(2-pyridin-2-yl-vinyl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide; 4-({[[1,3-Dioxo-6-(2-pyridin-4-yl-vinyl)-2.3-dihydro-1H-isoquinolin-4-ylJdenemethyl]-amino}methyl)-benzenesutfonamide; 4-{I(1,3-Dioxo-6-styryl-2,3-dihydro-1H-isoquinoltn-4-ylidenemethyl)-annino]-methyl}-benzenesulfonamide; 4-{[(1,3-Dioxo-6-(2-pyrazin-2-yl-vinyl)-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide; 4-({[[6-(2-C1-6dohexyl-vinyl)-1,3-dioxo2,3-dihydro--1H-isoquinolrn-4-ylidenernethyl]-amino}-methyl)-benzenesulfonamide; 4-({[[6-(3-lrnidazol-1 -yl-propenyl)-1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyr|-amino}-methyl)-benzenesulfonamide; 4-({[[6-(2-lmidazol-1 -yl-vinyl)-1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonannide; 4-[({[6-[2-(4-Methyl-thiazol-5-yl)-vinyl]- 1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl}-amino)-methyrl-benzenesulfonamide; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-phenyl-propenyl)-4H-isoquindlrne-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-naphthalen-2-yl-vinyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-{2-pyridin-2-yl-vinyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-pyridin-4-yl-vinyl)-4H-isoquinoline-1,3-dione; 6-(2-Cyclohexyl-vinyI)-4-[(3,4-dihydroxy-benzylamino)-niethyl8ne]-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-imidazoI-1-yl-propenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-piperazin-1-yl-propenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-irnidazol-1 -yl-vinyl)-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yi)-phenylamino]-methylene}-6-naphthalen-2-yl-4H-isoquinoline-1,3-dione; 6-Benzofuran-2-yl-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-Benzo[b]thiophen-2-yl-4-{[4-{4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-( 1 H-lndol-5-yl)-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-drone; 4-{[4-(4-Methyl-piDerazin-1-yl)-phenylamino]-methylene}-6-(1H-pyrrol-2-yl)-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1 -yl)-phenytamino]-methylene}-6-(1 H-pyrrol-3-yl)-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(2-naphthalen-2-yl-vinyl)-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(2-pyridin-2-yl-vinyl)-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(2-pyridin-4-yl-vinyi)-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-styryl-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(2-pyrazin-2-yl-vinyl)-4H-isoquinoline-1,3-djone; 6-(3-lmidazo)-1-yl-propenyl)-4-{I4-(4-methyl-piperazln-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-(2-lmidazol-1-yl-vinyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-t2-(4-methyl-thiazol-5-yl)-vinyl]-4H-isoquinoline-1,3-dione; B-(4-Methoxy-phenyI)-4-{l4-(4-methyl-piperazin-1-yl)-phenylamino)-methylene}-4H-isoquinoline-1,3-dione; 6-(2-Methoxy-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylannino]-methylene}-4H-isoquinoiine-1,3-dione; 6-(2-Fluoro-phenyl)-4-{[4-(4-methyl-piperazln-1-yl)-phenylannino]-methylene}-4H-isoquinoline-1,3-dione; 4-(4-{[4-(4-Methyf-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3.4-tetrahydro-isoquinolin-6-yl)-benzoic acid; 3-(4-{[4-(4-Methyl-piperaz»n-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzoic add; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylarnino]-rnethylene}-6-(4-trifluoromethyl-phenyl)-4H-isoquinoline-1,3-dione; 6-(4-Acetyl-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenyIamino]-methylene}-4H-isoquinoline-1,3-dione; 6-(4-Chloro-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-(3-Chloro-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino}-methylene}-4H-isoquinoline-1,3-dione; 6-(2-Chloro-phenyl)-4-{I4-(4-methyl-piperazin-1-yl)-phenylanninoJ-methylene}-4H-isoquinoline-1,3-dione; 4-{I4-(4-Methyl-piperazin-1-yl)-phenylpminb]-methylene}-6-p-tolyl-4H-isoquinoline-l,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-NR»-tolyl-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylaNRiinoJ-NRiethytene}-6-o-tolyl-4H-isoqulnoline-1,3-dione; 3-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzonitrile; 6-Biphenyl-4-yl-4-{[4-(4-methyl-piperazln-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-Biphenyl-3-yl-4-{[4-(4-methyI-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 3-[4-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-pheny1]-acrylicacid; 3-[3-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-phenyl]-acrylicacid; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(4-methylsulfanyl-phenyl)-4H-isoquinoline-1,3-dione; (4-{[6-(4-Methoxy-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; (4-{[6-(3-Methoxy-phenyl)-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-aceton!trile; (4-{£6-(2-Metiioxy-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; (4-{[6-(4-Fluoro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-yHdenemethyl]-amino}-phenyl)-acetonitrile; (4-{[6-(3-Fluoro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; (4-{[6-(2-Fluoro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenernethyl]-amino}-phenyl)-acetonitrile; 4-{4-[(4-Cyanomethyl-phenylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-benzoic acid; 3-{4-[(4-Cyanomethyl-phenylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-benzoic acid; (4-{[1,3-Dioxo-6-(4-trifluoromethyl-phenyl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; (4-{I6-(4-Acetyl-phenyl)-1,3-dioxo-2,3-dihydro-1H-tsoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; (4-{[6-(2-Acetyl-phenyl)-1,3-dioxo)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile; (4-{[6-(4-Chloro-phenyl)-1.3-dioxo-2,3-dihydro-1H-isoquino)in-4-ylidenemethyl]-amino}-phenylj-acetonitrile; (4-{[6-{3-Chloro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-phenyl]-acetonitrile; (4-{[6-(2-ChIoro-phenyl)-1,3-dioxo-2,3-dihydro-lH-isoquinolin-4-ylidenemethyl]-amino}-phenyl)hacetonitrile; {4-[(1,3-Dioxo-6-p-tolyl-2,3-dihydro-1H-isoquinoHn-4-ylidenemethyl)-amino]-phenyl}-acetonitrile; {4-[(1,3-Dioxo-6-m-tolyl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-acetonitrile; {4-[(1,3-Dtoxo-6-o-tolyl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyI}-acetonitrile; 4-{4-[(4-Cyanomethyl-phenylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-benzonitrile; 3-{4-[{4-Cyanomethyl-phenylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-benzonitrile; {4-[(6-Biphenyl-4-yl-1,3-dioxo2,3-dihydro-1H-isethylJ-annino}-methyl)-benzenesulfonamide; 4-({[[6-(3-ChIORophenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methylj-benzenesulfonamide; 4-({[[6-(2-ChlORo-phenyl)-1,3-dioxo-2,3-clihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonannide; 4-{[(1,3-Dioxo-6-p-tolyl-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-benzenesulfonamide; 4-{[(1,3-Dcoxo-6-m-tolyl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-arnino]-methyl}-benzenesulfonamide; 4-{[(1,3-Dioxo-6-o-tolyl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino}-methyl}-benzenesulfonamide; 4-({[[6-4-Cyano-phenyl)-1,3-dtoxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl )-benzenesulfonamide; 4-({[[6-(3-Cyanophenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl )-benzenesulfonamide; 4-{[(6-Biphenyl-4-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-benzenesulfonamide; 4-{[(6-Biphenyl-3-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-benzenesulfonamide; 3-(4-{1,3-Dioxo-4-[(4-sulfamoyl-benzylamino)-methylene]-1,2,3,4-tetrahydro-isoquinolin-6-yl}-phenyl)-aCRylic acid; 3-(3-{1,3-Dioxo-4-[(4-sulfamoyl-benzylamino)-methylene]-1,2,3,4-tetrahydro-isoquinolin-6-yl}-phenyl)-aCRylic acid; 4-({[[6-(4-lsopropyl-phenyl)-1,3-dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide; 4-({[I6-(3-lsopropyl-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide; 4-({[[6-(4-MethylsuIfanyI-phenyl)-1.3-dioxo-2,3-dihydro-1H-isoquinolin-4-yIidenemethyl-amino}-methyl)-benzenesulfonamide; 4-[(3,4-Dihydraxy-benzylamino)-methylenel-6-(4-methoxy-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-methoxy-phenyl)-4H-isoquinoline-1.3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methytene]-6-(2-methoxy-phenyl)-4H-isoquinoline-1.3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(4-fluORo-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-fluORo-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-fluORo-phenyl)-4H-isoquinORme-1,3-dione; 4-{4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-benzoic acid; 3-{4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2,3.4-tetrahydro-iseK|uino!in-6-yl}-benzoic acid; 4-[(3,4-Dihydroxy-benzylamino)-methyIene]-6-(4-trifluORomethyl-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-trifluORomethyl-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzyIamino)-rnethylene]-6-(2-trifluORomethyl-phenyl)-4H-isoquinoline-1,3-dione; 6-(4-Acetyl-phenyl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 6-(3-Acetyl-phenyl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3- dione; 6-(2-Acetyl-phenyI)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 6-(4-ChlORo-phenyl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinollne-1.3- dione; 6-(3-ChlORc-phenyl)-4-[(3,4-dihydroxy~benzylamino)-methylene]-4H-isoquinoline-l,3-dione; 6-(2-ChlORo-phenyl)-4-f(3,4-dihydroxy-benzylamino)-methylenB]-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methyIene]-6-p-tolyl-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-m-tolyl-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-ben2ylamino)-methylene]-6-o-tolyl-4H-isoquinoline-1,3-dione; 4-{4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-benzonitrile; 3-{4-[(3,4-Dihydroxy-ben2ylamino)-methylene]-1.3-dioxo-1,2,3,4-tetrahydro-iscxquinolin-6-yl}-benzonitrile; 6-Biphenyl-4-yl-4-[(3,4-dihydroxy-benzylamino)-methylenel-4H-isoquinoline-1,3-dione; 6-Biphenyl-3-yl-4-[(3,4-dihydroxy-benzyIamino)-methylenel-4H-iscxjuinoline-1,3-dione; 3-(4-{4-{(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dk)xo-1,2,3.4-tetrahydro-isoquinolin-6-yl}-pnenyl)-aCRylic acid; 3-(3-{4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2,3.4-tetrahydro-isoquinolin-6-yl}-phenyl)-aCRylicacid; 4-[(3,4-Dihydroxy-benzylamino)-methytene]-6-(4-isopropyl-phenyl)-4H-isoquinoline-1,3- dicne; 4-[{3,4-Dihydroxy-benzylamino)-methylene]-6-{3-isopropyl-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamfno)-methylene]-6-(4-methylsulfanyl-phenyl)-4H-lsoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-methylsulfanyl-phenyl)-4H-isoquinoline-1,3-dione; 6-[2-(2-Diethylamino-ethoxy)-vinyl]-4-{{4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 5-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-pent-4-enoic acid; 6-(4-Hydroxy-but-1-enyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-(5-Hydroxy-pent-1-enyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene)-4H-isoqurnoline-1,3-dione; 6-(6-Hydroxy-hex-1-enyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-[3-(2:Hydroxy-ethoxy)-propenyl]-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-[3-(2,4-Dioxo-imidazolidin-1-yl)-propenyl]-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-[3-(2-Hydroxy-phenyl)-propenyl]-4-{[4-(4-methyl-piperazin-1-yl)-phenylamind]-methylene}-4H-isoquinoline-1,3-dione; 2-Methyl-3-(4-{I4-(4-methyl-piperazin1-yl}-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoq uino!in-6-yl)-but-2-enenitrile; {4-[2-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylaminol-methylene}-1,3-dioxo-1,2,3.4-tetrahydro-isoquinolin-6-yl)-vinyl]-phenyl}-acetonitrile; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-[3-{2-hydroxy-3-methoxy-phenyl)-propenyl]-4H-isoquinoline-1,3-dione; [4-(^-{4-[(3,4-Dihydroxy-benzylamino)-methyleneJ-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-vinyl)-phenyl]-acetonitri!e; 6-Benzo[1,3}dioxol-5-yl-4-{[4-(4-methyl-piperazin-1-yl)-phenylannino]-methylene}-4H-isoquinoline-1,3-dione; 6-(4-Dimethylamino-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-(4-Hydroxymethyl-phenyl)-4-{[4-(4-rnethyl-piperazin-1-yl)-phenylatnino]-methylene}-4H-isoquinoline-1,3-dione; 3-[4-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-phenyl3-propiontcacid; 6-(3-Amino-phenyl)-4-{t4-(4-methyi-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 6-(2,4-DichlORo-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylaminol-methylene}-4H-isoquinoline-1,3-dione; 6-Benzo[1.3]dioxol-5-yl-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-nnethylene]-6-(3,4-dimethoxy-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methytene]-6-(2,4-dimethoxy-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3,4,5-trimethoxy-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-ben2ylamino)-methylene}-6-(4-dimethylamino-phenyl)-4H-isoquinol(ne-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(4-hydroxymethyl-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(4-trifluORomethoxy-phenyl)-4H-isoquinoline-1,3-dione; 3-(4-{4-[(3,4-Dihydroxy-benzylamino)-metnyiene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-phenyl)-propionicacid; 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-nitro-phenyl)-4H-isoquinoline-1,3-dione; 6-(3-Amino-phenyl)-4-[(3,4-dihydroxy-benzylamino)-methylBne]-4H-lsoquinoline-1,3-dione; N-(3-{4-[(3.4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2t3,4-tetrahydro-isoquinolin-6-yl}-phenyl)-acetamide; 6-(2,4-DichlORo-phenyl)-4-[(3l4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-[(3-Hydroxy-4-methoxy-benzylamino)-rnethylene]-6-(2-pyridin-4-yl-vinyl)-4H-rsoquinoline-1,3-dione; 4-t(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-styryl-4H-isoquinoline-1,3-dione; 6-[3-(2,4-Dioxo-imidazolidin-1-yl)-propenyl]-4-[(3-hydroxy-4-methoxy-benzylannino)-methylene]-4H-isoquinoline-1,3-dione; 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-[3-(2-hydroxy-3-methoxy-phenyl)-propenyl]-4H-isoquinoline-1,3-dione; 6-Cyclopentylidenemethyl-4-{[4-{4-methyl-piperazin-1-yl)-phenylaminoJ-methylene}-4H-isoquinoline-1,3-dione; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino)-miethylene}-6-[2-(4-nitro-phenyl)-vinyl)-4H-isoquinoline-1,3-dione; 6-Furan-2-yl-4-{[4-{4-NRrethyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 4-{I4-(4-Methyl-piperazin-1-yt)-phenylamino}-methylene}-6-phenyl-4H-isoquinoline-1,3~ dione; 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-phenyt-4H-isoquinolrne-1,3-dione; 4-[(3-Hydroxy-4-methoxy-benzyIamino)-methylene]-6-(4-methoxy-phenyl)-4H-isoquinoline-1,3-dione; 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-naphthalen-2-yl-4H-isoquinoline-1 ,3-dione; 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-(1H-indol-5-yl)-4H-isoquinoline-1 ,3-dione; 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-(1H-pyrrol-2-yl)-4H-isoquinoline-1 ,3-dione; 6-Furan-2-yl-4-[(3-hydroxy-4-methoxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione; 4-[(4-Pyrrolidin-1-ylmethyl-phenylamino)-melhylene]-6-(1H-pyrrol-2-yl)-4H-isoquinoline-1 ,3-dione; 4-{1,3-Dioxo-4-[(4-pyrrolidin-1-ylmethyl-phenylamino)-methylenel-1,2,3,4-tetrahydro-isoquinolin-6-yl}-benzonitrile; 6-(4-Hydroxymethyl-phenyl)-4-[(4-pyrrolidin-1-ylrnethyl-phenylamino)-methylene]-4H-isoquinoline-1 ,3-dione; 7-Bromo-4-[(4-methoxy-phenylarnino)-methylenel-1.4-dihydro-2H-isoquinoHn-3-one; 7-Bromo-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-1,4-dihydro-2H-isoquinolin-3-one; 6-[1-(2-Methoxy-ethyl)-1 H-pyrrol-3-yl]-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}-4H-isoquinoline-1 ,3-dione; 6-Bromo-4-[(4-methoxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one; 8-Bromo-4-[(4-methoxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one; 6-Bromo-4-{[4-{4-methyl-piperazin-1-yl)-phenylamino]-methylene}-i,4-dihydro-2H-isoquinolin-3-one; 8-Bromo-4-{[4-(4-methyl-piperazin-1 -yl)-phenylaininoj-methylene}-1 ,4-dihydro-2H-isoqu»nolin-3-one; 6-Bromo-4-[(4-pyrrol idin-1 -ylmethyl-phenylamino)-methylene]-1 ,4-dihydro-2H-isoquinolin-3-one; 8-Bromo-4-[(4-py rrolidin-1 -ylmethyl-phenylamino)-methylene]-1 ,4-dihydro-2H-isoquinolin-3-one; 7-Bromo-4-[(4-pyrrolidin- 1 -ylmethyl-phenylamino)-methylene]-1 ,4-dihydro-2H-isoquinolin-3-one; 4-{[4-(4-Methyl-piperazin-1-yl)-phenylarnino]-NRiethylene}-7-thiophen-2-yl-1,4-dihydro-2H-isoquinolin-3-one; 4-[(4-Methoxy-phenylamino)-methylene]-7-(1H-pyrrol-2-yl)-1,4-dihydro-2H-iscxiuinolin-3-one; 4-[(4-Methoxy-phenylamino)-methylene]-7-(1H-pyrrol-3-yl)-1,4-dihydro-2H-isoquinolin-3-one; 2-{5-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-y!)-indol-1-yl]-acetamide; 6-[1 -(2-Diethylamino-ethyl)-1 H-indol-5-yl]-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione; 2-[3-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-pyrrol-1-yl]-acetamide; 6-[1 -(2-Diethylamino-ethyl)-1 H-pyrrot-3-yl]-4-{[4-(4-methyl-piperazin-1 -yl}-pheny!amino]-methylene}-4H-lsoquinoline-1,3-dione; 4-[3-(4-{[4-(4-Methyl-plperazln-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-pyrrol-1-yl]-butyronitrile; 7-ChIORo-4-((3-hydroxy-phenylarnino)-rnethylene]-1,4-dihydro-2H-isoquinolin-3-one; 4-[(7-ChlORo-3-oxo-2,3Hiihydro-1H-isoquinolin-4-yiidenemethyl)-amino]-benzamidine; 7-Methyl-4-[(4-mORpholin-4-yl-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one; 4-[(3-Hydroxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one; 4-[(4-Piperidin-1 -yl-phenylamino)-methylene]-1,4-dihydro-2H-isoq uinolin-3-one; 4-[(7-Bromo-3-oxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-aminoJ-benzamidine; 7-Bromo-4-[(3-hydroxy-4-methoxy-phenyIamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one; 7-Bromo-4-[4-(2-hydroxy-ethyl)-phenylarnino]-methylene}-1,4-dihydro-2H-isoquinolin-3-one; (4Z)-6-Bromo-4-[({[4-[methyl(2-pyrroIiclin-1-ylethyl)amino]phenyl}amino)methylene]isoquinoIine-1,3(2H,4H)-dione; (4Z)-B-bromo-4-[({[4-[methyl(2-piperidin-1-ylethyl)amino]phenyl}amino)methylene]iscKiuinoline-1,3(2H,4W)-dione; (4Z)-6-Bromo-4-[({[4-[{2- [butyl(methyl)amino]ethyl}(methyl)amino]phenyl}amino)methylene]isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[2-(dimethylamino)ethoxy]phenyl}amino)methylene]iscK|uinoline-1.3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(2-methyl-2,3-dihydro-1H-isoirxlol-5-yl)aNRiino]methylene}iscxiuinORme-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[[4-(1H-irnidazol-1-yl)phenylJarnino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-{methyl[2-(4-methylpJpera23n-1-yl)ethyl]amino}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[methyl(2-mORpholin-4-ylethyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; 6-({[[(Z)-(6-Bromo-1,3-dioxo-2.3-dihydroisoquinolin-4(1H)-ylidene)methyr|arnino}methyl)-2,2-dimethyl-l ,3-benzodioxol-4-yl acetate; 6-{{[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydnoisoquinolin-4(1H)-ylidene)methyl]arnino}methyl)-2,2-dimethyl-1,3-benzodioxol-4-yl cyclopropanecarboxylate; (4Z)-6-Bromo-4-[({[4-[3-(dimethylamino)propyr|phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; (Methoxyamino)propyl]phenyl}amino)methylene]iscK|uinoline-1.3(2H,4H)-dione; (4Z)-6-Bromo-4-[({[4-[[3- (dimethylamino)propyl](methyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2W,4H)- dione; (4Z)-6-Bromo-4-[({[4-[(1-methylpyrrolidin-3-yl)oxy]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione; 6-Bromo-1,1 -dimethyl-4-{[4-(4-nnethyl-piperazin-1 -yl)-phenylamino]-methylene}-1,4-dihydro-2H-isoquinolin-3-one; 6-Fura n-3-yl-1,1 -dimethyl-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,4-dihydro-2H-isoquinolin-3-one; and (4Z)-1,2-Diacetyl-4-[(3-hydroxy-4-methoxybenzyl)arnino}methylene}-:l,4-dihyclroclnnolin-3(2H)-one; DETAILED DESCRIPTION OF THE INVENTION The compounds of this invention are certain substituted isoquinoline-1,3(2H,4H)-diones, 1-thioxo-1,4-dihydro-2Hsoquinoline-3-ones. and 1,4-dihydro-3(2W)-isoquinolones containing compounds which are particularly useful, in an embodiment of the invention, fOR the treatment of cancer. The isoquinoline-1,3(2M4H)-dione, 1-thioxo-1,4-dihydro-2H-isoquinoline-3-one, and 1,4-dihydro-3(2H)-isoquinolone ring systems will be numbered as indicated in the Formulae: . (Formula Removed)The terms used in this specification may have their ORdinary meanings in the art, the meaning within the context of the invention, and and the meaning in the specific context where each term is used. Certain terms are discussed below, OR elsewhere in the specification, to provide additional guidance to the practitioner in desCRibing the compounds, compositions, and methods of the invention and how to make and use them. MOReover, it will be appreciated that the same thing can be said in mORe than one way. Consequently, alternative language and synonyms may be used fOR any one OR mORe of the terms discussed herein, nOR is any special significance to be placed upon whether OR not a term is elabORated OR discussed herein. The use of examples anywhere in this specification, including examples of any terms discussed herein, is illustrative only, and in no way limits the scope and meaning of the invention OR of any exemplified term. Likewise, the invention is not limited to the examples presented. "About" OR "approximately" shall generally mean within 20 percent, but can be lower so as to be within 10 percent, OR within 5 percent of a given value OR range. AcCI is sometimes used fOR the chemical name "acetyi chlORide". Ac2O is sometimes used fOR the chemical name "acetic anhydride". "AcyP denotes a radical of the Formula -(C=O) alkyl OR -(C=O) perfluORoalkyl wherein the alkyl radical OR perfluORoalkyl radical is 1 to 7 carbon atoms; some examples include but are not limited to, acetyi, propionyl, butyryl, trifluORoacetyl. Alkenyl refers to unsaturated aliphatic groups analogous in length and possible substitution to alkyis desCRibed herein, but which contain at least one carbon-carbon double bond. Alkenyl may be used synonymously with the term olefin and includes alkylidenes and includes both straight and branched carbon chains of 2-6 carbon atoms in ail possible configurational isomers, fOR example cis and trans, and includes ethenyl, 3-hexen-1-yl and the like. Exemplary alkenyl groups include ethenyl, propenyl, 1,4-butadienyl, 3-hexen-1-yl and the like optionally substituted with phenyl OR phenyl optionally substituted with one OR mORe substttuents preferably from one to three substituents independently selected from alkyl, alkoxy, perhaloalkyl, halogen, nitro, hydroxy, amino, carboxy, carboxyalkyl, alkylamino and dialkylamino, thioalkyl, alkoxycarbonyl and acyl. The term "alkynyT refers to unsaturated aliphatic groups analogous in length and possible substitution to the alkyis desCRibed herein, but which contain at least one triple carbon-carbon bond, respectively. Analogous substitutions can be made to alkenyl and alkynyl groups to produce, fOR example, alkenylamines, alkynylamines, alkenylamides, alkynylamides, alkenylimines, alkynylimines. thioalkenyls, thioalkynyts, .carbonyl-substituted alkenyls OR alkynyls, alkenoxyls, alkynoxyls, metalloalkenyls and metalloalkynyls. The alkenyl pORtion of the alkenyl, alkenoyloxymethyl, alkenyloxy, alkenylsulfonamido, substituents include both straight chain as well as branched carbon chains and one OR mORe sites of unsaturation. The term "aralkyl", as used herein, refers to an alkyl group substituted with an aryl group (e.g., an aromatic OR heteroaromatic group). Alkoxy means an alkyl-O- group. Exemplary alkoxy groups include methoxy, ethoxy, n-propoxy, i-propoxy. n-butoxy, t-butoxy and polyethers including -O-(CH2)2OCH3. The term "alkyl" refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyi substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. In an embodiment, a straight chain OR branched chain alkyl has 12 OR fewer carbon atoms in its backbone. The term "alkyl" can be used alone OR as part of a chemical name as in fOR example, "trialkylORthofORmate". The alkyl pORtion of the alkyl, alkoxy, alkanoyloxy, alkoxymethyl, alkanoyloxymethyl, alkylsulphinyl, alkylsulphonyl. alkylsulfonamido, carboalkoxy, carboalkyl, alkanoylaminb aminoalkyl, alkylaminoalkyl, N.N-dicycloalkylaminoalkyl, hydroxyalkyl, and aikoxyalkyl substituents include both straight chain as well as branched carbon chains. MOReover, the term "alkyl" as used throughout the specification and claims is intended to include both "unsubstituted alkyls" and "substituted alkyls", the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one OR mORe carbons of the hydrocarbon backbone. alkylamino may be defined as a nitrogen atom substituted with an alkyl of t-to 12 carbon atoms. The term "aryl" includes 4-, 5-, 6-, 7- and 10-membered single ring OR fused polycydic aromatic carbocyclic moiety having two OR mORe rings in which two OR mORe carbons are common to two adjoining rings. aryl groups have 6 to 14 carbon atoms and include fOR example phenyl and bicyclicaryl fOR example napthyl. The aromatic rings can be optionally independently mono-, di-, tri- OR tetra-substituted. Substituents are selected from the group consisting of, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterpcydyl, aromatic OR heteroaromatic moieties and -CN. The fused rings require at least one of the carbocyclic rings to be aromatic, e.g., the other rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, and/OR aryls. The compounds of this invention may contain an asymmetric carbon atom and some of the compounds of this invention may contain one OR mORe asymmetric centers and may thus give rise to stereoisomers, such as enantiomers and diastereomers. The steretoisomers of the instant invention are named accORding to the Cahn-lngold-Prelog System. While shown without respect to stereochemistry in the Formulas the present invention includes all the individual possible stereoisomers; as well as the racemic mixtures and other mixtures of r and S stereoisomers (scalemic mixtures which are mixtures of unequal amounts of enantiomers) and pharmaceutically acceptable salts thereof. It should be noted that stereoisomers of the invention having the same relative configuration at a chiral center may nevertheless have different r and S designations depending on the substitution at the indicated chiral center. Azacydoalkyl-N-alkyl substituent refers to a monocyclic heterocycle that contains a nitrogen atom on which is substituted a straight OR branched chain alkyl radical. A mORpholino-N-alkyl substituent is a mORpholine ring substituted on the nitrogen atom with a straight OR branch chain alkyl radical. A piperidino-N-alkyl substituent is a piperidine ring substituted on one of the nitrogen atoms with a straight OR branch chain alkyl radical. A N-alkyl-piperidino-N-alkyl substituent is a piperidine ring substituted on one of the nitrogen atoms with a straight OR branched chain alkyl group and on the other nitrogen atom with a straight OR branch chain alkyl radical. The term "base" refers to any compound which yields hydroxyl ions in aqueous solution; and which reacts with an acid to fORm water and a salt. In the schemes presented herein the base may be selected from a catalyst, a ligand, Cs2CO3, KOt-Bu, and t-BuOK. The term "carbonyl" represents the radical -C=O. GDI is sometimes used fOR the chemical name "1,1'-carbonyldiimidazole". The term "cyano" represents the radical -CN. Cycloalkyl means a simple carbocycle having a saturated ring having from 3 to 10 carbon atoms optionally substituted with 1 to 3 independently selected alkyl groups of 1 to 12 carbon atoms. Exemplary cycloalkyl rings include, but are not limited to. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and adamantyl. Cycloalkyl rings may contain heteroatoms and be called a cycloheteroalkyl. Dialkylamino is defined as a nitrogen atom disubstituted with an alkyl of 1 to 12 carbon atoms. DME is sometimes used fOR the chemical name "1,2-dimethoxyethane". DMAP is sometimes used fOR the chemical name "4-N.N-dimethylaminopyridine". DMF-acetal is sometimes used fOR the chemical name "N,N-dimethylfORrnamide acetal". The compounds of this invention may include a "divalent group" as a linking group, fOR example, -CH2CH2-. Et3N is sometimes used fOR the chemical name "triethylamine". When referring to timing in the example and intermediate processes the symbol "h" OR "H" stands fOR "hour(s)". The term "halogen" refers to an atom of fluORine, chlORine, bromine, OR iodine. The term "heteroaryl" refers to a 4 to 10 membered ring structure, which ring structure includes one to four heteroatoms selected from O, N and S. heteroaryls include, but are not limited to aCRidine, benzofuran, benzothiophene, benzimidazole. benzotriazole, benzothiazole, benzoxazole, benzisoxazole, 1,2-benzopyran, cinnoline, carbazole. chromene, furan, furazan, isothiazole, isoxazole, indolizine, isoindole, indole, indazole, imidazole, isobenzofuran, isoquinoline, 2,3-dihydroindole, isoindazole, mORpholine, naphthyridine. 1,8-naphthyridine, oxazole, oxolane, phthalazine, pyrido[3,2-b]pyridine, pyrido[3,4-b]pyridine, pyrido[4,3-bjpyridine, pyrido[2,3-djpyrimidine, purine, and pteridine, perimidine, phenanthroline, phenazine, phenothiazine, phenoxazine, phenoxathiin, phenanthridine, piperidine, piperazine, pteridine, purine, pyrazole, pyran, pyridine, pyrazine, pyridazine and pyrimidine, pyrrole, pyrrolidine, quinazoline, quinolizine, quinoiine, quinoxaline, thiolane, thiophene, thiazole, triazole, thianthrene, tetrahydroquinoline, xanthene, and the like. In an embodiment, heteroaryl is a 5 -10 membered heteroary) ring system having one OR two rings and having up to four ring members selected from O, N, and S. A heteroaryl can fORm a heterocydic ring system of one to three fused rings, in which at least one ring may have an aromatic character and contains 1 to 4 heteroatoms the same OR different selected from the group consisting of S, N, and O. The remaining rings of the ring system may be fully unsaturated, partially saturated, OR fully saturated. The heteroaryl can be independently substituted at one OR mORe positions. In an embodiment heteroaryl may also be bicyclic heteroaryl having two fused rings. Preferred is a six membered ring structure having 1 to 4 heteroatoms. Heterocyclyl OR heterocyclic refers to a saturated OR partially unsaturated monocydlc radical containing preferably 3 to 8 ring atoms selected from carbon, nitrogen, oxygen and sulfur. Preferred is a ring having six ring atoms. Heterocycles can include 2 OR 3 fused rings. Specific examples include but are not limited to mORpholine, thiomORpholine, thiomORpholine-S-oxide, thiomORpholine-S.S-dioxide, piperidine, piperazine. pyrrolidine, aziridine, oxirane. tetrahydrothiophene, tetrahydrofuran, 1,2-pyran, 1,4-pyran, dioxane, 1,3-dioxolane, diazabicyclo[2.2.1]heptane and tetrahydropyran. The heterocyclyl ring may be oxidized on a tri-substituted nitrogen atom to provide the cORresponding N-oxide, such as N-ethylpiperazine-N-oxide, OR the heterocyclyl ring may contain a carbonyl group on one of the carbon atoms, such as pyrrolidinone, pyridine and pyrone. Preferred is pyridine and pyrone. The heteroaryl may be oxidized on a nitrogen atom to provide the cORresponding N-oxide, such as pyridine-N-oxide OR quinoiine -N-oxide. The heteroaryl may also be oxidized on a tri-substitued nitrogen atom to provide the cORresponding N-oxide, such as N-ethylpiperazine-N-oxide. In another embodiment the heteroaryl may contain a carbonyl group on one of the carbon atoms, such as pyrrolidinone, 1,3,4-oxadiazol-2-one, OR 2-indanone. The term "heteroatom" as used herein means an atom of any element other than carbon OR hydrogen and include fOR example nitrogen, oxygen, sulfur, phospORus, and selenium. Im is sometimes used fOR the chemical name "imidazole". IPrHCI is sometimes used fOR the chemical name "1,3-bis(2,6-di-i-propylphenyl)-4,5-dihydroimidazonium chlORide". The letter "J" is used in the schemes to symbolize Cl, Br, OR I. LAH is sometimes used in place of the chemical name "lithium aluminum hydride". LDA is sometimes used fOR the chemical name "lithium diisopropylamide". LG is sometimes used fOR the term "leaving group". Examples of leaving groups are Cl. Br, I, OTf. OMs, OTs. MDS is sometimes used in place of the chemical name "1,1,1,3,3,3-hexamethyldisilazane". Mel is sometimes used fOR the chemical name "methyl iodide". MOM is sometimes used in place of the term "methoxymethyr. MS is sometimes used to signify "mass spectroscopy" OR "mass spectrum". Ms is sometimes used to signify the compound "methanesulfonyl". Halogen is defined as I, Br, Cl, F. OTf is sometimes used fOR the chemical name "trifluORomethanesulfonate''. Pd2(dba)3 is sometimes used fOR the chemical name "tris(dibenzylideneacetone)dipalladium (0)". PPh3 is sometimes used fOR the chemical name "triphenylphosphine". Phenyl as used herein refers to a 6-membered aromatic ring. The term phenpxy represents the radical PhO, a fORm of phenol. A phenol is an aryl hydroxide. Both terms can be used alone OR in conjunction with terms desCRibed herein, such as, thipphenoxy OR phenylamino. FOR purposes of this invention "PEG" is any polyethylene glycol of the Formula-(OCH2CH2)rOCH3 where r is 2 to 1800. Starting material is periodically refered to as "SM" in the procedures fOR the intermediates and examples. A "spirocydic ring" is an ORganic compound having 2 rings joined by a carbon atom common to both. The term "substituted" is contemplated to include all permissible substituents of ORganic compounds. In-a broad aspect, the permissible substituents of ORganic compounds include acyclic and cydic, branched and unbranched, carbocydic and heterocyclic, aromatic and nonaromatic substituents of ORganic compounds. The permissible substituents can be one OR mORe and the same OR different fOR appropriate ORganic compounds. FOR purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and/OR any permissible substituents of ORganic compounds desCRibed herein which satisfy the valendes of the heteroatoms. It will be understood that "substitution" OR "substituted with" indudes the implicit proviso that such substitution is in accORdance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transfORmation such as by rearrangement, cydization, elimination, etc. Examples of possible substituents include but are not limited to halogen, alkyl, aralkyl, alkenyl, alkynyl, cydoalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, arnido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, acyl, aldehyde, ester, a cycloheteroalkyl, an aromatic OR heteroaromatic moiety. -CN. TBDMS OR TBS are sometimes used fOR the chemical name "tert-butyldimethylsilyl". TFA is sometimes used to signify the compound "trifluORoacetic acid". TLC is sometimes used to signify the term "thin-layer chromatography". THF is sometimes used fOR the chemical name "tetrahydrofuran". Tri-a!kylsilyl applies to alkyl (as hereinbefORe defined) derivatives of the silyl group, (alkyl)3Si, wherein each alkyl may be the same OR different. Ts is sometimes used fOR the chemical name "p-toluenesulfonyr. "Inhibition" refers to a method of contacting a cell with an amount of a compound of the invention effeotive to deCRease OR prevent cancer. The cell may be a mammalian cell and mORe specifically a human cell. The cell may also be a bacterial cell such as fOR example E.coli. The cell may include any cell that can be isolated and includes fOR example, a neuronal cell, an endothelial cell, a glial cell, a miCRoglial cell, a smooth muscle cell, a somatic cell, a bone marrow cell, a liver cell, an intestinal cell, a germ cell, a myocyte, a mononuclear phagocyte, an endothelial cell, a tumOR cell, a lymphocyte cell, a mesangial cell, a retinal epithelial cell, a retinal vascular cell, a ganglion cell OR a stem cell. The cell may be a nORmal cell, an activated cell, a neoplastic cell, a diseased cell, OR an infected cell. FOR purposes of this invention a "neoplasm" is used interchangeably with "cancer" and is defined as cells selected from fOR example the breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, panCReas, brain, bone, prostrate and lung. The cell is one having a mORphology not found in the majORity of the cells of a mammal. In one embodiment, the present invention provides fOR a method of inhibiting the neoplasm. The present invention accORdingly provides to a mammal (including a human), a pharmaceutical composition that comprises a compound of this invention in combination OR association with a pharmaceutically acceptable carrier. The compound of this invention may also be administered alone OR in combination with other therapeutically effective compounds OR therapies fOR the treatment OR prevention of the neoplasm. In one embodiment, the administration of an effective amount of a compound of Formula (I) and in combination an effective amount of another therapeutically effective anticancer agent inhibits the resistance of a cancer to the compound of Formula (I) and/OR the other anticancer agent In an embodiment, the cancer is a solid tumOR. In another embodiment, other anticancer agents useful in the methods and compositions of the present invention include, but are not limited to, therapeutically effective compounds OR drugs in the following lists OR a pharmaceutically acceptable salt thereof. Nitrogen mustards: Cydophosphamide, Ifosfamide, Trofosfamide, ChlORambucil; Nitrosoureas: Carmustine (BCNU), Lomustine (CCNU) alkylsulphonates: Busulfan, Treosulfan; Triazenes: Dacarbazine, Procarbazine, Temozolomide; Platinum complexes: Cispla'm, Carboplatin, Aroplatin, Oxaliplatin; Vinca alkaloids: VinCRistine, Vmblastine, Vindesine, VinORelbine Taxanes: Paclitaxel, Docetaxel; Epipodophyllins: Etoposide, Teniposide, Topotecan, Irinotecan, 9- aminocamptothecin, Camptothecin; DNA Topoisomerase InhibitORs, CRisnatol; Mitomycins: Mitomycin C; DHFr inhibitORs: Methotrexate. Trimetrexate; IMP dehydrogenase InhibitORs: Mycophenolic acid, Tiazofurin, ribavirin, EICAr; ribonuclotide reductase inhibitORs: Hydroxyurea, Oeferoxamine; Uracil analogs: 5-FluORouracJl, Fluoxuridine, Doxifluridine, ralitrexed; Cytosine analogs: Cytarabine, Cytosine arabinoside, Fludarabine, Gemcitabine, Capecitabine; Purine analogs: Mercaptopurine, Thioguanine, O-6-benzylguanine; DNA Antimetabolites: 3-HP. 2'-deoxy-5-fluORouridine, 5-HP, alpha-TGDr; DMA Antimetabolites: aphidicolin glycinate, ara-C, 5-aza-2'-deoxycytidine, beta- TGDr, cyclocytidine. guanazole, inosine glycodialdehyde, macebecin H, Pyrazoloimidazole; Anti-estrogen: Tamoxifen, ratoxifene. Megestrol; LHrH agonists: Goserelin, Leuprolide acetate; Anti-androgens: Flutamide, Bicalutamide; retinoids/Deltoids: Cis-retinoic acid Vitamin A derivative: All-trans retfnoic acid (ATrA-IV) Vitamin D3 analogs: EB 1089. CB 1093, KH 1060; Photodynamic therapies: VertopORfin (BPD-MA), Phthalocyanine, Photosensitizer Pc4, Demethoxy-hypoCRellin A, (2BA-2-DMHA); Cytokines: Interferon-α, Interferon-ß, Interferon-, TumOR neCRosis factOR, Interieukin- 2; Angiogenesis InhibitORs: Angiostatin (plasminogen fragment), antiangiogenic antithrombin III Angiozyme, ABT-627, Bay 12-9566, Benefin, Bevacizumab, BMS- 275291, cartilage-derived inhibitOR (GDI), CAI, CD59 complement fragment, CEP- 7055, Col 3, Combretastatin A-4, Endostatin (collagen XVIII fragment), Fibronectin fragment. Gro-beta, Hatofuginone, Heparinases, Heparin, hexasaccharide fragment, HMV833, Human chORionic gonadotropin (hCG), IM-862, Interieukins. Kringle 5 (plasminogen fragment), Marimastat; Metalloproteinase inhibitORs. 2- Methoxyestradiol, MMI 270 (CGS 27023A), MoAb IMC-1C11, Neovastat, NM-3, Panzem. PI-88, Placenta! ribonuclease inhibitOR, Plasminogen activatOR inhibitOR, Platelet factOR-4 (PF4), Prinomastat, Prolactin 16kD fragment, Proliferin-related protein (PrP), PTK 787/ZK 222594, retinoids, Solimastat. Squalamine. SS 3304, SU 5416, SU6668, SU11248, TetrahydrocORtisol-S, Tetrathiomolybdate, Thalidomide, Thrombospondin-1 (TSP-1), TNP-470, TransfORming growth factOR-beta (TGF-D), Vasculostattn, Vasostatin (calreticulin fragment); Angiogenesis InhibitORs: 2D6126, ZD 6474, farnesyl transferase inhibitORs (FTI), Bisphosphonates; Antimitotic agents: Allocolchicine, Halichondrin B, Colchicine, cotehicine derivative, dolastatin 10, Maytansine, rhizoxin, Thiocolchicine, trityl cysteine; Dopaminergic neurotoxins: 1 -methyl-4-pnenylpyridinium ion Cell cycle inhibitORs: StaurospORine; Actinomycins: Acttnomycin D, Dactinomycin; Bleomycins: Bleomycin A2, Bteomycin B2, Peplomydn; AnthracycKnes: DaunORubicin, DoxORubicin, Idarubicin, Epirubicin, Pirarubicin, ZORubidn, Mitoxantrone; MDr inhibitORs: Verapamil Ca2+ATPase inhibitORs: Thapsigargin Additional suitable other anticancer agents useful in the methods and compositions of the present invention indude, but are not limited to abiraterone, acivicin, adarubicin, acodazole, aCRonine, acyffulvene, adecypenol, adozelesin, aldesleukin, an AUL-TK antagonist, altretamine, ambamustine, ambomycin, ametantrone, amidox, amifostine, aminoglutethimide, aminolevulinic acid, amrubicin, amsaCRine, anagrelide. anastrozote. andrographolide, an angtogenesis inhibitOR, antarelix, anthramycin, an apoptosis gene modulatOR, apurinic acid. ara-CDP-DL-PTBA, arginine deaminase, L-asparaginase, asperiin, asulaCRine, atamestane. atrimustine, axinastatin 1, axinastattn 2, axinastatin 3. azacitidine, azasetron, azatoxin, azetepa, azatyrosine, azotomycin, batimastat, benzodepa, bisantrene, bisnaftde, bizeiesin, brequinar, bropirimine, balanol, a BCR/ABL antagonist, beta-alethine, betaclamycin B, betulinic acid, bisazfridinylspermine, bisnafide, bistratene A, bizeiesin, calcipotriol, calphostin CR calusterone, canarypox IL-2, carubicin, carboxyamidotriazole, Carest M3, CArn 700, carzetestn, castanospermine, ceCRopin B, cetrORelix, chlORoquinoxaline. cicaprost, cirolemycin, cladribine, clotrimazole. coHismycin A, colBsmycin B, conagenin, CRambescidin 816, CRisnatol, CRyptophya'n 8, CRyptophycin A derivatives, curacin A, cyclopentanthraquinones, cycloplatam, cypemycin, cytostatin, dadiximab, decitabine, dehydrodidemnin B, deslORelin, dexifosfamtde, dexORmaplatin, dexrazoxane, dexdiaziquone, didemnin B, didox, diethylnORspennine, dihydro-5-acytidine, dihydrotaxol, dioxamycln, diphenyl spiromustine, docosanol, dolasetron, droloxifene, dronabinol, duazomycin, duocarmycin SA, ecomustine, edatrexate, eflomrthine, elsamitrucin, enloplatin, enpromate, epipropidine, erbulozole, esonjbicin, estramustine, estramustine, an estrogen antagonist, etanidazole, etoprine, exemestane, fadrozole, fazarabine. feNRetinide, finasteride, flavopiridol, flezelastine, fluasterone, fluORodaunORunicin, floxuridine, flurocitabine, fORfenimex, fORmestane, fostriecin, fotemustine, gadolinium texaphyrin, galocitabine, ganirelix, a gelatinase inhibitOR, a glutathione inhibitOR, hepsulfam, herbimycin A, heregulin, hexamethylene bisacetamide, hypericin, ibandronic acid, idoxifene, idramantone, ilmofosine, ilomastat, imatinib rnesylate, imidazoaCRidones, imiquimod, an IGF-1 inhibitOR, iobenguane. iodoipomeanol, iproplatin, irsogladine, isobengazole, isohomohalicondrin B, itasetron, jasplakinolide, leucovORin, levamisole, leuprORelin, liarozole, lissodinamide 7, lobaplatin, lombricine, lometrexol.lonidamine, losoxantrone, lovastatin, loxORibine, lurtotecan. lutetium texaphyrin, lysofylline, mannostatin A, masoprocol, maspin, a matrix metalloproteinase inhibitOR, mechlORethamine, megestro! acetate melphalan, metoctopramide, mifepristone, miltefosine, mtrimostim, mitoguazone, mitolactol, mitonafide, mofarotene, molgramostim, mopidamol, a multiple drug resistance gene inhibitOR, myriapORone, N-acetyldinaline, nafarelin, nagrestip, napavin, naphterpin, nartograstim, nedaplat'n, nemORubicin, neridronic acid, nilutamide, nisamycin, a nitrogen mustard, a nitric oxide modulatOR, a nitrosourea, nitrullyn, nocodazole, octreotide, okicenone, onapristone. ORacin, ORmaplatin, osaterone, oxaunomycin, palauamine, palmitoylpamidronic acid, panaxytriol, panomifene, parabactin, pazetliptine, pegaspargase, peldesine, peltomycin, pentamustine, pentosan, pentostatin, pentrozole, peplomycin, perfosfamide, perflubron, perfosfamide. phenazinomycin, a phosphatase inhibitOR, picibanil, pilocarpine, pipobrcman, piposulfan, piritrexim, placetin A, placetin B, plicamycin, pORfiromycin, plomestane, pORfimer sodium, pORfiromycin, prednimustine. prednisone, prostaglandin J2, miCRoalgal, puromycin, pyrazoloaCRidine, pyrazofurin, a raf antagonist, rattitrexed, ramosetron, a ras famesyl protein transferase inhibitOR, a ras-GAP inhibitOR, retelliptine demethylated, rll retinamide, riboprine, rogletimide, rohitukine, romurtide, roquinimex, rubiginone B1, ruboxyl, safingol, saintopin, SarCNU, sarcophytol A, sargramostim, semustine, a signal transduction modulatOR, simtrazene, sizofiran, sobuzoxane, soiverol, sonermin. sparfosic acid, sparfosate, sparsomycin.spicamycin D, spiromustine, spiroplatin, splenopentin, spongistatin 1, a stem-cell division inhibitOR, stipiamide, streptonigrin, a stromeiysin inhibitOR, sulfinosine, suradista, suramin, swainsonine, talisomycin, tallimustine, tauromustine, tazarotene. tecogalan. tegafur. tellurapyrylium, a telomerase inhibitOR, teloxantrone, temopORfin. teroxirone, testolactone, tetrachlORodecaoxide, tetrazomine, thaliblastine, thiamiprine, thiocORaline, thrombopoietin, thymalfasin, thymotrinan, tirapazamine, titanocene, topsentin. tORemifene. trestolone, tretinoin, triacetyluridine, triciribine. trimetrexate, triptORelin, tropisetron. tubulozole, turosteride, a tyrosine kinase inhibitOR, ubenimex, uracil mustard, uredepa, vapreotide, variolin B, velaresol, veramine, vertepORfin, vinxaltine. vinepidine, vinglycinate, vinleurosine, viNRosidine, vinzolidine, vitaxin, vORozole, zanoterone, zeniplatin, zilascORb, zinostatin, and zORubictn. The other anticancer agent may optionally be an alkylating agent, a platinum-containing agent, an anthracycline, a vinca alkaloid, a taxane, a topoisomerase inhibitOR OR an angiogenesis inhibitOR. A "therapeutically effective amount" OR "therapeutically effective dose" is an amount sufficient to ameliORate symptoms of cancer, restenosis, atherosclerosis, blood vessel proliferative disORders, angiogenesis, chronic obstructive pulmonary disease, bone disease, osteopORosis, psORiasis, inflammatORy disORders, arthritis, central nervous system disORders, Alzheimers, pain sesation, autoimmune disease, transplant rejection, thrombosis, diabetes, metabolic disORders, infectious disease, viral infection, adenomatosis, neuro-flbromatosis, fungal infections, endotoxic shock, vascular smooth cell proliferation, atherosclerosis, pulmonary fibrosis, glomerulonephritis, post-surgcal stenosis and testenosis, apoptosis, prevention of AIDS, inflammatORy bowel disease, amyotrophic lateral sclerosis, retinitis pigmentosa, spinal muscular atrophy, cerebellar degeneration, chronic and aplastic anemia, ischemia, liver disease, osteopORosis, rhinosinusitis, cystic fibrosis. multipl sclerosis, kidney disease, pain, alopecia, and parasitic protozoa. FOR purposes of this invention the dose provided to a patient will vary depending upon what is being administered, the purpose of the administration, the manner of administration, and the like. The administration of compounds of the invention may be provided ORally, by intralesional, intraperitoneal, intramuscular OR intravenous injection, infusion, liposome-mediated delivery, topical, nasal, anal, vaginal, sublingual, uretheral, transdermal, intratheca). ocular OR otic delivery. In ORder to obtain consistency in providing the compounds of this invention the fORm administered is a unit dose. Suitable unit dose fORms include tablets, capsules and powders in sachets OR vials. Such unit dose fORms may contain from 0.1 to 1000 mg of a compound of the invention. The compounds of the present Invention can be administered ORally at a dose range determined by dose ranging studies. Such compounds may be administered multiple times a day. The effective amount will be dependent upon the fORm of the compound. One of skill in the art could routinely perfORm empirical activity tests to determine the bioactivity of the compound in bioassays and thus determine what dosage to administer. The compound of the present invention may be delivered locally via a capsule that allows a sustained release of the compound over a period of time. Controlled OR sustained release compositions include Formulation in lipophilic depots (fOR example, fatty acids, waxes, oils). The compounds of the invention may be Formulated with conventional excipients, such as a filler, a disintegrating agent, a binder, a lubricant, a flavORing agent, a colOR additive, OR a carrier. The carrier may be fOR example a diluent, an aerosol, a topical carrier, an aqueous solution, a nonaqueous solution OR a solid carrier. The carrier may be a polymer OR a toothpaste. A carrier in this invention encompasses any of the standard pharmaceutically accepted carriers, such as phosphate buffered saline solution, acetate buffered saline solution, water, emulsions such as an oil/water emulsion OR a tnglyceride emulsion, various types of wetting agents, tablets, coated tablets and capsules. When provided ORally OR topically, such compounds would be provided to a subject by delivery in different carriers. Typically, such carriers contain excipients such as starch, milk, sugar, certain types of clay, gelatin, stearic acid, talc, vegetable fats OR oils. gums, OR glycols. The specific carrier would need to be selected based upon the desired method of delivery, fOR example, phosphate buffered saline (PBS) could be used fOR intravenous OR systemic delivery and vegetable fats, CReams, salves, ointments OR gels may be used fOR topical delivery. The compounds of the present invention may be delivered together with suitable diluents, preservatives, solubilizers, emulsifiers, adjuvants and/OR carriers. Such compositions are liquids OR lyophilized OR otherwise dried Formulations and include diluents of various buffer content (fOR example, Tris-HCI, acetate, phosphate), pH and ionic strength, additives such as albumins OR gelatin to prevent absORption to surfaces, detergents (fOR example, TWEEN 20, TWEEN 80, PLUrONIC F68, bile acid salts), solubilizing agents (fOR example, glycerol, polyethylene glycerol), anti-oxidants (fOR example ascORbic acid, sodium metabisulfate), preservatives (fOR example, thimerosal, benzyl alcohol, parabens), bulking substances OR tonicity modifiers (fOR example, lactose, manNRtol), covalent attachment of polymers such as polyethylene glycol, complexation with metal ions, OR incORpORation of the compound into OR onto paniculate preparations of hydrogels OR liposomes, miCRo-emulsions, micelles, unilamellar OR muttilamellar vesicles, erythrocyte ghosts, OR spheroblasts. Such compositions will influence the physical state, solubility, stability, rate of in vivo release, and rate of in vivo clearance of the compound OR composition. The choice of compositions will depend on the physical and chemical properties of the compound. The terms "prevent" OR "prevention", as used herein, refer to the partial OR complete inhibition of the development of a condition that impairs the perfORmance of a function of the human body. The terms "treat" OR "treatment", as used herein, refer to an attempt to ameliORate a disease problem. Further, the term "suppress" OR "suppression" refers to a complete OR partial inhibition of a condition, e.g., as evidenced by a lessening of the severity of the symptoms associated with that condition. Pharmaceutically acceptable salts of the compounds of Formula (I) with an acidic moiety may be fORmed from ORganic and inORganic bases. FOR example with alkali metals OR alkaline earth metals such as sodium, potassium, lithium, calcium, OR magnesium OR ORganic bases and N- tetraalkylammonium salts such as N-tetrabutylammonium salts. Similarly, when a compound of this invention contains a basic moiety, salts may be fORmed from ORganic and inORganic acids. FOR example salts may be fORmed from acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochlORic, hydrobromic, phosphORic, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, camphORsulfonic, and similarly known acceptable acids. The compounds can also be used in the fORm of esters, carbamates and other conventional prodrug fORms, which when administered in such fORm, convert to the active moiety in vivo. In addition to the utilities, desCRibed herein some of the compounds of this invention are intermediates useful fOR the preparation of other compounds of this invention. An embodiment of this invention is a method of treating OR inhibiting familial adenomatosis polyposis, psORiasis, neuro-fibromatosis, fungal infections, endotoxic shock, tranplantation rejection, vescular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis, glomerulonephritis, and. post-surgical stenosis and testenosis, in a mammal in need thereof comprising administering to said mammal an effective amount of a compound of Formula (I). An embodiment of this invention is a method fOR treating OR treating viral infections, fOR example, herpevirus, poxvirus, Epstein-Barr virus, Sindbis virus and adenovirus; prevention of AIDS, autoimmune diseases, systemic lupus, erythenabsus, autoimmune medicated glomerulonephritis, rheumatoid arthritis, psORiasis, inflammatORy bowel disease, and autoimmune diabetes mellitus, neurodegenerative disORders, fOR example, Alzheimer's disease. AID-related dementia, Parkinson's disease, amyotrophic lateral sclerosis, retinitis pigmentosa. spinal muscular atrophy and cerebellar degeneration; myelodysplastic syndromes, splastic anemia, ischemic injury associated with myocardial infarctions, stroke and reperfusion injury, arrhythmia, atherosclerosis, toxin-induced OR alcohol related liver diseases, hematological diseases, fOR example, chronice anemia and aplastic anemia; degenerative diseases of the musculoskeletal system, fOR example, osteropORosis and arthritis, aspirin-sensentive rhinosinusitis, cystic fibrosis, multiple sclerosis, kidney diseases and cancer pain, in a mammal in need thereof comprising administering to said mammal an effective amount of a compound of Formula (I). Examples of synthetic pathways that are useful fOR making tsoquinoline-1,3(2H,4H)-diones, 1-thioxo-1,4-dihydro-2/7-lsoquinoline-3-ones, and 1,4-dihydro-3(2H)-isoquinolones of Formula (I) are set fORth in the Examples below and generalized in Schemes 1-52. In general, variables such as G1, G2, G3, G4, A1, A2. Y1, Y2 ,L1, Z, e and f and the like are as defined above fOR Formula (I). Scheme 1, illustrates further a method useful fOR making compounds of Formula (I). Substituted oxo compound 1 can be reacted with an ORthofORmate 2 which includes trimethyf ORthofORmate and triethyl ORthofORmate in the presence of an anhydride which includes acetic anhydride in a polar solvent such as N.N-dimethylfORmamide (DMF) to provide ether 3. Further, condensing ether 3 with intermediate 4 in the presence of a polar solvent which includs DMF affORds substituted oxo compound 5.(Scheme Removed) SCHEME 1As presented in Scheme 2, oxo compound 6 can be reacted with an acetal which includes DMF-acetal to provide amine 7 which can be further reacted with intermediate 4 in a solvent which includes DMF to give substituted oxo compound 8. SCHEME 2 (Scheme Removed) AccORding to Scheme 3. oxidation of substituted oxo OR di-one compound 1 provides tri-one 9 using methods which include ruthenium oxide, in the presence of aqueous sodium periodate in ethyl acetate. Intermediate 11 can be prepared by reaction of amlne 10 with sodium nitrite in the presence of aqueous acid followed by further treatment with tin (II) chlORide also in the presence of aqueous acid. Further reaction of tri-one 9 with intermediate 11 provides substituted oxo 12.SCHEME 3 (Scheme Removed) Alternatively, as shown in Scheme 4, reaction of substituted oxo compound 1 with diazonium 13 prepared by reacting amine 10 with sodium nitrite in the presence of aqueous acid in DMF to provide substituted oxo 12. Amine 10 may be reacted with sodium nitrite in the presence of aqueous acid to give the diazonium salt 13, which may be reacted with oxo compound 1 in ethanol containing sodium acetate to give hydrazone 12. SCHEME 4 (Scheme Removed) As desCRibed in Scheme 5, ester 15 is fORmed from carboxylic acid 14 where J is Halogen by reaction with an acetoacetate in the presence of alkoxide, copper bromide and an alcohol where r is fOR example methyl OR ethyl. Base hydrolysis which includes aqueous alkali metal hydroxide (lithium, potassium and sodium hydroxide) of ester 15 affORds di-carboxylic acid 16 which is further reacted with urea OR thiourea in a solvent such as 1,2-dichlORobenzene to provide dione 17. SCHEME 5(Scheme Removed) According to Scheme 6, carboxylic acid 18 can be converted to dicarboxylic acid 16 by reaction with lithium diisopropylamide (LDA) followed by reaction with a diakylcarbonate where R is for example methyl or ethyl, followed by treating with water. Reaction of dicarboxylic acid 16 with urea or thiourea in a solvent such as 1,2-dichlorobenzene to provide dione 17. Carboxylic add 18 can be converted to ester 15 by reaction with LDA followed by reaction with a dialkylcarbonate where R is for example methyl or ethyl, followed by treating with acetic acid. Ester 15 may be hydrolyzed with aqueous base to afford di-carboxylic acid 16. SCHEME 6 (Scheme Removed) As described in Scheme 7, ester 15 may be hydrolyzed with aqueous base to give di-carboxylic acid 16-which may be further reacted with acetyl chloride to afford dione 17. Amide 18 may be prepared by reaction of ester 15 or dione 17 with ammonia. Reaction of amide 18 with carbonyl diimidazole (CDI) provides dione 17. SCHEME 7 (Scheme Removed) As shown in Scheme 8, carboxylic acid 19 may be converted to isothiocyanate 20 by reaction with thionyi chloride followed by reaction with lead(ll) thiocyanate. Reaction of isothiocyanate 20 with aluminum chloride and carbon disulfide provides thioxo 21. SCHEME 8 (Scheme Removed) As presented in Scheme 9, treatment of thioxo 21 with aqueous base provides di-carboxylic acid 16 which when treated with urea forms dione 17. 102 SCHEME 9 (Scheme Removed) As illustrated in Scheme 10, amide 22 may be reacted with ketone 23 in the presence of pyrophosphoric acid (H4P2O7) to give oxo 6. SCHEME 10 (Scheme Removed) As shown in Scheme 11, amine 23 may be treated with dilute hydrochloric add followed by sodium carbonate to provide oxo compound 24. SCHEME 11 (Scheme Removed) 23 As illustrated in Scheme 12, ether 3 or amine 25 may be reacted with aniline 26 in a polar solvent such as DMF to provide substituted oxo compound 27. Substituted oxo compound 27 may be reacted with acid chloride 28 or anhydride 29 to provide amide 30. Thioamide 32 may be formed by reaction of substituted oxo 27 with sulfonyl chloride 31 where J Is halogen. SCHEME 12 (Scheme Removed) According to Scheme 13, substituted oxo 27 may be reacted with benzyl chloride to provide benzylamine 34 and dibenzylamine 35, that may be separated by chromatography. SCHEME 13 (Scheme Removed) As illustrated in Scheme 14, substituted one 27 may be reacted with amine 36 to provide piperazine 37 which is further alkylated with R21-J to further provide substituted piperazine 39. SCHEME 14 (Scheme Removed) As shown in Scheme 15, nitro compound 40 may be reacted with substituted piperidine 41 to provide piperazine compound 42 which is then reduced to give aniline 43. Reacting aniline 43 with ether 3 or amine 25 provides piperazine 44. SCHEME 15 (Scheme Removed) As described in Scheme 16, aniline 43 may be diazotized with sodium nitrite in the presence of hydrochloric acid in DMF to afford substituted piperazine 45 which may be further reacted with substituted oxo 1 to give substituted piperazine 46. SCHEME 16 (Scheme Removed) Sulfonamide 47 may be reacted with ether 3 or amine 25 to provide sulfonamide 48 which may be further reacted with aldehyde 49 in the presence of reducing agent including NaBH3CN and NaBH(OAc)a to provide substituted sulfonamide 50 as illustrated in Scheme 17. SCHEME 17 (Scheme Removed) As shown in Scheme 18, amine 51 may be reacted with acid chloride 52 where J is halogen to provide nitro compound 53 which may be reduced to give aniline 54. Aniline 54 may be further reacted with ether 3 or amine 25 to give amide 55. SCHEME 18 (Scheme Removed) As described in Scheme 19, aniline 54 may be diazotized with sodium nitrite in the presence of hydrochloric acid in DMF to afford diazonium 56 which may be further reacted with substituted oxo compound 1 to give substituted amide 57. SCHEME 19 (Scheme Removed) As illustrated in Scheme 20, amine 51 may be reacted with sufonyl chloride 58 to provide nitro compound 59 which may be reduced to give aniline 60. Aniline 60 may be further reacted with ether 3 or amine 25 to give substituted sulfonamide 61. Scheme 20 (Scheme Removed) As described in Scheme 21, aniline 60 may be diazotized with sodium nitrite in the presence of hydrochloric acid in DMF to afford diazonium 62 which may further be reacted with substituted oxo compound 1 to give substituted sulfonamide 63. SCHEME 21 (Scheme Removed) As described in Scheme 22, nitro compound 64 may be reacted with amine 65 then reduced to afford aniline 66. Alternatively, alcohol 67 may be reacted with methanesulfonyl chloride or p-toluenesulfonyl chloride to give nitro compound 68 which may be reacted with amine 65 followed by reduction to give aniline 66. Additional reaction of aniline 66 with ether 3 or amine 25 provides amine 69. SCHEME 22 (Scheme Removed) As described in Scheme 23, nitro compound 70 where J is halogen may be reacted with amine 65 to provide after reduction aniline 71. Alternatively, alcohol 73 may be reacted with methanesulfonyl chloride or p-toluenesulfonyl chloride to give nitro compound 72 which may be reacted with amine 65 followed by reduction to give aniline 71. Aniline 71 may be diazotized with sodium nitrite in the presence of hydrochloric acid in DMF to afford diazonium 74 which may be further reacted with substituted oxo 1 to give amine 75. SCHEME 23 (Scheme Removed) As described in Scheme 24, aniline 76 prepared by reduction of alcohol 73 may be reacted with ether 3 or amine 25 to afford alcohol 77 which may be further reacted with methanesulfonyl chloride or p-toluenesulfonyl chloride to give oxo 78. Reaction of oxo-78 with amine 65 affords amine 79. SCHEME 24 (Scheme Removed) As illustrated in Scheme 25, aniline 76 may be diazotized with sodium nitrite in the presence of hydrochloric acid DMF to afford diazonium 80 which may be further reacted with substituted oxo 1 to give alcohol 81. Alcohol 81 may be reacted with methanesulfonyl chloride or p-toluenesulfonyl chloride to give oxo 82 which may be further reacted with amine 65 to give oxo 83. SCHEME 25 (Scheme Removed) As presented in Scheme 26, aldehyde 84 may be converted to phenol 85 which may be subsequently converted to O-methyl-oxime 86 by reaction with O-methyl-hydroxylamine hydrochloride which may be further reduced to afford benzylamine 87. Additional reaction of benzylamine 87 with ether 3 or amine 25 provides phenol 88. SCHEME 26 (Scheme Removed) As shown in Scheme 27, aldehyde 89 may be converted to O-methyl-oxime 90 by reaction with O-metbyl-hydroxylamine hydrochloride and which may be further reduced to afford benzylamine 91. Reaction of benzylamine 91 with ether 3 or amine 25 provides aniline 92. SCHEME 27 (Scheme Removed) As shown in Scheme 28, one 93 containing a leaving group (LG) which includes Br, I or OTf (tirflate)may be reacted with organoboron (R211-BR213R214). organotin (R211-Sn(R21)3, organozinc reagents (R211-ZnBr), alkenes (R212-C=CH) or alkynes ((R2i2)2C=CH(R212)) in the presence of catalysts which include tetrakis (triphenylphosphine)palladium (0) [Pd(PPh3)4), bis(diphenylphosphine)palladium (II) chloride and [1,1'-bis(diphenylphosphino)ferrocene]palladium (II) dichloride [PdCI2 (dppf)^ to afford one 94. Other catalysts including palladium (II) chloride, palladium (II) diacetate, tris(dibenzylideneacetone)dipalladium (0) [Pd2(dba)3] in the presence of ligands including triphenylphosphine, tri-t-butylphosphine with or without copper (I) iodide may be used to generate one 94. Preferred solvents include N.N-dimethylformamide, N-methylpyrrolidinone, dimethoxyethane and dioxane. Preferred bases include aqueous sodium carbonate, cesium carbonate and triethyiamine.. The reactions take place by heating from 110C to 200C in oil bath or in microwave oven. R213 and R214 groups are independently hydroxyl, alkyl of 1 to 12 carbon atoms or alkoxy of 1 to 12 carbon atoms. In addition, the ligands R213R214 may be taken together with the boron to which they are attached to form a cyclic boron ester, where R213R214 may be oxyethyleneoxy. SCHEME 28 (Scheme Removed) As presented in Scheme 29, one 93 may be reacted with hexamethyiditin and a catalyst such as tetrakis(triphenylphosphine)palladium (o) in dioxane at elevated temperature to generate substituted one 96. SCHEME 29 (Scheme Removed) As described in Scheme 30, oxo 93 may be reacted with tin reagent 97 in the presence of Pd°to afford dioxolane 98 which may be treated with acid to afford oxo 101. Alternatively, treating oxo 93 with aldehyde 99 in the presence of Pd° affords oxo 101. Further treatment of oxo 101 with amine 102 in the presence of a reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride gives amine 103. SCHEME 30] (Scheme Removed) As described in Scheme 31. oxo 101 may be reduced using reducing agents which include catalytical hydrogenation, NaBH4 or BH3 to afford alcohoi 104 which may be converted to oxo 105 wherein R6C1 may be MsCI or TsCI followed by reacting with amine 106 to form amine 103. SCHEME 31 (Scheme Removed) As shown in Scheme 32, diester 106 containing a leaving group iphenyl-2-ol the title compound is prepared from 4-Azidomethyl-1-butyl-2-nethoxy-benzene (78 mg', 0.36 mmol) in 83% yield. (Formula Removed) Intermediate 77 4'-Fluoro-2-methoxy-biphenyl-4-carboxylic acid methyl ester 4-lodo-3-methoxy-benzoic acid methyl ester (292 mg, 1 mmol) and para-luorophenylboronic acid (160 mg, 1.14 mmol) and Pd(PPh3)4 (80 mg. 0.069 mmol) and Cs2COa (600 mg, 1.84 mmol) is mixed in N.N-dimethylformamide (10 mL) and degassed and then heated at 100 °C for 4 hours. After which, the mixture is allowed to cool to room temperature and an aqueous work up is performed and the esidue purified to afford the desired product (240 mg, 92%). (Formula Removed) Intermediate 78 (4'-Fluoro-2-methoxy-biphenyl-4-yl)-methanol 4'-Fluoro-2-methoxy-biphenyl-4-carboxylic add methyl ester (220 mg, 0.85 mmol) is allowed to dissolve in ether and cooled. LiAIH4 (80 mg, 2.12 mmol) is then added and the suspension is then stirred overnight. After aqueous work up, the alcohol is isolated and used directly in the next step. (Formula Removed) Intermediate 79 4-Chloromethyl-4'-fluoro-2-methoxy-biphenyJ Following the same procedure for the preparation of 4-Chloromethyl-2-rnethoxy-biphenyl, the title compound is prepared from (4'-Fluoro-2-methoxy-biphenyl-4-yl)-methanol (crude material from the previous step). The crude material is used directly in the next step. (Formula Removed) Intermediate 80 4-Azidomethyl-4'-fluoro-biphenyl-2-ol Following the same procedure for the preparation of 4-Azidomethyl-biphenyl-2-ol, the title compound is prepared from 1-Butyl-4-chloromethyl-2-methoxy-benzene (crude material from the previous step). The crude material is used in the next step. (Formula Removed) Intermediate 81 4-Aminomethyl-4'-fluoro-biphenyl-2-ol Following the same procedure for the preparation of 4-Aminomethyl-biphenyl-2-ol, the title compound is prepared from 4-Azkiorriethyl-4'-ftuoro-biphenyl-2-ol (crude material from the previous step) in 54% yield (over 4 steps). MS (ESI): 218(M+1)+1 (Formula Removed) Intermediate 82 6-Furan-2-yl-4-methoxymethylene-4H-isoquinoline-1,3-dione 6-Bromo-4-methoxymethylene-4H-isoqulnoline-1,3dione (1.24 g, 4.4 mmol) and PdCI2(PPh3)2 (200 mg, 0.28 mmol) and 2-furyltributyltin (2 g, 5.6 mmol) in N,N-dimethylformamide (20 mL) is degassed and heated at 100°C for 1 hour. Upon cooling to room temperature, the product precipitated out. After filtration, the precipitate is washed with Et2O and dried to provide the desired product (800 mg, 68%). MS (ESI): 270.1 (M+1)+1. (Formula Removed) Intermediate 83 5-Hydroxy-2-iodo-benzonitrile 3-Hydroxy-benzonitrile (15 g, 0.126 mol) and iodine rnonochloride (28 g, 0.172 mol) is heated in acetic acid for 15 hours at 45 °C. H2O) is added to precipitate the product out. After the precipitate is collected and washed with Na2SO3, the residue is chromatographed with chloroform to get the product (2 g, 7%). (Formula Removed) Intermediate 84 3-Aminomethyt-4-iodo-phenol To a solution of 5-Hydroxy-2-iodo-benzonitrile (245 mg, 1 mmol) in THF (3 mL) is added BH3THF (6 mL, 1 M solution in THF) under N2. The mixture is thenallowed to stir at room temperature for 24 hours. The reaction is then quenched with 6N HCI. THF is then removed and the aqueous layer is then neutralized with ammonium hydroxide to pH 9. The mixture is then extracted with CHCIa/MeOH (9:1). The organic layer dried and evaporated and the residue is chromatographed to provide the desired product (80 mg, 32%). (Formula Removed) Intermediate 85 2-Furan-2-yl-5-hydroxy-ben2onitrile 5-Hydroxy-2-iodo-benzonitrile (200 mg, 0.82 mmol) and PdCI2(PPh3)2 (20 mg, 0.028 mmol) and 2-furyltributyltin (400 g, 1.12 mmol) in N,N-dimethylformamide (5 mL) is degassed and heated at 100°C for 15 min. After the mixture cooled to room temperature, an aqueous work up is performed and the product is isolated from chromatography (100 mg, 66%). MS (ESI): 184 (M-1)"1. (Formula Removed) Intermediate 86 3-Am inomethyt-4-furan-2-yl-phenol 2-Furan-2-yl-5-hydroxy-benzonitrile (100 mg, 0.54 mmol) is dissolved in EtOH (10 mL) to which Raney Ni (excess) is added. The mixture is subjected to hydrogenation under H2 (50 psi) for overnight The mixture is then filtered and solvent removed to afford the crude product, which is carried over to the next step without further purification. (Formula Removed) Intermediate 87 5-Aminomethyl-2-iodo-phenol To a solution of 3-Hydroxy-4-iodo-benzonitrile (300 mg. 1.22 mmol) in THF (5 mL) is added BH3 THF (10 mL, 1 M solution in THF, 10 mmol) under N2. The mixture is then allowed to stir at room temperature for 24 hours. The reaction is quenched with 6N HCI. THF is removed and the aqueous layer is neutralized with ammonium hydroxide to pH 9. The mixture is extracted with CHCl3/MeOH (9:1). .The organic layer dried and evaporated and the residue is chromatographed to provide the desired product (60 mg, 20%). MS (ESI): 250 (M+1)+1. (Formula Removed) Intermediate 88 4-lodo-3-methoxymethoxy-benzonitrile 3-hydroxy-4-iodobenzonitrile (500 mg, 2.04 mmol) and MOMCI (350 mg, 4.37 mmol) were dissolved in anhydrous N.N-dimethylformamide (5 ml_) and cooled to 0 °C. NaH (100 mg, 60% suspension in mineral oil, 2.5 mmol) is then added. The resulting mixture is allowed to stir at room temperature for 1h before TLC analysis suggested the consumption of the starting iodide. Ether is then added and washed with H2O (3 X 20 mL) and brine. After drying over Na2SO4, the ether is removed and the residue is purified through chromatography to afford the desired MOM ether (570 mg. 96%). 1H NMR (300 MHz, CDCI3) δ 7.90 (1H, d, J = 8.01 Hz), 7.32 (1H, d, J = 1.7 Hz), 7.03 (1H, dd, J = 8.01 and 1.71 Hz), 5.27 (2 H, s). 3.51 (3H, s). (Formula Removed) Intermediate 89 4-Furan-3-yl-3-methoxyrnethoxy-benzonitrile 4-lodo-3-methoxymethoxy-benzonitrle (150 mg, 0.52 mmol) and 3-furanboronic acid (96 mg, 0.86 mmol) and Pd(PPh3)4 (60 mg, 0.052 mmol) and Cs2CO3 (500 mg, 1.53 mmol) is mixed in N,N-dimethylformamide (10 mL) and degassed and then heated at 100 °C for 4 hours. After which, the mixture is allowed to cool to room temperature and an aqueous work up is performed and the residue purified to afford the desired product (100 mg, 84%). (Formula Removed) Intermediate 90 4-Furan-3-yl-3-methoxymethoxy-benzylamine The cyanide obtained above (120 mg, 0.52 mmoi) is then dissolved in ether (10 mL). The resulting solution is slowly added to a suspension of LiAIH4 (100 mg, 2.6 mmol) in Et20. After addition, the mixture is stirred for another 10 min before quenching with H2O and 5 N NaOH. After which, EtOAc is added and the organic layer is collected and washed with brine and dried over Na2SO4- Removal of the solvent provided the crude amine (90 mg, 74%). (Formula Removed) Intermediate 91 4-Furan-2-yl-3-hydroxy-benzonitrile 3-Hydroxy-4-iodo-benzonitriie (120 mg, 0.49 mmol) and PdCI2(PPh3)2 (35 mg, 0.049 mmol) and 2-furyltributyltin (200 g, 0.56 mmol) in N.N-dimethylformamide (DMF) (5 mL) is degassed and heated at 100°C for 30 minutes (min). After the mixture cooled to room temperature, an aqueous work up is performed and the product is isolated from chromatography (80 mg, 88%). (Formula Removed) Intermediate 92 5-AminomethyI-2-furan-2-yl-phenol To a solution of 4-Furan-2-yl-3-hydroxy-benzonitrile (180 mg, 0.97 mmol) in THF (5 mL) is added BH3-THF (5 mL, 1 M solution in THF, 5 mmol) under N2. The mixture is then allowed to stir at room temperature for 24 hours. The reaction is then quenched with 6N HCI. THF is then removed and the aqueous layer is then neutralized with ammonium hydroxide to pH 9. The mixture is then extracted with CHCI3/MeOH (9:1). The organic layer dried and evaporated and the residue is chromatographed to provide the desired product (60 mg, 33%). MS (ESI): 190 (M+1)+1. Intermediate 93 3-Methoxymethoxy-4-pyridin-2-yl-benzonitrile The 4-lodo-3-methoxymethoxy-benzonitrile (190 mg, 0.66 mmol) and 2-pyridinyl tributyltin (370 mg, 1 mmol) and PdCI2(PPh3)2 (60 mg, 0.084 mmol) and Cul (40 mg, 0.21 mmol) were mixed in N,N-dimethylformamide (10 mL). This mixture is then degassed and heated at 100 °C for 1 h. TLC suggested full conversion and after aqueous workup, the residue is purified through chromatography to yield the desired product (162 mg, 93%). 1H NMR (300 MHz, CDCI3) 5 8.74 (1H, m), 7.26-7.91 (6H. m), 5.22 (2H, s), 3.46 (3H, s). MS (ESI): 241 (M+1)+1. (Formula Removed) Intermediate 94 3-Methoxymethoxy-4-pyridin-2-yl-benzylamine 3-Methoxymethoxy-4-pyridin-2-yl-benzonitrile (160 mg, 0.67 mmol) is then dissolved in ether (10 mL). The resulting solution is slowly added to a suspension of LiAIH4 (100 mg, 2.6 mmol) in Et2O. After addition, the mixture is stirred for another 10 min before quenched with H2O and 5 N NaOH. After which, EtOAc is added and the organic layer is collected and washed with brine and dried over Na2SO4. Removal of the solvent provided the crude amine, which is used directly in the next step. MS (ESI): 245 (M+1)+1. (Formula Removed) Intermediate 95 5-Aminomethyl-2-pyridin-2-yl-phenof This MOM protected amine (crude material from above) is then dissolved in 2N aq HCI / MeOH (1:1). The solution resulted is heated at reflux for 15 min and TLC suggested no starting material left. The mixture is then allowed to cool to room temperature and basified with aqueous ammonium hydroxide and the product is extracted with CH2CI2/MeOH (9:1). The organic layer is dried. After removal of the solvent, the residue is purified with chromatography to provide the desired primary amine (63 mg, 47% over two steps). 1H NMR (300 MHz, CDCI3) 58.50 (1H, m), 7.76-7.92 (3H, m), 7.24 (1H, m), 6.86-6.97 (2H, m), 3.87 (2H, s). MS (ESI): 201 (M+1)+1 Intermediate 96 3-Methoxymethoxy-4-pyridin-4-yl-benzonitrile The 4-lodo-3-methoxymethoxy-benzonitrile (200 mg, 0.69 mmol) and 4-pyridinyl tributyltin (360 mg, 0.97 mmol) and PdCI2PPh3)2 (60 mg, 0.084 mmol) and Cul (20 mg, 0.11 mmol) were mixed in N,N-dimethylformamide (10 mL). This mixture is then degassed and heated at 100 °C for 4 h. TLC suggested full conversion and after aqueous workup, the residue is purified through chromatography to yield the desired product (122 mg, 64%). (Formula Removed) Intermediate 97 3-Methoxymethoxy-4-pyridin-4-yl-benzylamine 3-Methoxymethoxy-4-pyridin-4-yl-benzonitrile ( 122 mg, 0.51 mmol) is dissolved in ether (10 mL). The resulting solution is slowly added to a suspension of LiAlH4 (100 mg, 2.6 mmol) in Et2O. After addition, the mixture is stirred for another 10 min before quenched with H2O and 5 N NaOH. After which, EtOAc is added and the organic layer is collected and washed with brine and dried over Na2SO4. Removal of the solvent provided the crude amine, which is used directly in the next step. MS (ESI): 245 (M+1)+1 (Formula Removed) Intermedlate 98 5-Aminomethyl-2-pyridin-4-yl-phenol This MOM protected amine (crude material from above) is dissolved in 2N aq HCI / MeOH (1:1). The resulting solution is heated at reflux for 15 min and TLC indicated that no starting material is left. The mixture is then allowed to cool to room temperature and basified with aqueous ammonium hydroxide and the product 192 is extracted with CH2Cl2/MeOH (9:1). The organic layer is dried. After removal of the solvent, the residue is purified with chromatography to provide the desired primary amine (40 mg, 39% over two steps). MS (ESI): 201 (M+1)+1 (Formula Removed) Intermediate 99 3-Methoxymethoxy-4-pyridin-3-yl-benzonitrile The 4-lodo-3-methoxymethoxy-benzonitrile (200 mg, 0.69 mmol) and 4-pyridinyl tributyltin (360 mg, 0.97 mmol) and PdCI2(PPh3)2 (60 mg, 0.084 mmol) and Cul (20 mg, 0.11 mmol) were mixed in N,N-dimethylformamide (10 mL). This mixture is then degassed and heated at 100 °C for 3 h. TLC suggested full conversion and after aqueous workup, the residue is purified through chromatography to yield the desired product (150 mg, 79%). (Formula Removed) Intermediate 100 3-Methoxymethoxy-4-pyridin-3-yl-benzylamine 3-Methoxymethoxy-4-pyridin-4-yl-benzonitrile (150 mg, 0.63 mmol) is then dissolved in ether (10 mL). The resulting solution is slowly added to a suspension of LiAIH4 (100 mg, 2.6 mmol) in Et2O. After addition, the mixture is stirred for another 10 min before quenched with H2O and 5 N NaOH. After which, EtOAc is added and the organic layer is collected and washed with brine and dried over Na2SO4. Removal of the solvent provided the crude amine, used directly in the next step. MS (ESI): 245 (M+1)+1. (Formula Removed) Intermediate 101 5-Aminomethyl-2-pyridin-3-yl-phenol This MOM protected amine (crude material frprrvabove) is dissolved in 2N aq HCI / MeOH (1:1). The resulting solution is heated at reflux for 15 min and TLC indicated that no starting material is left The mixture is then allowed to cool to room temperature and basified with aqueous ammonium hydroxide. The product is extracted with CH2Cl2/MeOH (9:1). The organic layer is dried. After removal of the solvent, the residue is purified with chromatography to provide the desired primary amine (53 mg, 42% over two steps). MS (ESI): 201 (M+1)+1 (Formula Removed) Intermediate 102 3-Formyl-2-methoxymethoxy-biphenyl-4-carbonitr 4-lodo-3-methoxymethoxy-benzonitrile (600 mg, 2.08 mmol), 3-formylphenylboronic acid (450 mg, 3.0 mmol), Pd(PPh3)4 (200 mg, 0.17 mmol) and Cs2CO3 (1.2 g, 3.7 mmol) were mixed in N.N-dimethylformamide (15 mL), degassed and heated at 100 °C for 2 hours. After which, the mixture is allowed to cool to room temperature, an aqueous work up is performed, and the residue purified to afford the desired product (500 mg, 90%). (Formula Removed) Intermediate 103 3,-Dimethylaminomethyl-2-methoxymethoxy-biphenyl-4-carbonitrile 3,-Formyi-2-methoxymethoxy-biphenyl-4-carbonitrile (128 mg, 0.48 mmol) is dissolved in CH2CI2 (5 mL), and to which dimethylamine (2 mL, 2 M solution in THF, 4 mmol) is added. Triacetylborohydride (300 mg, 1.59 mmol) is added and the mixture is stirred at room temperature for 1 hour before it is quenched with ice water. The organic layer is washed with NH4OH and dried over Na2SO4. After concentration, the residue is directly used in the next step. MS (ESI): 297 (M+1)+1. (Formula Removed) Intermediate 104 C-(3'-Dimethylaminomethyl-2-methoxymethoxy-biphenyl-4-yl)-methylamine 3'-Dimethylaminornethyl-2-methoxymethoxy-biphenyl-4-carbonitrile (crude material from above) is dissolved in ether (10 mL). The resulting solution is slowly added to a suspension of LiAIH4 (100 mg, 2.6 mrnol) in EtzO. After addition, the mixture is stirred for another 10 min before quenching with H2O and 5 N NaOH. After which, EtOAc is added and the organic layer is collected and washed with brine and dried over Na2SO4. Removal of the solvent provided the crude amine, which is used directly in the next step. MS (ESI): 301 (M+1)+1. (Formula Removed) Intermediate 105 4-Aminomethyl-3'-dimethylaminomethyl-biphenyl-2-ol This MOM protected amine (crude material from above) is dissolved in 2N aq HCI / MeOH (1:1). The resulting solution is heated at reflux for 15 min and TLC indicated that no starting material is left The mixture is allowed to cool to room temperature and basified with aqueous ammonium hydroxide. The product is extracted with CH2Cl2/MeOH (9:1). The organic layer is dried. After removal of the solvent, the residue is chromayography purified to provide the desired primary amine (50 mg. 40% over three steps). MS (ESI): 257 (M+1)+1. (Formula Removed) Intermediate 106 4-Bromo-2-fluoro-5-methoxy-benzaldehyde To a N2 purged flask is added TiCI4 (0.44 mL) followed by 2-Bromo-4-fluoro-1-methoxy-benzene (400 mg, 1.95 mmol). The stirred mixture is cooled in an ice water bath and treated dropwise with 1,1-dichk>romethyl methyl ether (0.35 mL, 1.95 mmol). After stirring for 90 minutes, the resulting slurry is treated with CH2CI2 (200 mL) and reaction is allowed to warm up to room temperature. After passing through a column, the title compound is isolated (220 mg, 48%). MS (ESI): 232.9 (M+1)+1. (Formula Removed) Intermediate 107 4-Bromo-2-fluoro-5-hydroxy-benzaldehyde 4-Bromo-2-fluoro-5-methoxy-benzaldehyde (100 mg, 0.43 mmol) is dissolved in CH2CI2 and cooled to -78 °C and then BBr3 (2 mL, 1 M solution In CH2CI2, 2 mmol) is added. The resulting mixture is allowed to stir at room iperature untill no starting material is left The reaction is quenched and the iuct is isolated after chromatography (60 mg, 57%). MS (ESI): 216.9 (M-1) (Formula Removed) Intermediate 108 4-Bromo-2-fluoro-5-methoxymethoxy-benzaldehyde 4-Bromo-2-fluoro-5-hydroxy-benzaldehyde (750 mg, 3.41 mmol) and MCI (545 mg, 6.82 mmol) were dissolved in anhydrous N.N-dimethylformamide (5 ML) and cooled to 0 °C. NaH (160 mg, 60% suspension in mineral oil, 4 mmol) is then added. The resulting mixture is allowed to stir at room temperature for 1h. Ether is then added and washed with H2O (3 X 20 mL) and brine. After dried over Na2SO4, the ether is removed and the residue is purified through chromatography to afford the desired MOM ether (700 mg, 78%). (Formula Removed) Intermediate 109 2-Fluoro-4-furan-3-yl-5-methoxymethoxy-benzaldehyde 4-Bromo-2-Tiuoro-5-methoxymethoxy-benzaldehyde (160 mg, 0.61 mmol) and 3-furanboronic acid (100 mg, 0.90 mmol) and Pd(PPh3)4 (60 mg, 0.052 mmol) and Cs2CO3(400 mg, 1.23 mmol) were mixed in N.N-dimethylforrnamide (10 mL) and degassed and then heated at 100 °C for 1 hour. The mixture is allowed to cool to room temperature and arraqueous work up is performed. The residue is purified to afford the desired product (60 mg, 39%). (Formula Removed) Intermediate 110 2-Fluoro-4-furan-3-yl-5-methoxymethoxy-benzaldehyde O-methyl-oxime 2-Fluoro-4-furan-3-yl-5-methoxymethoxy-benzaldehyde (200 mg, 0.8 mmol) is dissolved in pyridine (5 mL). Methoxylamine hydrochloride (100 mg, 1.2 mmol) is added. The mixture is stirred at room temperature for 1 hour, the pyridine is evaporated and the product purified through chromatography (248 mg, 100%). MS (ESI):280(M+1)+1. (Formula Removed) Intermediate 111 2-Fluoro-4-furan-3-yl-5-methoxymethoxy-benzaldehyde O-methyl-oxime The oxime ether (248 mg, 0.8 mmol) is dissolved in ether and LiAIH4 (250 mg, 6.57 mmol) is added. The resulting mixture is heated at reflux for 20 minutes and then quenched with EtOAc and 5 N NaOH. The product is extracted out with EtOAc. After the ethyl acetate layer is dried and evaporated, the product obtained is directly used in the next step. MS (ESI): 252 (M+1)+1. (Formula Removed) Intermediate 112 5-Aminomethyl-4-fluoro-2-furan-3-yl-phenol The MOM protected amine (crude material from above) is dissolved in 2N aq HCI / MeOH (1:1). The resulting solution is heated at reflux for 15 minutes and TLC suggested no starting material is left. The mixture is allowed to cool to room temperature and basified with aqueous ammonium hydroxide'and the product is extracted with CH2Cl2/MeOH (9:1). The organic layer is dried. After removal of the solvent, the product is purified with chromatography (96 mg, 58% over two steps). MS(ESI):208(M+1)+1. (Formula Removed) Intermediate 113 4-tert-Butyl-2-carboxymethyl-benzoic acid To a magnetically stirred solution of diisopropyl amine (0.75 g, 7.4 mmol) in THF (5 mL) at -30 °C is added BuLi (3.4 ml_. 2.5 M in hexanes, 8.5 mmol). The mixture is stirred for 10 minutes at this temperature and cooled to —78 °C. A solution of 4-tert-Butyl-2-methyl-benzoic acid [J. Am. Chem. Soc. 1944, 66, 154] (250 mg, 1.3 mmol) and dimethylcarbonate (150 mg, 1.67 mmol) in THF (3 mL) is added dropwise at -78 °C. The mixture is allowed to stir at this temperature for 2 hours before it is allowed to warm to room temperature. The mixture is quenched with MeOH and water once it reached room temperature. After removal of THF. the water layer is extracted with ether. The water layer is acidified with HCI and the product is extracted from ether. After chromatography, the title compound is isolated pure (125 mg, 41 %). MS (ESI): 237.1 (M+1 )+1. (Formula Removed) i Intermediate 114 6-tert-Butyl-4H-isoquinoline-1,3-dione 4-tert-Butyl-2-carboxymethyl-benzoic acid (90 mg, 0.38 mmol) and urea (45 mg, 0.75 mmol) were grinded and mixed in a round bottle flask, then placed into an oil bath, preheated to 145 °C. The flask is kept at this temperature for 1 hour before it is cooled to room temperature. Chromatography of the residue afforded the title compound (45 mg, 55%). MS (ESI): 216.1 (M-1)-1. (Formula Removed) Intermediate 115 6-tert-Butyl-4-methoxymethylene-4H-isoquinoline-1,3-dione 6-tert-Butyl-4H-isoquinoline-1,3-dione (45 mg, 0.21 mmol) is dissolved in N,N-dimethylformamide (1 mL) and acetic anhydride (2mL). Trimethylorthoformate (0.2 mL) is added and the mixture is heated to-120 °C for 1 hour. The volatiles were removed under vacuum and the residue passed through a column to afford the crude product, is used directly in the next step. MS (ESI): 258.3 (M-1 )-1 (Formula Removed) Intermediate 116 4-(4-Nitro-phenyl)-pyridine To a 25 mL round bottom flask is added 1-bromo-4-nitrobenzene (404 mg, 2.0 mmol ), 4-pyridinylboronic acid (248mg, 2.0 mmol), Na2CO3(424 mg, 4.0 mmol) and Pd(PPh3)4 (100 mg, 0.087 mmol), DME (10 mL) and HzO (3 mL). The mixture is degassed and heated at reflux for 14 h. TLC is used to establish the completion of starting bromide, the mixture is allowed to cool to room temperature. EtOAc is added, and the EtOAc layer is washed with H2O (15 mL) and brine (10 mL) and dried over MgSO4. After removal of EtOAc; the resulting residue is subjected to flash chromatography with CH2CI2 /EtOAc (3:1) as eluent to provide the coupling product 4-(4-nitro-phenyl)-pyridine (288 mg, 72%). 1H NMR (400 MHz, CDCl3) 3 8.75 (2H, dd, J = 6.0 and 2.8 Hz), 8.36 (2H, dd, J = 9.6 and 3.2 Hz), 7.80 (2H, dd, J = 8.8 and 2.4 Hz), 7.54 (2H, dd, J = 5.6 and 2.0 Hz). (Formula Removed) Intermediate 117 4-Pyridln-4-yl-phenylamine 4-(4-nitro-phenyl)-pyridine (250 mg, 1.25 mmol) is dissolved in MeOH (20 mL). To this solution is added FeCI3-6H20 (24 mg. 0.09 mmol) and active charcoal (12 mg, 1.0 mmol). The suspension is heated to reflux. Hydrazine hydrate (1.3 mL) is added, and reflux is continued for 3 hi After the mixture is cooled to room temperature, the active charcoal is filtered off through Celite, and the MeOH is removed under reduced pressure. The residue is purified with flash chromatography to provide the 4-pyridin-4-yl-phenylamine (200 mg, 94%). 1H NMR (400 MHz. CDCI3) a 8.57 (2H, d, J = 8.8 Hz), 7.44-7.52 (4H. m), 6.77 (2H. d. J = 7.2 Hz), 3.87 (2H. br); MS (ESI) m/z 171 (M+H)+1. (Formula Removed) Intermediate 118 4-Chloro-3,5-dimethyl-1(4-nitro-phenyl)-1H-pyrazole 4-Nitro-phenyl)-hydrazine (0.50 g, 3.3 mmol) and 3-Chloro-pentane-2,4-dione (0.45 g, 3.3 mmol) is heated in EtOH at reflux in the presence of concentrated HCI (1 mL). TLC is used to monitor the consumption of the starting material, the mixture is allowed to cool to room temperature at which time, a precipitate formed. The precipitate is collected and dried to provide the 4-Chloro- 3,5-dimethyl-1-(4-nitro-phenyl)-1H-pyrazoIe in the HCI salt form (0.5 g, 53%). 1H NMR (3p0 MHz, DMSO) d 8.33-8.38 (2H, m), 7.84-7.88 (2H, m), 4.37 (2H, br), 2.41 (3H, s), 2.24 (3H, s). (Formula Removed) Intermediate 119 4-(4-Chloro-3,5-dimethyl-pyrazol-1-yl)-phenylamine 4-Chloro-3,5-dimethyM-(4-nitro-phenyl)-1H-pyrazole hydrochloride (450 mg, 1.56 mmol) is dissolved in MeOH (40 mL). To this solution is then added FeCI3-6H20 (24 mg, 0.09 mmol) and active carbon (12 mg, 1 mmol). The suspension is heated to reflux. Hydrazine (2.0 mL) is added, and reflux is continued for 3 h or until TLC detected full conversion. After conversion the mixture is cooled to room temperature, the active carbon is filtered off using celite and the MeOH under reduced pressure. The residue is purified with flash chromatography to provide the 4-(4-Chloro-3,5-dimethyl-pyrazol-1-yl)-phenylamine (360 mg, 91%). MS (ESI): 222, 224 (M+1)+1. (Formula Removed) Intermediate 120 4-(1 -Pyrrolidin-1 -yl-ethyl)-phenylamine LiHMDS (1 mL, 1 M solution in THF, 1.0 mmol) is added to a 25 mi_ round bottom flask, THF is removed. Toluene (4 mL) is added followed by addition of Pd2(dba)3-CHCl3(10 mg, 0.01 mmol) and P(tBu)3 (20 mg, 0.05 mmol). The mixture is degassed. 1-[1-(4-Bromo-phenyl)-ethyl]-pyrrolidine (330mg, 1.3 mmol) in toluene (2 mL) is added to the flask. The resulting mixture is stirred at room temperature overnight. TLC is used to determine complete consumption of starting bromide, the reaction mixture is diluted with ether at this point and poured into dilute HCI (aq). The ether layer is discarded, the aqueous layer is basified with NH4OH and extracted with CH2CI2. The CH2CI2 layer is dried and concentrated. The residue is subjected to chromatography to provide the desired product 4-(1-Pyrrolidin-1-yl-ethyl)-phenyiamine {60 mg, 24% ). 1H NMR (300 MHz, CDCI3) d 7.09-7.13 (2H, m), 6.61-6.66 (2H. m), 3.47 (2H. br), 3.11 (1H, q, J = 6.6 Hz). 2.52-2.58 (2H, m), 2.33-2.39 (2H. m). 1.73-1.79 (4H, m). 1.38 (3H. d, J = 6.9 Hz). MS (ESI): 191 (M+1)+1. (Formula Removed) Intermediate 121 4-(1-Methyl-pyrrolidin-2-yl>-pr»enylamine LiHMDS (5.0 g. 30.0 mmol) is added to a 250 mL round bottom flask. Toluene (60 mL) is then added followed by addition of Pd2(dba)3-CHCI3 (390 mg, 0.39 mmol) and P(tBu)3-HBF4 (300 mg, 1.03 mmol) and 2-(4-Bromo-phenyl)-1-methyl-pyrrolidine (3.5 g, 14.5 mmol). The mixture is degassed. The resulting mixture is then stirred at room temperature overnight. After TLC suggested no starting bromide left, the reaction mixture is diluted with ether and poured into dilute HCI (aq). The ether layer is discarded, the aqueous layer is basified with NH4OH and extracted with CH2CI2. The CH2CI2 layer is dried and concentrated. The residue is judged by NMR to be 90% purity product (2.52 g, 90%). (Formula Removed) Intermediate 122 D-1-(4-Amino-benzyt)-pyrroiidine-2-carboxylic acid methyl ester D-1-(4-Nitro-benzyl)-pyrrolidine-2-carboxylic acid methyl ester (1.0 g, 3.7 mmol) is dissolved in MeOH (20 mL) and Fe (1.5 g, 26.7 mmol). NH,CI (1.5 g„ 28.0 mmol) is added followed by addition of H2O (10 mL). The mixture is heated at reflux for 2 h. The resulting solid is filtered and MeOH removed. EtOAc and NaHCO3 (aq) is added. The EtOAc layer is washed and dried over Na2S04. After removal of EtOAc, the residue is used directly in the next step. (Formula Removed) Intermediate 123 2-[1-(4-Nitro-ben2yl)-pyrrcrroidin-2-yrj-propan-2-oJ 2-Pyrrolidin-2-yl-propan-2-ol (100 mg, 0.78 mmol) is dissolved in CH3CN (5 mL) to which K2CO3 (300 mg. 2.17 mmol) and p-nitrobenzylbromide (250 mg, 1.16 mmol) were added. The resulting mixture is stirred until MS suggested no starting alcohol is present. The. suspension is filtered to remove the potassium salts and the acetonitrile is removed under vacuum. The residue is purified to afford the product (105 mg, 51%). 1H NMR (300 MHz, CDCI3).8.18 (2H, d, J = 8.7 Hz), 7.54 (2H, d, J = 8.7 Hz), 4.25 (1H, d, J = 15 Hz), 3.72 (1H, d, J = 15 Hz). 2.90-2.95 (1H, m), 2.76-2.80 (1H, m). 2.28-2.38 (2H, m), 1.71-1.91 (4H. m). 1.24 (3H, s), 1.20 (3H, s). Intermediate 124 2-[1-(4-Amino-benzyl)-pyrrolidin-2-yrj-propan-2-ol 2-[1-(4-Nitro-benzyl)-pyrrolidin-2-yl]-propan-2-ol (105 mg, 0.40mmol) is dissolved in MeOH (20 mL). To this solution is added FeCI3-6H20 (30 mg, 0.11 mmol) and active charcoal (15 mg, 1.2 mmol). The suspension is heated to reflux. Hydrazine hydrate (1.2 mL) is added, and reflux is continued for 3 h. After the mixture is cooled to room temperature, the active charcoal is filtered off through Celite, and the MeOH is removed under reduced pressure. The residue is purified with flash chromatography to provide the 4-pyridin-4-yt-phenylamine (72 mg, 77%). 1AH NMR (300 MHz. CDCI3) 07.14 (2H, d, J - 7.8 Hz), 6.62-6.67 (2H, m), 4.0 (1H, d, J = 12.9 Hz), 3.61 (2H, br), 3.46 (1H, d, J = 12.9 Hz), 2.82-2.89 (1H, m), 2.69-2.74 (1H, m), 2.39-2.47 (1H, m), 1.62-1.89 94H, m), 1.25 (3H, s), 1.15 (3H, s). (Formula Removed) Intermediate 125 2-(1-Hydroxy-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester L-2-Formyl-pyrrolidlne-1-carboxylic acid tert-butyl ester (2.0 g, 10.0 mmol) is dissolved in THF (30 mL) and cooled to -78 °C. MeMgBr (5.0 mL, 3.0 M in ether, 15.0 mmol) is added dropwise. the mixture is allowed to stir overnight to room temperature. After removal of THF, the residue is partitioned between EtOAc and H2O. The EtOAc layer is dried over Na2SO4. After removal of the EtOAc, the residue (2.0 g, 93%) is used directly in the next step. Intermediate 126 1 -[1 -(4-Nitro-benzyl)-pyrrolidin-2-yl]-ethanol 2-(1-Hydroxy-ethyl)-pyrrolidine-1-carboxylic add tert-butyl ester (1.0 g, 4.6 mmol) in CH2CI2 is cooled to 0 °C and TFA (2.5 mL) is added dropwise. The mixture is allowed to stir at room temperature overnight All the volatiies were removed and CH3CN (20 mL) is added. After addition of 4-nitrobenzyl bromide (1.25 g, 5.78 mmol) and K2CO3 (2.0 g, 14.4 mmol), the mixture is stirred at room temperature for 5 hours. (Formula Removed) Intermediate 127 1 -[1 -(4-Amino-benzyl)-pyrrolidin-2-ylJ-ethanol 1-[1-(4-Nitro-benzyl)-pyrrolidin-2-yl-ethahol (370 mg, 1.48 mmol) is dissolved in MeOH (15 mL), to this solution is added FeCI3-6H2O (30 mg, 0.11 mmol) and active charcoal (15 mg, 1.2 mmol). The suspension is heated to reflux. Hydrazine hydrate (1.0 mL) is added, and reflux is continued for 3 h. After the mixture is cooled to room temperature, the active charcoal is filtered off through Celite, and the MeOH is removed under reduced pressure. The residue (200 mg, 61%) is directly used in the next step. (Formula Removed) Intermediate 128 2-(1-Methoxy-ethyi)-pyiTolidine-1-carboxyIic acid tert-butyl ester 2-(1-Hydroxy-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.3 mmol) in N.N-dimethylformamide (15 mL) is cooled to 0 °C, Mel (1 mL) is added • followed by NaH (380 mg, 60% suspension in mineral oil, 9.5 mmol). The resulting mixture is allowed to stir at room temperature for 2 hours until TLC reported no remaining starting material. The reaction is quenched with ice and ether is added. N.N-dimethylformamide is washed away with H2O and the ether layer is dried and concentrated to afford the crude product used directly in the next step. (Formula Removed) Intermediate 129 2-( 1 -Methoxy-ethyl)-1 -(4-nitro-benzyl)-pyrrolidine 2-(1-methoxy-ethyi)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.4 mmol) in CH2C12 (25 mL) is cooled to 0°C and TFA (2.5 mL) is added dropwise. The mixture is albwed to stir at room temperature overnight. The volatiles were removed and CH3CN (20 mL) is added. After addition of 4-nitrobenzyl bromide (1.25 g, 5.78 mmol) and K2CO3 (2.0 g, 14.4 mmol) the mixture is stirred at room temperature for 5 hours. Aqueous workup followed by chromatography. (260 mg, 25%). 1H NMR (300 MHz, CDCI3) 38.17 (2H, d, J = 8.7 Hz), 7.51 (2H, d. J = 8.4 Hz), 4.29 (1H, d, J = 14.4 Hz), 3.48 (1H, d, J = 14.4 Hz), 3.30-3.33 (1H, m), 3.32 ( 3H, s), 2.88-2.91 (1H, m), 2.73-2.78 (1H, m), 2.14-2.19 (1H, m), 1.61-1.85 (4H, m), 1.15 (3H,d, J =6.6 Hz). (Formula Removed) Intermediate 130 4-[2-(1-Methoxy-ethyl)-pyrrolidin-1-ylmethyQ-phenylamine 2-(1-Methoxy-ethyt)-1-(4-nitro-benzyl)-pyrrolidine (250 mg, 0.95mmol) is dissolved in MeOH (10 mL). To this solution is added FeCi3-6H20 (25 mg, 0.09 mmol) and active charcoal (12 mg. 1.0 mmol). The suspension-is heated to reflux. Hydrazine hydrate (1.0 mL) is added, and reflux is continued for 4 h. After the mixture is cooled to room temperature, the active charcoal is filtered off through Celite, and the MeOH Is removed under reduced pressure. The residue (200 mg. 90%) is used directly in the next step. (Formula Removed) Intermediate 131 Allyl-[1-(4-bromo-pheryl)-but-3-eny-amine Allyl-(4-bromo-benzylidene)-amine (1.13 g, 5.0 mmol) is dissolved in THF (15 mL) and the mixture is cooled to 0 °C with an ice bath. Allyl magnesium bromide (6.0 mL, 1.0 M in ethyl ether, 6.0 mmol) is added. The resulting mixture is stirred at 0 °C for 1 hour and warmed to room temperature followed by reaction quenching. EtOAc and water were added and the EtOAc layer is washed with brine and dried. After removal of EtOAc, the product (1.0 g, 75%) is obtained. MS (ESI): 266, 268 ( (Formula Removed) Intermediate 132 Allyl-[1 -(4-bromo-phenyl)-but-3-enyll-carbam-c acid tert-butyl ester Ailyl-[1-(4-bromo-phenyl)-but-3-enyf]-arnine (1.0 g, 3.7 mmol) is dissolved in CH3CN (17 mL), (Boc)2O (1.2 g, 5.5 mmol) is added, followed by addition of DMAP (50-100 mg, 0.41-0.82 mmol). The mixture is stirred until no starting amine is left. After removal of CH3CN, the residue is subjected to chromatography to provide the desired product (0.9 g, 66%). 'H NMR (300 MHz, CDCI3) 7.47 (2H, d, J = 8.7 Hz), 7.20-7.27 (2H. m), 5.0-5.83 (7H, m), 3.60 (2H, m). 2.75 (2H, m), 1.52 (9H, s). (Formula Removed) Intermediate 133 2-(4-Bromo-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester Allyl-[1-(4-bromo-phenyl)-but-3-enyl]-carbamic acid tert-butyl ester (300 mg, 0.82 mmol) in CH2CI2 (10 mL) is degassed and the 2nd generation of Grubb's catalyst (40 mg, 5 %) is added under N2- The reaction did not proceed at room temperature and the mixture is brought to reflux. TLC is used to determine complete reaction of the olefin. The mixture is loaded onto a column and purified to provide the desired product {208 mg, 75%). 1H NMR (300 MHz. CDCI3) 37.43 (2H, d, J = 8.1 Hz), 7.17-7.26 (2H, m), 5.89-5.95 (1H. m), 5.34-5.58 (2H, m), 4.14-4.36 (1H, m), 3.35-3.44 (1H, m), 2.73-2.81 (1H, m), 2.41-2.62 (1H, m), 1.48 (9H, s). (Formula Removed) Intermediate 134 2-(4-Amino-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester To a solution of 2-(4-Bromo-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (400 mg, 1.18 mmol) in toluene (4 mL) is added Pd2(dba)3-CHCl3(50mg, 0.05 mmol) and P(tBu)3 (40 mg, 0.20 mmol). The mixture is degassed at -30 °C. KHMDS (7.0 mL, 0.5 M solution in toluene, 3.5 mmol)) is added to the flask. The resulting mixture is stirred at room temperature overnight. TLC is used to detect when the starting bromide is consumed, the reaction mixture is diluted with ether and poured into dilute HCI (aq). The ether layer is discarded, the aqueous layer is basified with NH4OH and extracted with CH2CI2. The CH2CI2 layer is dried and concentrated. The residue (300 mg) is directly employed in the next step. (Formula Removed) Intermediate 135 4-(4,5-Dihydro-3H-pyrrol-2-yl)-phenylamine LiHMDS (1.67 g, 10.0 mmol) is added to a 100 mL round bottom flask. Toluene (25 mL) is added followed by addition of Pd2(dba)3-CHCl3(100 mg, 0.1 mmol) and P(tBu)3-HBF4 (78 mg, 0.27 mmol). 5-(4-Bromo-phenyl)-3,4-dihydro-2H-pyrrole (1.5 g, 6.7 mmol) Is added to the flask. After degasing, the mixture is stirred at room temperature overnight. TLC is used to determine complete consumption of the starting bromide. The reaction mixture is diluted with ether and poured into dilute HCI (aq). The ether layer is discarded and the aqueous layer is basified with NH4OH and extracted with CH2CI2. The CH2CI2 layer is dried and concentrated to provide the desired product (820 mg, 76% ). 1H NMR (300 MHz, CDCI3) d 7.66 (2H. d, J = 8.4 Hz), 6.67 (2H, d, J = 8.1 Hz). 3.98-4.03 (2H, m), 3.88 (2H. br), 2.85-2.92 (2H, m), 1.97-2.04 (2H, m). MS (ESI): 162 (M+1)+1 (Formula Removed) Intermediate 136 2-(4-Bromo-phenyl)-pyrrolidlne-1 -carboxylic acid tert-butyl ester 5-(4-Bromo-phenyl)-3.4-dihydro-2H-pyrrole (5.0 g, 22.3 mmol) is dissolved in MeOH (100 mL). The resulting solution is cooled to 0 °C in an ice bath. NaBH4 (1.0 g, 26.3 mmol) is added to this solution slowly. After the mixture is stirred for 1 h, the MeOH is removed and the residue is suspended in CH2CI2. At this point, (Boc)20 (7.0 g, 32.1 mmol) is added. The resulting mixture is stirred for another 2 h and loaded on the column and purified to provide the Boc compound (3.5 g, 48%).1H NMR (300 MHz, CDCI3) .97.39-7.44 (2H, m), 7.03-7.06 (2H, m), 4.72-4.88 (1H, m). 3.58 (2H, br), 2.28-2.30 (1H, m), 1.72-1.94 (3H, m), 1.45 (3H, br), 1.20 (6H. s). (Formula Removed) Intermediate 137 2-(4-Amino-phenyl)-pyrrolidine-1-carboxylicacid tert-butyl ester LiHMDS (1.6 g, 9.6 mmol) is added to a 100 mL round bottom flask. Toluene (20 mL) is added followed by addition of Pd2(dba)3•CHCI3 (50 mg, 0.05 mmol) and P(tBu)3•HBF4 (40 mg, 0.14 mmol). 2-(4-Bromc-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.5 g, 4.6 mmol) is added to the flask. After degasing, the mixture is stirred at room temperature overnight. After TLC suggested no starting bromide is left, the reaction mixture is diluted with ether and poured into dilute HCI (aq). The ether layer is discarded, the aqueous layer is basified with NH4OH and extracted with EtOAc. The EtOAc layer is dried and concentrated to provide the desired product (1.0 g, 83% ). 1H NMR (300 MHz, CDCI3)  6.94-6.96 (2H, m), 6.60-6.67 (2H. m), 4.67-4.85 (1H, m). 3.58 (4H, br). 2.24 (1H. m), 1.73-1.97 (3H, m). 1.44 (3H, s), 1.21 (6H, s). (Formula Removed) Intermediate 138 1-(4-Bromo-benzyl)-2-ethoxymethyl-pyrrolidine [1-(4-Bromo-benzyl)-pyrrolidin-2-yl]-methanol (269 mg, 1.0 mmol) and Etl (234 mg, 1.5 mmol) is mixed at 0 °C in DMF (DMF) (10 mL). To this mixture is then added NaH (60 mg, 60% suspension in mineral oil, 1.5 mmol). The resulting mixture is stirred at room temperature for 1 h before aqueous workup. The resulting residue is directly used in the next step. (Formula Removed) Intermediate 139 4-(2-Ethoxymethyi-pyrrolidin-1-ylmethyl)-phenylamine Using the same procedure described for the preparation of 2-(4-Amino-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester, the title compound is prepared from 1-(4-Bromo-benzyl)-2-ethoxymethyl-pyrrolldine (using the crude product obtained in the previous step) in 47% yield (two steps, based on crude residue, -85%). (Formula Removed) Intermediate 140 1-(2-Fluoro-4-nitro-phenyl)-pyrrolidine-2-carbaldehyde [1-(2-Fluoro-4-nitro-phenyl)-pyrrolidin-2-yl]-methanol (100 mg, 0.42 mmol) and Dess-Martin periodate (175 mg. 0.42 mmol) is stirred in CH2CI2 overnight. After chromatography, the desired product is isolated (100 mg, -100%): 1H NMR (300 MHz, CDCI3) 39.67 (1H, s), 7.85-7.98 (2H, m), 6.66 (1H, t, J = 9.0 Hz), 4.65-4.72 (1H, m), 3.49-3.75 (2H, m), 1.89-2.30 (4H, m). (Formula Removed) Intermediate 141 [1-(2-Fluoro-4-nitro-phenyl)-pyrrolidin-2-ylmethyl]-dimethyl-amine 1-(2-Fluoro-4-n"itro-phenyl)-pyrrolidine-2-carbaldehyde (100 mg, 0.42 mmol) and dimethylamine (large excess) is stirred at room temperature in CH2CI2 for 5 min and NaBH(OAc)3 (120 mg, 0.57 mmol) is added. The reaction is stopped after 30 min as TLC suggested complete conversion and the desired product (77 mg, 69%) is isolated after chromatography. (Formula Removed) Intermediate 142 4-(2-Dimethylaminomethyl-pyrrolidin-1-yl)-3-fluoro-phenylamine [1-(2-Fluoro-4-nitro-phenyi)-pyrrolidin-2-ylmethyl}-dirriethyl-arnine (77 mg, 0.29 mmol) and Pd/C (16 mg, 10% weight) is shaken under H2 (50 psl) in MeOH overnight. After filtrating the Pd/C, the MeOH is removed and the residue obtained (65 mg, 95%) is directly employed in the next step. (Formula Removed) intermediate 143 1-Allyl-2-(4-bromo-phenyl)-pyn-olidine 2-(4-Bromo-phenyl)-pyrrolidine (640 mg, 2.83 mmol) and allyl bromide (343 mg, 2.83 mmol) is mixed in THF (15 mL) and K2CO3 (390 mg, 2.83 mmol) is then added. The mixture is heated at reflux for 2 h before THF is removed under reduced pressure and the residue is partitioned between EtOAc and H20. The EtOAc layer is dried and concentrated and the residue is then subjected to chromatography to provide the desired product (470 mg, 62.4%). (Formula Removed) Intermediate 144 4-(1-Allyl-pyrrolidin-2-yl)-phenylamine Using the same procedure described for the preparation of 2-(4-Amino-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester, the title compound is prepared from 1-Allyi-2-(4-bromo-phenyl)-pyrrolidine (470 mg. 1.77 mmol) in 87% yield. (Formula Removed) Intermediate 145 1 -(4-Nitro-benzyl)-2-vinyl-pyrrolidine 2-Vinyl-pyrrolidine-1-cart>oxylic acid tert-butyl ester (300 mg, 1.52 mmol) is dissolved in CH2CI2 (4 mL) to which TFA (0.55 mL) is added dropwisely. The resulting mixture is stirred until TLC showed no starting material. All the volatiles were removed under vacuum. CH3CN (5 mL) is added followed by 4-nitrobenzylbromide (400 mg, 1.85 mmol) and K2CO3 (1 g, 7.2 mmol). The mixture is stirred until TLC suggested no starting material left. EtOAc and H20 were added and the EtOAc layer is washed with brine and dried. After evaporating the EtOAc, the residue is purified with flash chromatography to provide the desired product (300 mg, 85%). (Formula Removed) Intermediate 146 4-(2-Ethyl-pyrrolkiin-1-ylmethyl)-phenylamine Using the same procedure described for the preparation of 2-(4-Amino-phenyi)-pyrrolidine-1-carboxylic acid tert-butyl ester, the title compound is prepared from 1-{4-Nitrp-benzyl)-2-vinyl-pyrrolidine (220 mg, 0.95 mmol) In 44% yield. (Formula Removed) Intermediate 147 6-Bromo-1,1-dimethy-1 ,4-dlhydro-2H-isoquinolln-3-one PPA (100 g) is heated to 140 °C. (3-Bromo*pbenyl)-acetonitrile (10 g, 5.1 mmol) is added. After stirring for 5 minutes, acetone (6 g, 0.1 mol) is added. The mixture is stirred for 1 hour at 140 °C. The viscous mixture is poured into ice H2O and extracted with chloroform. The chloroform layer is washed with H2O and NaHCO3, brine and dried. After evaporating the solvent, the crude product obtained is directly used in the next step. (Formula Removed) Intermediate 148 4-(4~Nitro-benzyl)-thiomorpholine 1,1-dioxide To a flask containing thiomorpholine 1,1-dioxide hydrochloride (0.65 g. 3.8 mmol) in CH3CN is added 4-nitrobenzylbromide (1.1 g, 5.1 mmol) and K2CO3 (1.9 g, 13.7 mmol). The mixture is then allowed to stir at room temperature overnight. After aqueous work up, the product is obtained through chromatography. MS (ESI): 271.1 (M+1)+1 (Formula Removed) Intermediate 149 4-(4-Amino-benzyl)-thiomorpholirie 1,1 -dioxide 4-(4-Nitro-benzyl)-thiomorpholine 1,1-dioxide (110 mg, 0.41mmol) is dissolved in MeOH (7 mL). To this solution is added FeCI3•6H2O (-20 mg, 0.07 mmol) and active Charcoal(12 mg, 1.0 mmol). The suspension is heated to reflux. Hydrazine hydrate (0.5 mL) is added, and reflux is continued for 4 h until full conversion, the active Charcoal is filtered off through Celite, and the MeOH is removed under reduced pressure. The residue (85 mg, 86%) is directly used in the next step. (Formula Removed) Intermediate 150 4-(N-Nitro-benzyl)-morpholine An amount of 10 g (46.30 mmol) of 1-bromomethyl-4-nito-benzene is stirred in dichloromethane (125 mL), followed by addition of triethylamine (12.90 mL, 92.6 mmol), and morpholine (4.03g, 46.30 mmol). The reaction mixture is reffuxed for 1 h, subsequently washed 3 times with aqueous sodium bicarbonate, dried over sodium sulfate, followed by evaporation to dryness, to give white crystals (7.5 g, 73%). (Formula Removed) Intermediate 151 4-Mopholin-4-ylmethyl-phenylamine Seven grams (31.52 mmol) of 4-N-nitrobenzyl-morpholine, ammonium chloride (15.14g, 283.68 mmol), and iron (10.56 g, 189.12 mmol) were added to 266 mL of methanol/water (4.75:1) and refluxed until there is no appearance of starting materials. After filtering through celite, the solvent is evaporated. The residue is dissolved in water, basified with potassium carbonate, and extracted three times with etheyl acetate. The organic solution is dried with magnesium sulfate, and evaporated to afford 6 g (99 % yield) of orange solid. (Formula Removed) Intermediate 152 3-hydroxy-4-methoxy-benzylaldehyde oxime 222 An amount of 1.52 g (10.0 mmol) of 3-hydroxy-4-methoxy- benzylaldehyde is added to ethanol (20 ml), and pyridine (10 ml) at room tempreture followed by addition of hydroxylamine hydrogen chloride (764.39 mg, 11.0 mmol). The mixture is stirred at ambient tempreture for 24 h, and 200 mL of water is added. After the solvents were evaporated, the residue is dissolved 400 mL of anhydrous ether, washed successively with 100 mL of aqueous sodium bicarbonate, 100 mL of sodium bisulfite, and 100 mL of brine, dried over magnissium sulfate, and evaporated to give a white solid 1.39 g (83 % yield). (Formula Removed) Intermediate 153 3-hydroxy-benzylamine hydrogen chloride An amount of 2 g (16.79 mmol) of 3-cyanophenol is dissolved in tetrahydroufuran (40 mL). After cooling to 0°C, borane tetrahydrofuran complex ( 32.0 mL, 2.0 M) is added dropwise to the solution. Allowed to stir at 0°C for 15 min, then at room temperature for 25 min. After refluxing for 3 h. It is cooled to room temperature and evaporated to dryness. Methanol (14 mL) is added, and evaporated to dryness. Concentrated hydrogen chloride (155 mL) is added, and evaporated to dryness. The residue is recrystallized from ethyl acetate to give 3 g of the product as a white solid. MS (ESI) m/z 123.15 (M+1). (Formula Removed) Intermediate 154 6-fluoroisoquinoline-1,3(2H,4H)-dione An amount of 200 mg (1.01 mmol) of 2-carboxymethyl-4-fluoro-benzoic acid and urea (72.47 mg, 1.25! mmol) were heated neat at 180-190°C for 45 min. The mixture is cooled to room temperature followed by recrystallization from water and anhydrous ether to give175 mg (80 % yield) of brown solid. MS (ESI) m/z 179.15 (M+1). (Formula Removed) Intermediate 155 (4E)-6-fluoro-4-(methoxymethylene)isoquirx>line-1,3(2H,4H)-dione An amount 2 g (11.16 mrnol) of 6-fluoro-isoquinoline-(4H)-1,3-dione is dissolved in N,N-dimethylformate and acetic anhydride (1:4) followed by addition of trimethyl orthoformate (2.37 mL, 22.32 mrnol). After the mixture is heated at 120°C for 1 h, it is cooled. The yellow precipitate is collected and washed several times with anhydrous ether to give 2.3 g (94 % yield) of yellow solid. MS (ESI) m/z 221.19 (M+1). (Formula Removed) Intermediate 156 (4E)^methoxyrnethylene)-6-(1H-thiophin-3-yl)isoquinoline-1,3(2H,4H)-dione: To a mixture of 4 g (13.93 mrnol) of 4-bromo-2-methoxycarbonylrnethyl-benzoic acid-methyl ester, Pd2dba)3 (446 mg. 0.49 mmol). P2(t-Bu)2 (299 mg, 1.07 mrnol), CS2CO3 (9.07 mg, 27.66 mrnol) and 3-thiophine boronic acid (2.67 g . 20.90 mrnol) is added dioxane (20 mL) under N2. The mixtures were placed in a pre¬heated oil bath 80°C for 4 hours. After cooling, the mixtures were filtered through celite and washed with etheyl acetate, extraction with aqueous NaHCO3 followed by drying with NaSO4 and evaporation. The resulting yellow oil is crystallized. The crystal is collected and washed with anhydrous ether to give 2.6 g (70 %) of 2- (Formula Removed) methoxycarbonylmethyl-4-thiophine-3-yl-benzoic acid methyl ester as a brown solid, 2-methoxycarbonylmethyl-4-thiophine-3-yl-benzoic acid methyl ester (2.4 g, 8.27 mmol) is added to 2.2 M solution of sodium hydroxide in water (10 ml_) at room temperature and stirred overnight. After adusting the pH to 4, 2.0 g of 2-carboxymethyi-4-thiophin-3-ylbenzoic acid is isolated as a yellow solid. Using the procedure described for the preparation of 6-fluoroisoquinoline-1,3(2H.4H)-dione, 1.3 g (80 % yield) of 6-thiophin-3-yl-isoquinoline-(4H)-1,3-dione as a brown solid is obtained from 1.6 g (6.11 mmol) of 2-carboxymethyl-4-thiophin-3-ylbenzoic acid is used. Using the procedure described for the preparation of (4E)-6-ftuoro-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione, 1.2g (95 % yield) of 4-methoxymethylene-6-thiophin-3-yt-isoquinilin-(4H)-1,3-dione as green-yellow solid is obtained from 1.10 g (4.11 mmol) of 6-thiophin-3-yl-isoquinoline-(4H)-1,3-dione. (Formula Removed) Intermediate 157 2-Amino-5-(aminomethyl)phenol Using the procedure described for the preparation of (4E)-6,7-dimethoxy-4-(methoxymethylene)isoquinoline-l ,3(2H,4H)-dione and 3-bydroxy-4-methoxy-benzylamine hydrogen chloride, 2.5g (89 % yield) of purple solid is obtained from 2.2g (16.1 mmol) of 3-hydroxy-4-nitrobenzaldehyde O-methyloxime; MS (ESI) m/z 138.9 (M+H)+. (Formula Removed) Intermediate 158 5-Aminomethyl-2-chloro-phenol hydrogen chloride An amount of 1 g (5.57 mmol) of 4-chloro-3-hydroxy benzoic acid is added ml (115.8 mmol) of oxafyl chloride and refluxed at 60°C till the solid had gone i solution. After cooling, the mixture is evaporated to dryness to give 4-chloro-3-roxy-benzoyl chloride. 4-Chloro-3-hydroxy-benzoyi chloride is cooled to 0°C and 20 ml of ammoriium hydroxide were added within 5 minutes. The mixture is allowed to stir at O0C for 30 minutes, then at room temperature for additional 30 minutes. 30 ml of er is added to the mixture and the white precipitate is filtered, the pH of the er layer is adjusted to 3, followed by extraction with ethyl acetate, dried over MG SO4 to give 4-chloro-3-hydroxy-benzamide as a white solid 850 mg (86 % yield). Using the procedure described for the preparation of 450 mg (50 % yield) of 5-Aminomethyl-2-chloro-phenol hydrogen chloride as white solid is obtained from I mg (4.95 mmol) of 4-chloro-3-hydroxy-benzamide and borane tetrahydrofuran nplex (25 ml, 2.0 M). Intermediate 159 N-(1,3-dioxo-1,2,3.4-tetrahydroisoquinolin-6-yl)acetamide Using the procedure described for the preparation of 4-Chloromethyl-2-methoxy-biphenyl, 450 mg (73 % yield) of green solid is obtained from 500 mg (2.8 mmol) of 6-aminoisoquinoline-1,3(2H,4H)-dione, and acetyl chloride 1.1 ml (14.2 mmol), substituting dimethyiacetamide as a solvent in place of N,N-lethylformamide. Base is excluded; MS (ESI) m/z 217.1 (M-1). (Formula Removed) Intermediate 160 (4E)-6-acetaminde-4-(methoxymethylene)isoquinoline-1,3(2b,4H)-dione Using the procedure described for the preparation of (4E)-6-fluoro-4-methoxymethylene)isoquinoline-1,3(2H,4H)-dione, 410 mg (73 % yield) of yellow olid is obtained from 450 mg (1.72 mmol) of N-(1,3-dioxo-1,2,3,4-strahydroisoq uinoli n-6-yl)acetamide. US (ESI) m/z 261.1 (M+1)+. (Formula Removed) intermediate 161 Using the procedure described for the preparation of 4-{[4(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahyro-isoquinolin-6-yl)-carbamic acid 4-nitr-pheyl ester 5 g (26.0 mmol) of para-nitroanilin and 4-nitrophenyl chlroroformate 14.6g (72.4 mmol) were reacted to give (4-nitro-phenyl)-arbomic acid 4-nitro-phenyl ester, 11.0 g (100 % yield) of yellow (Formula Removed) Intermediate 162 1-Methyl-4-(5-nitro-pyridin-2-yl)-piperazine An amount of 2 g (9.85 mmol) of 2-bromo-5-nitro-pyridin is stirred in dichloromethane (50 mL), followed by addition of 1-methylpiperazine (10.9 mL, 98.5 mmol). The reaction mixture is refluxed for 1 h. After cooling, the mixture is extracted 3x with sodium bicarbonate, followed by additional washing with brine, dried over sodium sulfate, evaporated, to afford 2 g (91 % yield) of yellow crystals; mp 75-76°C. MS (ESI) m/z 223.1 (M+1)(Formula Removed) (Formula Removed) Intermediate 163 '6-(4-methylpiperazin-1-yl)pyridin-3-arnine An amount of 1 g (4.48 mmol) of 1-Methyl-4-(5-nitro-pyridin-2-yl)-piperazine is dissolved in methanol (50 mL), followed by a catalytic amount of 10% Pd/C. The mixture is hydrogenated at 35-40 psi for 3 hours, filtratred through cilite followed by evaporation to give 900 mg (100 % yield) of purple solid; mp 97-98°C. MS (ESI) m/z 193.1 (M+1)+. (Formula Removed) Intermediate 164 '2-[(4-nitrophenoxy)methyrjpyridine An amount of 1.36 mL (14.14 mmol) of pyridin-2-yl-methanol is disolved in nh,N-dimrethylformamide (10 mL) and cooled to 0°C, addition of 678.72 mg (28.28 mmol) of sodium hydride followed. The reaction mixture is kept at 0°C for 1.5 hours. 1-Fluoro-4-nitrobenzene 1.5 mL (14.14 mmol) is subsequent added and stirred at room temperature overnight. 100 mL of water is added to the mixture and stirred for 10 more mins. The precipitate is filtered and washed many times with water. The white solid is re-dissolved in methylene chloride extracted three times with brine, dried over darko and magnesium sulfate, and evaporated to give the desired product as a white solid 2.7 g (85 % yield); mp: 116-117°C MS (ESI) m/z 231.1 (M+1) +. (Formula Removed) Intermediate 165 14-(pyridin-2-y1methoxy)pherryamine Using the procedure described for the preparation of 4-Mopholin-4-ylmethyl-phenylamine, 1.16 g (100 %) of white crystals is obtained from 1.5 g (5.55 mmol) of '2-[(4-nitrophenoxy)methyl]pyridine;mp 50-51°C. MS (ESI) mte201.1 (M+1)*. (Formula Removed) Intermediate 166 - Tert-butyl-(3R)-3-methoxypyrolidin-1-yl carboxylate An amount of 10.0g (53.41 mmol) of tert-butyH3R)-3-pyrrolidinol-1-carboxylate is dissolved in Tetrahydrofurane (200mL) and cooled to 0°C, sodium hydride 1.92g (80.12 mmol) is added and the reaction mixture is kept at 0°C for 1.5 hours. Methyl iodine 5 mL (80.12 mmol) is subsequently added and stirred at room temperature overnight. The solvent (tetrahydrofuran) is evaporated and the oil is re-dissolved in ethyl acetate and extracted three times with brine, dried over darko and magnesium sulfate, evaporated to give the first intermediate as a light-yellow oil 10.65g (99 % yield). Intermediate 167 3-Methoxy-1 -(4-nitrobenzyl)-pyrolidine An amount of 1.8g (9.02mmol) of fert-butyl-(3R)-3-methoxypyrolidin-1 -yl carboxylate is stirred in concentrated hydrogen chloride (10mL) for two hours. Anhydrous ether (100mL) is added and stirred for additional 30 minutes. The ether is decanted and this is repeated three times. The mixture is neutralized with excess triethylamine and after evaporating to dryness, the mixture is re-disolved in methylene chloride (100mL) and 1.5g (6.94mmoI) of 4-nitrobenzylbromide is added and refluxed for two hours. After cooling, the mixture is washed three times with aqueous sodium bicarbonate, dried over magnesium sulfate and evaporated to give 1. 1g (67% yield) of the nitro intermediates as a yellow oil. (Formula Removed) Intermediate 168 4-{[(3R)-3-methoxypyrrolidin-1-yIJmethyl}phenyl)amine Using the procedure described for the preparation of (4-Mopholin-4-ylmethyl-phenylamine) 910 mg (95% yield) is obtained as a dark yellow oil from 1.1g (4.66 mmol) of 3-Metnoxy-1-(4-nitro-benzyl)-pyrolidine. MS (ESI) m/z 207.1(M+1)+. (Formula Removed) Intermediate 169 3-hydroxy-4-nitrobenzaldehyde O-methyloxime Using the procedure described for the preparation of intermediate 168 4.38 g (94 % yield) is obtained as a yellow solid from 4.0 g (23.93 mmol) of 3-hydroxy-4-nitrobenzytaldehyde; MS (ESI) m/z 196.0 (M-1). (Formula Removed) Intermediate 170 4-nitro-3-[(triisopropylsilyl)oxy]benzaldehyde O-methyloxime An amount of 3.0 g (15.39 mmol) of 3-hydroxy-4-nitrobenzaldehyde O-methyloxime is stirred in N,N-dimethylformarhide (8 mL), followed by addition of imidazole (3.14g , 46.17 mmol) and 4.89 mL (23.1mmol) of triisopropylsilyl chloride. The reaction mixture is stirred at room temperature over night. 1:1 ethyl acetate: ether (300 mL) is added and extracted 3x with water, followed by additional washing with brine, dried over magnissium sulfate, evaporated, to afford 5.02 g (93 % yield) as a yellow crystals. MS (ESI) m/z 353.1 (M+1)+. (Formula Removed) Intermediate 171 {4-(aminomethyl)-2-[(tritsopropylsilyl)oxy]phenyl}arnine Using the procedure described for the preparation of 3-hydroxy-4-methoxy-benzylamine hydrogen chloride, 3.0 g (88 % yield) is obtained as a brown solid from 4.0 g (11.42 mmol) of 4-nitro-3[(triisopropylsilyl)oxy]benzaldehyde O-methyloxime; MS (ESI) m/z 294.0 (M+1 )+. (Formula Removed) Intermediate 172 {4-[(4-methoxypiperidin-1-yl)methylJphenyl}amine Using the procedure described for the preparation of (4-Mopholin-4-ylmethyl-phenylamine), 1.8 g (95% yield) is obtained as a yellow oil from 2.2g (8.79 mmol)4-methoxy-1-(4-nitrobenzyl)piperidine. MS (ESI)m/z221.1 (M+1)+. (Formula Removed) Intermediate 173 3-(dimethytamino)pyrroIidin-1-yI]methyl}phenyl)amine Using the procedure described for the preparation of (4-Mopholin-4-ylmethyl-phenylamine), 1.8 g (85% yield) is obtained as a yellow oil from 2.0g (8.03 mmol) 3-(dlmethylamino)-1-(4-nitrobenzyl)pyrrolidine (L27615-85). MS (ESI) m/z 220.4(M+1)+. (Formula Removed) intermediate174 (2R)-2-[(dimethylarnino)rnethyl]pyrrolidin-1-yl}methyl)phenyl]arnine An amount of 2.0 g (9.99 mmol) of (S)-2-(aminomethyl)-1-n-boc-pyrrolidine and formylaldehyde (2.4 g, 79.9 mmol) were dissolved in tetrahydrofuran (20 mL) and methanol (5 mL). After stirring for ten minutes, a mixture of sodium cyanoborohydried (5.1g, 79.9 mmoJ) and acetic acid (4.6 mL, 79.9 mmol) in methanol (5 mL) is added drop-wise. The mixture is allowed to stir over night. The mixture is concentrated to dryness and using the procedure described for the preparation of 4-{[(3R)-3-methoxypyrrolidin-1-ylJmethyl)phenyl)amine the desired product is obtain 200 (45 % yield) as a yellow oil. MS (ESI) m/z 235.0 (M+1 )+ . (Formula Removed) Intermediate 175 2-(hydroxymethyl)piperidin-1-yl]methyl}phenyl)amine Using the procedure described for the preparation of (4-Mopholin-4-ylmethyl-phenylamine), 2.5 g (57% yield) is obtained as a yellow solidl from 5.0g (19.9 mmol) of 2-( hydroxyrnethyl)-1-(4-nitrobenzyl)piperadine (L27615-90). MS (ESI)m/r220.4(M+1)+. (Formula Removed) Intermediate 176 tert-butyl 4-(6-nitropyridin-3-yl)piperazine-1 -carboxylate A mixture of 3g (14.78 mmol) of 5-bromo-2-nitropyridine, 5.5 g (29.56 mmol) of tert-butyl 1-piperazinecarboxylate, 5.46 g (14.78 mmol) of tetre-butylammonium iodine and 4.1 g (29.56 mmol) of potassium carbonate were placed in a flask. Dimethylsulfoxide (45 mL) is added and heat up to 80°C for 24 hours. After cooling to room temperature, the precipitate is filtered and washed with ethyl acetate. Excess amount of water is added and extracted 4x. Dried with sodium sulfate and evaporated to give 2.7 g (59 % yield) as a yellow solid. MS (ESI) m/z 309.1 (M+1) (Formula Removed) Intermediate 177 tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1 -carboxylate An amount of 2g (6.48 mmol) of, tert-butyl 4-(6-nitropyridin-3-yl)piperazine-1-carboxylate, 1.4 g (25.9 mmol) of iron, and acetic acid (3.1 ml_, 48.6mmol) were placed in a flask. Methanol (30 mL) is added and heat at 60°C for 2 hours. After cooling to room temperature, the precipitate is filtered, the methanol is removed in a vacuum and saturated sodium bi-carbonate is added. The mixture is extracted 3x with ethyl acetate. Dried over sodium sulfate, and evaporated to give 1.43 g (78 % yield) as a purple solid. MS (ESI) mfz 279.1 (M+1) +. (Formula Removed) Intermediate 178 5-(4-methylpiperazin-1 -yl)pyridin-2- yl]amine Using the procedure described for the preparation of tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate, 2.6 g (90 % yield) is obtained as a purple solid from 3.4g (15.3 mmol) of 1-Methyl-4-(2-nitro-pyridin-2-yl)-piperazine (L27615-112). MS (ESI) m/z 193.1(M+1)+. (Formula Removed) Intermediate 179 5-[(3R,5S)-3,5-dimethylpiperazin-1 -yl]pyridin-2- yl}amine Using the procedure described for the preparation of tert-butyi 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate, 1.4 g (47 % yield) is obtained as a orange solid from 3.4g (12.8 mmol) of 5-(3R,5S)-3,5-dimethyl-1-(6-nitro-pyridin-3-yl)pipirazine. MS (ESI) m/z 207.1 (M+1)+. (Formula Removed) Intermediate 180 5-Formyl-2-furan boronic acid An amount of 1.0 g (4.1 mmol) of 4-brorno-2-(diethoxymethyl)furan, is dissolved in ether (15 ml.) and cooled to -78°C. To this is added 4.3 mL (6.02 mmol) of sec-butylithium. After stirring at -78°C for 30 minutes, triisopropyl borate (1.10 mL, 5.01 mmol) is added dropwise. The mixture is stirred at -78°C for 1.5 hours and brought to room temperature for 2 hours. The mixture is hydrolized with 2N HCI and stirred at room temperature for 1 hour. The ether layer is separated and the water layer is washed once more with ether. The combined ether layers is washed once with brine and dried with sodium sulfate. Evaporated to give 563 mg of the boronic acid as dark oil. (Formula Removed) Intermediate 181 [6-(4-methylpiperazin-1 -yl)pyridazin-3- yl]amine An amount of 1.0 g (7.72 mmol) of 3-amino-6-chloropyridazine, 5-chloro pyridine hydrogen chloride (4.46 g, 38.6 mmol), and piperazine (5.1 mL, 72 mmol) were placed in a pre-heated oil bath at 165-170°C for 4 hours. After cooling, the mixture is basified with saturated potassium carbonate, extracted 3x with ethyl acetate and dried over magnesium sulfate. The oily residue is purified by column chromatography to give a brown solid 800 mg (53% yield). MS (ESI) m/z 194.3 (M+1)+ (Formula Removed) intermediate 182 4-(2-hydroxyethyl)piperidn-1-yl]methyl}phenyl)amine Using the procedure described for the preparation of (4-Mopholin-4-ylmethyl-phenylamine), 1.6 g (72% yield) is obtained as a yellow solid from 2.4 g (11.99 mmol) of 4-(2- hydroxyethyl)-1-(4-nitrobenzyl)piperadine (L27615-135). MS (ESI) m/z 234.3(M+1)+. (Formula Removed) Intermediate 183 [5-(4-isopropylpiperazin-1-yI)pyridin-2- yl-]amine Using the procedure described for the preparation of tert-butyl 4-(6-aminopyridin-3-yI)piperazine-1-carboxylate, 750 mg (68 % yield) is obtained as a brown solid from 1.2g (4.7 mmol) of 4-isopropyl -1-(6-nitro-pyridin-2-yl)pipirazine. MS (ESI) m/z 221.1 (M+1)+. Intermediate 184 N-Acethyl-N-(bromo-phenyl)-acetamide An amount of 3.0 g (17.24 mmol) of 2-amino-5-bromopyrazine is dissolved in NMN--dimethyformamide (20 mL) and cooled to 0°C. Sodium hydride (1.05g, 43.09 mmol) is added and stirred at 0°C for 10 minutes. Acetyl chloride (6.2 mL, 86.2 mmol) is added and stirred at room temperature for over night. The mixture is quenched with water and extracted 3x with ether. Dried over magnesium sulfate followed by column chromatography to give 1.35 g (31 %yield) of yellow oil. MS (ESI) m/z 259.0 (M+1)+ Intermediate 185 [5-(4-methylpiperazin-1 -yl)pyrazin-2- yljamine Using the procedure described for the preparation of (4Z)-6-(4-fluorophenyl)-4-({[4-(piperidin-1 - ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione 200 mg (20 % yield) is obtained as a dark oil from 1.33 g (5.14 mmot) N-Acethyl-A/-(bromo-phenyl)-acetamide and N-methylpiperazine 2.9 mL, (25.7 mmol). The A/-acetyl is cleaved with concentrated hydrogen chloride. MS (ESI) m/x 195.1 (M+1)+ (Formula Removed) Intermediate 186 3-Methoxymethoxy-4-(4-methylpiperazin-1 -yl )-benzonitrile Using the procedure described for the preparation of tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate except potassium t-butoxide is used as a base, 720 mg (46 % yield) is obtained as a yellow oil from 1.5 g (5.2 mmol) of 4-iodc-3-methoxymethoxy benzonitrile and 1-methylpiperazine 1.73 mL, (15.6 mmol). MS (ESI) m/z 263.1 (M+1)+ (Formula Removed) Intermediate 187 [3-hydroxy-4-(4-methylpiperazln-1-yl)benzyl]amine The desired product is obtained when 3-Methoxymethoxy-4-(4-methylpiperazin-1-yl)-benzonitrile is treated with lithium aluminum hydride and concentrated hydrogen chloride. (Formula Removed) Intermediate 188 3-Hydroxy-4-dif!uoromethoxy-benzylaIdehyde O-methyl-oxlme An amount of 734 mg (3.90 mmol) of 3-hydroxy-4-difluoromethoxy-benzaldehyde3 is added to ethanol (9 ml), and pyridine (4.5 ml) at room temperature, followed by addition of hydroxyiamine hydrogen chloride (669 mg, 8.01 mmol). The mixture is stirred at ambient temperature for 24 h, and 150 mL of water is added. After the solvents were evaporated, the residue is dissolved 400 mL of anhydrous ether, washed successively with 100 mL of aqueous sodium bicarbonate, 100 mL of sodium bisulfite, and 100 mL of brine. Dried over magnesium sulfate, evaporated, chromatographed with 10:1 hexanes/ethyl acetate to give the oxime as a white solid 0.169 mg (20 % yield), m.p. 78-9°C, MS (ES-): m/z 216.0 (M-H). (Formula Removed) Intermediate 189 3-Hydroxy-4-difluoromethoxy-benzylamine hydrochloride An amount of 500 mg (3.0 mmol) of 3-hydroxy-4-difluoromethoxy-benzylaldehyde O-methyl-oxime is dissolved in ethanol (50 mL). Then hydrochloric acid (2 mL) is added, followed by 10% Pd/C (200 mg). After hydrogenation at 45 psi for 2 h, the solution is filtered through Celite and evaporated to dryness. The residue is triturated with ether to give 419 mg (62%)g of hydrochloride salt as a white solid; mp195-196°C dec. MS (ES+): m/z 190.2 (M + H). (Formula Removed) Intermediate 190 2-Carboxymethyl-4-brorno-5-methoxy-benzoic Acid To a mixture of 5-bromo-6-methoxy-indan-1,2-dione 2-oxime (20.0 g, 74.0 mmole) and 160 mL of tetrahydrofuran is added lithium bis(trimethydisilyl)amide (74.0 mL of 1 M in hexanes, 74.0 mmole) and stirred. After stirring for 30 minutes p-toluenesulfonyl chloride (14.1 g, 74.0 mmole)is added. After 30 mins a solution of potassium hydroxide (25.0 g, 0.44 mole in 200 mL water) is added and stirred for 1 hour. The tetrahydrofuran is removed and the mixture refluxed overnight, cooled, acidified with 2 N hydrochloric acid and the solid collected, washed with water and dried, 8.45 g (34%). MS (ES-): m/z 287.1, 289.1 (M - H). (Formula Removed) Intermediate 191 6-bromo~7-methoxy-isoquinoline-1,3(2H ,4H)-dione 2-Carboxymethyl-4-brorno-5-rnethoxy-benzoic acid (228 mg, 0.785 mmole) and urea (0.110 g, 1.82 mmole) is stirred and heated using an oil bath at 195°C. After one hour the mixture is cooled to room temperature and treated with water, collected by filtration, washed with water and dried to give a brown-black solid, 106 mg, (50%); MS (ES-): m/z 268.1, 270.1 (M - H). (Formula Removed) Intermediate 192 (4E)-6-bromo-7-rnethoxy-4-(methoxymethyiene)isoquinoline-1,3(2H,4H)-dione A mixture of 6-Bromo-7-methoxy-4H-isoquinoline-1,3-dione (275 mg, 1.02 mmole), 7 mL of a 4:1 mixture of acetic anhydride and N,N-dimethylformamide and trimethylorthoformate (0.8 mL, 7.28 mmole) is stirred and heated to reflux. After 30 minutes the solvents are removed and the solid collected with ether. A brown solid, 202 mg, (63%). mp 245-248°C dec, MS (ESI): m/z 310.1, 312.1 (M - H). (Formula Removed) Intermediate 193 2-Amino-2-(4-amino-phenyl)-propionic acid A mixture of 5-(4-Amino-phenyl)-5-methyl-imidazolidine-2,4-dione2 (3.0 g, 14.6 mmole), 6N hydrochloric acid is stirred and refluxed for 6 hours, cooled, evaporated. The residue is treated with water and the pH adjusted to 6 and the light yellow solid collected by filtration, washed with water and dried, 1.47 g (55%), mp 120-155°C dec; MS (ES+): m/z 181.2 (M + H). (Formula Removed) Intermediate 194 2-Azldomethyl-5-methoxy-pyridin-4-ol To a suspension of sodium azide (1.30 g, 20.0 mmole) in 12 mL of N,N-dimethylformamide is added 2-chloromethyl-5-methoxy-pyridin-4-ol1 (3.47 g, 20.0 mmole). This is stirred for overnight at ambient temperature then quenched into ice water. The solid formed is filtered, washed with cold water dried to give a light brown solid, 1.53 g, (42%), mp 111-4°C dec; MS (ES-): m/z 179.3 (M - H). (Formula Removed) Intermediate 195 2-Aminomethyl-5-methoxy-pyridin-4-ol A mixture of 2-azidomethyi-5-methoxy-pyridin-4-ol (1.45 g, 8.05mole), is then suspended in 20 mL of tetrahydrofuran and treated with triphenylphosphine (2.11 g, 8.05 mmole) after stirring for 10 mins at ambient temperature water is added (1.76 mL, 15 equivalents) and the reaction mixture is stirred at ambient temperature overnight. The solids gradually dissolved followed by the formation of a precipitate. The resulting solid is filtered, washed with fresh 10:1 tetrahydrofuranrwater and.dried to give, 0.897 g, (88%), mp 196-201 °C dec; MS (ES+): m/z 155.3 (M + H). (Formula Removed) Intermediate 196 2-Hydroxymethyl-5-propoxy-pyran-4-one . A mixture of kojic acid (28.4 g, 0.20 mole), 120 mL of N,N-dimethylformamide, potassium carbonate powder (27.6 g, 0.20 mole), potassium iodide (1.66 g, 0.01 mole), and 1-bromopropane (24.6 g, 0.20 mole) is stirred for 15 minutes at ambient temperature then stirred at 90°C for 3 hours. The reaction mixture is cooled, evaporated to dryness in vacuo and then portioned between water and chloroform. The aqueous layer is extracted with chloroform (3x100 mL) and ethyl acetate (6x100 mL). The combined organics were dried with sodium sulfate and passed through a pad of magnesol and silica gel eluting with ethyl acetate. The eluate is evaporated in vacuo and crystallized with hexane/ethyl acetate (2/1) to give an off-white solid, 22.60 g, (61%); MS (ES+): m/z 185.3 (M + H). (Formula Removed) Intermediate 197 2-Hydroxymethyl-5-propoxy-pyrid in-4-ol A mixture of 2-hydroxymethyl-5-propoxy-pyran-4-one (30.0 g, 0.163 mole), 150 mL ammonium hydroxide is stirred and heated in a sealed vessel at 90°C for 2 hours. The reaction mixture is cooled, evaporated to dryness in-vacuo , taken up in 15% methanol in chloroform and passed thru a pad of magnesol and silica gel eluting with the same solvent. The eluate is evaporated, treated with acetone, filtered, washed with acetone and air dried to give a-grey solid. 8.03 g, (80%), m.p. 159-60°C; MS (ES+): m/z 184.3 (M + H). (Formula Removed) Intermediate 198 2-Chloromethyl-5-propoxy-pyridin-4-ol To a mixture of 2-hydroxymethyl-5-propoxy-pyridin-4-ol (5.56 g» 30.3 mmole) and 30 mL of chloroform stirred cooled with an ice bath is added 30 mL of thionyl chloride (x g, 0.x mole). This is stirred for 15 minutes at ice bath temperature and then refluxed for 1 hour. The reaction mixture is cooled, evaporated to dryness in vacuo and then treated with isopropanol. The solid is filtered, washed with fresh isopropanol, then ether and air dried to give an off-white solid, 3.4 g, (48%). m.p. 165-7°C; MS (ES+): m/z 202.3 (M + H). (Formula Removed) Intermediate 199 2-Azidomethyl-5-propoxy-pyridin-4-ol To a suspension of sodium azide (2.82 g, 43.3 mmole) in 30 mL of N,N-dimethyrformam'ide is added 2-choromethyl-5-propoxy-pyridin-4-ol (8.74 g, 43.3 mmole). This is stirred for overnight at ambient temperature then quenched into ice water. The solid formed is filtered, washed with cold water and dried to give an off white solid, 5.74 g, (63%); MS (ES+): m/z 209.3 (M + (Formula Removed) Intermediate 200 2-Aminomethyl-5-propoxy-pyridin-4-ol A mixture of 2-azidomethyl-5-propoxy-pyridin-4-ol (9.70 g, 46.6 mole), is then suspended in 120 mL of tetrahydrofuran and treated with triphenylphosphine (12.22 g, 46.6 mmole) after stirring for 10 mins at ambient temperature water is added (.12.6 mL, 15 equivalents) and the reaction mixture is stirred at ambient temperature overnight. The solids gradually dissolved followed by the formation of a precipitate. The resulting solid is filtered, washed with fresh 10:1 tetrahydrofuranrwater and dried to give, 5.92 g, (69%), mp 159-60°C; MS (ES+): m/z 183.3 (M + H). (Formula Removed) Intermediate 201 2-Hydroxyrnethyl-5-phenyl-pyran-4-one A mixture of 2-(tert-butyf-dirriethyl-silanyloxymethyl)-5-phenyl-pyran-4-one1 (791 mg, 2.5 mmole), tetrahydrofuran (7.5 mL) and tetrabutylammonium fluoride 1M solution in tetrahydrofuran (7.5 mL, 7.5 mmole)is stirred at room temperature overnight. The reaction mixture is diluted with water and extracted with ethyl acetate. The combined ethyl acetate layers were combined and washed with water, dried over sodium sulfate, filtered, diluted with an equal volume of hexanes and passed thru a short column of magnesol and silica gel eluting with 1:1 hexanes/ethyl acetate. The product is eluted with 2:1 ethyl acetate/hexanes, the solvents were evaporated, the resulting residue is triturated with 1:1 hexanes/ethyl acetate, filtered, washed with the same solvent and air dried to give an off white solid, 404 mg, (80%); MS (ES+): m/z 203.3 (M + H). (T. Kamino, et. al.; Tet. Lett. 44 (2003) 7349) (Formula Removed) Intermediate 202 2-Aminomethyl-5-phenyl-pyridin-4-ol To a mixture of 2-hydroxymethyl-5-phenyl-pyridin-4-ol (0.40 g, 2.0 mmole) and 5 mL of thionyl chloride stirred and heated to a gentle reflux. After 4 hours the reaction mixture is coo!sd and evaporated to dryness in vacuo, the residue is treated with water and neutralized with sodium bicarbonate. The resulting solid is collected by filtration, washed with water and dried to give 256 mg of the chloromethyl compound. This chloromethyl compound (252 mg, 1.15 mmole) is then stirred with 3 mL of dimethyl formamide and sodium azide is then added (75 mg, 1.15 mmole) and the reaction mixture stirred for 24 hrs at ambient temperature. The solvent is removed in vacuo and the residue treated with water, filtered, washed with water and dried to give 231 mg of the azidomethyl compound. This azidomethyl compound (228 mg, 1.01 mmole) is then suspended in 3 mL of tetrahydrofuran and treated with triphenylphosphine (264 mg, 1.01 mmole) after stirring for 10 mins at ambient temperature water is added (272 uL, 15 equivalents) and the reaction mixture warmed with an oil bath at 60°C and stirred at that temperature overnight. The reaction mixture is evaporated to dryness in vacuo and treated with a 2:1 mixture of ethyl acetate and hexanes. The resulting solid is filtered, washed with fresh 2:1 ethyl acetate and hexanes and dried to give a grey solid, 116 mg, (57%); MS (ES+): m/z 201.1 (M + H). (Formula Removed) Intermediate 203 2-Hydroxymethyl-5-furan-3-yl-pyran-4-one A mixture of trifluoro-methanesulfonic acid 6-(tert-butyl-dimethyl- silanyloxymethyl)-4-oxo-4H-pyrari-3-yl ester1 (6.94 g, .17.8 mmole), furan-3-boronic add (4.0 g, 35.7 mmole), tetrakistriphenylphosphine palladium (1.024 g, 0.87 mmole), cesium carbonate (16.32 g, 50.1 mmole) and potassium bromide (10.63 g, 89.3 mmole) in (250 mL) dioxane (250 mL) is heated to 60°C and stirred overnight. o The reaction mixture is cooled to room temperature and diluted with saturated aqueous ammonium chloride and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried over sodium sulfate, filtered, diluted with an equal volume of hexahes and passed thru a short column of magnesol and silica gel eluting with 1:1 hexanes/ethyl acetate. The product is eluted with 2:1 ethyl acetate/hexanes, the solvents were evaporated, triturated with 1:1 hexanes/ethyl acetate, filtered, washed with the same solvent and air dried to give an off white solid, 2.58 g; MS (ES+): m/z 307.3(M + H). This solid is dissolved in tetrahydrofuran and tetrabutylammonium fluoride solution in tetrahydrofuran (40.0 mL, 40.0 mmole) is added and the mixture stirred at room temperature overnight. The reaction mixture is diluted with water and extracted with ethyl acetate. The combined ethyl acetate layers were combined and washed with water, dried over sodium sulfate, filtered, dilted with an equal volume of hexanes and passed thru a short column of magnesol and silica gel eluting with 1:1 hexanes/ethyl acetate. The product is eluted with 2:1 ethyl acetate/hexanes, the solvents were evaporated, triturated with 1:1 hexanes/ethyl acetate, filtered, washed with the same solvent and air dried to give an off white solid, 2.06 g, (37%); MS (ES+): m/z 193.2(M + H). (T. Kamino, et. al.; Tet. Lett. 44 (2003) 7349) (Formula Removed) Intermediate 204 2-Hyd roxymethyl-5-(3-furyl)-pyridin-4-oI A mixture of 2-hydroxymethyl-5-furan-3-yl-pyran-4-one (1.92 g, 10.0 mmole) and 7 M ammonia in methanol (50.0 mL)is stirred and heated in a sealed vessel at 90°C overnight. The reaction mixture is cooled, evaporated to dryness in-vacuo , taken up in 15% methanol in chloroform and passed thru a pad of magnesol and silica gel eiuting with the same solvent. The eluate is evaporated, treated with acetone, filtered, washed with acetone and air dried to give a-grey solid, 1.21 g, (63%); MS (ES+): m/z 192.2 (M + H). (Formula Removed) Intermediate 205 2-azdomethyl-5-furan-3-yl)-pyridin-4-ol To a mixture of 2-hydroxymethvl-5-furan-3-yl-pyridin-4-c4 (1.148 g, 6.00 mmole) and 30 mL of N.N-dimethylforrnamide stirred and cooled with an ice bath to 0°C is added triphenylphosphine (2.361 g, 9.00 mmole) followed by carbon tertabromide (2.988 g, 9.00 mmole). This is stirred for 15 minutes maintaining temperature between 0 - 5°. Sodium azide is then added (1.172 g, 18.03 mmole) and the reaction mixture stirred for 24 hrs at ambient temperature.. The reaction mixture is diluted with water and extracted with ethyl acetate. The combined extracts were dried over sodium sulfate, filtered, evaporated and the residue chromatographed on silica gel eiuting with ethyl acetate to give a-white solid, 0.417 g, (32%), mp 198-200°C dec; MS (ES+): m/z 217.3 (M + H). (Formula Removed) Intermediate 206 2-Aminomethyl-5-furan-3-yl-pyridin-4-ol To a mixture of 2-azidoxymethyl-5-(3-furyl)-pyridin-4-ol (216 mg, 1.00 mmole), 6 mL of tetrahydrofuran, and triphenylphosphine (262 mg, 1.00 mmole) then water (270 DL, 15.0 mmole) is added and this is stirred for overnight at ambient temperature then stirred at 60°C for overnight The reaction mixture is cooled, evaporated to dryness in vacuo and then treated with warm toluene. This mixture is cooled and the solid is filtered, washed with toluene and dried, to give an off-white solid, 0.170 g, (89%), mp 183-7°C dec; MS (ES+): m/z 191.3 (M + H). (Formula Removed) intermediate 207 2-Aminorhethyl-1-methyl-5-propoxy-1 H-pyridin-4-one A mixture of 2-hydroxymethyl-5-propoxy-pyran-4-one (3.69 g, 20.0 mmole) and 40% methylamine in water (25.0 mL) is stirred and heated in a sealed vessel at 90°C overnight The reaction mixture is cooled, evaporated to dryness in-vacuo , taken up in 15% methanol in chloroform and passed thru a pad of magnesoland silica gel eluting with the same solvent. The eluate is evaporated, treated with acetone, filtered, washed with acetone and air dried to give a-grey solid, 3.43 g, (87%); MS (ES+): m/z 198.3 (M + H). To this hydroxy compound is added 25 mL of thionyl chloride stirred and heated to a gentle reflux. After 4 hours the reaction mixture is cooled and evaporated to dryness in vacuo, the residue is treated with 2-propanol. The resulting solid is collected by filtration, washed with 2-propanol and dried to give 3.51 g (69%) of the chloromethyl compound as the HCI salt, MS (ES+): m/z 218.3 (M + H). This chloromethyl compound (3.28 g, 13.0 mmole) is then stirred with 30 mL of dimethyl formamide and triethylamine (1.81 mL, 13.0 mmole) for 15 mins. Then sodium azide is then added (0.85 g, 13.0 mmole) and the reaction mixture stirred for 24 hrs at ambient temperature. The solvent is removed in vacuo and the residue treated with water, extracted 6 times with ethyl acetate. The combined extracts were dried over sodium sulfate passed thru a short pad of magnesol, evaporated and dried to give a light brown solid, 1.23 g of the azidornethyl compound. This azidomethyl compound (1.11 mg, 5.0 mmole) is then suspended in 30 mL of tetrahydrofuran and treated with triphenylphosphine (1.31 g, 5.0 mmole) after stirring for 10 mins at ambient temperature water is added (1.36 mL, 15 equivalents) and the reaction mixture warmed with an oil bath at 60°C and stirred at that temperature overnight. The reaction mixture is evaporated to dryness in vacuo and treated with a 2:1 mixture of ethyl acetate and hexanes. The resulting solid is filtered, washed with fresh 2:1 ethyl acetate and hexanes and dried to give a brown solid, 398 mg, (40%); MS (ES+): m/z 197.4 (M + H). (Formula Removed) Intermediate 20B 2-Benzyloxy-4-methoxymethylene-4H-isoquinoline-1,3-dione A mixture of 2-benzyloxy-4H-isoquinoline-1,3-dione1 (4.01 g, 15.0 mmole), 50 mL of a 4:1 mixture of acetic anhydride and N,N-dimethyrformamide and trimethylorthoformate (12 mL, 0.11 mole) is stirred and heated to reflux. After 30 minutes the solvents are removed, the residue treated with hexarte-ethyl acetate, the solid collected by filtration, washed with fresh hexane-ethyl acetate and dried to give a yellow solid, 3.67 g, (79%), mp 161-2°C, MS (ESI): m/z 310.1 (M + H). (Ames and Gray: J. Chem Soc; 3518 (1955) (Formula Removed) Intermediate 209 6-methoxy-isoquinoline-1,3(2H,4H)-dione 2-Carboxymethyl-4-methoxy-benzoic acid (946 mg, 4.5 mmole) and urea (629 mg, 10.4 mmole) is stirred and heated using an oil bath at 180°C. After one hour the mixture is cooled to room temperature and treated with water, collected by filtration, washed with water and dried to give a brown solid, 498 mg, (57%); mp 212-5°C, MS (ESI): m/z 192.1 (M + H).. (Formula Removed) Intermediate 210 6-Methoxy-4-rnethoxymethylene-4H-isoquinoline-1.3-dione A mixture of 6-methoxy-4H-isoquinoline-1,3-dione (400 mg, 2.1 mmole), 8 mL of a 4:1 mixture of acetic anhydride and N,N-dimethylformamide and trimethylorthoformate (1.7 mL, 15.5 mmole) is stirred and heated to reflux. After 30 minutes the solvents are removed, the residue treated with hexane-ethyl acetate, the solid collected by filtration, washed with fresh hexane-ethyl acetate and dried to give a yellow solid, 317 mg, (65%), mp 245-7°C, MS (ESI): m/z 234.1 (M + H). (Formula Removed) Intermediate 211 252 Chloro-(4-methoxy-5-nitro-pyridin-2-yl)-acetic acid tert-butyl ester A solution of 4-methoxy-3-nitro-pyridine (5.15 g, 33.4 mole) and t-butyl dichloroacetatel (6.80 g, 36.8 mmole) in 30 mL N,N-dimethylformamide is added dropwise to a stirred solution of potassium t-butoxide (11.24 g, 0.10 mole) in 90 mL N.N-dimethylformamide at -5°C. After the addition is complete the reaction is stirred for 15 minutes and quenched into 400 mL of cold 5% hydrochloric acid and extracted with dichloromethane. The organic layer is dried with anhydrous magnesium sulfate, filtered, evaporated and chromatogaphed on silica gel with hexanes/ether, to yield a yellow orange oil 3.07 g, (30%), MS (ES+): m/z 303.2, 305.2 (M + H). Intermediate 212 2-Chloromethyl-4-methoxy-5-nitro-pyridine A mixture of chloro-(4-methoxy-5-nitro-pyridin-2-yl)-acetic acid tert-butyl ester (2.98 g, 9.84 mole) and acetic acid (25 mL) is refluxed for 6 hours, cooled and evaporated. The residue is dissolved in dichlromethane, passed thru a pad of magnesol, evaporated to dryness and crystallized from 3:1 hexanes/ethyl acetate to give a light yellow solid, 1.78 g. (89%); MS (ES+): m/z 203.2. 205.2 (M + H). (Formula Removed) intermediate 213 5-Amino-2-aminomethyl-pyridin-4-ol A mixture of 2-(4-methoxy-5-nitro-pyridin-2-ylmethyl)-isoindole-1,3-dione (0.24 g, 7.7 mmole) and 48% hydrobrornic acid (3 mL), is refluxed for 3 hours. The reaction mixture is cooled, evaporated to dryness in vacuo, dissolved in absolute ethanoi (25 mL) and 10% Palladium on carbon (100 mg) is added under an inert atmosphere. This is then hydrogenated on a Par apparatus at 45 psi for 2 hours. The reaction mixture is filtered and evaporated to give a brown sofid solid, 60 mg, (23%), MS (ES+): m/z 140.2 (M + H). Used as is for the next step. (Formula Removed) Intermediate 214 (6-Chloro-5-propoxy-pyridin-2-yl)-methanol A mixture of 2-chloro-6-hydroxymethyl-pyridin-3-ol8 (27.92 g, 0.175 mole), 120 mL of 2-butanone, potassium carbonate powder (48.37 g, 0.35 mole) and 1-iodopropane (37.19 g, 0.219 mole) is stirred for 15 minutes at ambient temperature then stirred at 90°C for 3 hours. The reaction mixture is cooled, evaporated to dryness in vacuo and then portioned between water and dichloromethane. The organic layer is dried, filtered and crystallized with 2/1 hexane/ethyi acetate to give a pale yellow solid, 5.875 g, (16%), mp 59-60°C; MS (ES+): m/z 160.3,162.3 (M + H) (Wishka et a!.; J Org. Chem.; 63(22) 7851 (1998) (Formula Removed) Intermediate 215 2-Benzyloxy-3-prapoxy-6-triisopropylsilanyloxymethyl-pyridine A mixture of (6-chloro-5-propoxy-pyridln-2-yl)-methanol (0.93 g. 4.61 mmole), 20 mL of dichloromethane, tri(isopropyl)silyl chloride (1.0 g, 5.19 mmole) and imidazole (0.47 g, 6.9 mmole) is stirred overnight at ambient temperature. The reaction mixture is washed with water, dried over sodium sulfate, filtered and evaporated in-vacuo to give an oil which is chromatographed on silica gel with 10:1 hexane/ethyl acetate to give 2-chloro-propoxy-6-triisopropylsilanyloxymethyl-pyridine as a clear liquid, 1.06 g, (64%); MS (ES+): m/z 358.2, 360.2 (M + H). A portion of this (716 mg, 2.0 mmole) and 5 mL of 1M sodium benzyloxide in benzyl alcohol is heated in a microwave reactor 5 minutes at 120°C. The reaction mixture is cooled, transferred to a separatory funnel with ethyl acetate, washed with water, the organic layer is dried, filtered, evaporated and chromatographed on silica gel with hexane/ethyl acetate to give a clear liquid, 524 mg, (61%); MS (ES+): m/z 430.3 (M + H). (Formula Removed) Intermediate 216 (6-Benzytoxy-5-propoxy-pyridin-2-yl)-methanol To a solution of 2-benzylxy-3-propoxy-6-triisopropylsilanyloxymethyl-pyridine (860 mg, 2.0 mmole) is added 1M tetrabutylammonium fluoride solution in tetrahydrofuran (4.0 mL, 4.0 mmole) and the mixture stirred at room temperature for four hours. The reaction mixture is diluted with water and extracted with ether. The combined ether layers were combined and washed with water, dried over sodium sulfate, filtered, chromatographed on silica gel eluting with 1:1 hexanes/ether to give a white solid, 355 mg, (65%); m.p. 50-1 °C, MS (ES+): m/z 274.1 (M + H). Intermediate 217 6-Azidomethyl-2-benzyloxy-3-propoxy-pyridine To a mixture of (6-benzyloxy-5-propoxy-pyridin-2-yl)-metbanol (1.09 g, 4.0 mmole) and 20 mL of N.N-dimethylformamide stirred and cooled with an ice bath to 0°C is added triphenylphosphine (1.57 g, 6.0 mmole) followed by carbon tertabromide (1.99 g, 6.0 mmole). This is stirred for 15 minutes maintaining temperature between 0 — 5°. Sodium azide Is then added (781 mg, 12.0 mmole) and the reaction mixture stirred for 24 hrs at ambient temperature. The reaction mixture is diluted with water and extracted with ether. The combined extracts were dried over sodium sulfate, filtered, evaporated and the residue chromatographed on silica gel eluting with hexane/ethyl acetate to give a-clear liquid, 1.05 g, (88%); MS (ES+): m/z 299.1 (M + H). (Formula Removed) Intermediate 218 6-Aminomethyl-3-propoxy-pyridin2-ol To a mixture of 6-azidomethyl-2-benzyloxy-3-propoxy-pyridine (544 mg, 2.00 mmole), 12 mL of tetrahydrofuran, and triphenylphosphine (524 mg, 2.00 mmole) then water (540 DL, 30.0 mmole) is added and this is stirred at ambient temperature overnight. The reaction mixture is evaporated to dryness in vacuo and then washed with 2:1 hexanes/ethyl acetate and filtered. This resulting solid is taken up in ethanol and hydrogenated over 10% palladium on carbon at 1 atmosphere. The reaction mixture is filtered washed with ethanol, evaporated to give a brownish green solid, 93 mg, (25%), MS (ES+): m/z 183.3 (M + H). This is used as is for the next step. (Formula Removed) Intermediate 219 1-[2-Methyl-4-(2-rnorpholin-4-yl-ethoxy)-phenylr-ethanone A mixture of 1-(4-hydroxy-2-methyl-phenyl)-ethanone (15.0 g, 0.10 mole), sodium iodide (15.0 g, 0.10 mole), 4-(2-chioro-ethyl)-morpholine; hydrochloride (18.6 g, 0.10 mole), anhydrous powdered potassium carbonate (67.0 g, 0.50 mole) and 2-butanone (500 mL) is stirred and heated at a gentle reflux overnight. The mixture is cooled to room temperature, filtered, the solids washed with acetone. The combined filtrates were evaporated in-vacuo, the residue treated with water and extracted with ether. The ether layer is washed with 1N sodium hydroxide, water, brine, dried over anhydrous sodium sulfate, filtered and evaporated to give an oil, 19.2 g.(73%) used as is for the next step. (Formula Removed) Intermediate 220 2-Methyl-4-(2-morpholin-4-yl-ethoxy)-benzoicacid A solution of sodium hypobromite, prepared at 0°C by dissolving sodium hydroxide (45.71 g, 1.14 mole) in water (200 mL) and bromine (16.3 mL, 0.30 mole) over 5 minutes. This solution is then added dropwise over 30 minutes to a solution of 1-[2-methyl-4-(2-morpholin-4-yl-ethoxy)-phenyrj-ethanone (19.2 g, 0.073 mole) in dioxane (140 ml_), then warmed to 40°C and stirred for 30 minutes. Sodium bisulfite is added to destroy the excess sodium hypobromite and then diluted with water (800 mL) and stirred overnight at ambient temperature. The volume is reduced in-vacuo by about 300 mL and then acidified with 3 N hydrochloric acid to pH 6. This is then extracted repeatedly with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and evaporated to give a white solid, 4.09 g (21%), MS (ESI): m/z 266.2 (M + H). (Formula Removed) Intermediate 221 2-Ethoxycarbonylmethyl-4-(2-morpholin-4-yl-ethoxy)-benzoic cid A solution of 2-methyl-4-(2-morpholin-4-yl-ethoxy)-benzoic acid (3.58 g, 13.5 mmole) and diethylcaebonate (2.40 g\ 20.4 mmoJe) in tetrahydrofuran (30 mL) is added dropwise to a solution of lithium diisopropylamide (30.0 mmole) at-78°C (freshly prepared from diisopropylamine (3.04 g, 30.0 mmole) and n-butyllithium (18.8 mL of 1.6M in hexanes, 30.1 mmole) in tetrahydrofuran (20 mL)) over 15 minutes. This mixture is allowed to warm to room temperature and stirred for 1.5 hours. The reaction mixture is cooled with an ice bath then glacial acetic acid (3.1 mL, 54.0 mmole) is added dropwise. The tetrahydrofuran evaporated in vacuo and the mixture is then extracted with ethyl acetate (3x25 mL). The ethyl acetate layer is dried over sodium sulfate, filtered and evaporated. This is purified by HPLC (acetonitrile-water without trifluoroacetic acid and dried to give, 2.81 g, (61%), MS (ESI): m/z 338.1 (M + H). (Formula Removed) Intermediate 222 2-Carbamoyfmethyl-4-{2-morpholin-4-yf-ethoxy)-benzoicacid A solution of 2-ethoxycart)onylmethy 1-4-(2-rnorpholin-4-yl-ethoxy)-ben2oic acid (2.65 g, 10.0 mmole) and saturated ammonia in dioxane (15 mL) in a pressure bottle is stirred and heated using an. oil bath at 95°C overnight. This mixture is cooled and followed by Ic/ms, reaction not complete. The dioxane is evaporated and replaced with 15 mL of 7M ammonia in methanol and heated overnight in a pressure bottle using an oil bath at 70 °C, still a small amount of starting material left. The solvent is removed in vacuo and used as is in the next step MS (ESI): m/z 309.3 (M + H). (Formula Removed) Intermediate 223 To 2-carbamoylmethyl-4-(2-morpholin-4-yl-ethoxy)-benzoic acid (224 mg, 0.726 mmole) in 4 mL of N.N-dtmethylformamide is added N,N-carbonyldiimidazoie (118 mg, 0.726 mmole) and stirred for 15 minutes at room temperature. The reaction mixture stirred and heated using an oil bath at 110°. After 2 hours the mixture is cooled to room temperature, 20 mL of water is added, stirred, filtered, washed with water and dried to give a brown solid, 134 mg (63%) MS (ESI): m/z 291.2 (M + H). (Formula Removed) Intermediate 224 4-Methoxymethylene-6-(2-morpholin-4-yl-ethoxy)-4H-isoquinoline-1,3•dione A mixture of 6-(2-morpholin-4-yl-ethoxy)-4H-isoquinoline-1,3-dlone (390 mg, 1.34 mrnole). 10 mL of a 4:1 mixture of acetic anhydride and N,N-dimethylformamide and trimethylorthoformate (1.1 mL, 10.1 mmole) is stirred and heated to reflux. After 30 minutes the solvents are removed and the residue treated with 2:1 hexanes/ethyl acetate, the product is collected by filtration, a yellow solid, 230 mg, (52%). MS (ES+): m/z 333.2 (M + H), used as is in the next step. Intermediate 225 2-Hydroxymethyl-5-(2-pyrrolidin-1-y1-ethoxy)-pyran-4-one A mixture of kojic acid. (28.4 g, 0.20 mole), 300 mL of 2-butanone, potassium carbonate powder (27.6 g, 0.20 mole), potassium iodide (1.66 g, 0.01 mole), and 1-(2-chloro-ethyl)-pyrrolodirne (26.7 g, 0.20 mole) is stirred at a gentle reflux overnight. The reaction mixture is cooled, filtered, washed with acetone and the filtrate evaporated. Water is added and extracted with chloroform (3x100 mL) and ethyl acetate (6x100 mL). The combined organics were dried with sodium sulfate and passed through a pad of magnesol and silica gel eluting with ethyl acetate. The eluate is evaporated in vacuo and crystallized with hexane/ethyl acetate (2/1) to give an off-white solid, 3.05 g, (6%); MS (ES+): m/z 240.3 (M + H). (Formula Removed) Intermediate 226 2-Aminomethyl-5-(2-pyrrolidin-1-yl-ethoxy)-pyridin-4-ol A mixture of 2-hydroxyrnethyl-5-(2-pyrrolidin-1-yl-ethoxy)-pyrarv4-one (479 mg, 2.0 mmofe) and 7 M ammonia in methanol (5.0 ml)is stirred and heated in a sealed vessel at 90°C overnight. The reaction mixture is cooled, evaporated to dryness, to give the pyridine as a brown solid (MS (ES+): m/z 239.3 (M + H)). This is treated with 12 mL of N,N-dimethylforrnamide stirred and cooled with an ice bath to 0°C is added triphenylphosphine (786 mg, 3.00 mmole) followed by carbon tertabromide (995 mg, 3.00 mmole). This is stirred for 15 minutes maintaining temperature between 0 - 5°. Sodium azide is then added (390 mg, 6.0 mmole) and the reaction mixture stirred for 24 hrs at ambient temperature. The reaction mixture is filtered and chromatographed on the HPLC (acetonitrile, water without trifluoroacetic acid), to give the azide as a light brown solid 221 mg, (42%), (MS (ES+): m/z 264.4 (M + H)). To this is added 6 mL of tetrahydrofuran, and triphenylphosphine (262 mg, 1.00 mmole) followed by water (270 µL, 15.0 mmole) this is then stirred at ambient temperature overnight. The reaction mixture is evaporated to dryness in vacuo, dissolved in N,N-dimethyiformamide, filtered and chromatographed on the HPLC (acetonitrile, water without trifluoroacetic acid), to give the amine as an off white solid 95 mg. (47%) (MS (ES+): m/z 238.3 (M + H)). This is used as is for the next step. (Formula Removed) Intermediate 227 2-Carboxy-5-nitrobenzeneacetamide A stirred mixture of 2.25 g (10 mmol) of 2-carboxy-5-nitrobenzeneacetic acid (J. Org. Chem. 1998. 63. 4116). 2.5 ml (35 mmol) of acetyl chloride, and 8 ml of acetone is refluxed for 60 m. The resulting solution is evaporated to dryness. The resulting tan solid is shown to be the corresponding cyclic anhydride by 1H NMR (DMSO-d6)  4.40 (s, 2H). The anhydride is mixed at 0° with 16 ml of conc NH4OH and 16 ml of H2O. The resulting mixture is warmed to 25°, stirred 15 m, and evaporated to dryness at <30° The residue is stirred in 25 ml of H2O, acidified at 10° with 4 ml of 4N HCI, and stirred 10 m. The resulting tan solid is filtered, washed with H2O, and dried to give 2.01g (90%), mp 185-190° (dec); 1H NMR (DMSO-d6)  8.20 (d, J = 2.4 Hz. 1H). 8.16 (dd, J = 2.4. 8.4 Hz, 1H), 8.02 (d, J = 8.4Hz, 1H), 7.47 (s, 1H). 6.96 (s. 1H), 3.96 (s. 2H); MS (ES-) m/z 223A (M-H)-1 Analysis for C9H8N2O5: Calcd: C, 48.22; H. 3.60; N. 12.50. Found: C, 48.27; H, 3.40; N, 12.10. (Formula Removed) Intermediate 228 6-Nitroisoquinoline-1,3(2H, 4H)-dione A stirred suspension of 11.1 g (49.3 mrnol) of 2-carboxy-5-nitrobenzeneacetamide in 99 ml of 1,2-dlchlorobenzene is refluxed for 3 h. The residue obtained after evaporation of the solvent under vacuum is washed with ether and dried to give 7.34 g (72%) of a tan solid, mp 255-260° (dec); 1H NMR (DMSO-d6)  11.6 (s. 1H), 8.2-8.3 (m. 3H), 4.17 (s, 2H); MS (ES-) m/z 205.2 (M-H)" (Formula Removed) Intermediate 229 (4E)-4-(Methoxymethylene)-6-nitroisoquinoline-1,3(2H,4H)-dione To a stirred mixture of 0.41 g (2.0 mmol) of 6-nitroisoquinoline-1,3(2H, 4H>-dione, 3.2 ml (34 mmol) of Ac20, and 0.80 ml of N.N-DIMETHYLFORMAMIDE is added 0.44 ml (4.0 mmol) of trimethyl orthoformate. The mixture is heated to 125° and maintained for 30 m, cooled, diluted with ether, and stirred for 10 m. The resulting brown solid is filtered, washed with ether, and dried to give 372 mg (74%); 1H NMR (DMSO-d6)  11.55 (s, 1H), 8.99 (d, J = 2.0 Hz, 1H), 8.30 (d, J = 8.6 Hz, 1H), 8.19 (dd J = 2.0, 8.6 Hz, 1H), 4.33 (s, 3H). (Formula Removed) Intermediate 230 6,7-Dimethoxyisoquinoline-1,3(2H, 4H)-dione A solution of 8.2 g (34.1 mmol) of 2-carboxy-4,5-dimethoxybenzeneacetic acid (Tetrahedron 1975. 31.2607) in 17 ml of concentrated NH,OH is evaporated to dryness. This operation is repeated. The resulting tan solid ammonium salt is suspended in 34 ml of 1,2-dichIorobenzene. The stirred mixture is boiled in an oil bath at 210° while collecting some distillate during 90 m. The cooled mixture is stirred in hexane and H2O, and the resulting solid is collected by filtration. The A/hite solid is stirred in satd NaHCO3 for 15 m, filtered, washed with H2O, and dried 0 give 3.45 g (46%), mp 234-238°; MS (ES-) m/z 220.1 (M-H)'1. (Formula Removed) Intermediate 231 6-Aminoisoquinoline-1,3(2H, 4H)-dione A solution of 6.19 g (30 mmol) of 6-nitroisoquinoline-1.3(2H, 4H)-dione in 15 ml of MeOH and 150 ml of N.N-DJMETHYLFORMAMIDE is hydrogenated at 1 atmosphere of H2 at 25° in the presence of 1.5 g of 10%Pd/C for 7h. The catalyst is removed by filtration through Cefite. The filtrate is evaporated to give 5.4 g (100%) of a tan solid, mp 200-220° (dec); MS (ES+) m/z 177.2 (M+H)+(Formula Removed) Intermediate 232 N-[(4E)-1,3-Dioxo-4-(methoxy)methylene-1,2,3,4-tetrahydroisoquinolin-6- yl]acetamide To a stirred mixture of 90 mg (0.50 mmol) of 6-aminoisoquinoline-1,3(2H, 4H)-dione, 0.80 ml (8.5 mmol) of Ac2Oand 0.20 ml of N,N-DIMETHYLFORMAMIDE (DMF) is added 0.11 ml 1.0 mmol) of trimetbyl orthoformate. The mixture is heated to 125° and maintained for 30 m, cooled, diluted with ether, and stirred for 10 m. The resulting amber solid is filtered, washed with ether, and dried to give 96 mg (74%); MS (ES+) m/z 261.1 (M+H)+1. (Formula Removed) Intermediate 233 N-Methyl-2-carboxybenzeneacetamide To 20 ml of 2.0 M methylamine in THF is added 1.62 g (10 mmol) of isochroman-1,3-dione at 0°C. The mixture is stirred at 25°C for 45 m and concentrated to dryness. The residue is stirred in 40 ml of 0.3 N HCI. The white solid is filtered off, washed with water, and dried to give 1.74 g (90%); 1H NMR (DMSO-d6)  7.80 (s, 1H). 7.81 (s, 1H), 7.40 (m, 3H), 3.83 (s, 2H). 2.57 (s. 3H); MS (ES-) m/z 192.1 (M-H)-1. Analysis for C10H11NO3 Calcd: C„ 62.17; H, 5.74; N, 7.25. Found: C. 62.16; H, 5.81; N, 7.24 (Formula Removed) Intermediate 234 N-Methylisoquinoline-1,3(2H, 4H)-dione A mixture of 2.28 g (11.8 mmol) of N-rnethyl-(2-carboxybenzeneacetamide and 24 ml of 1,2-dichlorobenzene is refluxed for 1 h and evaporated to dryness. The residue is recrystallized from EtOAc-hexane to give an off-white solid, 1.55 g (75%), mp 113-115°C; MS (ES+) m/z 176.1 (M+H)+1. MefX (Formula Removed) Intermediate 235 (4E)-N-Methyl-4-(methoxymethylene)isoqutnoiine-1,3(2H,4H)-dione To a stirred mixture of 0.35 g (2.0 mmol) of (N-methyl)isoquinoline-l ,3(2H. 4H)-dione, 3.2 ml of Ac2O and 0.80 ml of N.N-DIMETHYLFORMAMIDE (DMF) is added 0.44 ml (4.0 mmol) of (MeO)3CH at 25°C. The mixture is stirred at 125°C for 30 m, cooled, and concentrated under high vacuum. The residue is recrystallized from EtaO-hexane to give 0.20 g of tan solid, mp 145-150°C (dec); MS (ES+) m/z 218.2 (M+Hf1. Analysis for C12H11NO3 Calcd: C, 66.35; H, 5.10; N, 6.45. Found: C, 65.98; H, 4.99; N, 6.42. (Formula Removed) Intermediate 236 1 -(3-Nitro-benzyl)-azepane To a solution of 3-nitrobenzyl bromide (10.5 g, 48.7 mmol) in methylene chloride is added azepane (5.5 mL, 48.7 mmol) and 20.0 mL (146.1 mmol) of triethylamlne, and the reaction solution is heated at 60DC under N2 for 20 minutes. After evaporating to dryness, the resulting brown residue is dissolved in methylene chloride and washed twice with saturated Na2CO3 solution, and once with brine solution. After drying over Mg2SO4, the organic solution is filtered and concentrated to give 8.0 g (70.1 % yield) of brown oil. (Formula Removed) Intermediate 237 3-(azepan-1 -ylmethyl)aniline To a solution of 1-(3-nitro-benzyl)-azepane (4.0 g, 17.05 mmol) in 120 mL of 20 % H2O/MeOH is added 5.05 g (102.3 mmol) of fresh iron powder, 8.25 g (153.5 mmol) of NH4CI and the reaction mixture is refluxed under N2 for 45 min. The reaction mixture is filtered through a pad of celite to give yellow solution. After evaporating to dryness, the yellow residue is dissolved in EtOAc, washed twice with saturated NaHCO3 solution. After drying over Mg2SO4, the organic solution is filtered and concentrated to give 3.12 g (89.4 % yield) of yellow oil. (Formula Removed) Intermediate 238 1 -(3-Nitro-benzyl)-piperidine Using the procedure described for the preparation of 1-(3-nitro-benzyl)-azepane, 4.7 g (46.5 % yield) of yellow oil is obtained from 10.0 g (46.3 mmol) of 3-nitrobenzyl bromide, 4.58 mL (46.3 mmol) of piperidine, and 16.1 mL (115.7 mmol) of triethylamine. (Formula Removed) Intermediate 239 3-Piperidin-1 -ylmethyl-phenylarnine Using the proceduie described for the preparation of 3-(azepan-1-yimethyl)aniline, 3.37 g (83 % yield) of colorless solid is obtained from 4.7 g (21.4 mmol) of 1-(3-Nitro-benzyl)-piperidine, 7.17 g (128.1 mmol) of iron powder. 10.28 g (192.2 mmol) of NH4CI. (Formula Removed) Intermediate 240 1 -(3-Nitro-benzyl)-pyrroiidine Using the procedure described for the preparation of 1-(3-Nitro-benzyl)-azepane, 7.67 g (62.0 % yield) of brown oil is obtained from 13.0 g (60.2 mmo!) of 3-nitrobenzyl bromide, 5.0 mL (60.2 mrnol) of pyrrolidine, and 21 mL (150.4 mmol) of triethylamine. (Formula Removed) Intermediate 241 3-Pyrrolidin-1 -ylmethyl-phenylamine Using the procedure described for the preparation of 3-(azepan-1-ylmethyl)aniline, 2.63 g (40.1 % yield) of colorless solid is obtained from 7.67 g (37.2 mmol) of 1 -(3-Nitro-benzyl)-pyrrolidine, 12.5 g (223.0 mmol) of iron powder, 17.9 g (334.8 mmol) of NH4CI. (Formula Removed) Intermediate 242 4-bromo-2-(carboxymethyl)benzoic acid In a 500 mL 3-neck round bottom flask, an amount of diisopropylamine (28.0 mL 200 mmol) in 65 mL of tetrahydrofuran is cooled to -78°C and slowly added 80.0 mL (200 mmol) of n-butyllithium (2.5 M in hexane) with vigorous stirring. Allow to warming up to 0°C and keeping at this temperature for 5 min, the reaction is cooled back to -78°C. To this mixture Is slowly added a solution of 10.8 g (50.0 mmol) of 4-bromo-2-methylbenzoic acid and 8.42 mL (100 mmol) of dimethylcarbonate in 65 mL of tetrahydrofuran keeping the internal temperature of the reaction mixture below -50°C. After addition, the dry-ice bath is removed and the reaction mixture is stirred at room temperature for 4 h. Precipitate is observed as the internal temperature raising to room temperature. The reaction is quenched with 80 mL of water and stirred overnight to give a homogenous solution. Separate the organic layer. The aqueous solution is acidified with concentrated HCI to pH ~ 2 and extracted with 3 x 100 mL of ethyl acetate. The combined organic solution is washed twice with water. After drying over Mg2SO4, the organic solution is filtered and concentrated to give white solid. Recrystallization from EtOAc (hot)/hexane yielded 8.86 g (68.2 % yield) of white solid: +H NMR (DMSO-da) 5 12.62 (bs, 1H); 7.82 (d, J = 6.3 Hz, 1H), 6.18 (m, 2H), 3.95 (s, 2H); MS (ESI) m/z-257.1 and 259.1 (M-H)-1 Analysis for C9H7BrO4+ . (0.2 EtOAc) Calcd: C, 42.54; H, 3.13; N, 0.00 Found: C, 42.41; H, 2.93; N, -0.25 (Formula Removed) Intermediate 243 6-chloroisoquinoline-1,3(2H,4H)-dione An amount of 2-(carboxymethyl)-4-chlorobenzoic acid (8.4 g, 39.14 mmol) and 2.82 g (47 mmol) of urea is vigorously stirred at 160°C. Solids were melted, boiled and hardened after 15 min. Continue to heat and blow nitrogen through to remove water generated from reaction until total dryness. After cooling, the solid is ground to fine powder. After successively washing with saturated NaHCC+3 solution, water, methanol, ether and hexane, the powder is dried in oven (60°C) overnight to give 2.6 g (34.0 % yield) of light yellow solid: MS (ESI) m/z 194.0 (M-H)"1 Analysis for C9H6CINO2 Calcd: C, 55.26; H, 3.09; N, 7.16, Found: C, 54.86; H, 2.96; N, 7.12 (Formula Removed) Intermediate 244 (4E)-6-Chloro-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione A solution of 4b (2.40g, 1Z2 mmol), 2.68 mL (24.4 mmol) of trimethylorthoformate, and 20 mL of acetic anhydride in 10 mL of N.N'-dimethylformamide is heated at 120°C under N2 for 2 hrs. Mass spectroscopy suggested that the reaction is completed. After cooling, ethyl ether is added, and the precipitate is collected, and washed successively with MeOH, EtaO and hexane. After drying in oven (60°C) overnight, 2.1 g (72.5 % yield) of brown solid is obtained: MS (ESI) mfc 221.95 (M+H)+' Analysis for C11H8CINO3 Calcd: C, 55.60; H, 3.39; N, 5.89 Found: C, 54.20; H, 3.14; N. 5.92 (Formula Removed) Intermediate 245 6-Bromo-1,3-bis{[tert-butyl(dirnethyl)silyl)oxy}isoquinoline A solution of 6-bromo-isoquinoline-1,3(2H,4H)-dione (1.0 g, 4.17 mmol), 1.875 g (12.51 mmol) of fert-butyldimethylsilyl chloride, 1.13 g (16.68 mmol) of imidazole in N.N'-dimethylforrnamide is stirred at room temperature overnight. After evaporating to dryness, the brown oil is extracted with 4 x 100 mL of 25% diethyl ether/hexane. The organic solution is washed with 3 x 100 mL of water, dried over Mg2SO4. filtered and concentrated to give brown oil. This brown oil is dissolved in 50 mL of 20% CH2Cl2/hexane and passed through a pad of magnesol, followed by rinsing with 500 mL of the same solvent mixture. The organic solution is concentrated to give 1.184 g (60.6 % yield ) of colorless solid: MS (ESI) m/z 468.2 and 470.2 (M+H)+1 Analysis for C21H34BrNO2Si2 Calcd: C, 53.83; H, 7.31; N, 2.99 Found: C, 53.86; H. 7.11; ISI. 2.99 (Formula Removed) Intermediate 246 6-Jodoisoquinoline-1,3(2H ,4H)-dione An amount of 6-bromo-1,3-bis{[tert-butyl(dimethyl)silyr]oxy}isoquinoline (15.0 g, 32.0 mmol) in 100 mL of anhydrous tetrahydrofuran is cooled to -78°C and then 47 mL (80.0 mmol) of terf-butyllithium (1.7 M in pentane) is added slowly with stirring. After stirring at this temperature for 2 hr, 12.0 g (48 mmol) of fresh iodine crystal is quickly add into the mixture, and stirred at this temperature for additional 5 h. The dry-ice bath is removed, and the reaction mixture is allowed to warm up to room temperature and stirred over weekend. Evaporating the brown solution yielded brown oil. The reaction mixture is acidified with 48 mL of 2 M HCI solution and stirred at room temperature for 1 h. The mixture is filtered to give light tan solid. The solid is dissolved in hot DMSO, then 20% MeOH/H20 solution is added to give a precipitate. The precipitate is collected and washed successively with water, methanol, ether and hexane to afford 5.1 g (55.6 % yield) of off-white solid: MS (ESI) m/z 286.08 (M-HT)1 (Formula Removed) Intermediate 247 3-Hydroxy-4-(2-methoxyethoxy)benzaldehyde An amount of 3,4- dihydroxybenzaldehyde (5.0 g, 36.2 mmol) in 20 mL of N,N'-dimethylformamide is added 2-bromoethyl methyl ether (3.4 mL, 36.2 mmol), and sodium carbonate (5.0 g, 72.4 mmol). The reaction mixture is stirred at room temperature for 3 days. After removal solids by filtration, the solution is subsequently evaporated under high-pressure vacuum to dark brown liquid. The residue is added water and acidified with 12 N HCI solution to pH - 2, then extracted 4 x 100 mL of EtOAc. The combined organic layer is washed with brine, dried over Mg2SO4, stirred in darko, filtered and evaporated to give yellow liquid. Purification is performed by column chromatography over silica gel using 40% EtOAc/Hex as eluent to give 2.13 g of colorless solid: mp 74-75 °C; MS (ESI) m/z 195.1 (M+Hr1 Intermediate 248 3-Hydroxy-4-(2-methoxyethoxy)benzaldehyde O-methyloxime An amount of 3-hydroxy-4-(2-methoxyethoxy)benzaldehyde (1.24 g, 6.32 mmol) in 20 mL of EtOH and 10 mL of pyridine Is added methoxylamine hydrochloride (1.06 g, 12.64 mmol). The reaction mixture is stirred at room temperature over weekend. Solvent is removed under vacuum to give colorless oil which is added ether, washed twice with saturated NaHCO3 solution, once with brine, dried over Mg2SO4, filtered and evaporated to give colorless oil. Leaving this oil overnight at room temperature gave 1.15 g (81.0 % yield) of colorless solid: mp: 63-64 °C; MS (ESI) m/z 226.1 (M+H)+1 (Formula Removed) Intermediate 249 5-(Aminomethyl)-2-(2-methoxyethoxy)phenol An amount of 3-hydroxy-4-(2-methoxyethoxy)benzaldehyde O-methyloxime (0.75 g, 3.33 mmol) in 10 mL of EtOH is added 1 mL of 12 N HCI and palladium on carbon. The reaction mixture is hydrogenated for 4 h. After removal of solid by filtration, solvent is evaporated to give yellow oil. Colorless solid is afforded after the oil is washed 5 times with EtOAc. Recrystallization from MeOH / EtOAc afforded 0.45 g (68.5 % yield) of colorless solid: mp: 89-90 °C; MS (ESI) m/z 198.1 (M+H)+1 Intermediate 250 3-Hydroxy-4-propoxybenzaldehyde Using the procedure described for the preparation of 3-hydroxy-4-(2-methoxyethoxy)benza!dehyde, 5.26 g (40.5 % yield) of colorless solid, after purified by column chromatography over silica gel using 40% EtOAc/Hex as eluent, is obtained from 3,4- dihydroxybenzaldehyde (10.0 g, 72.4 mmol), 7.77 mL (80 mmol) of 1-iodo propane, and 10 g of sodium carbonate: mp 67-68 °C; MS (ESI) m/z 179.1 (M+H)"1. (Formula Removed) Intermediate 251 3-Hydroxy-4-propoxybenzaldehyde O-methyloxime Using the procedure described for the preparation of 3-hydroxy-4-(2-methoxyethoxy)benza!dehyde O-methyloxime, 1.12 g (42.0 % yield) of colorless solid, after purified by column chromatography over silica gel using 25% EtOAc/Hex as eluent, is obtained from 3-hydroxy-4-propoxybenzaldehyde (2.30 g, 12.76 mmol), 2.13 g (25.52 mmol) of methoxylamine hydrochloride: mp 39-40 °C; MS (ESI) m/z 210.1 (M+H)+1 (Formula Removed) Intermediate 252 5-(Aminomethyi)-2-propoxyphenoI 275 Using the procedure described for the preparation of 5-(aminomethyl)-2-(2-methoxyethoxy)phenol, 2.35 g (75.3 % yield) of colorless solid is obtained from 3-hydroxy-4-propoxybenzaldehyde O-methyloxime (3.0 g, 14.34 mmol): mp 125-126 °C; MS (ESI) m/z 182.1 (M+H)° (Formula Removed) Intermediate 253 3,5--Dimethyl-1-(4-nitrophenyl)piperazine An amount 4-nitrophenylfluoride (2.0 mL, 18.85 mmol) in 20 mL of acetonitrile is added 2,6-dimethylpiperazine (2.58 g, 22.62 mmol). The reaction mixture is reflux under N2 overnight Mass spectroscopy suggested the completion of reaction. Solvent is subsequently evaporated under vacuum. The collected yellow solid is dissolved in chloroform and washed twice with 200 mL of saturated NaHC03 solution, and once with 100 mL of brine. The organic portion is dried over Mg2SO4. filtered, evaporated to give yellow solid which is re-crystallized from EtOAc/Hexane to give 3.98 g (89.8 % yield) of bright yellow crystals: mp 124-125 °C; MS (ESI) m/z 236.1 (M+H)+1 (Formula Removed) Intermediate 254 [4-(3,5-Dimethylpiperazin-1-yl)phenyl]amine An amount of 3,5-dimethyl-1-(4-nitrophenyl)piperazine (1.86 g, 7.90 mmol) in EtOH is hydrogenated with Pd/C catalyst for 4 h. The solid is removed by filtration, and solvent is evaporated under vacuum to give pinkish residue. Recrystallization of this residue from MeOH/ether gives 1.30 g (80.2 % yield) of pinkish crystal: mp 124-125 °C; MS (ESI) m/z 206.1 (M+H)+1 (Z)-1,1 '-(4-(Methoxymethylene)-3-oxo-3,4-dihydrocinnoline-1 ,2-diyl)diethanone (Formula Removed) Intermediate 257 To a solution of 1,2-diacetyl-1,4-dihydro-3(2H)cinnolinorie (0.34 g, 1.5 mmol) in dimethylformamide (3.5 mL) is added acetic anhydride (5 mL), followed by trimethylorthoformate (0.64 mL). The mixture is heated at reflux for 12 hours. After cooling to room temperature, the mixture is purified by semi-preparative reverse-phase HPLC, employing a gradient elution from 5 % acetonitrile in water with 0.1 % trifluoroacetic acid to 100 % acetonitrile over 60 minutes. The desired fractions were concentrated under reduced pressure to afford 0.18 g of (Z)-1,1'-(4-(methoxymethylene)-3-oxo-3,4-dihydrocinnoline-1,2-divi)diethanone. Calculated MW: 274.3 MS(ES): 273.0 (M-H)"observed (Formula Removed) Example 1 (4Z)-4-{{(4-Methoxyphenyl)arnino]methylene}tsc)quinoline-1,3(2H,4H)-dione A toluene (3 mL) solution containing (4E)-4-[(dimethylamino)methylene]-1I4-dihydro-3(2AV)-isoquinolinone (300 mg, 1.48 mmol) and 4-rnethoxyphenylamine (204 mg, 1.66 mmol) is heated at 110°C for 4 h. After cooling in the refrigerator, the crystalline product is collected and washed with ether to give 0.11 g (26.5%) yellow solid mp 150-151 °C; HRMS (ESI) m/z calcd for C17H16N2O6 281.12846, found 281.12865 (M+H)+1. Analysis for C17H16N2O6,: Calcd: C, 72.84; H, 5.75; N, 9.99: Found: C. 72.72; H, 5.88; N, 9.76. (Formula Removed) Example 2 (4Z)4-({[4-(4-IV»ethyl-1 -piperazinyl)phenyl]amino}methylene)-1,4-dihydro-3(2H)- isoquinoiinone A toluene (3 mL) solution containing (4E)-4-[(dimethylamino)methylene]-1,4- dihydro-3(2H)-isoquinolinone (300 mg, 1.48 mmol) and 4-(4-methyl-piperazin-1-yl)-phenylamine (318 mg, 1.66 mmol) is heated at 110°C for 4 h. Using the same workup as example 1, 0.13 g (25%) orange solid is obtained: mp 186-187 °C (dec); HRMS (ESI) m/z calcd for C21H24N40 349.20229, found 349.20180 (M+H)+1. (Formula Removed) Example 3 (4Z)-4-({[4-(1 H-lmidazol-4-yl)phenyl}amino}methylene)-1,4-dihydro-3(2H)- isoquinolinone A toluene (3 mL) solution containing (4E)-4-[(dimethylamino)methylene]-1,4-dihydro-3(2H)-isoquinolinone (300 mg, 1.48 mmol) and 4-(1H-imidazol-4-yl)aniline (265 mg, 1.66 rnmol) is heated at 110°C for 4 h. Using the same workup as example 1, 0.13 g (28%) orange solid is obtained: mp 151-152 °C (dec.); HRMS (ESI) m/z calcd for C19H16N40 317.139C9, found 317.13894 (M+H)+1. (Formula Removed) Example 4 (4Z)-4-({[4-(4-Methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoJine 1,3(2H,4H)-dione A mixture of 4-methoxymethylene-4H-isoquinoline-1,3-dione (101.5 mg, 0.5 mmol), 4-(4-methyl-piperazin-1-yl)-phenylamine (95.6 mg, 0.5 mmol) in 1 mL of 279 N,N-dimethylformamide is heated at 110°C for 1 h. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 163 mg (90%) of yellow solid mp 245-246 °C; MS (ESI) m/z 363.19 (M+1); Analysis for C21H22N4O2: Calcd: C, 69.59; H, 6.12; N, 15.46: Found: C, 69.49; H, 6.10; N. 15.36. (Formula Removed) example 5 (4Z)-4-({[4-(2-Pyrrolidin-1-ylethyl)phenyrjamino}methylene)isoquinoline- 1,3(2H,4H)- dione A mixture of 4-methoxyrnethylene-4H-isoquinoline-1,3-dione (101.5 mg, 0.5 mmol), 4-(2-pyrrolidin-1-yl-ethyl)-phenylamine (95.2 mg, 0.5 mmol) in 1 mL of N.N-dimethylformamide is heated at 110°C for 1.5 h. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 129 mg (71%) of yellow solid mp 224-225 °C; MS (ESI) m/z 362.20 (M+1); Analysis for C22H23N3O2: Calcd: C, 73.11; H, 6.41; N, 11.63: Found: C, 72.33; H, 6.45; N, 11.59. (Formula Removed) Example 6 (4Z)-4-(4-Morpholin-4-ylphenyl)amino]methylene}isoquinoiine-1,3(2H,4H)-dione A mixture of 4-methoxymethylene-4H-isoquinoline-1,3-dione (101.5 mg, 0.5 mmol), 4-morpholin-4-yl-phenylamine (89.12 mg, 0.5 mmol) in 1 mL of N,N-dimethylfonmamide is heated at 110°C for 1 h. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 139 mg (80%) of greenish yellow solid rnp 257-258 °C; MS (ESI) m/z 350.17 (M+1), Analysis for C2oH19N3O3: Calcd: C. 68.75; H, 5.48; N, 12.03: Found: C, 68.49; H, 5.57; N, 11.90. (Formula Removed) Example 7 (4Z)-4-[(1 H-lndazol-6-ylamino)methylene]isoqulnoline-1,3(2H,4H)-dione A mixture of 4-methoxymethylene-4H-isoquinoline-1,3-dione (101.5 mg, 0.5 mmol), 1H-indazol-6-ylamine (66.6 mg, 0.5 mmol) in 1 mL of N,N-dimethylformamide is heated at 110°C for 1 h. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 79.4 mg (52%) of yellow solid mp >300 °C; MS (ESI) m/z 305.10 (M+1); (Formula Removed) Example 8 (4Z)-4-[(Quinolin-6-ylamino)methylene]isoquinoline-1,3(2H,4H)-dione A mixture of 4-methoxymethylene-4H-isoquinoline~1,3-dione (101.5 mg, 0.5 mmol), quinolin-6-ylamine (72.2 mg, 0.5 mmol) in 1 mL of N.N-dimethylformamide is heated at 110°C for 1 h. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 130 mg (82%) of greenish yellow solid mp 277-278 °C; MS (ESI) m/z 316.10 (M+1); Analysis for C19H13N3O2: Calcd: C, 72.37; H, 4.16; N, 13.33: Found: C, 71.86; H, 4.02; N, 13.25. (Formula Removed) Example 9 (4E)-4-(2,3-dimethoxybenzylidene)isoquinoline-1,3(2H,4H)-dione - (4Z)-4-(2,3-dimethoxybenzylidene)isoquinoline-1,3(2H,4H)-dione (1:1): An amount of 100 mg (0.62 mmot) of isoquinoline-1,3(4H)dione (CL -243165) and 2,3-dimethoxybenzylaldehyde (168.53mg, 0.070 mmol) were stirred in 1% piperidine in isopropanol (2-propanol) (3.0 mL) at 90°C for four hours. After . cooling, the mixture is concentrated to dryness. The residue is dissolved in ethyl acetate and the precipitate is filtered. The solution is purified by preparative thin layer chromatography (1:2 = ethyl acetate: hexane), to give a yellow solid 41 mg (21 % yield): mp 154-155°C; MS (ESI) m/z 310.1 (M+1) 'H NMR (400 MHz, DMSO-D6) ppm 3.74 - 3.78 (m. 3 H) 3.82 - 3.89 (m. 3 H) 6.84 (d. J=7.05 Hz. 1 H) 6.98 - 7.23 (m. 2 H) 7.34 - 7.54 (m, 3 H) 7.92 - 8.23 (m. 2 H) 11.64 (s, 1 H) Anal. (C18H15NO C18H15NO4) C. H. N Calcd: C. 69.41; H. 4.93;; N, 4.50 Found: C, 69.34; H. 5.15; N, 4.35 Example 10 (4E)-4-[4-(dimethylamino)benzylidene]isoquinoline-1,3(2H.4H)-dione - (4Z)-4-{4-(dimethylamhio)benzylidene]isoquinoline-l ,3(2H,4H)-dione (1:1): Using the procedure described for the preparation of (4E)-4-(2,3-dimethoxybenzylidene)isoquinoline-1,3(2H,4H)-dione - (4Z)-4-(2,3-dimethoxybenzylidene)isoquinoline-1,3(2H,4H)-dione (1:1) 60 mg (33 % yield) of red solid is obtained from 100 mg (0.68 mmol) of lsoquinoline-1,34H)-dione (CL -243165) and 4-dimethylamlnobenzylaldehyde (204 mg, 1.24 mmol): mp 179-180°C; MS (ESI) m/z 293.2 (M+1). 1H NMR (400 MHz, DMSO-D6) 5 ppm 3.01 (s, 6 H) 3.06 (s, 4 H) 6.73 (dd, 7=14.86, 9.07 Hz. 3 H) 7.29 - 7.55 (m, 5 H) 7.70 (s, 1 H) 7.93 - 8.00 (m, 2 H) 8.01 - 8.08 (m, 2 H) 8.12 (d, Ji=8.06 Hz, 1 H) 8.17 (d, J=8.81 Hz, 2 H) 11.27 (s, 1 H) 11.40 (s, 2 H) Anal. (C16H11NO3- C16 H16NO3.O.4H2.O) C, H, N Calcd: C, 70.52; H, 4.37; N. 5.14 Found: C, 70.68; H, 4.16; N, 5.02. Example 11 (4E)-4-(4-hydroxybenzylidene)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4E)-4-(2,3-dimethoxybenzylidene)isoquinoline-1,3(2H,4H)-dione - (4Z)-4-(2,3-dirnethoxybenzylidene)isoquinoline-1,3(2H,4H)-dione (1:1), 160 mg (24 % yield) of orange solid is obtained from 400 mg (2.48 mmol) of isoquinoline-1,34H)-dione and 4-hydroxybenzylaldehyde (666 mg, 5.46 mmol): mp 242-243°6; MS (ESI) m/z 266.2 (M+1). 1H NMR (400 MHz, DMSO-D6) 5 ppm 6.45 - 7.04 (m, 3 H) 7.35 - 7.58 (m. 5 H) 7.66 - 7.82 (m, 2 H) 7.89 - 8.00 (m, 2 H) 7.93 - 7.99 (m. 2 H) 8.01 - 8.09 (m, 2 H) 8.12 (d, J=8.06 Hz, 1 H) 10.10 (s. 2 H) 11.36 (s, 1 H) 11.51 (s, 1 H) Anal. (Cl8H15NO4C18H15NO4O.1H2O) C, H. N Calcd: C, 69.48; H, 4.93; N, 4.50 Found: C, 69.41; H, 4.85; N, 4.39 (Formula Removed) Example 12 (4E)-4-(3,4-dimethoxybenzylidene)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4E)-4-(2,3-dimethoxybenzylidene)isoquinoline-1,3(2H,4H)-dione - (4Z)-4-(2,3-dimethoxybenzylidene)isoquinoline-1.3(2H,4H)-dione (1:1), 300 mg (39 % yield) of yellow solid is obtained from 400 mg (2.48 mmol) of isoquinoline-1,34H)-dione and 3,4-dimethoxybenzylaldehyde (618.19 mg, 3.72 mmol): mp 194r195°C; MS (ESI) m/z 310.1 (M+1). 1H NMR (400 MHz, DMSO-D6) ppm 2.35 (s, 6 H) 7.16 - 7.27 (m, 2 H) 7.30 - 7.38 (m, 2 H) 7.47 {dd, 7=7.55, 1.76 Hz, 2 H) 7.62 (dd, J=7.93, 1.13 Hz, 2 H) Anal. (C18H16N2O2- C18H16N2O2- 0.3H2O) C, H, N Calcd: C, 72.60; H, 5.62; N, 9.41 Found: C, 72.64; H, 5.72; N, 9.34. (Formula Removed) Example 13 (4Z)-4-({[4-(Piperidin-1-ylmethyl)phenyl]arnino}methylene)isoquinoline-1,3(2H,4H)- dione A mixture of 4-methoxymethylene-4H-isoquinoline-1,3-dione (101.5 mg, 0.5 mmol). 4-piperidin-1-y1metfiyl-phenylamine (95.14 mg, 0.5 mmol) in 1 mL of N,N-dimethylformamide is heated at 110°C for 2 h. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 92 mg (51%) of yellow solid mp 185-186 °C; HRMS (ESI) m/z calcd for C22H23N302 362.18546, found 362.18631 (M+H)+1. (Formula Removed) Example 14 (4Z-4-[{3-Chloro-4[(1 -methyl-1 H-imidazole-2-uy)thio]phenyl}amio)methylene]isoqu»noline-1,3(2H,4H)-dione An amount of 150 mg (0.74 mmol) (4£)-4-(methoxymethylene)isoquinoline-1,3{2H,4H)-dione is stirred in N.N-dimethylformamide (8.5 mL) followed by addition of 3-chloro-4-(1H-imidazole-2-ylsulfanyl)-phenyiamine (168.53rng, 0.070 mmol). The reaction mixture is heated at 110 °C for 1 h. After cooling to room temperature, ether is added, and the precipitate is filtered to give a yellow solid (170 mg, 56%): mp 264-265'»C; MS (ESI) m/z 410.2 (M+1) (Formula Removed) Example 15 (4Z)-4-[({3-Chloro-4-{(4chlorobenzyl)oxy]phenyl}amino)methylene]isoquinorme- 1,3(2H,4H-dione Using the procedure described for the preparation of example 14 165mg, (48% yield) of brown-yellow solid is obtained from 150 mg (0.74 mmol) of (4E)-4- 286 (methoxymethylene)isoquinoline-1,3(2H,4H)-dione, and 187.72 mg (0.95 mmol) of 4-chloro-3-(4-chloro-benzyloxy)-phenylamine; mp 278-279°C, MS (ESI) m/z 457.4 (M-1) (Formula Removed) Example 16 (4Z)-4-({[3-(Piperidin-1-ylmethyl)phenyGamino}methylene)isoquinoline-1,3(2H,4H)- dione) (1b) Using the procedure described for the preparation of (4Z)-4-({[3-(azepan-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 0.52 g (58.5 %) of yellow solid is obtained from 0.5 g (2.46 mmol) of (4E)-4-(methoxymethylene)-isoquinoline-1,3(2H,4H)-dione and 0.47 g (2.46 mmol) of 3-Piperidin-1-ylmethyl-phenylamine. mp 173-174°C; +H NMR (DMSO-d6)  12.44 (d, J = 9 Hz. 1H), 11.33 (s. 1H)„ 8.90 (d, J = 9 Hz, 1H), 8.18 (d. J = 9 Hz, 1H), 8.03 (d, J = 9 Hz, 1H), 7.63 (m, 1H), 7.46 (s, 1H), 7.39 (m, 2H), 7.29 (t, J = 6 Hz, 1H), 7.12 (d, J = 6 Hz, 1H), 3.46 (s, 2H), 2.35 (s, 4H), 1.52 (m, 4H), 1.40 (d, J = 3.6 Hz. 2H); MS (ESI) m/z 362.2 (M+H)+1; Analysis for C22H23N3O2+ Calcd: C, 73.1; H, 6.41; N, 11.60; Found: C, 72.85; H. 6.33; N, 11.42. (Formula Removed) Example 17 (4Z)-4-({[3-(Azepan-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)- dione An amount of (4E)-4-(methoxymethylene)-isoquinoiine-1,3(2H,4H)-dione (1.0 g» 4.9 mmol) is added to N,W-dimethylformamide, followed by 3-(azepan-1-ylmethyl)aniline (1.0 g, 4.9 mmol). The reaction mixture is heated at 120°C under N2 for 40 minutes. After evaporating to dryness, the red oil is dissolved in warm ethyl acetate and filtered through a pad of celite to give a yellow solution. Addition of hexane into this organic solution yielded an orange precipitate, which is collected and recrystallized from EtOAc/Hex to give orange crystal (0.925 g, 50.05 % yield): mp 116-117°C; 1H NMR (DMSO-d8) 5 12.43 (d. J = 9 Hz. 1H). 11.33 (S. 1H), 8.80 (d, J=9Hz, 1H). 8.18 (d, J=9 Hz. 1H), 8.04 (d, J= 9 Hz, 1H). 7.63 (t. J = 6 Hz, 1H), 7.46 (s. 1H), 7.39 (m. 2H). 7.30 (t, J = 3 Hz. 1H). 7.17 (d, J= 6 Hz. 1H), 3.64 (s, 2H). 2.60 (s. 4H), 1.58 (m. 8H); MS (ESI) m/z 376.1 (M+H)+1; Analysis for C23H25N3O2; Calcd: C. 73.6; H, 6.71; N. 11.2; Found: C. 72.92; H. 6.45; N, 11.03 Example 18 (4Z>4-({[3-(Pyrrolidin-1-ylrnethyl)phenyl]amino}methylene)isoquinoline-1.3(2H,4H)- dione)(1c) Using the procedure described for the preparation of (4Z)-4-({[3-(azepan-1-ylmethyl)phenyr|amino}methylene)isoquinoline-1,3(2H,4H)-dione, 0.61 g (71.3 %) of yellow solid is obtained from 0.5 g (2.46 mmol) of (4E)-4-(methoxymethytene)-isoquinoline-1,3(2H.4H)-dione and 0.434 g (2.46 mmol) of 3-Pyrrolidin-1 -ylmethyl-phenylamine, mp 172-173°C; 'H NMR (DMSO-d6)  12.43 (d, J = 9 Hz. 1H), 11.33 (s, 1H), 8.90 (d. J= 9 Hz, 1H), 8.18 (d, J = 6 Hz, 1H). 8.03 (d, J = 6 Hz, 1H), 7.64 (t, J = 6 Hz, 1H), 7.46 (m, 2H), 7.38 (t, J = 6 Hz. 1H ), 7.29 (d, J = 6 Hz, 1H), 7.13 (d, J = 6 Hz, 1H), 3.61 (s, 2H), 2.46 (s. 4H), 1.70 (t, J= 2.7 Hz. 4H); MS (ESI) m/z 346.2 (M-H)'1; Analysis for C21H21N3O2; Calcd: C, 73.6; H, 6.09; N, 12.1; Found: C, 72.2; H, 5.99; N, 11.96. (Formula Removed) Example 19 (4Z)-4-({[4-(Morhpolin-4-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)- dione (3) Using the procedure described for the preparation of example 14, 100 mg (15% yield) of a yellow solid from 300 mg (1.47 mmol) of (4E)-4-(methoxymethylene)isoquinoline-l ,3(2H,4H)-dione and 4-mopholin-4-ylmethyl-phenylamine 283.5 mg (1.47 mmol); mp 221-2MS (ESI) m/z 463.1 (M-1). (Formula Removed) Example 20 (4Z)-4-t({4-[(4-Methylpipera2an-1-yl)methyrjphenylamino)mathylene]isoquilin- 1,3(2H.4H)-dione(4) Using the procedure described for the preparation of example 14, 170 mg (18% yield) is obtained as a yellow solid from 500 mg (2.46 mmol) of (4E)4-(methoxymethylene)isoquinoline-l ,3(2H,4H)-dione and 500 mg (2.46 mmol) 4-(4- 289 methylpiperazi.+1 -yl)methyl-phenylamine (4-Mopholin-4-ylmethyl-phenylamine); mp 231-232°C; MS (ESI) m/z 376.5 (M-1). (Formula Removed) Example 21 (4Z)-4-{(1,1'-BiphenyI-4-ylamino)methylene]isoquinoline-1,3(2H, 4H)-dione A mixture of 0.500 g (2.46 mmol) of 4-methoxymethylene-4H-isoquinoline-1,3-dione and 0.416 g (2.46 mmol) of 4-aminobiphenyl in 8 mL of N,N-dimethylformamide is heated at 105°C under N2 for 1.5 h. The reaction is then chilled in ice and the solid product is collected. It is washed with cold N,N-dimethylformamide (DMF) and EtzO and dried in vacuo to give 0.295 g (35%) of yellow crystals: mp 261-262°C; 1H NMR (DMSO-d6)  12.5 (d. 1H, J = 9 Hz). 11.4 (s. 1H), 9.94 (d, 1H, J = 9 Hz). 8.21 (d, 1H. J = 6 Hz), 8.05 (d. 1H. J = 6 Hz), 7.68 (m, 7H), 7.47 (m, 2H), 7.36 (m. 2H); HRMS (ESI) m/z calcd for C=H16N2O2 341.12846, found 341.12811 (M+H)+1; Analysis for C22H16N2O2, Calcd: C, 77.63; H, 4.74; N, 8.23; Found: C. 77.36; H, 4.66; N, 8.25. (Formula Removed) Example 22 (4Z)-4-({3-(2-Pyrrolidin-1-ylethyl)phenyl]amino}methylene)isoquinoline-1,3(2H, 4H)- dione Prepared from a solution of 0.256 g (1.26 mmol) of 4-methoxymethylene-4H-isoquinoline-1,3-dione and 0.240 g (1.26 mmol) of 3-(2-pyrrolidm-1-yl-ethyl)-phenylamine in 4 mLof N,N- dimethylformamide (DMF) at 100°C under N2 as described for example 21. After heating for 1h, solvent is removed and the residue is filtered through Magnesoi (20% MeOH in CHCI3). Solvent evaporation gave 0.420 g (92%) of a red glass: 1H NMR (DMSO-d6)  12.40 (d, 1H, J = 9.0 Hz), 11.33 (s, 1H), 8.90 (d. 1H, J- 9.0 Hz), 8.17 (d, 1H, J = 6.0 Hz), 8.03 (d, 1H, J = 6.0 Hz), 7.62 (m, 1H), 7.46 (s, 1H), 7.30 (m, 3H), 7.04 (d. 1H, J= 6.0 Hz), 2.70 (m, 4H), 2.50 (m, 4H), 1.67 (m, 4H);. HRMS (ESI) m/z calcd forC22H23N3O2362.18631, found 362.18574 (M+H)+1; Analysis for C22H23N3O2.0.75 HzO; Calcd: C, 70.46; H, 6.60; N, 11.21; Found: C, 70.83; 6.61; N, 11.24. Example 23 (4Z)-4-[({4-[(4-Hydroxypiperidin-1-yl)methyl]phenyl}amino)methylene]isoquinoIin- 'l,3(2H,4H)-dione Using the procedure described for the preparation of -(4Z)-4-[(1H-lndazol-6-ylamino)methyleneJisoquinoline-1,3(2W,4H)-dione, 450 mg (48% yield) of a white solid is obtained from 500 mg (2.46 mmol) of (4E)-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-(4-hydroxypiperidin-1-yl)methylphenyl-amine 500 mg (2.46 mmol) (4-Mopholin-4-ylmethyl-phenylamine); mp 224-225°C; MS (ESI) m/z 377 A (M+1). (Formula Removed) Example 24 (4Z)-6-Bromo-4-([(4-piperidin-1-ylmethyl)phenyl]amino}methyleneisoquinoline- 1,3(2H,4H)-dione Using the procedure described for (4Z)-4-({[4-(prperidin-1-ylmethyl)phenyl]amino)methylene)isoquinoline-1,3(2H,4H)-dlone (Example 13), 141 mg (0.50 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoiine-1,3(2H,4/-/)-dione is reacted with 100 mg (0.525 mmol) of 4-(pieridin-1-ytmethyl)phenylamine to give 138 mg (63%) of off-white solid, mp 222-225°; MS (ES+) m/z 440.1, 442.1 (M+H)+1. (Formula Removed) Example 25 (4Z)-4-[({4[(Dimethylamino)methyl]phenyl}amino)methylene]isoquinolin-1,3(2H,4H)- dione Using the procedure described for the preparation of example 14, 320 mg (40 % yield) of yellow crystals is obtained from 500 mg (2.46 mmol) of (4E)-4-(methoxymethylene)isoquinoline-l ,3(2H,4H)-dione and 4-dimethylaminomethyl-phenylamine 334.90 mg (2.46 mmol) (4-Mopholin-4-ylmethyl-pheny!amine); mp 151-152°C, MS (ESI) m/z 321.4 (M-1). (Formula Removed) Example 26 r (4Z)-4-({[4r(Azepan-1-ylmethyl)phenyI]amino}methylene)isoquinoline-1,3(2H,4H)- dione) (1d) Using the procedure described for the preparation of (4Z)-4-({[3-(azepan-1-ylmethyl)phenyr}amino}methylene)isoquinoline-1,3(2H,4H)-dione, 0.64 g (69.6 %) of yellow solid is obtained from 0.5 g (2.46 mmol) of (4E)-4-(methoxymethylene)-isoquinoline-1,3(2H,4H)-dione, and 0.5 g (2.46 mmol) of 4-{azepan-1-ylmethyl)-aniline: mp 198-200°C; 'H NMR (CDCI3) 5 12.20 (d, J = 9 Hz, 1H), 8.46 (s,lH), 8.25 (d, J = 6 Hz, 1H); 7.63 (m, 2H), 7.40 (d, J = 6 Hz, 2H), 7.29 (m, 1H), 7.18 (d, J = 9 Hz, 2H ), 3.64 (s, 2H), 2.62 (s. 4H), 1.63 (s, 8H); MS (ESI) m/z 374.2 (M-H)1' Analysis for C23H25N3O2 . (0.67 H2O). Calcd: C, 71.29; H, 6.85; N, 10.84. Found: C, 71.02;H, 6.72; N, 10.76. (Formula Removed) H3 Example 27 (4Z)-6-Bromo-4-({4-(4-methylpiperazin-1-yl)phenyl}amino}methylene)isoquinoline- 1,3(2H.4H)-dione To a stirred mixture of 0.24 g (1.0 mmol) of 6-bromoisoquinoline-1,3(2H, 4H)-dione. 0.20 g (1.05 mmol) of 4-(4-methylpiperazin-1-yl)methyl-phenylamine, and 1.0 ml of ethylene glycol is added 0.18 ml of triethyl orthoformate. The mixture is stirred for 5 m at 150°, warmed to 180° during 10 m, and maintained at that temperature for 20 m. After cooling to 25°, the mixture is stirred in 5:1 ether-hexane and H20. The resulting solid is filtered, washed with water and 5:1 ether-hexane, and dried to give 0.4 g of foam. Recrystallization from DCM-EtOAC-hexane gave 78 mg (18%) of amber solid, mp 220-223°; MS (ES+) m/z 441.0,443.0 (M+H)+1 '(Formula Removed) 28 (4Z)-6-Bromo-4-{[(4-hydroxy-3-methoxybenzyl)amiho]methylene}isoquinoline- 1.3(2H,4H)-dione(3a) An amount of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.3 g. 1.06 mmol) in N,N-dimethylforrnamide is added to 0.2 g (1.06 mmol) of 4-hydroxyl-3-methoxybenzylamine hydrochloride, and 0.22 mL (2.12 mmol) of triethylamine. The reaction mixture is stirred at room temperature under N2 for 2 h. Diethyl ether is added and the resulting tan precipitate is collected and washed successively with methanol, ether, and hexane to yield 0.28 g (65.1 % yield) of light yellow solid: mp 260-261°C; 1H NMR (DMSO-d6)  11.07 (s. 1H), 10.69 (m, 1H), 9.02 (bs, 1H), 8.71 (d, J = 9 Hz. 1H), 8.10 (s, 1H). 7.87 (d. J = 9 Hz, 1H), 7.30 (d, J = 6 Hz, 1H), 7.02 (s, 1H), 6.78 (m, 2H), 4.60 (d, J = 4.8 Hz, 2H), 3.78 (s, 3H); MS (ESI) m/z 403.1 (M-HV1, Analysis for C18H15BrN2O4 - (0.33 H20), Calcd: C, 52.98; H. 3.76; N, 6.96, Found: C, 52.83; H. 3.86; N, 6.85. (Formula Removed) Example 29 N(-4([4[(Z)-(1,3-Dioxo-2,3-dihydroisoquinolin-4(1H)-ylidie)mthyamino}phenyl)-1,3(2H, 4H)-dione N-Methy!-2-piperidin-1-ylacetamide Prepared from a solution of 0.600 g (2.96 mmol) of 4-methoxymethylene-4H-isoquinoline-1,3-dione and 0.730 g (2.96 mmol) of N-methyl-N-phenyl-2-piperidin-1-yl-acetamide in 10 mL of N,N-dimethylformamide (DMF) at 100°C under N2 as described for example 21.- Solvent removal after heating for 1h gave a red oil which is diluted with 5% MeOH in CHCI3. Insoluble material is filtered off and the filtrate is evaporated. The residue is again treated with 5% MeOH in CHCI3 and filtered to give 0.187 g (15%) of insoluble orange crystals: mp 223-224°C; 1H NMR (DMSO-d6) 12.43 (d. 1H. J= 12 Hz), 11.37 (s. 1H), 8.90 (d, 1 H.J = 12 Hz), 8.19 (d, 1H, J = 9 Hz), 8.04 (d„ 1H, J = 6 Hz), 7.63 (d, 3H, J = 9 Hz), 7.37 (m, 3H), 3.16 (s, 2H), 2.88 (m, 2H). 2.27 (s, 4H). 1.35 (m. 7H); HRMS (ESI) m/e calcd for C24H28N4O3 419.20777, found 419.20746 (M+H)+1, Analysis for C24H26N4O3.CHCI3;. Calcd: C, 55.83; H, 5.07; N, 10.42, Found: C. 56.23; H. 4.96; N, 10.24. (Formula Removed) Example 30 (4Z)-6-Bromo-4-{[(pyridin-3-ylmethyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione To a solution of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.2 g, 0.71 mmol) in NN-dimethylforrnamide is added 3-(aminomethyl)pyridine (0.073 mL, 0.71 mmol). The reaction mixture is heated at 60°C under N2. After reaction is completed, diethyl ether is added, and the red precipitate is isolated and washed with methanol, ether, and hexane respectively to afford 0.16 g (63.2 % yield) of orange solid: mp 299-300°C; 1H NMR (DMSO-d6) 11.09 (s, 1H), 10.69 (m, 1H), 8.74 (d. J = 9 Hz, 1H), 8.63 (s. 1H), 8.52 (d, J - 3 Hz. 1H). 8.10 (s, 1H), 7.84 (m, 2H), 7.42 (m, 1H ), 7.31 (d, J - 9 Hz, 1H), 3.40 (d, J = 4.8 Hz, 2H); MS (ESI) m/z 355.7 and 357.7 (M-H)\ Analysis for C18H12BrN3O2, Calcd: C. 53.70; H. 3.38; N. 11.70, Found: C. 53.45; H. 3.23; N. (Formula Removed) 11.74. Example 31 (4Z)-6-Bromo-4-{[(pyridin-4-ylmethyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione Using the procedure described for the preparation of 4-bromo-2-(carboxymethyl)benzoic acid, 0.11 g (43.5 % yield) of tan solid is obtained from 0.2 g (0.71 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 0.072 mL (0.71 mmol) of 2-(aminomethyl)-pyridine: mp 258-259°C; +H NMR (DMSO-d6) 5 11.12 (s, 1H), 10.69 (m, 1H), 8.71 (d, J = 9 Hz, 1H), 8.56 (s, 2H), 8.08 (s, 1H), 7.88 (d, J = 9 Hz, 1H), 7.33 (m. 3H), 3.75 (d, J = 4.8 Hz. 2H); MS (ESI) m/z 355.7 and 357.7 (M-H)-1 Analysis for C=H25N3O2 H20, Calcd: C, 51.08; H, 3.75; N, 11.17. Found: C, 50.89; H, 3.49; N, 11.16. (Formula Removed) Example 33 (4Z)-6-Nitro-4-({[4-(4-methylpiperazin-1-yl)phenyl}amino}methylene)isoquinoIine- 1,3(2H,4H)-dione Using the procedure described for (4Z)-6-bromo-4-({[4-(4-methylpiperazin-1-yl)phenyl}amino}methylene)isoquinoline-1,3(2H, 4H)-dione (Example 27), 0.21 g (1.0 rnmol) of 6-nitroisoquinoline-1,3(2H, 4H)-dione, 0.20 g of 4-(4-methylpiperazin-1-yl)methyl-phenylamine, 0.18 ml (1.1 rnmol) of triethyl orthoformate, and 2.0 ml of ethylene glycol were reacted to give 0.13 g (32%) of amber solid, mp 250-260° (dec); MS (ES+) m/z 408.2 (M+H)+1 (Formula Removed) Example 34 tert-Butyl 4-(4-{[(Z)-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]am{no}piperazine-1-carboxylate Using the procedure described for the preparation of example 14, 3.2g (70 % yield) of a yellow solid is obtained from 2.0 g (9.84 rnmol) of (4E)-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-(4-amino-benzyl)-piperazine-1-carboxylic acid tert-butyl ester 2.86 g (9.84 rnmol) (4-Mopholin-4-ylmethyl-phenylamine); mp 219-220°C, MS (ESI) m/z 462.6 (M-1). (Formula Removed) Example 37 (4Z)-6,7-Dimethoxy-4-({[4-(-methylpiperazin-1-yl) phenly}amino)methylene] isoquinolin-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 260 mg (76 % yieldO of a yellow solid is obtained from 200 mg (0.80 mmol) of (4E)-6,7-dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-(4-methylpiperazin-1-yl)phenylamine (153.08 mg, 0.80 mmol) mp 273-274°C, MS (ESI) m/z 422.48 (M-1). o=(Formula Removed) Example 38 (4Z)-6-Bromo-4-{[(4-{[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione Using the procedure described for the preparation of example 14 , 200 mg (40 % yield) of a yellow solid is obtained from 300 mg (1.063 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenylamine) (253.35 mg, 1.063 mmol), mp 129-130°C, MS (ESI) m/z 470.4 (M-1). (Formula Removed) Example 39 (4Z)-6-Bromo-4-{[-4-{[(2R)-2-(methoxymethyl)pyrrolidiri-1-yl]methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione Using the procedure described for the preparation of example 14, 250 mg (50 % yield) of an orange solid is obtained from 300 rhg (1.063 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenylamine) (253.35 mg, 1.063 mmol), mp 129-130°C, MS (ESI) m/z 470.4 (M-1). (Formula Removed) Example 40 (4Z)-6-Bromo-4-{[(3.4-dihydroxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione According to general procedure 1, an amount of of 3, 4 dihydroxybenzylamine (0.596 g, 4.3 mmol), is dissolved in N.N-dimethylformamide (61 mL). 1.8 ml (12.9 mmol) of triethylamine is added followed by 1.21 g (4.3 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione. After the mixture is stirred at room temperature for 30 min, water (5 mL) is added and the reaction mixture is stirred for 60 min. The precipitate is filtered and washed several times with anhydrous ether. The crude solid is then purified by high performance liquid chromatography to give 910 mg of a white solid. MS (ESI) m/z 389.7 (M+1). (Formula Removed) Example 41 (4Z;>-^Brorno-4-({[2-(piperidin-1-ylmethyl)phenyl}arnino)methylenelisoquinolin- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 200 mg (43 % yield) of a yellow solid is obtained from 300 mg (1.06 mmol) of (4E)-6,7-dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2W,4H)-dione and 2-piperidin-1-ylmethyl-phenylamine (213.11mg, 1.06 mmol); mp 170-171°C, MS (ESI) m/z 440.34 (M+1). Example 42 (4Z)-6-Nitro4-{[(4-piperidin--1-ylmethyl)prienynamino}rnethyleneisoquinoline-1,3(2H, 4H)-dione Using the procedure described for (4Z)-4-[({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione, 115 mg (0.46 mmol) of (4E)-4-(methoxy)methylene-6-nitroisoquinoline-1,3(2H,4H)-dione is reacted with 93 mg (0.49 mmol) of 4-piperidin-1-ylmethyl-phenylamine to give 137 mg (73%) of brown solid, mp 225-235 (dec); MS (ES-) m/z 405.2 (M-H) (Formula Removed) Example 43 (4Z)-6-Bromo-4-({[2-(1H-indol-3-yl)ethyl]amino}methylene)isoquinoline-1.3(2W,4H)- dione A mixture of 6-bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (124.5 mg, 0.44 mmol), tryptamine (70.7 mg, 0.44 mmol) in 1 mL of N,N- dimethylformamide is heated at 110°C for 1.5 h. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 100 mg (55%) of yellow solid mp 278-280 °C; HRMS (ESI) m/z calcd for C2OH17BrN3O2 408.03531. found 408.03493 (M+H)*1, Analysis for C2OH17BrN3O2; Calcd: C, 58.55; H. 3.93; N, 10.24; Found: C, 58.34; H, 3.63; N, 10.21. (Formula Removed) Example 44 (4Z)-7-Bromo-4-({[4-(Piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 200 mg (43 %) yield of a yellow solid is obtained from 300 mg (1.06 mmol) of (4E)-7-bromo- 4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-piperidin-1-ylmethyl- phenylamine, mp 242-243°C, MS (ESI) m/z 440.34 (M+1). (Formula Removed) Example 45 (4Z)-7-Bromo-4-({[4-(4-methylPipemri-1-y1)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 380 mg (81 % yield) of a green-yellow solid is obtained from 300 mg (1.06 mmol) of (4E>7- bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-(4- methylpiperazin-1-yt)-phenylamine (211.10mg, 1.06 mmol), mp °C, MS (ESI) m/z 441.33 (M+1). (Formula Removed) Example 46 (4Z)-6-Bromo-4-{[(3-hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4-dione An amount of 56 mg (0.35 mmol) of 3-hydroxy benzylamine hydrogen chloride (CL-119773), is dissolved in N,N-dimethylformamide (5 ML). 50u/ (0.75 mmol) of triethylamine is added followed by 100 mg (0.35 mmol) of (4E)-6-bromo- 4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione. After the mixture is stirred at room temperature for 30 min, water (5 mL) is added and the reaction mixture is stirred for 5 min. The precipitate is filtered and washed several times with anhydrous ether to give 120 mg of example 46 as a off white solid (92 % yield); mp °C, MS (ESI) m/z 373.21 (M+1). (Formula Removed) Example 47 2-(Acetyloxy)-4-({l(ZH1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- yliderte)methyl]amino}-methyl)phenyl acetate A solution of 4Z)-4-{{(3,4-dihydroxybenzyl)amino]methylene}-isoquinoline- 1,3(2H,4H)-dione, (0.2 g, 0.644 mmol) in 0.27 mL (1.93 mmol) of triethylamine and 5 mL of pyridine is stirred at room temperature for 10 min, then 0.1 mL (1.42 mmol) of acetyl chloride is added. The reaction mixture is stirred at room temperature under N2 for 3-h. After evaporating the solvent, the residue is dissolved in dichloromethane, washed twice with water, dried over Mg2S04, filtered and concentrated to give yellow solid. Recrystallized in EtOAc/Hex to afford 0.28 g (65.1 % yield) of light yellow solid: mp 184-186°C; MS (ESI) m/z 395.3 320°. MS (ES+) m/z419.3 (M+H)*1. (Formula Removed) Example 49 (4Z)-2-Methyl-4-{[(4-piperidin-1-ylmethyl)pheny0amino}methyieneisoquinoline- 1,3(2H, 4H)-dione Example 50 A solution of 119 mg (0.55 mmol) of (4E)-N-methyl-4- (methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 110 mg (0.58 mmol) of 4- piperidin-1-ylmethylaniline in 1.1 ml of N,N-dimethylformamide (DMF) is heated at 110°C for 45 m, cooled, and diluted with Et20. After filtration the solution is concentrated under high vacuum to give 173 mg amorphous solid (82%), homogeneous on TLC; MS (ES+) m/z 376.3 (M+H)*1, Analysis for C23H25N3O2 0.33H2O, Calcd: C, 72.42; H, 6.78; N, 11.02, Found: C, 72.68; H, 7.01; N, 11.15. (Formula Removed) (4Z)-6-Bromo-4-{[(3-hydroxy-4-methoxybenzyl)amino)methylene}isoquinoline- 1,3(2H,4H-dione Using the procedure described for the preparation of example 46, 340 mg of light-brown solid (77 % yield) is obtained from 300 mg (1.06 mmol) of (4£)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride (201.2 mg, 1.06 mmol); mp 243-244°C, MS (ESI) m/z 413.23 (M+1). (Formula Removed) Example 51 (4Z)-4-({[4-(4-Methylpiperazin-1 -yl)phenyT]amino}methylene)-1,3-dioxo-1,2,3,4- tetrahydroisoquinoHne-6-carboxylic acid A mixture of 4-methoxymethylene-1,3-dioxo-1,2,3,4-tetrahydro-isoquinoline- 6-carboxyiJc acid (90 mg, 0.364 mmol), 4-(4-methyl-piperazin-1-yl)-phenylamine (69.6 mg, 0.364 mmol) in 1 mL of N,N-dimethylformamide is heated at 100°C for 1 h. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 96 mg (65%) of yellow solid mp 278-280 DC; HRMS (ESI) m/z calcd for C22H22N4O4 407.17139, found 407.17128 (M+Hf \ Analysis for C22H22N4O4. Calcd: C, 63.60; H, 5.58; N, 13.49, Found: C, 63.67; H, 5.98; N, 13.20. (Formula Removed) Example 52 (4Z)-4-{[(3-AiTiinobenzyl>amino]methylene3-6-bromoisoquinoline-1,3(2H,4H)-dione A mixture of 6^brorno-4-methoxymethylene-4H-isoquirioline-1,3-dione (141 mg, 0.5 mmol), 4-(4-methy^iperazin-1-yl)-phenylamine (61.1 mg, 0.5 mmol) in 1 ml_ of N.N-dimethylformamide is stirred at room temperature for 40 min. After cooling in the refrigerator, the precipitate is collected, and washed with ether to give 61 mg (33%) of yellow solid mp 214-215 °C; HRMS (ESI) m/z calcd for C17H14BrN302 370.01966, found 370.01900 (M+H)+1, Analysis for C17H14BrN302 (0.33 H20); Calcd: C, 53.98; H. 3.91; N. 11.11; Found: C, 54.07; H. 3.52; N, 10.91. (Formula Removed) Example 53 (4Z)^-Bromo-4^[(4H3hlororjenzy1)amino)methylene}isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 46, 300 mg of brown solid (72 % yield) is obtained from 300 mg (1.06 mmol) of (4E)-6,7- dimethoxy-4-(methoxymethylene)is6quinoline-1,3(2H,4H)-dione and 4-chloro- benzyiamine (150.10 mg, 1.06 mmol); mp 234-235°C, MS (ESI) m/z 391.65 (M+1). (Formula Removed) Example 54 2-(Acetyloxy)-4-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- ylidene)methyQ-amino}methyl)phenyl acetate Using the procedure described for the preparation of 2-(acetyloxy>-4-({[(Z)- (1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}-methyl)phenyl acetate, 0.21 g (86.4 % yield) of yellow solid is obtained from 0.2 g (0.51 mmol) of (4Z)^-bromo-4^(3,4-dihydroxybenzyl)-afrtno]-rnethylene)isoquinoline-1,3(2H,4H)- dione (3b) and 0.91 mL (1.28 mmol) of acetyl chloride: mp 239-240°C, MS (ESI) m/z 473.1 and 475.2 (M+H)*1, Analysis for C21H17BrN2O6. (0.67 HzO + 0.3 EtOAc), Calcd: C, 52.30; H, 3.91; N, 5.44, Found: C, 52.12; H, 4.11; N, 5.44. (Formula Removed) Example 55 (4Z)-6^Chloro-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}rnethylene)isoquinoline- 1,3(2H,4H>-dione Using the procedure described for the preparation of (4Z)-6-bromo-4-({[4- (pyrrolidin-1-ylrnethyl)phenyl]amino}rriethylene)isoquinoline-1,3(2H,4H)-dione, 0.165 g (66.0 % yield) of yellow solid is obtained from 0.15 g (0.63 mmol) of (4E)-6- chloro-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 0.145 g (0.756 mmol) of 4-piperidin-1-ylmethyl-phenylamine: mp 225-226°C, MS (ESI) m/z 396.1 (M+H)*1, Analysis for C22H22ClN3O2 . (0.167 N,N-dimethylformamide (DMF) + 0.167 H20), Calcd: C, 65.74; H, 5.76; N, 10.79, Found: C, 65.76; H, 5.78; N, 10.34. (Formula Removed) Example 56 4-({[(Z)-(6-Bromo-1,3-dioxo-2,3-didroisoquinolin-4(1 H)- yiidene)methyl]amino)methyl)benzenesulfonamide Using the procedure described for the preparation of example 46,180 mg of green solid (39 % yield) is obtained from 300 mg (1.06 mmol) of (4E)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4- aminornetheyl-benzenesulfonamde (197.5 mg. 1.06 mmol); mp 273-274°C, MS (ESI) m/z 434.29.65 (M+1). (Formula Removed) Example 57 5-({[(ZH6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4( 1H)- ylidene)methylJamino}methyl)-2-methoxyphenyl acetate Using the procedure described for the preparation of 2-(acetyloxy)-4-(fJ(Z)- (1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}-methyl)phenyl acetate, 0.132 g (70.2 % yield) of tan solid is obtained from 0.17 g (0.42 mmol) of (4Z)-6-bromo-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}lsoquinoline- 1,3(2H,4H)-dione and 0.75 mL (1.05 mmol) of acetyl chloride: mp 226-227 and . 246-247°C, MS (ESI) m/z 445.0 and 446.9 (M+H)*1, Analysis for C20H17BrN205. (0.8 H20), Calcd: C, 51.86; H, 3.64; N. 5.99. Found: C. 52.26; H. 4.08; N. 6.09. (Formula Removed) Example 58 5-{[(2)-(6-Bromo-1I3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}-2- hydroxybenzoic acid Using the procedure described for the preparation of (4Z)-6-bromo-4- {[(pyridin-3-ylmethyl)amino]methylene}isoquinoline-1.3(2H,4H)-dione, 1.46 g (68.2 % yield) of tan solid is obtained from 0.15 g (0.53 mmol) of (4E)-6-bromo-4- (methoxy-methylene)isoquinoline-1,3(2H,4H)-dione and 0.0814 g (0.53 mmol) of 5- aminosalicylic acid heating at 120°C: mp 336-337°C; 1H NMR (DMSO-d6) 5 12.57 (d. J - 12 Hz. 1H), 11.37 (s, 1H), 8.88 (d. J = 12 Hz. 1H), 8.43 (s. 1H). 7.89 (m, 3H), 7.39 (d. J = 9 Hz. 1H), 7.05 (d. J = 6 Hz, 1H); MS (ESI) m/z401.0 (M-H)Analysis for C22H22BrN3O2 . (0.75 HzO). Calcd: C, 49.00; H, 3.02; N. 6.72, Found: C. 48.72; H. 2.77; N. 6.60. (Formula Removed) Example 59 (4Z)-6-Bromo-4-({[4-(pyrrolidin-1-ylmethyt)phenyl]amino}methylene)isoquinoline- 1,3(2H.4H)-dione To a solution of (4E)-6-bromo-4-(methoxymethylene)isoquinolihe- 1,3(2H,4H)-dione, (0.15 g, 0.53 mmol) in N,N-dimethylformamide is added 4- (pyrrolidinyl-methyl)aniline (0.10 mL, 0.58 mmol). The reaction mixture is heated at 120°C under N2. Reaction is monitored by mass spectroscopy. After reaction is completed after 1.5 h. After evaporating the solvent, warm ethyl acetate is added to the residue to generate reddish orange residue. It is filtered through a pad of celite to give a yellow solution, which upon addition of hexane generated 0.24 g (62.8 % yield) of orange solid: mp 165-166°C. Analysis for C21H2oBrN302, Calcd: C, 59.17; H. 4.73; N, 9.86, Found: C, 58.77; H, 4.42; N, 9.81. (Formula Removed) Example 60 (4Z)-4-({[4-(4-Methylpiperazin-1 -yl)phenyl]amino}methylene)-6-(1 H-pyrrol-1 - yl)isoquinoline-1,3(2H,4H)-dione A mixture of 4-methoxymethylene-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione, (100 mg, 0.3727 mmol), 4-(4-methyl-piperazin-1-yl)-phenylamine (71.3 mg, 0.3727 mmol) in 1 mL of N.N-dimethylformamide is heated at 100°C for 0.5 h. After the solvent is evaporated, ether is added to the residue. The precipitate is collected, and washed with ether to give 122 mg (77%) of light brown solid mp 239-240 °C; HRMS (ESI) m/z calcd for C25H25N5O2 428.20811, found 428.20865 (M+H)+1, Analysis for C25H25N502 (0.6 H20), Calcd: C, 68.51; H, 6.02; N. 15.98, Found: C, 68.67; H, 5.85; N, 15.62. (Formula Removed) Example 61 (4Z)-4-{[(4-Hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-d!one Using the procedure described for the preparation of example 46, 200 mg of red-brown solid (46 % yield) is obtained from 300 mg (1.48 mmol) of (4E)-4- (methoxymethylene)isoquinoline-l ,3(2H,4H)-dione and 4-hydroxy-benzylamine (235.0 mg, 1.48 mmol), mp 272-273°C, MS (ESI) m/z 294.31 (M-1). (Formula Removed) Example 62 (4Z)-6-Bromo-4-{[(4-hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-dione Using the procedure described for the preparation of example 46, 250 mg of red-brown solid (63 % yield) is obtained from 300 mg (1.06 mmol) of (4E)-6.7- dimethoxy-4-(methoxymethylene)feoquinoline-1,3(2H,4f/)-dione and 4-hydroxy- benzylamine (169.73 mg, 1.06 mmol); mp 296-297°C; MS (ESI) m/z 373.21 (M+1). (Formula Removed) Example 63 (4Z)-4-{[(3-Hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-dione Using the procedure described for the preparation of example 46, 200 mg reddish-brown solid (46 % yield) is obtained from 300 mg (1.48 mmol) of (4E)-4- (methoxymethylene)isoquinoline-l ,3(2H,4H)-dione and 3-hydroxy-benzyiamine (235.0 mg, 1.48 mmol), mp 261-262°C, MS (ESI) m/z 294.31 (M-1). (Formula Removed) Example 64 (4Z)-6-Bromo-4-{[(3,5-dihydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H- dione Using the procedure described for the preparation of example 46, 250 mg of brown solid (56 % yield) is obtained from 322.9 mg (1.15 mmol) of (4E)-6,7- dlmethoxy-4-(methoxyrnetbylene)isoquinoline-1,3(2H,4H)-dione and 3,5-dihydroxy- benzylamine (201 mg, 1.15 mmol), mp 318-319°C, MS (ESI) m/z 389.21 (M+1). (Formula Removed) Example 65 (4Z)-N,N-Dimethyl-4-({[4-(4-rnethylpipera2in-1-yl)phenyl]amino}rnethylene)-1l3- dioxo-1,2,3,4-tetrahydroisoquinoline-6-carboxamide Prepared from a slurry of 81.7 mg (0.298 mmol) of 4-methoxymethylene- 1,3-dioxo-1,2,3,4-tetrahydro-isoquinoline-6-carboxylicacid dimethylamide and 56.9 mg (0.298 mmol) of 4-(4-methylpipera23'n-1-yl)methyl-phenylamine in 1.5 ml_ of N,N-dimethylformamide (DMF) at 100°C under N2as described for example 21. After heating for 0.5 h. the reaction is chilled in ice. The solid product is collected, washed with N,N-dimethylformamide (DMF) and Et20 and dried to give 111 mg (86%) of yellow crystals: mp > 300°C; 1H NMR (DMSO-d6) 5 12.55 (d, 1H, J = 12.8 Hz), 11.25 (s, 1H), 8.88 (d, 1H, J = 12.8 Hz), 8.14 (s. 1H). 8.03 (d, 1H, J = 8.07 Hz), 7.46 (d, 2H. J = 8.94), 7.16 (d, 1H, J = 8.07 Hz), 6.98 (d, 2H, J = 8.94 Hz), 3.14 (m, 4H), 3.04 (s, 3H), 2.90 (s. 3H), 2.46 (m, 4H), 2.22 (s, 3H); HRMS (ESI) m/e calcd for C24H27N503 432.20411, found 432.20337 (M+H)*1, Analysis for C24H27N503, Calcd: C, 66.50; H, 6.28; N, 16.16, Found: C, 66.33; H, 6.43; N, 16.28. (Formula Removed) Example 66 (4Z)-N,N-Dimethyl-1,3-dioxo-4-({[4-(piperidinylmethyl)phenyl]amino}methylene)- 1,2,3,4-tetrahydroisoquinoline-6-carboxamide Prepared from a solution of 70 mg (0.255 mmol) of 4-methoxymethylene- 1,3-dioxo-1,2,3,4-tetrahydro-isoquinoline-6-carboxyIic acid dimethylamide and 48.5 mg (0.255 mmol) of 4-piperidin-1 -ylmethyl-phenylamine in 1.6 mL of N,N- dimethylformamide (DMF) at 110°C under N2 as described for example 21. After heating for 0.25h, the reaction is chilled in ice. The solid product is collected, washed with N.N-dimethylformamide (DMF) and Et20 and dried to give 82.4 mg (74%) of bright yellow crystals: mp 266-267°C (dec); 1H NMR (DMSO-d6)5 12.45 (d, 1H, J = 9 Hz), 11.40 (s, 1H), 8.95 (d, 1H, J = 9 Hz), 8.17 (s, 1H), 8.06 (d, 1H, J = 6 Hz), 7.53 (d, 2H, J = 9 Hz), 7.32 (d, 2H, J = 9 Hz), 7.20 (d, 1H, J = 6 Hz), 3.42 (s, 2H), 3.04 (s. 3H), 2.90 (s, 3H), 2.32 (s, 4H), 1.48 (m, 4H), 1.38 (s. 2H); HRMS (ESI) m/z calcd for C25H28N403 431.20886. fond 431.20820 (M-H)"1. Analysis for C25H28N4O3.0.25 H20: Calcd: C, 68.70; H, 6.59; N. 12.82. Found: C, 68.73; H, 6.38rN. 13.08. (Formula Removed) Example 67 (4Z)-6-Chloro-4-(3-hydroxy-4-methoxybenzyl)amino]rnethylene}isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-bromo-4-{[(4- hydroxy-3-methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione, 0.182 g (80.2 % yield) of tan solid is obtained from 0.15 g (0.63 mmol) of (4E)-6-chloro-4- (methoxymethylene)-isoquinoline-1,3(2H,4H)-dione and 0.114 g (0.756 mmol) of 3- hydroxyl-4-methoxyl-benzylamine hydrochloride, and 0.264 mL (1.89 mmol) of triethylamine: mp 265-266°C; MS (ESI) m/z 357.5 (M-H)1 Analysis for C18H15CIN204 . (0.8 HzO) Calcd:: C, 57.93; H, 4.48; N, 7.51 Found: C, 57.56; H, 4.06; N, 7.45 (Formula Removed) Example 68 (4Z)-6-Fluoro-4-{{(3-hydroxy-4-methoxybenzyJ)amino)methylene}isoquinoline- 1,3(2H.4H-dione Using the procedure described for the preparation of example 46, 340 mg of light-brown solid (94 % yield) is obtained from 300 mg (1.06 mmol) of (4E)-6- fluoro-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride, (201.2 mg, 1.06 mmol); mp 200-201 °C MS (ESI) m/z 342.33 (M+1). (Formula Removed) Example 69 Acetic acid 3-acetoxy-5-{[(6-bromo-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4- ylidenernethyl)-amino]-methyl}-phenyl ester An amount of 100mg (0.26 mmol) of (4Z)-6-bromo-4-{[(3t5- dihydroxybenzyl)amino)methylene}isoquinoline-1,3(2H4H-dione is dissolved in N.N-dimethylformamide (5 mL), and pyridin (5 mL), and acetic anhydride (5 mL) is subsequently added. The mixture is allowed to stir at room temperature for 1 h, then 10 mL of water is added and stirring continued with white precipitate formed. The precipitate is filtered to give 120 mg of the title compound as a white-brown solid (98 %) yield; mp 257-258°C MS (ESI) m/z 471.1 (M-1) (Formula Removed) Example 70 (4Z)-6-Fluoro-4-({[4-(4-methylPiperzir^1-yl)phenylJamino}methylene)isoquirioline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 280 mg (81 % yield) of green-yellow solid is obtained from 200 mg (0.91 mmol) of (4E)-6- fluoro-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-(4- methylpiperazin-1-yl)-phenylarnine(172.95mg, 0.91 mmol); mp 242-243 °C. MS (ESI) m/z 380 (M+1). (Formula Removed) Example 71 (4Z)-6-Fluoro-4-{[(3-hydroxy-4-methoxybenzyl)amino)methylene}-6-(1H-pyrrol-1- yl)isoquinoline-1,3(2H,4H-dione Using the procedure described for the preparation of example 46, 90 mg of light-brown solid (66 % yield) is obtained from 100 mg (0.038 mmol) of (4EH- (methoxymethylene)-6-(1H-pyrrol-1-yl)isoqutnoline-1,3(2H,4H)-dione and 3- hydroxy-4-methoxy-benzylamine (60 mg, 0.35 mmol; mp 252-253°C MS (ESI) m/z 389.41 (M+1). (Formula Removed) Example 72 (4Z)-4-({[4-Pyrro!(din-1-ylmethyl)phenyl3amtno)methylene))-6-(1H-pyrrol-1- yl)isoquinoline-1,3(2H ,4H)-dione Using the procedure described for the preparation of example 14, 80 mg (51 % yield) of yellow solid is obtained from 100 mg (0.38 mmol) of (4E)-4- (methoxyme1hylene)-^(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione of and 4- pyrroiidin-1-ylmetrtyl)-phenylamine (65.70 mg, 0.38 mmol); mp 2002-203 °C. MS (ESI) m/z 412.49 (M+1). (Formula Removed) Example 73 (4Z)-6-Bromo-4-(((4-{l(4- [(dimethylamino)methyl)methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H- dione Using the procedure described for the preparation of example 14, 200 mg (47 % yield) of a yellow solid is obtained from 300 mg (1.063 mmol) (4E)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4- dimethylamino-methyl-phenylamine (144.7 mg, 1.063 mmol); mp 159-160°C. MS (ES|) m/z 400.27 (M+1). (Formula Removed) Example 74 (4Z)-4-({[4-Piperidin-1-ylmethyl)phenyl]amino}methylene)}-6-(1H-pyrrol-1- yl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 50 mg (31 % yield) of yellow solid is obtained from 100 mg (0.38 mmol) of (4E)-4- (methoxymethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione of and 4- piperidin-1-ylmethyl)-phenylamine, preparation similar to 4-Mopholin-4-ylmethyl- phenylamine (70.70 mg, 0.38 mmol).; mp 207-208°C. MS (ESI) m/z 426.21 (M+1). (Formula Removed) Example 75 (4Z)-6-Bromo-4-{I(4-{(4-hydroxypiperidin-1 - yl)methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione Using the procedure described for the preparation of example 14, 250 mg (51 % yield ) of a yellow solid is obtained from 300 mg (1.063 mmol) of (4E)-6.7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-4- hydroxypiperidin-methyl-phenytamine (144.7 mg, 1.063 mmol) (prepared similarly as 4-Mopholin-4-ylmethyl-phenylamfne, mp 249-250°C. MS (ESI) m/z 456.34 (M+1). (Formula Removed) Example 76 Carbonic acid 5-{[(6-bromo-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4- ylidenemethyl)-aminoJ-methyl}-2-methoxycarbonyloxy-phenyl ester methyl ester An amount (4Z)-6-bromo-4-{[(3,4- dihydroxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (0.15 g, 0.385 mmol) is stirred in 2 mL of pyndine and cooled to 0°C, followed by a slow addition of 0.124 mL (1.156 mmol) of dimethyl pyrocarbonate. The reaction mixture is stirred under N2 at 0°C for 15 min and then allowed to warm up to room temperature and continued to stir for 2,5 h. Mass spectroscopy suggested the reaction is completed. The reaction mixture is evaporated to dryness, and the residue is recrystallized from ethyl acetate/Hexane to afford 0.162 g (83.1 % yield) of light yellow solid: mp 239-240°C; MS (ESI) m/z 473.1 and 475.2 (M+Hf1 Analysis for C21H17BrN208. (0.33 H20) Calcd: C, 49.33; H, 3.48; N, 5.48 Found: C, 49.09; H, 3.11; N. 5.5 (Formula Removed) Example 77 5-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- ylidene)methyl]amino)methyl)-2,3-dimethoxyphenyl acetate Using the procedure described for the preparation of example 69, 160 mg (99 % yield) of white-brown solid is obtained from 150 mg (0.34 mmol) of example 78 is used and; mp 244~245°C MS (ESI) m/z 475.30 (M+1). (Formula Removed) Example 78 (4Z)-6-Bromo-4-{[(34iydroxy-4,5-dimenthoxybenzyl)amino)methylene}isoquinoline- 1,3(2H,4H-dione Using the procedure described for the preparation of example 46, 400 mg of brown solid (65 % yield) is obtained from 400 mg (1.42 mmol) of (4E)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2W,4W)-dione and 3-hydroxy~4,5- dimethoxybenzylamine (272 mg, 1.15 mmol), (preparation similar to (4E)-6,7- dirnethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride, except methoxy amine hydrogen chloride is used instead of hydroxylamine hydrogen chloride ); mp 262-263°C. MS (ESI) m/z 433.26 (M-1). (Formula Removed) Example 79 (4Z)-6-Bromc-4-{[(3,4,5-trihydroxybenzyl)amino)rnethylene}isoquinoline-1,3(2H,4H- dione Using the procedure described for the preparation of example 46, 300 mg of green solid (70 % yield) is obtained from 300 mg (1.06 mmol) of (4E)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3,4,5- trihydroxybenzylamine 203.68 mg (1.06 mmol), (prepared similarly to (4E)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride, except methoxy amine hydrogen chloride is used instead of hydroxylamine hydrogen chloride); mp 244-245°C. MS (ESI) m/z undetectable. (Formula Removed) Example 80 (4Z)-6-lodo-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}isoquinoIine- 1,3(2H,4H)-dione(5c) Using the procedure described for the preparation of (4Z)-6-bromo-4-{[(4- hydroxy-3-methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione, 0.28 g (68.3 % yield) of tan solid is obtained from 0.3 g (0.91 mmol) of (4E)-6-iodo-4- (methoxymethylene)-isoquinoline-1,3(2H,4H)-dione and 0.19 g (1.00 mmol) of 3- hydroxyl-4-methoxyl-benzylarnine hydrochloride, and 0.14 mL (1.37 mmol) of triethylamine: mp 209-210°C; MS (ESI) m/z 449.0 (M-HV1 Analysis for C18H15IN204 Calcd: C, 48.02; H, 3.36; N, 6.22 Found: C, 47.65; H, 3.12; N, 6.03 (Formula Removed) Example 81 (4Z)-6-lodo-4-({[4-4-rnethylpiperazin-1-yl)phenyl]amino}rnethylene)isoquinoline- 1,3(2H,4H)-dione (11 c) To a solution of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)- dione (0.15 g, 0.61 mmol) in 2 mL of rV,Af-dimethylformamrde is added benzenamine, 4-(4-methyl-1-piperazinyl) (0.096 g, 0.67 mmol). The reaction mixture is heated at 120°C under Na for 2 h. The reaction mixture is concentrated under high-pressure vacuum, then treated with MeOH to give tan precipitate. It is filtered and washed successivly with MeOH, Et20 and hexane to afford 0.202 g (91.0 % yield) as brown solid: mp 220-221 °C; MS (ESI) m/z 489.1 (M+H)*1 Analysis for C21H21IN402 . (0.33 HjO) Calcd: C, 51.02; H, 4.42; N, 11.33 Found: C, 50.65; H. 4.07; N, 11.02 (Formula Removed) Example 82 (42)-6-lodo-4-({[4-(piperidln-1-ylmethyl)phenyr|amino}methylene)isoquinoline- 1.3(2H,4H)-dione(11a) To a solution of 0.2 g (0.60 mmol) of (4E)-6-iodo-4- (methoxymethylene)isoquinoline-1,3(2H,4H)-dione in 2 mL of N,N- dimethylformamide is added 4-piperidin-1-ylmethyl-phenylamine (0.127 mL, 0.67 mmol). The reaction mixture is heated at 120°C under N2 for 1.5 h. After coofing, ethyl ether is added and left in refrigerator overnight to give dark brown crystal. The crystal is collected and dissolved in 4 mL of dimethyl sulfoxide, followed by addition of 6 mL of 65% MeOH/H20 solution to give a precipitate. The solid is collected and washed thoroughly with water, MeOH, Et20 and hexane, and air- dried to give 0.143 g (48.3 % yield) of tan solid: mp 202-203°C, MS (ESI) m/z 488.1 (M+H)*1 Analysis for C22H22IN3O2 Calcd: C, 54.22; H, 4.55; N. 8.62 Found: C, 53.82; H, 4.57; N. 8:50 (Formula Removed) Example 83 5-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- ylidene)methyl]amino}methyl)-2-methoxyphenyl methyl carbonate (8b) Using the procedure described for the preparation of carbonic acid 5-fJ(6- bromo-1,3-dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-2- methoxycarbonyloxy-phenyl ester methyl ester, 0.083 g (70.2 % yield) of brown solid is obtained from 0.10 g (0.25 mmol) of (4Z)-6-brbmo-4-{[(3-hydroxy-4- methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione and 0.04 mL (0.30 mmol) of dimethyl pyrocarbonate: mp 186-187°C; MS (ESI) m/z 445.0 and 446.9 (M+H)*1 Analysis for C2oH17BrN206 Calcd: C. 52.08; H, 3.71; N, 6.07 Found: C, 51.74; H, 3.65; N, 6.0 (Formula Removed) Example 84 (4Z)-5-Bromo-4[(3-hydroxy-4-methoxybenzyl)amino]rnethylene}isoquinoline-1, 3(2H. 4H)-dione A solution of 88.5 mg (0.468 mmol) of 3-hydroxy-4-methoxy-benzylamine hydrogen chloride in 1.8 mL of N,N-dimethylformamide(DMF) at RT under N2 is treated with 94.5 mg (0.936 mmol) of Et-N. (4E)-5-bromo-4- (methoxymethylene)isoquinoline-1.3(2H,4H)-dione (132 mg, 0.468 mmol) is added and the mixture is stirred for 3.5 h. Water is added and the product is collected, washed with HzO and EtzO and dried to give 163 mg (86%) of pale yellow amorphous solid: mp 204-206°C; 1H NMR (DMSO-d6) 5 11.11 (s, 1H). 10.56 (m, 1H), 9.08 (s, 1H), 8.93 (d. 1H, J= 13.6 Hz). 8.05 (d. 1H, J = 6.9 Hz), 7.87 (d, 1H, J = 6.9 Hz), 7.09 (m. 1H), 6.91 (d, 1H, J = 8.07 Hz), 6.78 (m, 2H), 4.49 (d, 2H, J = 5.37 Hz), 3.75 (s, 3H); HRMS (ESI) m/z calcd for C18H15BrN2O4 403.02880, found 403.02840 (M+H)+1. Analysis for C18H15bRN2 .1.25 H20: Calcd: C, 50.77; H.4.15; N, 6.59. Found: C, 51.14; H, 4.08; N, 6.64. (Formula Removed) Example 85 (4Z)-4-{[(3-Hydroxy-4,5-dimethoxybenzyl)amino)methylene}-6-thien-3- ylisoquinoline-1,3(2H,4H-dione Using the procedure described for the preparation of example 46,140 mg of brown solid (60 % yield) is obtained from 150 mg (0.53 mmol) of 4- methoxymethylene-6-thiophin-3-yl-isoquinilin-(4H)-1,3-dione and 3-hydroxy-4,5- dimethoxybenzylamine 115 mg (0.53 mmol), (prepared similarly to (4E)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride, except methoxy amine hydrogen chloride is used instead of hydroxylamine hygrogen chloride); mp 255-256°C MS (ESI) m/z 436.49 (M-1). (Formula Removed) Example 86 (4Z)-4-{[(3-Hydroxy-4,5-dimethoxybenzyl)amino)nnethylene}-6-phenylisoquinoline- 1,3(2H,4H-dfone Using the procedure described for the preparation of example 46, 50 mg of orange solid (40 % yield) is obtained from 80 mg (0.29 mmol) of 4- methoxymethylene-6-phenyl-3-yl-isoquinilin-(-4H)-1,3-dione and 3-hydroxy-4,5- dimethoxybenzylamine 115 mg (0.29 mmol), (prepared similarly to (4E)-6,7- dimethoxy-4-(methoxymethytene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride, except methoxy amine hydrogen chloride is used instead of hydroxylamine hydrogen chloride); mp 250-251CC MS (ESI) m/z. 430.46 (M-1). (Formula Removed) Example 87 (4Z)--(3-Furyl)-4-(3-hydroxy-,5-dimethoxybenzyl)amtno)rnethylene}isoquInoline- 1,3(2H,4H-dione Using the procedure described for the preparation of example 46. 120 mg of brown solid (50%) yield is obtained from 150 mg (0.57 mmol) of (4E)-6-(3- furyl)methoxymethylene-isoquinoline-1,3(2H,4H-dione, (prepared similarly to 4- methoxymethylene-6-thiophin-3-yl-isoquinifin-(4H)-1,3-dione) and 3-hydroxy-4,5- dimethoxybenzylamine (115 mg, 0.57 mmol). (prepared similarly to (4E)-6,7- dimethoxy-4-(methoxymethytene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride, except methoxy amine hydrogen chloride is used instead of hydroxylamine hydrogen chloride); mp 263-264°C. MS (ESI) m/z 420.43 (M-1). (Formula Removed) Example 88 (42)--{[(3-Hydroxy-4-rnethoxybenzyl)arnino]rnethyleneJ-6-thien-3-ylisoquinoline- 1,3(2H,4H)-dbne(5b) Using the procedure described for the preparation of (4Z)-6-bromo-4-{[(4- hydroxy-3-methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione, 0.18 g (85.7 % yield) of tan solid is obtained from 0.15. g (0.53 mmol) {4EM- (methoxymethylene)-6-(1H-thiophin-3-yl)isoquinoline-1,3(2H,4H)-dione and 0.11 g (0.62 mmol) of 3-hydroxyl-4-methoxyl-benzylamine hydrochloride, and 0.08 mL (0.8 mmol) of triethylamine: mp 219-220°C, MS (ESI) m/z 407.1 (M+H)+1 Analysis for C22H18N2O2S. (0.8 HzO) Calcd: C, 64.06; H, 4.56; N. 6.79 Found: C, 63.75; H, 4.34; N, 6.90 (Formula Removed) Example 89 (42)-6-lodo-4-{[(3-hydroxy-4,5-dimethoxybeN2yl)amino)methylene}isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 46,110 mg of brown solid (50%) yield is obtained from 150 mg (0.46 mmol) of (4E)-6-iodo-4- (methoxymethylene)isoquinoline-1,3(2H,4H)-dlone and 3-bydroxy-4,5- dimethoxybenzylamine 101 mg (0.46 mmol), (prepared similarly to (4E)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride, except methoxy amine hydrogen chloride is used instead of hydroxylamine hydrogen chloride); mp 265-266°C MS (ESI) m/z 480.30 (M+1). (Formula Removed) Example 90 4-[(3-Hydroxy-4-methoxy-beN2ylamino)-methylene]-6-methoxy-4H-isoquino!ine-1,3- dione A mixture of 5-aminomethyt-2-methoxy-phenol hydrochloride (145 mg, 0.50 mmole), 4 mL of N,N-dimethylformamide and triethylamine (75 DL, 0.54 mmole) is stirred for 15 minutes. Then (4E)- 6-methoxy-4-methoxymethylene-4H- isoquinoline-1,3-dione (117 mg, 0.50 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is diluted with ether, filtered washed with water, washed with ether and dried to give an light beige solid, 161 mg, (91%), mp 240-2°C dec; MS (ESI): m/z 355.2 (M - H). (Formula Removed) Example 91 6-Methoxy-4-[(4-piperidin-1-ylmethyl-phenylamino)-methylene]-4H-isoquinoline-1,3- dione A mixture of (4E)- 6-methoxy-4-methoxymethylene-4H-isoquinoline-1,3- dione (117 mg, 0.50 mmole), N.N-dimethylformamide (1 mL) and 4-piperidin-1- ylmethyl-phenylamine (95 mg, 0.50 mmole) is stirred and heated at 110°C for one hour, cooled in the refrigerator overnight. The reaction mixture is evaporated to dryness, taken up in 7.5% methanol in chloroform and passed through a short pad of Florisil eluting with 7.5% methanol chloroform. The eluate is evaporated in vacuo, treated with acetonitrile, filter and dried to give a yellow solid 152 mg (78%). mp 272-5 °C dec; MS (ESI): rn/z 392.4 (M + H). (Formula Removed) Example 92 (4Z)-6-(3-Furyl)-4-{[(3-hydro)cy--methoxybenzyl)amino)methylene}isoquinoline- 1,3(2H,4H-dione Using the procedure described for the preparation of example 46, 150 mg of brown solid (65 % yield) is obtained from 160 mg (0.59 mmol) of (4E)-6-(3- fury|)methoxymethylene-isoquinolSne-1,3(2H,4H-dione and 3-hydroxy-4- methoxybenzylamine (94.63 mg, 0.59 mmol), (prepared similarly to (4E)-6,7- dimethoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4- methoxy-benzylamine hydrogen chloride); mp 254-255°C Example 93 MS (ESI) m/z 390.40 (M-1). (Formula Removed) (4Z)--3-Furyl)--({[4-piperidin-1-ylmethyl)phenyl}amino}rnethylene)}isoquinoline- 1,3(2H.4H)-dtone Using the procedure described for the preparation of example 14, 50 mg (32 %) yield of a yellow solid is obtained from 100 mg (0.37 mmol) of (4E)-6-(3- furyl)methoxymethylene}isoqutnoline-1,3(2H,4H-dione and 4-piperidin-1 -ylmethyl)- phenylamine (70.53 mg, 0.37 mmol), (prepared simtlariy to 4~mopholin-4-ylmethyl- phenylamine), mp 204-205°C. MS (ESI)m/z427.50 (M+1). (Formula Removed) Example 94 (4Z)-Brornc»-4-(3,5-dibromo-4-ydroxybenEyridene-soquinoline-1,3(2Hr4H)-dione Example 95 6-Bromo-4H-isoquino)ine-1,3-dione (0.12 g, 0.5 mmol), 3,5-dibromo-4- hydroxybenzaldehyde (0.14 g, 0.5 mmol). and piperidine (0.075 mL. 0.75 mmol) were dissolved in i-propanol (2 mL). After heating at 95°C for 3 h, it is cooled, and the solid is filtered and washed with I-propanol, ether and hexane to yield 0.25 g (99.6%)solid; mp 167-168 °C; HRMS (ESI) m/z499.8 (M-H) (Formula Removed) Example 95 (4Z)-6-Phenyl-4-({[4-piperidin-1-ylmethyl)prienyf|amino}methylene)}isoquinoline- 1,3(2H,4H)-dione: A mixture of 300 mg (0.68 mmol) of (4Z)-6-bromo-4-({[4-(Piperidin-1- ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dioneI Pd(PPh3)4 (118.0 mg, 0.102 mmol), saturated aqueous sodium carbonate (2 mL), and phenyl boronic acid (123.42 mg, 1.02 mmol) is placed In a three neck flask. Under N2, N.N- dimethylformamide (8 mL) is added, and the mixture is then placed in a pre-heated oil bath at 120°C for 45 mirt. After cooling, the mixture is treated with CH2CIZ and filtered through celite. After evaporating all the solvents, the residue is dissloved in methylene chloride, washed three times with soduim bicarconate solution, dried over magnissium sulfate and evaporated. The yellow oily residue is purified by preparative thin layer chromatography (5:95 = methanol: methylene chloride), to give a yellow solid 90 mg (30 % yield); mp 214-215 °C. MS (ESI) m/z 437.54 (M+1). Formula Removed) Example 96 (4Z)-6-(3-Hydroxyphenyl)-4-({[4-piperidin-1 - ylmethyl)phenyl]amino}methylene)}isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 95,120 mg (39 %) of yellow solid is obtained from. 300 mg (0.68 mmol) of (42>6-bromo-4-({[4- (piperidin-1 -ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione and 3- (4,4,5,5-teramethyl-[1,3,2]dioxaboralan-2-yl)-phenol (300 mg, 1.36 mmol); mp 235-236°C MS (ESI) m/z 453.54 (M+1). Formula Removed) Example 97 3-[(4Z)-1,3-Dioxo-4-({[4-piperidin-1 -ylmethyl)phenyI]amino}methylene)-1,2,3,4- tetrahydroisoquinoline-6-yl]thiophene-2-carbaldehyde Using the procedure described for the preparation of example 95, 100 mg (31 %) of yellow solid is obtained from 300 mg (0.68 mmol) of (42)-6-bromo-4-({[4- (piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione and 2- formyl-3-thienylboronic acid (213.48 mg. 1.36 mmol); mp 224-225°C MS (ESI) m/z 471.58 (M+1). (Formula Reoved) Example 98 (4Z)-4-{[(3-Hydroxy-4-methoxybenzyl)amino]methylene}isoquinpline-1,3(2H,4H)- dione (3d) Using the procedure described for the preparation of (4Z)-6-bromo-4-{[(4- hydroxy-3-methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione, 0.25 g (78 % yield) of off-white solid is obtained from 0.2 g (0.98 mmol) of (4E)-4- (methoxymethylene)-isoquinoline-1,3(2H,4H)-dione and 0.2 g (1.08 mmol) of 4- methoxyl-3-hydroxyl-benzylamine hydrochloride, and 0.3 mL (2.94 mmol) of triethytamine: mp 192-193°C; 'H NMR (DMSO-d6) 5 10.97 (s, 1H), 10.60 (m, 1H), 9.04 (s, 1H), 8.62 (d, J = 9 Hz, 1H), 7.98 (d, J = 6 Hz, 1H), 7.83 (d, J = 6 Hz, 1H). 7.55 (t, J = 6 Hz, 1H), 7.17 (t, J = 6 Hz, 1H), 6.91 (d, J = 6 Hz, 1H), 6.78 (m, 2H), 4.55 (d, J = 4.5 Hz, 2H), 3.75 (s, 3H); MS (ESI) m/z 325.1 (M+H)*1. Analysis for C18H17N204 . (0.25 H26) Calcd: C, 65.75; H, 5.06; N, 8.52 Found: C, 65.70; H, 5.02; N, 8.54 (Formula Removed) Example-99 5-({[(Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- ylidene)methyrjamino}methyl)-2-methoxyphenyl diethylcarbamate To a solution of (42)-6-iodo-4-{I(3-hydroxy-4- methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (0.30 g, 0.67 mmol) in 3 mL of N, N-dimethylformamide and 2 mL of pyridine is added diethylcarbamylchloride (0.10 mL, 0.80 mmol) and 0.21 mL (2.00 mmol) of triethylamrne. The reaction mixture is stirred at 80°C for 4 h and then at room temperature over weekend under N2. Mass spectroscopy suggested the completion of reaction. The reaction mixture is concentrated, and 2 mL of MeOH is added to break up the solid, followed by addition of excess amount of Et20. The precipitate is filtered, washed successively with water, methanol, ether and hexane, and dried in oven (60°C) overnight to afford 0.207 g (56.6 % yield) of tan solid: mp 128-130°C; MS (ESI) m/z 548.2 (M-H)"1 Analysis for C23H24lN3O5 Calcd: C, 50.29; H, 4.40; N, 7.65 Found: C, 49.89; H, 4.17; N, 7.49 (Formula Removed) Example 100 (4Z)-6-(4-Phenoxyphenyl)-4-{[(3-hydroxy-4,5- dimethoxybenzyl)amino]methylene}lsoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 95, 250 mg (70 %) of green solid is obtained from 300 mg (0.68 mmol) of example 78 and 4- phenoxyphenyl boronic acid (216.56 mg, 1.38 mmol); mp 240-241°C MS (ESI) m/z 522.18 (M-1). (Formula Removed) Example 101 (4Z)-6-(4-Phenoxyphenyl)-4-({[4-piperidin-1 - ylmethyl)phenyl]amino}methylene)}isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 95, 70 mg (19 %) of yellow solid is obtained from 300 mg (0.68 mmol) of (42)-6-bromo-4-({[4- (pip«ridin-1-ylmethyl)phenyQamino}methytene)isoquinoline-1 „3(2H,4H)-dione and 4- phenoxyphenyl boronic acid (291.1 mg, 1.36 mmol).; mp 132-133°C MS (ESI) m/z 529.64 (M+1). (Formula Removed) Example 102 (4Z)-4-({[4-Piperidin-1-ylmethyl)phenyl]arnino}rnethylene)-6-pyridin-3-ylisoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 95, 100 mg (34 %) of yellow solid is obtained from 300 mg (0.68 mmol) of (4Z)-6-bromo-4-({[4- (piperidin-1-ylmethyl)pheny0amino}methylene)isoquinoline-1,3(2H,4H)-dione and 3- pyridylboronic acid (166.21 mg, 1.36 mmol); mp 247-248°C. MS (ESI) m/z 438.53 (M+1). (Formula Removed) Example 103 (4Z)-6-(4-Hydroxyphenyl)-4-({[4-piperidin-1- ylmethyl)phenyl]amino}methylene)}isoquinoline-1(3(2H,4H)-dJone Using the procedure described for the preparation of example 95, 120 mg (39 % yield) of yellow solid is recovered is obtained from 300 mg (0.68 mmol) of (4Z)-6-bromo-4-({[4-(piperidin-1-ylmethyl)pheny0amino}mettiylene)isoquinoline- 1,3(2H,4H)-dione and 4-(4,4,5,5-teramethyl-[1,3,2]dioxaboralan-2-yl)-phenol (300 mg, 1.36 mmol); mp 244-245°C. MS (ESI) m/z 453.54 (M+1). (Formula Removed) Example 104 (4Z)-4-({[4-(Piperidin-1-ylmethyl)phenyl]amJno}methylene)-6-thien-3-ylisoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-4-({[4-(4- methylpiperazin-1-yl)pheny0amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)- dione, 0.041 g (13.7 % yield) of yellow solid is obtained from 0.3 g (0.68 mmol) of (4Z)-6-bromo)-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione, 0.13 g (1.0 mmol) of 3-thiopheneboronic acid, 0.06 g (0.068 mmol) of tris(dibenzyldenea-acetone)-dipalladium(0), 0.04 g (0.136 mmol) of 2-(di- t-butyl-phosphino)-biphenyl, 0.144 g (1.36 mmol) of sodium carbonate and 4 mL of 80 % N,N-dimethylformamide (DMF)/HzO solution: mp 166-167°C, MS (ESI) m/z — (M+H)+1 Analysis for C26H25N3O2S . (0.33 H20) Calcd: C, 69.46; H, 5.75; N, 9.35 Found: C, 79.49; H, 5.75; N, 9.11 (Formula Removed) Example 105 (4Z)-6-Bromo-4-{[4-(2-morpholin--ylethyl)piperazin-1-ylJrnethylene}isoquinoline- 1,3(2H,4H)-dione A mixture of 6-bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (200 mg, 0.709 mmol), 2-morpholinytethylpiperazine (141.3 mg, 0.709 mmol) in 1 mL of N.N-dimethylformamide is stirred at room temperature for 15 min. After cooling in the refrigerator, the precipitate is collected, and washed with N,N- dimethytfbrmamide (DMF) and ether to give 64 mg (20%) of yellow solid mp 156- 156.5 °C; HRMS (ESI) m/z 449 (M+H)+1. (Formula Removed) Example 106 (4Z)-6-Bromo--({4-{2-(dimethylamino)-)ethyl3piperazin-1-yl}methylene)isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 105, the title compound is obtained from (4E)-6-bromo-4-(methoxy-methylene)isoquinoline- 1,3(2H,4H)-dione (282 mg, 1 mmol), 2-dimethylaminoethylpiperazine (162 mg, 1 mmol), and N,N-dimethylformamide(DMF) (1.5 mL) in 54% yield as a yellow solid: mp 166-167 °C; MS (ESI) m/z 431.1, 407.1 (M+H)+1 (Formula Removed) Example 107 (4Z)-4-({[4-(4-Methylpiperazin-1-yl)phenyl]amino}rnethylene)-6-thien-3- ylisoquinoline-1,3(2H ,4H}-dione A mixture of example 27 (1.0 g. 2.26 mmol), 0.43 g (3.4 mmol) of 3- thiopheneboronic acid, 0.2 g (0.226 mmol) of tris(dibenzyldenea-acetone)- dipalladium(O), 0.126 g (0.45 mmol) of 2-(di-t-butyl-phosphino)-biphenyl. and 0.5 g (4.52 mmo!) of sodium carbonate In 10 mL of N, N-dimethylformamide and 2 mL of water is added to a 50 mL round bottom flask, sealed with a rubber septum. It is degassed and flushed wrth nitrogen gas three times. The reaction mixture is stirred vigorously at 120°C in an oil bath under nitrogen. Mass spectroscopy suggested the completion of reaction after 1.5 h. The reaction mixture is evaporated under high-pressure vacuum to give a brown residue. It is dissolved in chloroform, filtered through a pad of celite to give a reddish brown solution. It is concentrated and re-dissolved in 10 mL of chloroform and filtered through a pad of florisil, followed by washing 5% MeOH/CHCI3 solution to give a dark orange solution. The organic solution is concentrated to give orange residue. Addition of methanol to the solid gave a yellow predpttate, which is collected and washed successively with an excess amount of methanol, ether and hexane to yield 0.38 g (38 % yield) of yellow solid: mp 224-226°C; MS (ESI) m/z 445.2 (M+H)+1 Analysis for C25H24N4O2S . (0.25 H20 + 0.25 N.N-dimethyiformamide (DMF)) Calcd: C, 66.18; H, 5.66; N, 12.74 Found: C, 65.56; H, 5.37; N, 12.23 (Formula Removed) Example 108 (4Z)-4-({[4-(4-Methylpiperazin-1-yl)phenyl]amino}methylene)-6-thlen-3- ylisoquinoline-1,3(2H,4H)-dione A mixture of example 27, (1.0 g, 2.26 mmol), 0.43 g (3.4 mmol) of 3- thiopheneboronlc acid, 0.2 g (0.226 mmol) of tris(dibenzyldenea-acetone)- dipalladium(O), 0.126 g (0.45 mmol) of 2-(di-t-butyl-phosphino)-biphenyl. and 0.5 g (4.52 mmol) of sodium carbonate in 10 mL of N, N-dimethylformamide and 2 ml_ of water is added to a 50 mL round bottom flask, sealed with a rubber septum. It is degassed and flushed with nitrogen gas three times. The reaction mixture is stirred vigorously at 120°C in an oil bath under nitrogen. Mass spectroscopy suggested the completion of reaction after 1.5 h. The reaction mixture is evaporated under high-pressure vacuum to give a brown residue. It is dissolved in chloroform, filtered through a pad of celite to give a reddish brown solution. It is concentrated and re-dissolved in 10 mL of chloroform and filtered through a pad of florisil, followed by washing 5% MeOH/CHCI3 solution to give a dark orange solution. The organic solution is concentrated to give orange residue. Addition of methanol to the solid gave a yellow precipitate, which is collected and washed successively with an excess amount of methanol, ether and hexane to yield 0.38 g (38 % yield) of yellow solid: mp 224-226°C; MS (ESI) m/z 445.2 (M+H)*1 Analysis for C2SH24N4O2S . (0.25 HzO + 0.25 N.N-dimethylformamide (DMF)) Calcd: C. 66.18; H, 5.66; N, 12.74 Found: C, 65.56; H, 5.37; N, 12.23 (Formula Removed) Example 109 (4Z)-4-{[(l,3-BeN2odioxol-5-ylmethyl)amino]methylene}-6-bromoi5oquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-bromo-4-{l(4- hydroxy-3-methoxybenzyl)aminoJmethylene}isoquinoline-1,3(2H,4H)-dione, 0.0.196 g (92.0 % yield) of white solid is obtained from 0.15 g (0.53 mmol) of 4-bromo-2- (carboxymethyl)benzoic acid and 0.08 mL (0.636 mmol) of 1,3-Benzodioxole-5- methanamine: mp 227-228°C; MS (ESI) m/z 400.9 (M+H)+1 Analysis for C18H13BrN204 Calcd: C, 53.89; H, 3.27; N, 6.98 Found: C, 53.71; H, 3.28; N, 6.97 (Formula Removed) Example 110 (4Z)-1, 3-Dioxo-4-({[4-(pipen\iiiv1-ylmethyl)pheny0amino}rnethy1ene)1, 2, 3, 4- tetrahydroisoquinoline-6-carbonitrile A mixture of 1.00 g (2.27 mmol) of 4Z)--brorno-4-({[4-(piperidin-1- ylmethyl)phenyl]amino}methylene)isoquinoHne-1,3(2H,4H)-dione, 239 mg (2.05 mmol) of Zn(CN)2 and 394 mg (0.341 mmol) of (PPh3)4Pd in 17 mL of IM.N- dimethylformamide(DMF) under N2 is heated at 100°C in the dark for 1.75h.The reaction is then poured into 40 mL of ice water and the product is collected, washed with H20 and Et20 and dried. The crude product is boiled with 10% MeOH in CHCI3 and filtered. The filtrate is washed with 2 M NH4OH and brine, dried and evaporated. The residue is washed with boiling CH3CN and the insoluble material is dried to yield 200 mg (23%) of yellow-orange crystals: mp 254-256°C (dec); 'H NMR (DMSO-cfe) 5 12.46 (d, 1H, J= 9 Hz), 11.58 (s, 1H), 9.01 (d, 1H, J = 9 Hz), 8.76 (s. 1H), 8.13 (d. 1H. J = 6 Hz), 7.60 (m, 3H), 7.35 (d, 2H, J = 6 Hz), 3.43 (s. 2H). 2.33 (s, 4H), 1.49 (m, 4H), 1.39 (m, 2H); HRMS (ESI) m/e calcd for C23H22N4O2.18156, found 387.18121 (M+H)+1. Analysis for C23H22N4O2.0.25 CHCI3: Calcd: C, 67.07; H, 5.40; N, 13.46. Found: C, 65.63; H, 5.05; N, 13.87. (Formula Removed) Example 111 (4Z)-6-(4-Chlorophenyl)-4-({[4-(piperidin-1 - ylmethyl)phenyl]amino}metfiylene)isoquinoiine-1,3(2H,4H)-dione Using the procedure described for the preparation of example 95, 250 mg (79 %) of yellow solid is obtained from 300 mg (0.68 mmol) of (4Z)-6-bromo-4-({[4- (piperidin-1 -ylmethyl)phenyrjamino}methylene)isoquinoline-1,3(2H,4H)-dione and 4- chloro phenyl boronic acid (214.0 mg, 1.36mmol); mp 204-205°C. Example 112 MS (ESI) m/z 464:90 (M+1). (Formula Removed) Example 112 (4Z)-6-[(1E)-5-Chloropent-1-enyO-4-({[4-(piperidin-1- ylmethyl)phenylJamino}methylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 95,100 mg (32 %) of yellow solid is obtained from 300 mg (0.68 mmol) of (4Z)-6-bromo-4-({[4- (piperidin-1-ylmethyl)phenyL]amino}methylene)isoquinoline-1,3(2H,4H)-dioneand (1E)-5-chloropent-1-enylboronlcacid (202.04 mg, 1.36 mmol); mp 268-269°C. MS (ESI) m/z 464.0 (M+1). (Formula Removed) Example 113 (4Z)-6-(4-Chlorophenyl)-4-{[(3-hydroxy-4,5- dimethoxybenzyl)amino]methylene}isoquinoline-1I3(2H,4H)-dione Using the procedure described for the preparation of example 95, 250 mg (79 %) of green solid is obtained from 300 mg (0.68 mmol) of example 78 ((4Z)-6- brorno-4-{[(3-hydroxy--4)-5-dimethoxybenzyl)amino)methylene}isoquinoline- 1,3(2H,4H-dione) and 4-chlorophenyl boronfc acid (216.56 mg, 1.38 mmol); mp 240-241°C. MS (ESI) m/z 464.11 (M-1). (Formula Removed) Example 114 (4Z)-6-(4-methoxyphenyl)-4-({t4-(4-methylpiperazin-1-yl)phenyl]amino}methylenB)- isoquinollne-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-4-({[4-(4- methyJpiperazirv1-yl)phenyt]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)- dione, 0.11 g (37.1 % yield) of brown solid is obtained from 0.3 g (0.68 mmol) of (4Z)-6-bromo-4-({[4-(4-rnethylplpera2in-1-yl)phenylJamino}-rnethylene)-isoquinoline- 1,3(2H,4H)-dione, 0.155 g (1.02 mrnol) of 4-methoxyphenylboronic acid, 0.0623 g (0.068 mmol) of tris(dibenzyldeneaacetone)-dipalladlum(0), 0.041 g (0.136 mmol) of 2-(di-t-butyl-phosphino)-biphenyl, 0.144 g (1.36 mmol) of sodium carbonate and 5 mL of 80 % N.N-dimethylformamide (DMF)/H20 solution: mp 224-225°C, MS (ESI) m/z 469.3 (M+H)+1 Analysis for C28H28N4O3 . (0.67 HzO) Calcd: C, 69.98; H, 6.15; N, 11.66 Found: C, 69.75; H. 5.97; N, 11.31 (Formula Removed) Example 115 4-[(4Z)-4-({[4-(4-Methylpiperazin-1 -yl)phenyl]amino}methylene)-1,3-dioxo-1,2,3,4- tetra-hydroisoquinolin-6-yl]benzaldehyde Using the procedure described for the preparation of (4Z)-4-({[4-(4- nTethylpiperazin-1-yl)phenyl]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)- dione, 0.054 g (10.2 % yield) of yellow solid is obtained from 0.5 g (1.13 mmol) of (4Z)-6-brc)-mcM-({[4-(4-methylpipera2in-1-y1)phenyl}amino)-nriethylene)-isoqulnoline- 1,3(2H,4H)-dione, 0.25 g (1.7 mmol) of 4-fonmylphenylboronic acid, 0.10 g (0.113 mmol) of tris(dibenzyldenea-acetone)-dipalladium(0), 0.067 g (0.226 mmol) of 2-(di- t-butyl-phosphino)-biphenyl, 0.24 g (2.26 mmol) of sodium carbonate and 6 mL of 80 % N.N-dimethytformamide (DMF)/HzO solution: mp 152-153°C, MS (ESI) m/z 467.2 (M+H)+1 Analysis for C28H26N4O3 . (0.67 H20) Calcd: C. 70.28; H, 5.76; N, 11.71 Found: C. 70.09; H, 5.62; N. 12.10 (Formula Removed) Example 116 (4Z)-6-(4-Methoxy phenyl )-4-({[4-(pip©ridin-1-ylmethyl)phenyriamino}metriyiene)- isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-4-({[4-(4- methylpiperazin-1-yl)phenylJamino}methylene)-6-thien-3-ylisoquinoline-1.3(2H,4H)- dione, 0.12 g (22.6 % yield) of yellow solid Is obtained from 0.5 g (1.136 mmol) of (4Z)-6-bromc-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}rnethylene)isoquinoline- 1,3(2H,4H)-dione, 0.26 g (1.7 mmol) of 4-methoxyphenylboronic acid, 0.10 g (0.14 mmol) of tris(dibenzyldenea-acetone)-dipalladium(0), 0.068 g (0.28 mmol) of 2-(di- t-butyl-phosphino)-biphenyl, 0.25 g (2.27 mmol) of sodium carbonate and 6 mL of 80 % N.N-dimethylformamlde (DMFyH20 solution: mp 168-169°C, MS (ESI) m/z 468.2 (M+H)+1 Analysis for C29H28N3O3 . (1.2 HzO) Calcd: C, 71.20; H. 6.47; N, 8.59 Found: C. 70.81; H, 6.06; N, 8.52 (Formula Removed) Example 117 (4Z)-6-(3-Methoxyphenyl)-4-({[4-(piperidin-1-ylmethyl)phenyrjamino}methylene)- isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-4-({[4-(4- methylpiperazin-1-yl)phenyrjamino}methytene)-6-thien-3-ylisoquinoline-1,3(2H,4H)- dione, 0.096 g (18.1 % yield) of yellow solid is obtained from 0.5 g (1.136 mmol) of (4Z)--brorno-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}methytene)isoquinoline- 1,3(2H,4H)-dione (14), 0.26 g (1.7 mmol) of 3-methoxyphenylboronic acid, 0.10 g (0.14 mmol) of tris(dibenzyldenea-acetone)-dipalladium(0), 0.068 g (0.28 mmol) of 2-(di-t-butyl-phosphino)-biphenyl, 0.25 g (2.27 mmol) of sodium carbonate and 6 mL of 80 % N,N-dimethylformamide (DMF)/H2O solution: mp 169-170°C, MS (ESI) m/z 468.3 (M+H)+1 Analysis for C29H29N3O3 . (0.2 HzO) Calcd: C, 73.78; H, 6.30; N, 8.90 Found: C, 73.62; H, 6.33; N, 8.55 (Formula Removed) Example 118 (4Z)-6-Piperidin-1 -yl-4-({[4-(piperidin-1 - ylmethyl)phenyl]amino}methylene)isoquinollne-1,3(2H,4H)-dione A mixture of 300 mg (0.68 mmol) of (4Z)-6-bromo-4-({f4-(Piperidin-1- ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3) (118.30 mg, 0.129 mmol), 1,3-bis(2,6-di-isopropylphenyl)irnidazolium chloride (Ipr.HCI) 78.04 (0.184 mmol), potassium f-butoxide, (194.41 mg,-1.36 mmol), and piperidine (200 mg, 2.04 mmol) is placed in a three neck flask. Under N2 .N.N-dirnethylformamide (8 ML) is added, and the mixture is then stirred in a pre-heated oil bath 100°C for 45 min. After cooling, the mixture is treated with CH2CI2 and filtered through celite. After evaporating all the solvents, the residue is dissolved in methylene chloride, washed three times with soduim bicarconate solution, dried over magnissium sulfate and evaporated. The yellow oily residue is purified by preparative thin layer chromatography (5:95 = methanol: methylene chloride), to give a yellow solid 80 mg (25 % yield); mp 211 -212 °C MS (ESI) m/z464.0 (M+1). (Formula Removed) Example 119 (4Z)-6-Piperidin-1-yl-4-({I4-(methylPiperzln-1- yl)phenyl]amino)methylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 118, 70 mg (23 % yield) of yellow solid is obtained from 300 mg (0.68 mmol) of 4Z)-6-bromo-4- ({[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1.3(2H,4H)-dione and piperidine (200 mg, 2.04 mmol); mp 223-224°C. MS (ESI) m/z 445.56 (M+1). (Formula Removed) Example 120 (4Z)-6-Mon)-holin-4-yl-4-({I4-(piperidin-1- ylmethyl)phenyljamino}methylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 118, 95 mg (31 % yield) of yellow solid is obtained from 30O mg (0.68 mmol) of 4Z)-6-bromo-4- ({r4-(piperidin-1-ylmetfiyl)phenyl]amino}methylene)isoquinoline-1.3(2H,4H)-dione and morphline (178 mg, 2.04 mmol); mp 216-217*0. MS (ESI) m/z 446.55 (M+1). (Formula Removed) Example 121 (4Z)-6-{(2R)-2-(Methoxymethyl)pyrrolidin-1 -y0-4-({[4-(piperidin-1 - ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 118, 120 mg (37 % yield) of yellow solid is obtained from 300 mg (0.68 mmol) of 4Z)-6-bromo-4- ({[4-(piperidin-1-ylmethyl)phenyl]amino}methytene)isoquinoline-1,3(2H,4H)-dione and (2R)-2-methoxymethy-pyrrlidine 234.95 mg (2.04 mmol); mp 135-136°C. MS (ESI) m/z 474.60 (M+1). (Formula Removed) Example 122 (4Z)-4-fJ(4-Amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 46,200 mg of yellow-brown solid (60% yield) is obtained from 250 mg (0.76 mmol) of 6-iodo-4- methoxmethylene-isoquinoline-4H-1,3-dione and 2-amino-5-(amlnomethyl)phenol (160.43 mg, 0.76 mmol); mp 250-251 °C. MS (ESI) m/z 435.22 (M+1). (Formula Removed) Example 123 (4Z)-6-[(4-Methyl-piperizin-1 -yl]-4-((J4-(piperidin-1 - ylmethyl)phenyl]amino}nnethylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 118, 90 mg (29 % yield) of yellow solid is obtained from 300 mg (0.68 mmol) of 4Z)-6-bromo-4- ({[4-(piperidin-1-ylmethyl)phenylJamino}methylene)isoquinoline-1,3(2H,4H)-dione and 4-methyl-piperazine 204.41 mg (2.04 mmol); mpl92-193°C. MS (ESI) m/z 459.59 (M+1). (Formula Removed) Example 124 5-[(4Z)-4-({[4-(4-Methylpiperazin-1-yl)phenyOamino}methylene)-1,3-dioxo-l ,2,3,4- tetradydroisoquinonlin-6-yl]-2-furaldehyde Using the procedure described for the preparation of (42)-4-({[4-(4- methylpiperazin-1-yl)phenylJarnlno}rnethylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)- dione, 0.36 g (36 % yield) of yellow solid is obtained from 1.00 g (2.27 mmol) of (4Z)-6-bromo-4-({[4-(4-methylpiperazirM-yl)phen- 1,3(2H,4H)-diorie, 0138 g (2.72 mmol) of 2-formylfuran-5-boronic acid, 0.20 g (0.227 mmol) of tris(dibenzyldenea-acetone}-dipalladium(0), 0.135 g (0.534" mmol) of 2-(di-t-butyl-phosphino)-biphenyl, 0.5 g (5.34 mmol) of sodium carbonate and 6 ml of 80 % N,N-dimethylformamide (DMF)/H20 solution: mp 218-220°C, MS (ESI) m/z 457.2 (M+H)+1 Analysis for C26H24N404 . (0.57 H20) Calcd: C, 66.90; H, 5.43; N. 12.00 Found: C, 66.86; H, 5.38; N, 12.13 (Formula Removed) Example 125 6-(4-Piperidin-1-ylmethyl-phenyl)-4-[(4-piperidin-1-ylmethyl-phenylamino)-methylene]-4 isoquinoline-1,3-dione A solution of (4Z)-6-bromo-4-({[4-(piperidin-1- ylmethyl)phenyl]amino}methyIene)lsoquinoline-1,3(2H,4H)-dione (14) (0.40 g, 0.90 mmol) in 5 mL of N,AT-dimethylformamide is added to 1-(4-tributylstannanyl- benzyl)-pipei1dine (0.60 g. 1.35 mmol) and 0.03 g (0.045 mmol) of dichlorobis(triphenylphosphirte)-pal!adiurn(ll). The flask is sealed with a rubber septum, degassed and flushed with nitrogen gas three times. The reaction mixture is heated at 110°C under N2. Mass spectroscopy suggested the completion of reaction after 2 h. The reaction mixture is concentrated to give dark brown residue. Purification is performed by florisil chromatography using 10% MeOH/CHCI3 solution as eluting solvent to generate 0.045 g (9.87 % yield) of yellow solid: mp 159-160°C; MS (ESI) m/z 455.2 (M+H)+1 Analysis for C34H38HN4O2C Calcd: C, 50.29; H, 4.40; N, 7.65 Found: C, 49.89; H, 4.17; N, 7.49 (Formula Removed) Example 126 4Z)-6-lodo-4-({[4-(pyrrolidin-1 -ylmethyi) phenyl}amino)methylene] isoquinolin- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 200 mg (56 % yield) of yellow solid is obtained from 250 mg (0.76 mmol) of 6-iodo-4- methoxmethylene-isoquinoline-4H-1,3-dione and 4-pyrrolidin-1 -ylmethyl- phenylamine 133.96 mg (0.76 mmol), (prepared similarly to 4-mopholin-4-ylmethyl- phenylamine); mp 186-187°C. MS (ESI) m/z 473.31 (M+1). (Formula Removed) Example 127 (4Z)-6-(4-Fluorophenyl)-4-({[4-(pyrrolidin~1- ylmethyl)phenyl]amino}methylene)isoquirtoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 95, 80 mg (27 %) of yellow solid is obtained from 300 mg (0.68 mmol) of example 126 and 4- fluorophenyl boronic acid (214.0 mg, 1.36mmol); mp 152-153 °C. MS (ESI) m/z 443.51 (M+1). (Formula Removed) (4Z)-6-Anilino-4-({l4-(piperidin-1 - ylmethyl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 118, the title compound is obtained as yellow solid (70 % yield) from 6-bromo-4-[(4-piperidin-1- ylmethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione and aniline. MS (ESI)m/z 453.22 (M+1). (Formula Removed) Example 129 (4Z)-6-Bromo-4-[(1H-indol--ylmethyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione General procedure 1: An amount of 200 mg (1.30 mmol) of C-(1H-lndol-6- yl)-methylamine, is dissolved in N,N-dimethylformamide (.10 mL). 0.542 mL (3.9 mmol) of triethylamine is added followed by 366 mg (1.30 mmol) of (4E)-6-bromo- 4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione. After the mixture is stirred at room temperature for 30 min, water (2 mL) is added and the reaction mixture is stirred for 60 min. The precipitate is filtered and washed several times with anhydrous ether. The crude material is purified by high performance liquid chromatography to give 45 mg of a pink solid. MS (ESI) m/z 396.1 (M+1). According to general procedure 1, an amount of 100 mg (0.35 mmol) of C- (1H-lndol-4-yl)-methylamine, is dissolved in N,N-dimethylformamide (5 ML). 106 u/ (1.05 mmol) of triethylamine is added followed by 52 mg (0.35 mmol) of (4E)-6- bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione. After the mixture is stirred at room temperature for 30 min, water (2 mL) is added and the reaction mixture is stirred for 60 min. The precipitate is filtered and washed several times with anhydrous ether to give a red solid. The crude solid is then purified by high performance liquid chromatography to give 7 mg of a pink solid. MS (ESI) m/z 396.2 (M+1). (Formula Removed) Example 130 (4Z)-6-Bromo-4-{[(3-hydroxy-4-propoxybenzyl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione According to the general procedure of example 129, an amount of 100 mg (0.55 mmol) of 5-(aminomethyl)-2-propoxypheno! is dissolved in N.N-dimethylformamide (5 ML). 228 µl(1.65 mmol) of triethylamine is added followed by 171 mg (0.607 mmol) of (4E)-6-bromo-4-(methoxymethylene) ispquinoline- 1,3(2H»4H)-dione. After the mixture is stirred at room temperature for 30 min, water (3 mL) is added and the reaction mixture is stirred for 3 hours. The precipitate is filtered and washed several times with anhydrous ether. The crude solid is then purified by high performance liquid chromatography to give 67 mg of a white solid. MS (ESI) m/z 430.8 (M+1). (Formula Removed) Example 131 (3Z)-3-(1-{I4-(4-Methylpiperazin-1-yl)phenyfjamino}ethylidene)piDeridine-2,6-dione Following the procedure of Kato and Noda (Chem. Pharm. Bull. Jpn 22, 12, 2947-2952, 1974), to a 0.6 M solution of sodium ethoxide (50 mL, 30 mmol) is added acetoacetamide (3.5 g, 35 mmol). followed by ethyl acrylate (3.2 mL 30 mmol). After 10 minutes of stirring at room temperature an additional volume of ethanol (40 mL) is added. The reaction mixture'is stirred at room temperature for one week, then neutralized to pH 7 by the addition of 10 % aqueous hydrochloric acid solution. The quenched mixture is then concentrated under reduced pressure to give a white suspension. The suspension is partitioned between ethyl acetate and water. The aqueous phase is extracted 3x with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, decanted, and concentrated under reduced pressure to give a dark oil (1.0 g), which is purified by flash chromatography (50 % ethyl acetate/hexanes) to give (3Z)-3-(1-hydroxyethylidene)-piperidine-2,6-dione as white powder. To a suspension of 4-(4-methyl-1-piperazinyl)-benzenamine (43 mg, 0.23 mmol) and (3Z)-3-(1-hydroxyethylidene)-piperidine-2,6-dione (35 mg, 0.23 mmol) in absolute ethanol (1.5 mL) is added concentrated ethanolic hydrogen chloride (2 drops), which caused the precipitation of a white solid. The mixture is heated in a 65 °C oil bath for 20 minutes. Then N.N-dirnethylforrnamide (0.4 mL) is added to the mixture and the temperature of the oil bath is increased to 70 CC. An additional volume of N,N-dimethylformamide (0.6 mL) is added and the temperature of the oil bath is increased to 135 °C, at which setting it stirred for 30 minutes. The mixture is stirred overnight at 130 °C. After cooling to room temperature, the semi-solid reaction mixture is triturated with methanol. The solid that formed is collected by filtration and washed with diethyl ether, water, and methanol to give (3Z)-3-(i-{[4- (4-methylpiperazin-1-yl)phenyl]amino}ethylidene)piperidine-2,6-dione as a light beige solid. (Formula Removed) Example 134 (4Z)-4-{[(4-Amino-3-hydroxybenzyl)amino]methylene}-6-(4 fluorophenyl)tsoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 95,80 mg of brown solid (39 % yield) is obtained from 200 mg (0.52 mmol) (4Z)-4-{[(4-amino-3- hydroxyDenzyl)amino]methylene}-6-bronr)-oisoquinoline-1,3(2H,4H)-dione and 4- Flurophenyl boronic acid 215.57 mg. (1.55 mmol).; mp 227-228°C. MS (ESI) m/z 404.3 (M+1)+ (Formula Removed) Example 135 (4Z)-7-Bromo-4-[(3-hydroxy--methoxybenzyl)arnlno]methylene}isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 46, 150 mg (52 %) yield of a brown solid is obtained from 200 mg (0.71 mmol) of (4E)-7-bromo- 4-(methoxymethylene)isoquinoline-1,3(2H,-4H)-dione and 3-hydroxy-4-methoxy- benzylarnine); mp 297-298°C. MS (ESI) m/z 403.13 (M+1). (Formula Removed) Example 136 (4Z)-4-([(3-Hydroxy-4-methoxybenzyl)amino]methylene}-6-(1H-pyrazol-4- yl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 95, 200 mg of green solid (82 % yield) is obtained from 250 mg (0.62 mmol) (4Z)-6-bromo-4-{[(3- hydroxy-4~methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione and 4- (4,45,5-tetramethyl-1,2-dioxaborolan-2-yl)-1H-pyTazol, 361.26 mg (1.86 mmol).; mp 252-253°C MS (ESI) m/z 390.3 (M+1) (Formula Removed) Example 137 (4Z)-6-Bromo-4-{[(3-hydroxy-4-isopropoxybenzyl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione To a solution of (4Z)-6-bromo-4-{[(3,4-dihydroxybenzyl)- amino]methylene}isoquinoline-1,3(2H,4H)-dione (0.74 g, 1.9 mmol) in 5 mL of A/,Af- dimethylformamide is added 2-iodopropane (0.19 mL, 1.9 mmol) and 0.52 g (3.8 mmol) of potassium carbonate. The reaction mixture is heated at 70°C under N2. Mass spectroscopy indicated the completion of reaction after 3.5 h. The reaction mixture is filtered through a pad of celite, and water is added to give a precipitate. It is filtered and washed successively with MeOH, Et20 and hexane, dried in oven (60°C) overnight to afford 0.58 g (70.7 % yield) of tan solid: rnp 212-213°C; MS (ESI) m/z 431.2 and 433.2 (M+H)+1 Analysis for C2oH19BrN2O4 . (1.6 HzO) Calcd: C. 52.21; H. 4.86; N, 6.09 (Formula Removed) Example 138 Found: C, 51.86; H, 4.42; N. 6.21 (4Z)-6-lodo-4-[({4-[(2-methylpyrrolidin-1- yl)methyl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione To a solution of 0.2g (0.61 mmol) of (4E)-6-iodo-4-(methoxymethylene)- isoquinoline-1,3(2H,4H)-dione in 2 mL of N, N-dimethylformamide is added {4-[(2- methylpyrrolidin-1-yl)methyl]phenyl}amine (0.14 mL, 0.73 mmol). The reaction mixture is heated at 100°C under N2. Mass spectroscopy suggested the completion of reaction after 45 min. The reaction mixture is concentrated under high-pressure vacuum. Purification is performed by silica gel chromatography using 5% MeOH/CHCI3 as solvent. Concentrating the organic layer containing product afforded 0.043 g (14.5 % yield) of yellow solid: mp 157-158°C; MS (ESI) m/z 488.4 (M+H)+1 Analysis for C22H22IN3O2 Calcd: C. 54.22; H, 4.55; N, 8.62 Found:: C, 53.55; H, 4.63; N, 8.33 (Formula Removed) Example 139 (4Z)-6-Bromo-4-({[3-hydroxy-4-(2- hydroxyethoxy)benzyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-Bromo-4-{[(3- hydroxy-4-isopropoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione, 0.41 g (73.7 % yield) of tan solid is obtained from 0.5 g (1.29mmol) of (4Z)-6-bromo-4- {[(3,4-dihydroxybenzyi)amino]methylene}isoquinoline-1,3(2H,4H)-dione, 0.10 mL (1.29 mmol) of 2-iodoethanol, and 0.36 g (2.58 mmol) of potassium carbonate: mp 166-167°C; MS (ESI) m/z 431.1 and 433.0 (M+H)+1 Analysis for C18H15BrN204 . (0.5 H20) Calcd: C, 51.60; H, 4.10; N, 6.33 Found: C, 51.58; H.4.11; N, 6.30 (Formula Removed) Example 140 (3Z)-3-(1-[(3-hydroxy-4-methoxybenzyl)aminoJethylidene}-4-phenylpiperidine-2,6- dione Following the procedure of Kato and Noda (Chern. Pharm. Bull. Jpn 22, 12, 2947-2952, 1974), to a 0.6 M solution of sodium ethoxide (50 mL, 30 mmol) is added acetoacetamide (3.5 g, 35 mmol), followed by methyl cinnamate (4.9 mL, 30 mmol). After 10 minutes of stirring at room temperature an additional volume of ethanol (40 mL) is added. The reaction mixture is stirred at room temperature for three weeks, then neutralized to pH 7 by the addition of 10 % aqueous hydrochloric acid solution. The quenched mixture is then concentrated under reduced pressure to give a white suspension. The suspension is partitioned between ethyl acetate and water. The aqueous phase is extracted thrice with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, decanted, and concentrated under reduced pressure to give a white suspension, which is triturated with hot ethanol and then cooled in freezer. The white solid is collected by Buchner filtration, washed with ethanol, and dried under vacuum to give (3Z)-3-(1-hydroxyethylidene)-4- phenylpiperidine-2,6-dione as white powder (1.2 g, 17 %). To a suspension of (3Z)-3-(1-hydroxyethylidene)-4-phenylpiperidine-2,6- dione (0.12 g, 0.52 mmol) and 5-(aminomethyl)-2-methoxyphenol (98 mg, 0.52 mmol) in absolute ethanol (5 mL) is added sodium acetate (0.75 mmol). The mixture is heated at reflux overnight and then allowed to cool to room temperature. The solvent is evaporated under reduced pressure and the residue is triturated with diethyl ether. The solid is collected, washed with diethyl ether, water, and methanol, and dried under vacuum to give (3Z)-3-{1-[(3-hydroxy-4- methoxybenzyl)amino]ethylidene}-4-phenylpiperidine-2,6-dione as a white powder (0.17 g, 88%). MS (ES+): 367.4 (M+H)+ (Formula Removed) Example 141 2-(Acetylamino)-5-({[(ZM6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- *ylidene)methyrjamino}methyl)phenyl acetate Using the procedure described for the preparation of example 69, 450mg (99 % yield) of brown solid is obtained from 500 mg (1.29 mmol) of (4Z)-4-{[(4- amino-3-hydroxybenzyl)aminoJmethylene}-6-bromoisoquinoline- 1,3(2H,4H)-dione, and acetic anhydride 529.42mg(5.16mmol); mp 264-265°C MS (ESI) m/z472.1 (M-N). (Formula Removed) Example 142 N-[4-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- 'ylidene)methyl]amino}methyl)-2-hydroxyprienyl]acetamide An amount of 200 mg (0.74 mmol) of 2-(acetylamino)-5-({[(Z)-(6-broiTio-1,3- dioxo-2,3-dihydroisoquinolin-4(1 H)-,ylidene)methyl]amino}methyl)phenyl acetate is stirred in A/,A/-dimethylformamide followed by addition of potassium carbonate 176.7 mg (1.27 mmol). The reaction mixture is stirred at room temperature for 3 hours, and then neutralized with 1N solution of hydrogen chloride to PH 7. The precipitate is filtered and washed with water and ether to give a brown solid (150 mg, 83 %); mp: 252-253 MS(ESI)m/z:428(M-1) (Formula Removed) Example 143 (4Z)-6-Bromo-4-({[3-hydroxy-4-(2-pyrrolidin-1-ylethoxy)benzyl]amino)rnethylene) isoquinoline-1,3(2H,4H)-dione - An amount of 33.5 mg (0.142 mmol) of 5-Aminomethyl-2-(2-pyrrolidin-1-yl- ethoxy)-phenol, is dissolved in N.N-dimethylformamide (2 ML). 30 pi (0.213 mmol) of triethylamine is added followed by 20 mg (0.071 mmol) of (4E)-6-bromo-4- (methoxymethylene)isoquinoline-l ,3(2H,4H)-dione. After the mixture is stirred at room temperature for 30 min, water (2 mL) is added and the reaction mixture is stirred for 60 min. The precipitate is filtered and washed several times with anhydrous ether. The crude solid is then purified by high performance liquid chromatography to give 23 mg of a yellow solid. MS (ESI) m/z. 486.3 (M+1). (Formula Removed) Example 144 6-Bromo-4-[(4-plperidin-1-ylmethyl-phenyl)-hydrazono]-4H-isoquinoline-1,3-dione Hydrochloride A solution of 4-piperidin-1-ylmethyl-phenylamrne (0.110 g, 0.580 mmol) in 1.12 mL of cone HCL is chilled in an ice-salt bath and treated with 100 u.L (0.040 g, 0.580 mmol) of 40% aq NaNC)-2 for a few minutes. In a separate flask, a solution of 0.127 g (0.530 mmol) of the homophthalimide in 3 mL of N,N-dimethylformamide (DMF) is chilled to 20°C. The diazonium salt solution is then added and the mixture is stirred at 25°C for 6 hr. The reaction is filtered and the insoluble material is washed with a small amount of N,N-dimethylformamide (DMF). The remaining precipitate is dissolved in 90% EtOH and filtered. This solution is evaporated and the residue is slurried in a few mL of 90% EtOH. Filtration, washing the solid twice with small volumes of 90% EtOH and drying in vacuo gave 0.212 g (76%) of yellow solid: mp 298-299°C (dec); 1H NMR (DMSO-d6) 5 11.95 (s, 1H), 10.39 (s. 1H), 8.34 (s, 1H), 7.96 (d, 1H. J= 2.4 Hz), 7.69 (m, 3H). 4.25 (d, 2H, J = 4.77 Hz), 3.34 (s, 1H), 2.83 (s(br), 2H), 1.77 (m, 5H), 1.21 (s(br), 1H); HRMS (ESI) m/z calcd for C21H21BrN4O2 441.09207, found 441.09244 (M+H)+1. Analysis for C21H21BrN402 . HCI. HzO: Calcd: C. 51.24; H, 4.84; N, 11.38. Found: C, 51.37; H, 4.87; N, 11.31. (Formula Removed) Example 145 N-[4-({I(Z)-(1.3-Dioxo-6-thien-3-yl-2,3-dihydroisoquinolin-4( 1H)- ylidene)methylJamino}methyl)-2-hydroxyphenyl]acetamide Using the procedure described for the preparation of example 95, 250 mg of brown solid (91 % yield) is obtained from 300 mg (0.64 mmol) '2-(acetyfamino)-5- ({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- ylidene)methylJamino}methyl)phenyt acetate and 3-thiophine boronic acid 162.66 mg, (1.27 mmol).; mp 286-287°C MS (ESI) m/z43.1 (M+H)+ (Formula Removed) Example 146 2-(Acetylaroino)-5-({f(Z)-(6-iodo-1,3-dfoxo-2,3-dihydroisoquinolin-4(1 H)- 'ylidene)methyl]amino}methyl)phenyl acetate Using the procedure described for the preparation of example 69, 300 mg (84 % yield) of brown solid is obtained from 300 mg (0.69 mmol) of (4Z)-4-{[(4- amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline- 1,3(2H,4H)-dione and acetic anhydride 422.28 mg (4.14mmol); mp: 264-265°C MS (ESI) m/z 520.0 (M+H)+ (Formula Removed) Example 147 (4Z)-4-({[4-(Benzyloxy)-3-hydroxybeN2ylJamino}methylene)-6-bromoisoquinoline- 1,3(2H,4H)-dione To a solution of benzyl bromide (33.0 \x\, 0.28 mmol) and tetrabutylammonium iodide (104 mg. 0.283 mmol) in anhydrous N.N- dimethylformamide (2 ML) is added of potassium carbonate (207 mg, 1.5 mmol). The mixture stirred at room temperature and (4Z)-6-bromo-4-{[(3,4- dihydroxybenzyl)amino] methylene}isoquinoline-1,3(2H,4H)-dione (100 mg, 0.26 mmol) is added. After the mixture is stirred at 65° C for 30 min, the resulting mixture is concentrated and the residue is then partitioned between water (20 ml) and ethyl acetate (20 ml). The organic layer is then dried and purified by high performance liquid chromatography to give 22 mg of a white solid. MS (ESI) m/z 478.9 (M+1). (Formula Removed) Example 148 (4Z)-6-Bromo-4-{[(4-butoxy-3-hydroxybenzyl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione Example 149 To a solution of 1-bromobutane (30.4 p\, 0.28 mmol) and tetrabutylammonium iodide (104 mg, 0.283 mmol) in anhydrous N,N- dimethylformamide (2 ML) is added potassium carbonate (207 mg, 1.5 mmol). The mixture stirred at room temperature and (4Z)-6-bromo-4-{[(3f4-dihydroxybenzyl) aminojmethylene} isoquinoline-1,3(2H,4H)-dione (100 mg, 0.26 mmol) is added. After the mixture is stirred at 65° C for 30 min, the resulting mixture is concentrated and the residue is then partitioned between water (20 ml) and ethyl acetate (20 ml). The organic layer is then dried and purified by high performance liquid chromatography to give 43 mg of a white solid. MS (ESI) m/z 444.1 (M+1). (Formula Removed) Example 149 (4Z)-4-({I4-(Allyloxy)-3-hydroxybenzyl]amino}methy]ene)-6-bromoisoquinoIine- 1,3(2H,4H)-dione To a solution of of allyl iodide (25.6 pi, 0.28 mmol) and tetrabutylammonium iodide (104 mg, 0.283 mmol) in anhydrous N,N- dimethylformamide (2 ML) is added of potassium carbonate (207 mg, 1.5 mmol). The mixture stirred at room temperature and (4Z)-6-bromo-4-{[(3,4- dihydroxybenzyl)amino] methylene}isoquinoline-1,3(2H,4H)-dione (100 mg, 0.26 mmol) is added. After the mixture is stirred at 65° C for 30 min, the resulting mixture is concentrated and the residue is then partitioned between water (20 ml) and ethyl acetate (20 ml). The organic layer is then dried and purified by high performance liquid chromatography to give 36 mg of a white solid. MS (ESI) m/z 428.6 (M+1). (Formula Removed) Example 150 (4Z)-6-Bromo-4-({[4-(hexyioxy)-3-hydroxybenzyl]amino}methylene)isoquinoline- 1.3(2H,4H)-dione To a solution of of 1-bromohexane (40.0 jJ, 0.28 mmol) and tetrabutylammonium iodide (104 mg. 0.283 mmol) in anhydrous N,N- dimethylformamide (2 ML) is added of potassium carbonate (207 mg. 1.5 mmol). The mixture stirred at room temperature and (4Z)-6-bromo-4-{[(3,4- dihydroxybenzyl) amino] methylene}isoquinoline-1,3(2H,4H)-dione (100 mg, 0.26 mmol) is added. After the mixture is stirred at 65° C for 30 min. the resulting mixture is concentrated and the residue is then partitioned between water (20 ml) and ethyl acetate (20 ml). The organic layer is then dried and purified by high performance liquid chromatography to give 35 mg of a white solid. MS (ESI) m/z 472.5 (M+1). (Formula Removed) Example 151 N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- 'ylidene)methyQamino}methyl)phenyfJacetamide Using the procedure described for the preparation of N-[4-({[(Z)-(6-bromo- 1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- ylidene)methyl]amino}methyl)-2- hydroxyphenyl]acetarnide, 150 mg (84 % yield) of light brown solid is obtained from 200 mg (0.39 mmol) of 2-(acetylamino)-5-({J(Z)-(6-iodo-1,3-dioxo-2,3- dihydrolsoquinolin-4(1H)- ylidene)methyQamino}methyl)phenyl acetate, and potassium carbonate 10.69 mg (1.16 mmol); mp: 345-346°C MS (ESI) m/z 478.2 (M+H)+. (Formula Removed) 4-[(4-Piperidin-1-ylmethyl-phenyl)-hydrazono]-6-thiophen-3-yl-4H-isoquinoIine-1,3- dione The following reactants were placed in a 25 mL 3-neck RBF with an N2 inlet and a vacuum outlet: 0.200 g (0.418 mmol) of example 144, 0.080 g (0.627 mmol) of 3-thiopheneboronicacid, 0.0249 g (00836 mmol) of Ph2P(t-Bu)2, 0.136 g (1.28 mmol) of Na2C03, 2.1 mL of N.N-dimethylformamide(DMF) and 0.51 mL of H20. The vessel is evacuated and refilled with N2 (6X) and 0.040 g (0.0397 mmol) of Pd2(dba)3 is added. The mixture is heated at 125°C for 1.5 h. It is then diluted with N,N-dimethylformamide(DMF), filtered, the insoluble material is washed with N.N- dimethylformamide (DMF) and the filtrate is evaporated. The crude product is redissolved in 8% MeOH in CHCI3 and filtered through Magnesol. The yellow eluent is collected and evaporated. The residue is boiled with MeOH and the crystalline product is collected. After further washing with MeOH and Et20 and drying in vacuo, there is obtained 0.070 g (38%) of yellow-orange crystals: mp 164-168°C (dec); 1H NMR (DMSO-tf6) 5 11.8 (s, 1H), 8.41 (s, 1H), 8.21 (s, 1H), 8.06 (d, 1H, J= 8.16 Hz), 7.86 (d, 2H, J = 8.16 Hz), 7.75 (s, 2H), 7.59 (d, 2H, J = 8.22 Hz). 7.35 (d, 2H, J= 8.22 Hz), 3.43 (s, 2H), 2.33 (s(br), 2H). 1.40 (m, 6H); HRMS (ESI) m/e calcd for C25H24N402S 445.16928, found 445.16907 (M+H)+1 Analysis for C25H24N402S: Calcd: C, 67.54; H, 5.44; N, 12.60. Found: C, 68.99; H, 5.76; N, 11.27. (Formula Removed) Example 153 4-(4-{r4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methyIene}-1,3-dioxo-1,2,3,4- tetrahydro-isoquinolin-6-yl)-benzonitrile Step 1: To a suspension of 6-Bromo-4H-isoquinoline-1,3-dione (1.0 g, 4.15 mmol) in 8.7 mL of a 4:1 mixture of acetic anhydride and N,N-dimethylformamide, respectively, is added trimethylorthoformate (940 µl, 8.6 mmol). The reaction mixture is shaken in a heating block at 125°C for 1 hour. Upon cooling to room temperature, the product precipitated out. The precipitate is then filtered off, rinsed with copious amounts of ether, and dried under vacuum to yield 1.0 g of 6-Bromo- 4-methoxymethylene-4H-isoquinoline-1,3-dione. HPLC: Rt = 2.02 min; MS 282.0 [M+H]. Step 2: To a suspension of crude 6-Bromo-4-methoxymethylene-4H-isoquinoline- 1,3-dione (423 mg, 1.5 mmol) in N,N-dimethylformarnide (3 mL) is added 4-(4- Methyl-piperazin-1-yl)-phenylamine (290 mg, 1.5 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. Upon cooling to room temperature and addition of 2 mL of water, the product precipitated out The precipitate is then filtered off, washed with water, and dried to yield 0.5 g of crude 6-bromo-4-{[4-(4-rnethyl- piperazin-1 -yl)-phenylamino]-methyIene}-4H-isoquinoline-1,3-dione, which is used as such for the next reaction. HPLC: Rt = 1.69 min; MS 440.0 [M-H]. Step 3: To a suspension of 6-bromo-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]- methylene}~4H-isoquinoline-1,3-dione (221 mg, 0.5 mmol) in N,N- dimethylformamide (5 mL) is added 4-cyanophenylboronic acid (88 mg, 0.6 mmol), followed by 300 DL of 2M aqueous cesium carbonate and tetrakis triphenyiphosphine palladium (30 mg, 0.06 mmol). The reaction mixture is subjected to microwave heating at 180°C for 300 seconds. The reaction mixture is then diluted with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield 4-(4-{[4-(4-Methyl- piperazirt-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6- yl)-benzonitrile (68.4 mg). 1H NMR (DMSO-d6): pi2.6 (1H. d); 11.4 (1H, s); 9.0 (1H. d); 8.4 (1H, s); 8.12 (1H, d); 8.09 (2H, d); 8.0 (2H, d); 7.6 (1H, d); 7.5 (2H, d); 7.1 (2H. d); 3.7 (4H, dd); 3.1 (4H, dt); 2.9 (3H, s). MS (ESI) m/z 464.1 HPLC: Rt = 1.79 min; MS 464.0 [M+H]. (Formula Removed) Example 154 6-(3-Fluoro-phenyl)-4-{I4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoline-1,3-dione Step 1: To a suspension of 6-Bromo-4H-isoquinoline-1,3-dione (1.0 g, 4.15 mmol) in 8.7 mL of a 4:1 mixture of acetic anhydride and N.N-dimethylformamide, respectively, is added trimethylorthoformate (940 µL, 8.6 mmol). The reaction mixture is shaken in a heating block at 125°C for 1 hour. Upon cooling to room temperature, the product precipitated out. The precipitate is then filtered off, rinsed with copious amounts of ether, and dried under vacuum to yield 1.0 g of 6-Bromo- 4-methoxymethylene~4H-isoquinoline-1,3-dione. HPLC: Rt = 2.02 min; MS 282.0 [M+H]. Step 2: To a suspension of crude 6-Bromo-4-methoxymethylene-4H-isoquinoline- 1,3-dione (423 mg, 1.5 mmol) in N.N-dimethylformamide (3 mL) is added 4-(4- Methyl-piperazin-1-yl)-phenyiamine (290 mg. 1.5 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. Upon cooling to room temperature and addition of 2 mL of water, the product precipitated out. The precipitate is then filtered off, washed with water, and dried to yield 0.5 g of crude 6-bromo-4-{[4-(4-methyl- piperazin-1-yl)-phenylaminoJ-methylene}-4H-isoquinoline-1,3-dione, which is used as such for the next reaction. HPLC: Rt = 1.69 min; MS 440.0 [M-HJ. Step 3: To a suspension of 6-bromo-4-{[4-{4-methyl-piperazJn-1-yl)-phenylamino]- methylene}-4H-isoquinoline-1,3-dione (221 mg, 0.5 mmol) in N,N- dimethylformamide (5 mL) is added 3-fluorobenzeneboronic acid (84 mg, 0.6 mmol), followed by 300 DL of 2M aqueous cesium carbonate and tetrakis triphenylphosphine palladium (30 mg, 0.06 mmol). The reaction mixture is subjected to microwave heating at 180°C for 300 seconds. The reaction mixture is then diluted with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield 6-(3-Fluoro-phenyl)-4- {[4-(4-methyl-piperazin-1-yi)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione (65.2 mg). 1H NMR (DMSO-d6): pi2.6 (1H, d); 11.3 (1H, s); 9.0 (1H, d); 8.3 (1H, s); 8.1 (1H, d); 7.8 (1H, d); 7.7 (1H, d); 7.6 (2H, m); 7.5 (2H, d); 7.3 (1H, t); 7.1 (2H, d); 3.7 (4H, dd); 3.1 (4H. dt); 2.9 (3H. s). MS(ESI)nm/z457. HPLC: Rt = 1.88 min; MS 457.0 [M+H]. (Formula Removed) 4-{[4-(4-Methyl-piperazin-1-yl)-phenylaminol-methylene}-6-(2-morpholin-4-yl- ethoxy)-4H-isoquinoline-1,3-dione A mixture of 4-methoxymethylene-6-(2-morpholin-4-yl-ethoxy)-4H- isoquinoline-1,3-dione (115 mg, 0.35 mmole), N.N-dimethylformamide (1 mL) and 4-(4-methyl-piperazin-1-yl)-phenylamine (66 mg, 0.35 mmole) is stirred and heated at 110°C for one hour, cooled in the refrigerator. The reaction mixture is evaporated to dryness, taken up in 5% methanol in chloroform and passed through a short pad of Florisil eluting with 5% methanol in chloroform. The eluate is evaporated in vacuo and treated with ether, filtered and dried to give a yellow solid 72 mg (42%), mp 142-143°C; MS (ES+): m/z 492.2 (M + H). (Formula Removed) Example 156 6-Furan-3-yl-4-[(4-piperidin-1-ylmethyl-phenyl)-hydrazono]-4H-isoquinoline-1,3- dione The following reactants were placed in a 3-neck 25 mL round-bottom flask with an N2 inlet and a vacuum outlet: 0.200 g (0.418 mmol) of example 144, 0.070 g (0.627 mmol) of furan-3-boronic acid, 0.136 g (1.28 mmol) of Na2C03, 2.1 mL of N,N-dimethylformamide (DMF) and 0.5 mL of H20. The reaction vessel is evacuated and filled with N2 (6X) and then protected from light. Tetrakistriphenylphosphine Pd (0) (0.048 g, 0.0418 mmol) is added and the mixture is heated at 120°C for 4.5 h. An additional 0.5 mL of N.N-dimethyJformamide (DMF), 0.020 g of boronic acid and 0.015 g of the Pd catalyst were added and the mixture is heated for 3.5 h. The reaction is diluted with N,N- dimethylformamide(DMF), filtered and the insoluble material is washed well with N.N-dimethylformamide (DMF). The combined filtrate and wash were evaporated and the residue is filtered through Magnesol (5% MeOH in CHCI3). The yellow eluent is collected and evaporated. This residue is slurried with MeOH, collected, washed with small quantities of MeOH and Et20 and dried to give 0.115 g (64%) of yellow crystals: mp 223-225°C (dec); 1H NMR (DMSO-cfe) 8 11.8 -palladium(0) and 0.5 rnL of saturated sodium carbonate solution: mp 193-194 °C; MS (ESI) m/z 471.2 (M+H)+1 (Formula Removed) Example 206 (4Z)-4-({[4-(3,5-DimethyJpiperazin-1-yl)phenyQamino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of(42)-6-(4-fluorophenyl)-4-{{(3-hydroxy-4-propoxybenzyl)amino]methylene}-isoquinoline-1,3{2H,4H)-dione, 0.021 mg (15.0 % yield) of brown solid is obtained from 0.15 g (0.33 mmol) of 4Z)-6-bromo-4-({[4-(3,5-dJmethylpiperazin-1-yl)pheny1]amino}-methylene)isoquinoline-1,3(2H,4H)-dione, 0.063 g of 3-thiopheneboronic acid. 0.02 g (0.017 mmol) of tetrakis-(tiipheynylphosphine)-palladium(0) and 0.5 mL of saturated sodium carbonate solution: mp 164-165 °C; MS (ESI) m/z 459.1 (M+H)+1. (Formula Removed) Example 207 (4Z)-4-({[4-(3,5-Dimethylpiperazin-1-yl)phenyl]amino}methylene)-6-(3-furyl)iso- quinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of(42)-6-(4-fluorophenyl)-4-{[(3-hydroxy-4-propoxybenzyl)amino]methylene}-isoquinoline-1,3(2H,4H)-dione, 0.045 mg (31.0 % yield) of brown solid is obtained from 0.15 g (0.33 mmol) of 4Z)-6-bromo^({I4-(3,5-dirnethylpiperazin-1-yl)phenyl]amino}-rnethylene)isoquinoline-1,3(2H,4H)-dione, 0.055 g of 3-furanboronic acid, 0.02 g (0.017 mmol) of tetrakis-(tripheynylphosphine)-palladium(O) and 0.5 mL of saturated sodium carbonate solution: mp 199-200 °C; MS (ESI) m/z 443.2 [M+H]1+ (Formula Removed) Example 208 (4Z)-6-(4-Ruorophenyl)-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}iso- quinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of(4Z)-6-(4-fluofophenyl)-4^(3-hydroxy^-propoxybenzyI)amino]methylene}-isoquirioline-1,3(2H,4H)-dione, 0.12 g (61.1 % yield) of tan solid is obtained from 0.20 g (0.55 mmol) of (4Z)-6-bromo^4[(3-hydroxy-4-methoxybenzyi)amino]rnethylene}isoquinoline-1,3(2H,4H)-dione,, 0.1 g (0.74 mmol) of 4-fluorophenylboronic acid, 0.028 g (0.025 mmol) of tetrakis-(tripheyny!phosphine)-palladium(0) and 0.5 mL of saturated sodium carbonate solution: mp 239-240 °C; MS (ESI) m/z 419.1 (M+H)*1 (Formula Removed) Example 209 (4Z)-6-(3-Fluorophenyl)-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}iso- quinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of(4Z)-6-(4-fluorophenyl)-4-fl(3-hydroxy-4-propoxybenzyl)amino]methylene}-isoquinoHne-1»3(2H,4H)-dione, 0.092 g (46.0 % yield) of tan solid is obtained from 0.20 g (0.55 mmol) of (4Z)-6-bromo-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione, 0.1 g (0.74 mmol) of 4-fluorophenylboronic acid, 0.028 g (0.025 mmol) of tetrakis-(tripheyny!-phosphine)palladium(0) and 0.5 mL of saturated sodium carbonate solution: mp 204-205 °C; MS (ESI) m/z419.1 (M+H)1+ (Formula Removed) Example 210 (42)-6-Bromo-4-[(3,5-lihydroxy-4-methoxybenzyl)arnino]methylene}isc)quinoline- 1,3(2H,4H)-dione 6-Brorr-4-methoxymethylene-4H-isoquinoline-1,3-dione (89 mg, 0.32 mmol), 5-aminomethyl-2-methoxy-benzene-1,3-diol hydrochloride salt (66 mg, 0.32 mmol) and EUN (111µL, 0.8 mmol) in N,N-dimethylforrnamide (DMF) (2 mL) is stirred at 25 °C for 24 hours. H20 (10 mL) is added to the reaction mixture. The resulting precipitate is filtered, washed with H20 and dried in vacuo to give 144 mg of the title compound as a beige powder. HRMS (ESI) m/z calcd for d8 H15BrN2Os (M+ H)+1 419.02371, found:419.02294. (Formula Removed) Example 211 (4Z)-6-Bromo-4-{K4-hydroxybutyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione 6-Bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (250 mg, 0.89 mmol), and 4-amino-butan-1-ol (79mg, 0.89 mmoi) in N.N-dimethylformamide (DMF) (5 mL) is stirred at 25 °C for 3 days. A precipitate formed. The reaction mixture is cooled to 0°C. The precipitate is filtered and dried in vacuo to give 195 mg (64.5 %) of the title compound as a tan powder. HRMS (ESI) m/z calcd forC14 H1sBrN203 (M+ H)+1 339.03389, found: 339.03308. (Formula Removed) Example 212 (4Z)-6-Brorrmo4-3-hydroxy-4,5-dlpropoxybenzyl)amino]rnethyIene}isoquinoline- 1,3(2H,4H)-dione 6-Bromo-4-methoxymethy)ene-4H-isoquinoline-1,3-dione (110 mg, 0.39 mmol), 5-aminomethyl-2,3-dipropoxy-phenol hydrochloride salt (93mg, 0.39 mmol) and Et3N (112 µL, 0.8 mmol) in N.N-dimethylformamide (DMF) (2 mL) is stirred at 25 °C for 24 hours. H2O (10 mL) is added to the reaction mixture. The resulting precipitate is filtered, washed with H2O and dried in vacuo to give 170 mg (91 %) of the title compound as a tan powder. HRMS (ESI) m/z calcd forC23, H2sBrN205 (M+ H)*1 489.10196, found: 489.10078. (Formula Removed) Example 213 N-l5K{[(2z)(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyq-2,3- dihydroxyphenyljacetamide (4Z)-4-{f(3-Amino-4,5-dihydroxybenzyl)amino]methylene}-6 bromoisoquinoline-1,3 (2H,4H)-dione (50 mg, 0.12 mmol) and acetic anhydride (1 mL, 10.59 mmol) in N,N-dirnethytformamide (DMF) (4 mL) is stirred overnight. The reaction mixture is concentrated in vacuo and the residue is stirred in H20 for 24 hours. The precipitate is filtered, and dried in vacuo to give the title compound (30 mg, 44.6 %) as a tan solid. HRMS (ESI) m/z calcd forC,19 H18BrN3O5 (M+ H)+1 446.03461, found: 446.03378. (Formula Removed) Example 214 (AZ) (4Z)6-Bromo-4-[(2,3-dihydro-1 H-indol-5-ylamino)rnethylene] isoquinoline-1,3 (2H, 4N)-dione 6-Bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (250 mg, 0.89 mmol), 2,3-dihydro-1H-indol-5-ylamine x 2HCI (184 mg, 0.89 mmol) and EtaN (0.37 mL, 2.67 mmol) in N,N-dimethylformamide (DMF) (10 mL) is stirred for 4 days. The reaction mixture is concentrated in vacuo and the residue is triturated in H20 for 24 hours. The precipitate is filtered, washed with HzO and dried In vacuo to give 370 mg of the title compound as a brown solid. HRMS (ESi) m/z calcd for ZiB H14BrN302 (M+ H)+1384.03422, found: 384.03553. The compound is contains 29% of 4-(5-amino-2,3-dihydro-indoI-1 -ylmethylene)-6-bromo-4H-isoquinoline-1,3-dione. (Formula Removed) Example 215 N-(4-{l(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-Vlidene)rriethyl]amino}phenvl)-4-methylpiperazine-1-cart)oxarnide Using the procedure described for the preparation of example 14, 120 mg (34 % yield) is obtained as a yellow solid from 200 mg (0.71 mmol) of (4E-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 166 mg (0.71 mmol) of N-(4-aminophenyl)-4-methylpiperazine-1-carboxamide ; mp >300°C. MS (ESI) m/z 484.1 (M+1)+ (Formula Removed) Example 216 (42>-4-({[4-(3,5-Dimethylpiperazin-1-yl)phenyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione (30) Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethyipiperazin-1-yl)phenyf]amJno}methylene)isoquinoline-1,3(2H,4H)-dione, 0.15 g (63.5 % yield) of light brown solid is obtained from 0.15 g (0.46 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and [4-(3,5-dimethylpiperazin-1-yi)phenyrjamine (0.44 g, 2.13 mmol): mp 222-223°C; MS (ESI) m/z 503.1 (M+H)+1 (Formula Removed) Example 217 N-(4-{[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- 'ylidene)methyl]amino}phenyl)-N,-(4-methylpipera2in-1-yl)urea o Using the procedure described for the preparation of example 14, 179.4 mg (68 % yield) of the title compound is obtained as a yellow solid from 200 mg (0.71 mmol) of (4E>6-bromo-4-(methoxymethylene)isoquinoline-1,3(2/-/,4H)-dione and 177 mg (0.71 mmol) of 1-(4-amino-phenyl)-3-(4-methyl-piperazin-1-yl)-urea; mp 270-271 °C. MS (ESI) m/z 499.0 ([M+H]1+ (Formula Removed) Example 218N-[4-({[(Z)-6-Bromo-1,3-dioxo-2,3-dihydrolsoquinolin-4(1 H)-ylidene)methyf|amino}methyl)-2-hydroxyphenyl]-2,2,2-trifluoroacetaiTiide Using the procedure described for the preparation of example 69, 80 mg (32 % yield) of the title compound as an orange solid is obtained from 200 mg (0.52 mmol) of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-bromoisoquinoline-1,3(2H,4H)-dione and 0.22 ML (1.56 mmol) of trifluoroacetic anhydride; mp: 278-279°C MS (ESI) m/z 482.1 [M+H]1+ (Formula Removed) Example 219 (4Z)-6-Bromo-4-({[4-(cyclopropylmethoxy)-3-'hydroxybenzyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione Using the same procedure as intermediate 45, intermediate 9 is reduced to 5-aminomethyl-2-cyclopropylmethoxy-phenol hydrogen chloride. Using the procedure described for the preparation of example 46, 300 mg (64%) yield of the title compound as a brown solid is obtained from 300 mg (1.06 mmol) of (4E-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4W)-dtone and 5-aminomethyl-2-cyclopropyimethoxy-phenol hydrogen chloride. ; mp 210-211°C. MS (ESI) m/z 445.0 (M+1)*. (Formula Removed) Example 220 (4Z)-6-Bromo-2-(hydroxymethyL-4-({[4-(4-methylpiperazin-1-yl)phenyQamino}methylene)isoquinoline-1,3(2H,4H)-dione An amount of 300 mg of ( 0.68 mmol) example 27 and paraformyl aldehyde 612 mg (20.4 mmol) were dissolved in 1:1 water : N,N-dimethylformamide. The mixture is agitated in a microwave at 180°C for 400s. Followed by filtration through celite, evaporated after washing with methylene chloride. The yellow residue is then stirred in water for 20 minutes, the solid is collected with methanol to give 200 mg (63 % yield) of the desired product; mp: 141-142 MS (ESI) m/z 473.1 [M+H]+. Example 221 6-lodo-4-{[4-(5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)enylamino]-methylene}- 4H-isoquinoline-1,3-dione A solution of 2-methyl-2,5-diaza-bicyclo[2.2.1]heptane (0.4402 g, 1.6 mmol), p-fluoro-nitrobenzene (0.56 mL, 5.4 mmol), N,N-diisopropylethylamine (0.84 mL, 4.82 mmol) in 5 mL of acetonitrile is heated at 100 °C overnight. After the solvent is removed, the residue is treated with saturated sodium bicarbonate solution and extracted with chloroform. The organic layer is washed with brine, dried over magnesium sulfate, filtered, and evaporated to dryness. The oil is washed with hexane to give a yellow solid, which is recrystallized from ethyl acetate/hexane to yield 0.246 g (65% yield) of 2-methyi-5-(4-nitro-phenyl)-2,5-diaza-bicyclo[2.2.1]heptane. A mixture of 2-methyl-5-(4-nitro-phenyl)-2,5-diaza-bicyclol2.2.1]heptane (0.19 g, 0.815 mmol) and a catalytic amount of Pd/C in ethanol (0.2 mL) is hydrogenated at 1 atmosphere at room temperature overnignt. It is filtered through Celite, and the organic solution is evaporated, and then treated with 10 mL of methanol. It is then treated with hydrochloric acid in methanol, followed by ethyl ether, and filtered to give 4-(5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-phenylamine as blueish solid (0.107 g, 65%). MS (ESI) m/z 204.2 (M-H)*1. A solution of 4-(5-methyl-2,5ldia2a-bicyclo[2.2.1]hept-2-yl)-phenylamine (0.1 g, 0.49 mmol), 6-lodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (0.2 g, 0.6 mmol), and N,N-dimethylforrnamide (0.2 mL) is heated at 90°C overnight. After the solvent Is removed, the residue is treated with ethyl ether and filtered to give crude product as light brown solid. It is purified by HPLC to yield 97 mg (39% yield) of 6-iodo-4-{[4-(5-methyl-2,5-dia2a-bicyclo[2.2.1]hept-2-yl>-phenylamino)-methylene}-4H-isoquinoline-1,3-dione as bright orange solid, mp 210-211°C. (Formula Removed) Example 22 (42--Bromo-4-({H2-methoxypyridin-4-yl)methyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione 2-Methoxy-4-cyanopyridine is prepared according to Brown, T.H. et al. Eur J Med Chem. 28,1993, 601-608. Reduction of 2-methoxy-4-cyanopyridine to 4-(2-methoxypyridyl)methylamine is achieved through the method of Walpole, C.S. J. J Med Chem. 36, 16, 1993, 2362-2372. (4E)-6-bromo-4-(methoxymethylene)isoquinoiine-1,3(2H,4H)-dione (0.15 g, 0.53 mmol) and 4-(2-methoxypyridyl)methylamine hydrochloride (93 mg, 0.53 mmol) were coupled in tetrahydrofuran (3 mL) with triethylamine (0.21 mL) at room temperature. After addition of methanol, the solid material is collected by Buchner filtration, washed with diethyl ether and water. The crude material is dissolved in a minimum of 5% methanol in chloroform and then passed through a Florisil plug, eluting with the same solvent mixture. The filtrate is concentrated under reduced pressure to give (4Z)-6-bromo-4-({l(2-methoxypyridin-4-yl)methyl3amino}methylene)isoquinoline-1,3(2H,4H)-dione (0.13 g, 62 %) as a golden solid. MS (ES+): 388.0, 390.0 (M+H]+ (Formula Removed) Example 223 (4Z)-6-Bromo-4-({[4-(4-methylpiperazin-1 -yl)phenyl]amino}methylene)-1,4-dihydroisoquinolin-3(2H)-one A toluene solution (0.75 mL) of 6-bromo-4-[(dirnethyiarnino)methylene]-1,4-dihydroisoquinolin-3(2H)-one (60 mg, 0.213 mmol) and 4-(N-methylpiperazinyOaniline (42.9 mg, 0.224 mmol) is heated at 110 °C for 3 h. It is dried up and triturated with ether and hexane to yield 23 mg (25%) of the title compound as a light-brown solid. (Formula Removed) Example 224 (4Z)-6-Bromo-4-({[(7-hydroxy-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]amino}methylene)isoquinol Jne-1,3(2H,4H-dione 7-Hydroxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylicacid methyl ester is prepared from methyl gallate and acetone according to Percec, Virgil; Bern, Tushar K.; Tetrahedron;. 58; 20; 2002; 4031 - 4040. TOF MS (ES): 223.0 (M-H)' 7-Hydroxy-2F2-dimethyl-benzo[1,3]dioxole-5-cart>oxylicacid methyl ester (1.5 g, 6.7 mmol) is converted to 7-benzytoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid methyl ester by reaction with benzyl bromide (1.2 mL, 10 mmol) in acetone (35 mL) and in the presence of potassium carbonate (13 g). After an aqueous work-up, the crude solid is triturated with hexanes and then filtered to give the desired product in quantitative yield. TOF MS (ES+): 315.1 (M+H)+ A —78 °C solution of 7-benzytoxy-2,2-dimethyl-benzo[1.3Jdioxole-5-carboxylic acid methyl ester (0.62 g, 2.0 mmol) in toluene (17 mL) is treated with di-isobutylaluminum hydride (1.0 M solution I hexanes, 4.4 mL, 4.4 mmol), which is added dropwise over 15 minutes. After 5 minutes of stirring, the reaction is quenched by the addition of 10 % aqueous hydrochloric acid solution. After warming to room temperature, the mixture is extracted 3X with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to provide (7-benzyloxy-2,2-dimethyl-benzo[1,3]dtoxoI-5-yl)-rnethanol in quantitative yield. To a 0°C mixture of (7-benzyloxy-2,2-dimethyl-benzo[1,3]dioxol-5-yl)-metha'nol (0.57 g, 2.0 mmol) and diphenylphosphoryl azide (0.52 mL? 2.4 mmol) in tetrahydrofuran (10 mL) is added 1,8-diazabicyclo[5.4.0Jundec-7-ene (DBU, 0.33 ml_, 2.2 mmol). The mixture is allowed to warm to room temperature over the weekend and then quenched with the addition of water. The reaction mixture is extracted 3X with ethyl acetate, and the combined extracts were washed with 5 % aqueous potassium hydrogen sulfate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated to give 6-aadomethyl-4-benzyloxy-2,2-dimethy1-benzo[1,3]dioxole, which is used in the next step without purification. A solution of 6-azidomethyl-4-benzyloxy-2,2-dimethyl-benzo[1,3]dioxole (2.0 mmol maximum) in ethanol (20 mL) and 6 M aqueous hydrochloric acid (2 mL) is hydrogenated at 50 psi over 5 % Pd/C. After 18 hours, the reaction mixture is filtered through a Celite pad and concentrated under reduced pressure to give C-(7-benzyloxy-2,2-dimethyl-benzo{1,3Jdtoxol-5-yl)-rnethylamine hydrochloride. MS (ES*): 196.2 (M+H)* (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.42 g, 1.5 mmol) and C-(7-berJzytoxy-2,2-dimethyl-benzo[1,3]dioxol-5-yl)-methylarnine hydrochloride (1.5 mmol) were coupled In N,N-dimethytformamide (10 mL) with triethylamine (0.6 mL). The crude material is dissolved in a minimum of 7.5% methanol in chloroform and then passed through a Florisil plug, eluting with 5 % methanol in chloroform. The filtrate is concentrated under reduced pressure to give (4Z)-6-bromo-4-({£(7-hydroxy-2,2-dimethyl-1,3-benzodioxol-5-yl)methyrjamino}methylene)ispquinoline-1,3(2H,4H)-dione as a light pink powder. MS (ES*): 445.0, 446.9 (M+H]+ (Formula Removed) Example 225 (4Z)--Bromo-4-({[(2-oxo-1,2-dihydropyridin-4-yl)methyI]amfno}methyIene)isoquinoline-1,3(2H,4H)-dione A solution of 4-(2-methoxypyridyl)methylamine (0.19 g, 1.1 mmol) in water (50 mL) and 3 M aqueous hydrochloric acid (25 mL) is heated at reflux for 5 hours and then solvent is reduced to approximately 10 mL. The remainder of the water is then removed under reduced pressure to give 4-aminomethyl-1 H-pyridin-2-one hydrochloride (0.15 g, 83 %) as an off-white solid. (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.26 g. 0.94 mmol) and 4-aminomethyl-1 H-pyridin-2-one hydrochloride (0.15 g, 0.94 mmol) were coupled in tetrahydrofuran (5 mL) and N,N-dimethylformarnide (3 mL) with triethyiamine (0.28 g) at room temperature overnight. After the addition of water, the solid material is collected by Buchner filtration, washed with diethyl ether, water, and methanol, and dried under vacuum to give (4Z)-6-brorno-4-({[(2-oxe-1,2-dihydropyridin-4-yl)methyf|amino)methylene)isoquinoline-1,3(2H,4H>dione (0.19 g, 54 %) as a gray powder. MS (ES): 372.0, 347.0 (M-H)- (Formula Removed) Example 226 (4Z)-6-(2,5-DimethyM H-pyrrol-1 -yl)-4-({[4-(4-methylpiperazin-1 -V0phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione An amount of 300 mg (0.74 mmol) of (4Z)-6-amino-4-({[4-(4-methylPiperzin-1yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione and tolunene sulfonic acid (226.45,1.19 mmol), and acetonylacetone is stirred in rV.rV-dimethylforrnamide (5 mi_). The reaction mixture is heated at 110 °C for 1 h. After cooling to room temperature, the mixture is filtered through celite and washed with methylene chloride, evaporated. The residue is purified by preparative thin layer chromatography (10:90 = methanol: methylene chloride), to give a yellow solid 100 mg (28 % yield); mp 222-223°C mp 264-265°C; MS (ESI) m/z 456.1 (M+1) Example (Formula Removed) (4Z>4-{[(4-Amino-3-hydroxybenzyl)arnino]methy1ene}-6-bromoisoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of example 46, 700 mg of yellow-brown solid (100% yield) is obtained from 500 mg (1.77 mmol) of 6-bromo-4-methoxmethylene-isoquinoline-4H-1,3-dione and 2-amino-5-(am!nomethyl)pheno) (448 mg, 0.76 mmol); mp 245-246°C. MS (ESI) m/z 390 (M+H)(Formula Removed) Example 228 PEG5000thio-acetic acid 5-{[(6-bromo-1,3-dioxo-2,3^dihydro-1 H-isoquinolin-4-ylidenerriethyl)-amino]-methyl}-2-propoxy-phenyl ester To iodoacetic acid (43 mg, 0.232 mmol) in dimethylformamide (DMF) (1 mL) at -20 °C is added N-methylmorpholine (25 uL, 0.232 mmol) and isobutylchloroformate (30 uL, 0.232 mmol). After 5 min (4Z)-6-bromo-4-{l(3-hydroxy-4-propoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (100 mg. 0.232 mmol) is added. The reaction mixtue is alowed to warm to 25 °C. After 2h N-methyimorpholine is added (25 uL). After 1h 15% aq. citric acid is added. The resulting precipitate is Filtered and washed with water to give as a tan solid (116 mg). A solution of this material In CH3CN is treated with mPEGSH 5000 (500 mg, 0.1 mmol) and Hunig's base. After 1h tetrabutylammoniumiodide (10 mg) and dimethyHaminopyridine (DMAP) (5 mg) is added. After 4 days the reaction mixture is concentrated in vacuo dissolved in water and extracted with CH2CI2 to give a solid after concentration. Chromatography on silica gel (CH2CI2/methanol) gave the desired compound (235 mg) as a tan powder. (Formula Removed) Example 229 (4Z)-6-Bromo-4-{[(4-{[2-(dimethylamino)ethyl]thio}phenyl)arnino]rnethylene}isoquinoline-1,3(2H,4/-0-dione To a solution of N,N-dimethylaminoethanethiol hydrochloride (2.9 g, 14 mmol) in N,N-dimethylformamide (DMF) (70 mL) is added potassium carbonate (19 g, 140 mmol), followed by 4-fluoronitrobenzene (1.5 mL, 14 mmol). After stirring overnight at room temperature, the reaction mixture is diluted with water and extracted 3X with ethyl acetate. The combined extracts were washed five times with water and with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude oil is purified by flash chromatography (Isco 40 g Redi-Sep column, MeOH/CHCI3) to give N,N-dimethyl-N-{2-[(4-nitrophenyl)thio]ethyl}amine (2.3 g, 72 %) as a golden oil. TOF MS (ES*): 227.2 (M+H)" To a solution of N,N-dimethyl-N-{2-[(4-nitrophenyl)thio]ethyl}amine (0.58 g, 3.0 mmol) in ethanol (45 mL), tetrahydrofuran (23 mL), and saturated aqueous ammonium chloride solution is added iron powder (1.1 g, 6.4 mmol). The mixture is heated in a 100 °C oil bath for one hour. While still hot, the reaction mixture is filtered through a pad of diatomaceous earth. The concentrated filtrate is partitioned between ethyl acetate and saturated aqueous sodium chloride solution. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude material is purified by reverse-phase high performance liquid chromatography to give 4-(2-dimethylamino-ethylsulfanyl)-phenylamine. MS(ES): 195.0 [M+H]+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1 r3(2H,4H)-dione (0.21 g, 0.76 mmol) and 4-(2-dimethylamino-ethylsulfanyl)-phenylamine (0.15 g, 0.76 mmol) were stirred in N.N-dimethylformamide (5 mL) and triethylamine (0.3 mL) at 60 - 70 °C for 5 minutes and then at room temperature for 10 minutes. The reaction mixture is quenched by the addition of water. The- solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-bromo-4-{[(4-{[2- (dirnethylamino)ethyr)thio}phenyl)arnino]rnethylene}isoquinoline-1,3(2H,4H)-dione (0.22 mg, 65 %) as a golden powder. MS (ES*): 446.1, 448.1 [M+H]+ (Formula Removed) 2-Hydroxy-4-C(3-hydroxy-4-propoxy-benzylamino)-methylene]-4H-isoquinoline-1,3- dione A mixture of 5-Aminomethyl-2-propoxy-phenol hydrochloride (109 mg, 0.50 mmole), 4 ml_ of N,N-dirnethylforrnam>de and triethylamine (75 DL. 0.54 mmole) is stirred for.15 minutes. Then (4E)-6-bromo-7-methoxy-4- Example 231 427 (methoxymethylene)isoquinoline-1,3(2H,4H)-dione (225 mg, 0.50 mmole) is added and the reaction mixture stirred for one hour. The product is isolated as before, to give an off-white solid, 81 mg, (44%), mp 176-8°C; MS (ESI): m/z 369.1 (M + H). (Formula Removed) (4Z)-6-Bromo-4-[({4-[[2-(dimethylamino)ethyl)(methyl)amino]phenyl}amino)methylene]lsoquinoline- 1,3(2H,4H)-dione A mixture of 4-fluoronitrobenzene (0.35 g, 2.5 mmol) and N.N.N trimethylethylenediamlne (1.5 g, 1.9 mmol) in N-methylpyrrolidinone (10 mL) is heated for 19 hours in a 100 °C shaking block. After cooling to room temperature, the reaction mixture is partitioned between ethyl acetate and water. The organic phase is washed four times with water and with saturated aqueous sodium chloride solution and then concentrated under reduced pressure to give N,N,N'-trimethyl-N'-(4-nitrophenyI)ethane-1,2-diamine as a brown semisolid. TOF MS (ES+): 224.1[M+H]+ A solution of N,N,N,-trimethyl-N,-(4-nitrophenyl)ethane-1,2-diamtne in ethanol, containing 5 drops of concentrated hydrochloric acid, is hydrogenated overnight at atmospheric pressure over 10 % Pd/C. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give N-[2-(dimethyiamino)ethyrj-N-methylbenzene-1,4-diamine as a dark maroon oil. TOF MS (ES*): 194.1 (M+H)+ (4E)^-bromo-4-(methoxymethylene)isoquinoline-1,3(2H>4H)-dione (0.28 g, 1.0 mmol) and N-[2-(dimethylamino)ethyl]-N-methylbenzene-1,4-diamine hydrochloride (0.30 g, 1.0 mmol) were stirred in N,N-dimethylformamide (5 mL) with triethylamine (0.6 mL). The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol and then dried under vacuum to give (4Z)-€-bromo-4-[({4-[[2-(dimethylamino)ethyl](methyl)amino]pheny1}amino)methylene]isoquinoline-1,3(2H,4H)-dione (0.24 g, 55 %) as a golden powder. MS(ES*): 443.1, 445.1 [M+H]+ Example 232 (4Z)-6-Bromo-4-({[4-(4-methyl-1,4-diazepan-1 -yl)phenyl]amino}methylene)isoquinoline-1,3(2/-/,4H)-dione A mixture of 4-fluoronitrobenzene (0.35 g, 2.5 mmoi) and 1-methylhomopiperazine (1.7 g, 15 mmol) in N-rriethylpyrrolidinone (10 mL) is heated for 19 hours in a 100 °C shaking block. After cooling to room temperature, the reaction mixture is poured onto ice, precipitating 1-methyl-4-(4-nitrophenyl)-1,4-diazepane as a fine tan solid, which is collected by Buchner filtration and used in the next step without further purification. TOF MS (ES*): 236.1 [M+H]+ A solution 1-methyl-4-(4-nttrophenyl)-1,4-diazepane in ethanol is hydrogenated overnight at atmospheric pressure over 10 % Pd/C. The mixture is filtered through a pad of dlatomaceous earth and concentrated under reduced pressure to give 4-(4-methyl-[1,4]-diazepan-1-yl)phenylamine as a dark maroon oil. TOF MS (ES*): 206.1 (M+Hf (4E)-6-bromo-4-(methoxymethylene)isbquinoline-1,3(2H,4H)-dione (0.15 g, 0.54 mmol) and [4-(4-methyl-1,4-diazepan-1-yl)phenyl3arnine (0.11 g, 0.54 mmol) were stirred in N.N-dimethyJformamide (3 mL) with triethylamine (0.3 mL). The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol. The crude material is dissolved in a minimum of 5% methanol in chloroform and then passed through a Florisil plug, eluting with 5 % methanol in chloroform. The filtrate is concentrated under reduced pressure to give and then dried under vacuum to give (4Z)-6-bromo-4-({[4-(4-methyl-1,4-dia2epan-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (64 mg, 26 %) as a rust colored powder. MS (ES+): 455.1, 457.1[M+H]+ (Formula Removed) Example 233 » (4Z)-6-lodo-4-[({4-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]phenyl>amino)methylene]- isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpipera2in-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 0.078 g (49.7 % yield) of light brown solid is obtained from 0.10 g (0.30 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H>-dione and 4-(2,4,5-trimethyl-piperazin-1-yl)-phenylamine (0.073 g. 0.33 mmol) after purified by column chromatography over silica gel using 5% MeOH/CHCI3 as eluent: mp 199-200 °C; MS (ESI) m/z517.1 [M+H]+ (Formula Removed) Example 234 (4Z)^»odo-4-[<{4-[(3R,5S)-3,4,5-trimethylpipera2in-1-y1]phenyl>amino)methyiene]- isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of4Z)-6-bromo-4-({[4-(3,5-dirnethylpiperazin-1-yI)phenyl]arnino}rnethylene)isoquinoline-1,3(2H,4H)-dione, 0.069 g (56.7 % yield) of light brown solid is obtained from 0.10 g (0.3O mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione, and 0.073 g (0:33 mmol) of4-(3,4,5-trimethyl-piperazirw1-yl)-phenylamine after purified by column chromatography over silica gel using 5% MeOH/CHCI3 as eluent mp 224-225°C; MS (ESI) m/z5MA (M+H)+1 Example 235 (4Z)-4-({I4-(3,5-Dimethylpiperazin-1-yl)phenyllamino}methylene)-6-nitroisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({t4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 0.032 g (12.8 % yield) of dark brown solid is obtained from 0.15 g (0.60 mmol) of 4-methoxymethylene-6-nitro-4H-isoquinoIine-1,3-dione and [4-(3,5-dimethylpiperazin-1-yl)phenyl]amine (0.15 g, 0.72 mmol): mp >300°C; MS (ESI) m/z 422.2 (M+H)+1 Example 236 (4Z)-6-(3-Furyl)-4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (42) Example 237 432 Using the procedure described for the preparation of(4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yGphenyl}amino)methyleneIisoquinoline-1,3(2H,4H)-dione, after purified by column chromatography over silica gel using 5% MeOH/CHCI3 as eluent, 0.096 mg (66.2 % yield) of yellow solid is obtained from 0.15 g (0.34 mmol) of (4Z)-6-bromo-4-({[(4-methylpiDerazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)ione, 0.076 g (0.64 mmol)of 3-furanboronic acid, 0.02 g (0.017 mmol) of tris(dibenzyldeneaacetone)-dipalladium(O), 0.02 g (0.064 mmol) of 2-(di-t-butyl-phosphino-biphenyl, and 0.072 g (0.64 mmol) of sodium carbonate: mp 190-191 °C; MS (ESI) m/z 429.2 (M+H)+1 (4Z)-6-lodo-4-({[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)tsoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 300 mg (68% yield) is obtained as a orange solid from 300 mg (0.91 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 175 mg (0.91 mmol) of 6-(4-methylpiperazin-1-yl)pyridin-3-amine; mp 189-190°C. MS (ESI) m/z 490.0 [M+H]+ (Formula Removed) Example 238 (4Z)-6-Bromo-4-[({4-[(2S,5R)-2,4,5-trimethylpiperazin-1-y|]phenyi}amino)methylene]-isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of4Z)-6-bromo-4-({t4-(3,5-dimethylpiperazin-1-yi)phenyl]aimino}methylene)isoquinoline-1,3(2H,4H)-dione, 0.68 g (91.0 % yield) of yellow solid is obtained from 0.45 g (0.46 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoqulnoIine-1,3(2H.4H)-dione and 4-(2,4,5-trimethyl-piperazin-1-yl)-phenylamine (0.38 g, 1.76 mmol): mp 184-185°C; MS (ESI) m/z 469.1 -471.1 (M+H)+1 Example 239 (4Z)-6-lodo-4-({[4-( 1 -methylpiperidin-4-y l)phenyl]amino}methylene)isoq uinoline- 1,3(2H,4H-dione Using the procedure described for the preparation of4Z)-6-bromo-4-({[4-(3,5-dirnethy!pipera2un-1-yl)phenyrjarnino}methyfene)isoquinoline-1,3(2H,4H)-dione, after purified from HPLC, 0.064 g (53.4 % yield) of light brown solid is obtained from 0.082 g (0.25 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and [4-(3,5-dimethylpiperazin-1-yl)phenyr]amine (0.048 g, 0.25 mmol): mp 215-216°C; MS (ESI) m^r488.1 (M+H)*1 (Formula Removed) Example 240 (42)-6-Bromo-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)methylene]-isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of4Z)-6-bromo-4-({[4-(3,5^imethylpiperazI-1-yl)phenyL)ir}methylene)isoquinolirie-1,3(2H,4H)-dione. after purified using silica! gel chromatography (using 5% MeOH/CHCI3 as solvent), 0.68 g (91.0 % yield) of light brown solid is obtained from 0.45 g (1.60 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoiine-1,3(2H,4H)-dione, and 0.38 g (1.76 mmol) of4-(3,4,5-trimethyl-piperazin-1-yl)-phenylamine: mp 213-214 °C; MS (ESI) m/x 469.1 -471.1 (M+Hf1 (Formula Removed) Example 241 (4Z)6-(3-FurylH-[({4-t(3R,5S)-3,4,5-trimethy!pipera2in-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione Example 242 435 An amount of 0.15 g (0.32 mmol) of (4Z)-6-bromo-4-[({4-[(3R,5S)-3,4,5-trirnethylpierazin-1-yl]phenyl}amlno)-rTrethylene]-isoquinollne-1,3{2H>4H)-d}one in 2 mL of DMF is added 0.076 g (0.64 mmol) of 3-furanboronic acid, 0.02 g (0.017 mmol) of tris(dibenzyldeneaacetone)-dipalladiurn(0), 0.02 g (0.064 mmol) of 2-(di-t-butyl-pbosphino)-biphenyl, and 0.072 g (0.64 mmol) of sodium carbonate. The reaction mixture is stirred at 100oC under N2 for 2 h. Mass spectroscopy suggested the completion of reaction. Solids were removed by filtration, and solvent is subsequently evaporated under high-pressure vacuum to brown solid. The residue is purified using silica gel chromatography (using 5% MeOH/CHCI3 as eluent), 0.064 mg (43.8 % yield) of yellow solid is obtained: mp 204-205 oC; MS (ESI) m/z 457.2 (M+H)+1 (Formula Removed) 6-Bromo-7-methoxy-4-{[4-(4-methyl-piperazin-1~yl)-phenylamino]-methylene}-4H- isoqulnoline-1,3-dione A mixture of (4E)-6-bromo-7-methoxy-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (156 mg, 0.50 mmole), N,N-dirnethylformamide (1 mL) and 4-(4-Methyl-piperazln-1-yl)-phenylamine (96 mg, 0.50 mmole) is stirred and heated at 110°C for one hour, cooled in the refrigerator. The reaction mixture is evaporated to dryness, taken up in 5% methanol in chlororform and passed through a short pad of Florisil eluting with 5% methanol in chloroform. The eluate is evaporated in vacuo and treated with acetonitrile, filtered and dried to give a brown solid 110 mg (47%). mp 274-276°C;; MS (ESI): m/z 471.1, 473.1 (M + H). (Formula Removed) Example 243 (4Z)-6-Bromo-4-{[(4-{[2-(dimethylamino)ethyrjsuifonyl}phenyl)amino]methylene}isoquinoline-1,3(2H4H)- dione To a 0 °C solution of give N,N-dimethyl-N-{2-[(4-nitrophenyl)thio]ethyl}amine (0.50 g, 2.2 mmol) in rnethanol/tetrahydrofuran/water (33 mL, 1:1:1) is added dropwise an aqueous solution of OXONE®, monopersulfate compound (2.7 g, 9.5 mL). The reaction mixture is stirred for one week at room temperature and then quenched by the addition of an aqueous sodium hydrogen sulfite solution (3 g , 20 mL). The mixture is then basified to pH 8 with concentrated ammonium hydroxide and extracted 3x with dichloromethane. The combined extracts were washed with aqueous 5 % sodium thiosulfite solution (100 mL) and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a golden oil. which solidified upon standing. The crude solid (0.31 g) is purified by flash chromatography (Isco 12 g Redi-Sep column, MeOH/CHCI3) to give dimethyl-[2-(4-nitro-benzenesuIfonyl)-ethyl]-amine. MS (ES*): 259.2 (M+H)* A solution of dimethyl-[2-(4-nitro-benzenesulfonyl)-ethy0-amine (0.39 mmol) in ethanol (15 ml_) is hydrogenated for 90 minutes at atmospheric pressure over 10 % Pd/C. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 4-(2-dimethylamino-ethanesulfonyl)-phenylamine as a white solid. MS (ES*): 229.3 [M+H]+ (4E)-6-bromo-4-(methoxyrnethylene)isoquinoline-1,3<2H,4H)-dione (0.17 g, 0.61 mmol) and 4-(2-dimethylamino-ethanesulfonyl)-phenylamine (0.14 g, 0.61 mmol) were stirred in N.N-dimethylformarnide (3 ml_) and triethylamine (0.16 mL) at 60 — 70 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-bromo-4-{[(4-{[2- (dimethylamino)ethyl]sulfonyl}phenyl)amino]methylene}isoquinoHne-1,3(2H,4H)-dione (0.11 g, 36 %) as a golden powder. Example 244 437 MS (ES*): 478.1, 480.0 [M+H]+ (Formula Removed) (4Z)-6-Bromo-4-[({4-[(2-hydroxyethyl){methyl)amino]phenyl}amino)methylene]isoquinoIine-1l3(2H,4H)- dione A mixture of 4-fluoronitrobenzene (2.8 g, 20 mmol) and 2-(methylamino)ethanol (8.9 g, 120 mmol) in N-methylpyrrolidinone (80 mL) is heated for 19 hours in a 85 °C oil bath. After cooling to room temperature, the reaction mixture is partitioned between ethyl acetate and water. The organic phase is washed five times with water and with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give 2-(methyl-4-nitroanilino)ethanol (3.1 g, 79 %) as a yellow solid. MS(ES+): 197.2 [M+H]+ A solution of 2-(methyl-4-nitroanilino)ethanol (0.20 g, 1.0 mmol) in ethanol (25 mL) is hydrogenated for two hours at atmospheric pressure over 10% Pd/C. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 2-[(4-aminc-phenyl)-methyi-amino]-ethanol as a dark oil, which solidified upon standing. MS (ES+): 167.3 [M+H]+ (Formula Removed) (4E)-6-bromo-4^(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.17 g, 0.61 mmol) and 2-l(4-amino-phenyl)ethyl-amino]-ethanol (0.10 g, 0.61 mmol) were stirred in N,N-dimethylforrnamide (3 mL) and triethytamine (0.16 mL) at 60 — 70 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-bromo-4-[({4-[(2- hydroxyethyi)(methyl)amino]phenyl}amino)methylene]isoquinolJne-1,3(2H,4H)-dione (0.16 g, 64 %) as a rust colored powder. MS (ES*): 416.0, 418.1 [M+H]+ Example 245 (42}-6-Brtmo--[({4-{methyl(1-niethylpyrrolidin-3-yl)amino)phenyl}amino)melhytene]isoquinolJne-1.3(2H,4H)-dione To a suspension of potassium hydroxide (1.4 g, 25 mmol) and N,N'-dimethyl-3-aminopyrrolidine (1.4 g, 12 mmol) in dimethylsulfoxide (13 mL) is added dropwise 4-fluoronitrobenzene (1.1 mL, 10 mmol). The mixture is heated in a 60 -65 °C oil bath for 4 hours. After cooling to room temperature, ice is added to the reaction mixture. The resulting precipitate is collected, washed with water, and dried under vacuum to give methyl-(1-methyl-pyrrolidin-3-yl)-(4-nitro-phenyl)-amine. MS (ES*): 236.3 (M+H)+ A solution of methyl-(1-methyl-pyrrolidln-3-yl)-(4-nitro-phenyl)-amine (0.25 g, 1.1 mmol) in ethanol (20 mL) is hydrogenated overnight at atmospheric pressure over 10 % Pd/C. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give N-methyl-N-(1-methyl-pyrrolidin-3-yl)-benzene-1,4-diamine as a dark oil (0.21 g, 95 %). MS (ES+): 206.3 [M+H]+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.17 g, 0.61 mmol) and N-methyl-N-(1-methyl-pyrrolidin-3-yl)-benzene-1,4-dlamlne (0.12 g, 0.61 mmol) were stirred in N,N-dimethylformarnide (3 mL) and triethylamine (0.16 mL) at 60 - 70 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-brorno-4-[({4-[rnethyl(1-mettiylpyrrolidin-3- yOaminoJphenytyaminoemylenelisoquinoline-l3 (2H,I-O-dione (0.12 g, 44 %) as a rust colored powder. MS (ES+): 455.1, 457.1 (M+H)* (Formula Removed) Example 246 6-Bromo-4-[(3-hydroxy-4-propoxy-benzylamino)-methylene]-7-methoxy-4H- isoquinoline-1,3-dione A mixture of 5-Aminomethyl-2-propoxy-phenol hydrochloride (109 mg, 0.50 mmole), 4 mL of N.N-dlmethylformamide and triethylamfne (75 uL, x mmole) were stirred for 15 minutes. Then (4E)-6-bromo-7-methoxy-4- (methoxymethylene)isoquinoline-1,3(2H,4H)-dione (156 mg, 0.50 mmole) is added and the reaction mixture stirred for one hour. The product is isolated as before, to give an off-white solid, 119 mg, (51 %), mp 212-214°C dec; MS (ESI): m/z 459.1, 461.2 [M+H]+ (Formula Removed) Example 247 (4Z)-6-!odo-4-{{[4-{pyridin-2-ylmethoxy)phenyqamin 'methylene)isoquinoline1,3(2H,4H)-dfone Using the procedure described for the preparation of example 14,400 mg (77% yield) is obtained as a orange-yellow solid from 300 mg (0.91 mmol) (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 183.72 mg (0.91 mmol) of *[4-(pyridin-2-ylmethoxy)phenyl]amine; mp 265-266°C. MS (ESI) m/z 498.0 (M+1)* Example 248 (4Z)-4-(((4-(3,4-Dimethylpiperazin-1'iyl)pnenyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione Example 249 Using the procedure described for the preparation of4Z)-6-bromo-4-({I4-(3,5-dimethyipiperazin-1-yl)phenyl]amino}mettiylene)isoquinoline-1,3(2H,4H)-dione, after purified from HPLC, 0.052 g (22.6 % yield) of light brown solid is obtained from 0.15 g (0.46 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 4-(3,4-Dimethyl-piperazin-1-yl)-phenylamine (0.11 g, 0.50 mmol): mp 157-158°C; MS (ESI) m/z 503.1 (M+H)1 (Formula Removed) (4Z)-6-{3-Furyl)-4-({[6-(4-methylp}perazin-1-yl)pyridin-3-•yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione: A mixture of 300 mg (0.68 mmol) of (4Z)-6-bromo-4-({[6-(4-methylpiperazin-1-yl)pyridin-3- 'yl]airiino}methylene)isoquinoline-1,3(2H,4H)-dione *(4Z)-6-(3-furyl)-4-({[6-(4-methylpiperazin-1-yl)pyridin-3-'yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, Pd2(dba)3 (125 mg, 0.136 mmol), tri-tert-butylphosphine (0.13 mL.0.64 mmol), cesium carbonate, (663 mg, 1.36 mmol), and 3-furan boronic acid (189.72 mg, 1.7 mmol) is placed In a three neck flask under N2. N,N-dimethylformamide (8 ML) is added, and the mixture is then stirred in a pre-heated oil bath 130°C for 30 minutes. After cooling, the mixture is treated with CH2CI2 and filtered through celite. After evaporating all the solvents, the residue is dissolved in methylene chloride, washed three times with Brine, dried over sodium sulfate and evaporated. The orange oily residue is purified by silica plug chromatography (10:90 = methanol: methylene chloride), to give a yellow solid 130 mg (45 % yield); mp 200-201 ?C MS (ESI) m/z 430.2 (M+1f (Formula Removed) Example 250 (4Z)-6-Bromo-4-({I6-(4-methylpiperazin-1-yl)pyridin-3-"yl]arnino}methylene)isoquinoline-1 ,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 400 mg (66 % yield) is obtained as a orange-yellow solid from 384.6 mg (1.36 mmol) (4E> 6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H.4H)-dione and 262 mg (1.36 mmol) of '6-(4-methyIpiperazin-1-yl)pyridin-3-arrtine; mp 265-266°C. MS (ESI) m/z 444.0 [M+H]+ (Formula Removed) Example 251 (4Z)-6-(4-Fluorophenyl)-4-({[4-(piperidin-1-yimethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(4-fluorophenyl)-4-({[4-(piperidin-1-,ylmethyI)phenyriamino}methylene)isoquinoline-1,3{2H,4H)-dione, 100 mg of yellow solid (20 % yield) is obtained from 500 mg (1.13 mmol) (42)-6-bromo-4-({[4-(piperidin-1- ylmetnyl)phenyfjamino}methylene)isoquinoline-1,3(2H,4H)-dione and 4-Flurophenyl boronicacid 395.27 mg, (2.83 mmol).; mp 195-196°C MS (ESI) m/z 456.2 ([M+H]+ 6-Bromo-7-methoxy-4-[(4-Piperidin-1-ylmethyl-phenylamino)-methylene]-4H- isoquinoiine-1,3-dione A mixture of (4E)-6-bromo-7-methoxy-4-(methoxymethylene)isoquinoline-1,3(2H.4H)-dione (156 mg, 0.50 mmole), N.N-dimethylformamide (1 mL) and 4-piperidin-1-ylmethyl-phenylamine (95 mg, 0.50 mmole) is stirred and heated at 110°C for one hour, cooled in the refrigerator. The reaction mixture is evaporated to dryness, taken up in 5% methanol in chloroform and passed through a short pad of Florisil eluting with 5% methanol in chloroform. The eluate is evaporated in vacuo, treated with acetonitrile, filtered and dried to give a dull yellow solid 134 mg (57%), mp 264-7°C; MS (ESI): m/z 470.1[M+H]+ (Formula Removed) Example 253 6-(4-Fluqro-phenyl)-7-nnethoxy^-[(4-piperidin-1-ylrnethyI-phenylamino)-rnethylene]- 4H-isoquinoline-1,3-dione A mixture of 6-Bromo-7-methoxy-4-[(4-piperidin-1-ylmethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione (272 mg, 0.57B mmole), N.N-dimethylformamide (2 mL), 4-fluorophenylboronic acid (202 mg, 1.44 mmole), tris(dibenzylideneacetone)dipaHadium(0)-chloroform adduct (78 mg, 0.075mmole), tri(t-butyl)phosphine (28 mg, 0.138 mmole) and cesium carbonate (377 mg, 1.16 mmole) is stirred and heated at 110°C for one hour, cooled in the refrigerator. The reaction mixture is evaporated to dryness, taken up in 5% methanol in chlororform and passed through a short pad of Florisil eluting with 5% methanol in chloroform. The eluate is evaporated in vacuo and treated with acetonitrile, filtered and dried to give a yellow-brown solid 138 mg (48%), mp 227-230"C; MS (ESI): m/z 486.2 (M + H). (Formula Removed) Example 254 6-Furan-3-yl-7-methoxy-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}- 4H-isoquinoline-1,3-dione A mixture of 6-Bromo-7-methoxy-4-{I4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione (241 mg, 0.51 mmole), N,N-dimethylformamide (2 mL), furan-3-boronic acid (143 mg, 1.28 mmole), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (64 mg, 0.062mmole). tri(t-butyl)phosphine (25 mg, 0.124 mmole) and cesium carbonate (334 mg, 1.02 mmole) is stirred and heated at 110°C for one hour, cooled in the refrigerator. The reaction mixture is evaporated to dryness, taken up in 5% methanol in chlororform and passed through a short pad of Florisil eluting with 5% methanol in chloroform. The eluate is evaporated in vacuo and treated with acetonitrile, filtered and dried to give a brown solid 161 mg (68%), mp 198-220°C; ; MS (ESI): m/z 459.2, 461.2 (M + H). (Formula Removed) Example 255 (42)-6-Bromo-4-[({4-[methyl(2-pyrrolidin-1-ylethyl)amino]phenylamino)methyJene]isoquinoline-1,3(2W,4H)-dione To a solution of 2-(methyl-4-nitroanilino)ethanol (2.9 g, 15 mmol) in pyridine {75 mL) is added p-toluenesulfonyt chloride (3.1 g, 1.6 mmol) and 4-(dimethylamino)pyridine (1.8 g, 15 mmol). After stirring for three days at room temperature, the reaction is quenched by the addition of saturated aqueous sodium chloride solution and then extracted 3x with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a viscous brown oil, which is purified by reverse phase high performance liquid chromatography to give toluene-4-sulfonic acid 2-[methy!-(4-nitro-phenyl)-amino]-ethy! ester as a trifluoroacetic acid salt (0.52 g, 9.8 %). LC/MS (ES+): 351.0 (M+H]+ To a solution of toluene-4-sulfonic acid 2-[methyl-(4-nitro-phenyl)-amino]-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 u.L) and pyrrolidine (53 fiL, 0.63 mmol). The mixture is shaken in 70 °C block shaker overnight. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give methyl-(4-nitro-phenyl)-(2-pyrrolidin-1-yl-ethyl)-amine as a di-TFA salt (85 mg). A solution of methyl-(4-nitro-phenyl>-(2-pyrrolidin-1-yl-ethyl)-amine»2 TFA (85 mg) in ethanol/tetrahydrofuran (1:1, 5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-rnethyl-N-(2-pyrroIidin-1-yl-ethyl)-benzene-1,4-diamine as a di-TFA salt (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-methyl-N-(2-pyrrolidin-1-yl-ethyl)-benzene-1,4-diamine»2 TFA (0.21 mmol maximum) were stirred in N.N-dimethylforrnarnide (1 mL) and triethylamine (50 pL) at 60 - 70 °C for 12 hours. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4Z)-6-bromo-4-[({4-[methyl(2-pyrrolidin-1-ylethyi)aminolphenyi}amino)methylene]isoquinoline-1,3(2H,4H)-dione. (Formula Removed) Example 256 (42>6-Bromo-4-t({4-[methyl(2-piperidin-1 -y!ethyl)amJno}phenyl>amino)methytene]isoquinoline-1»3(2H,4/-/)-dione To a solution of toluene-4-sulfonic acid 2-[methyl-(4-nitro-phenyl>-amino]-ethyl ester TFA sail (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 nL) and piperidine (62 pi, 0.63 mmol). The mixture is shaken in 70 *C block shaker overnight. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give methyl-(4-nitro-phenyl)-(2-piperadin-1-yl-ethyl)-amine as a di-TFA salt (74 mg). MS (ES*): 264.3 [M+H]+ A solution of methyl-(4-nitro-phenyl)-(2-piperidin-1-yl-ethyl)-amine»2 TFA (74 mg) in ethanol/tetrahydrofuran (1:1. 5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-methyl-N-(2-piperidin-1-yl-ethyl)-benzene-1.4-diamine as a di-TFA salt. (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-methyl-N-(2-piperidin-1 -yl-ethyl)-benzene-1,4-diamine»2 TFA (0.21 mmol maximum) were stirred in N,N-dimethyIformamide (1 mL) and triethylamine (50µL) at 60 - 70 °C for 12 hours. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4Z)-6-bromo-4- [({4-[methyl(2-piperidin-1-ylethyl)amino]phenyl}amino)methylene]isoquinoIine-1,3(2H,4H)-dione. MS (ES+): 483.2[M+H]+ (Formula Removed) Example 257 (42>6-Bramo-4-[({4-[{2-fbutyl(methyl)amino]Bthyl}(rrM9thyl)arnino]phenyl}arnino)methylene]isoquinoline- 1,3(2H,4H)-dione To a solution of toluene-4-sulfonic add 2-[methyH4Hiitro-phenyl)-amin6j-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 u.L) and N-methylbutylamine (75 jiL, 0.63 mmol). The mixture is shaken in 70 °C block shaker overnight. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give N-butyl-N,N'-dimethy H-(4~nitro-phenyJ)-ethane-1,2-diamine as a di-TFA salt (71 mg, 68 %). A solution of N-butyl-N,N,-dimethyl-N'-(4-nitro-phenyl)-ethane-1,2-diamine»2 TFA (71 mg) in ethanol/tetrahydrofuran (1:1, 5 mL) is hydrogenated at atmospheric pressure over 10% palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-[2-(butyl-methyl-amino)-ethyrj-N-methyl-benzene-1,4-diamine as a di-TFA salt. (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-[2-(butyl-methyl-amino)-ethyrj-N-methyt-benzene-1,4-diamine»2 TFA (0.21 mmol maximum) were stirred in N,N-dimethylformamide (1 mL) and triethylamine (50 nL) at 60 - 70 °C for 12 hours. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (42-6-bromo-4- H{4-[{2-[butyl(methyl)amino]ethyl}(methyl)amino]p>henyl}amino)methylene]isoc|uinoline- 1,3(2H,4H)-dione. MS (ES+): 487.3 (M+H)+ (Formula Removed) Example 258 (4Z)-6-Bromo-4-[({4-[2-(dimethylamino)ethoxy]phenyl}amino)methylene]isoquinoline-1.,3(2H,4H)-dione Dimethyl-[2-{4-nitro-phenoxy)-ethyl]-amine is prepared according to Hunter, D.H.; Ponce, Y.Z.; Brown, G.W.; Chamberlain. M.J.; Driedger, A.A.; Morrissey, G. Can J Chem. 62, 2015-2019,1984. MS (ES*):: 211.3 (M+H)* A solution of dimethyl-[2-(4-nitro-phenoxy)-ethyl]-amine hydrochloride (0.29 g, 1.2 mmol) in ethanol (20 mL) fs hydrogenated at atmospheric pressure over 10% palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give 4-(2-dimethylamino-ethoxy)-phenylamine hydrochloride (0.24 g, 96 %). MS(ES+): 181.3 [M+H]+ (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (70 mg, 0.25 mmol) and 4-(2-dimethylamino-ethoxy)-phenyIamine hydrochloride (50 mg, 0.23 mmol) were stirred in N.N-dimethylfornnarnide (1 mL) and triethylamine (50 jiL) at 70 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-bromo-4-[({4-[2- (dimethylamino)ethoxy]pheny]}amino)methylene]isoquinoline-1,3(2H,4H)-dione (81 mg, 82 %). MS (ES+): 430.0, 432.0 (M+H)+ (Formula Removed) Example 259 (4Z)-6-Bromo-4-{[(2-methyl-2,3-dihydro-1H-isoindol-5-yl)amino]methylene}isoquir»oline-1,3(2H,H)-dione The methytation of 4-nitrophthalimide to give 2-methyl-5-nitro-tsoindole-1,3-dione (0.93 g, 43 %) is accomplished via the procedure of Billman, J.H. and Cash, V. J Am Chem Soc. 75(10), 1953, 2499-2501. A solution of give 2-methyl-5-nitro-isoindole-1,3-dione (1.1 g, 5.3 mmol) in ethand/tetrahydrofuran (1:1, 50 mL) is hydrogenated at 45 psi over Raney nickel catalyst. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give 5-amino-2-methyl-isoindole-1,3-dione as a yellow cottony solid (0.85 g, 91 %). 1H NMR (300 MHz, DMSO-dB) ppm 2.94 (s, 3 H), 6.44 (s, 2 H), 6.77 (dd. J=8.2 Hz, 1H), 6.91 (d, J=2.0 Hz, 1H), 7.47 (d, J=8.2 Hz, 1H). To a suspension of lithium aluminum hydride (0.55 g, 14 mmol) in tetrahydrofuran (7 mL) is added solid 5-amino-2-methyl-isoindole-1.3-dione (0.85 g, 4.8 mmol). The resulting suspension is heated at reflux for 15 minutes and is then cooled to 0 °C. At this temperature, the reaction is quenched by the addition of ethanol and then water. The resulting slurry is filtered through a pad of diatomaceous earth, and the filtrate is concentrated under reduced pressure to give a brown solid. The crude solid is dissolved in absolute ethanol and acidified with concentrated ethanolic hydrochloric acid. With the addition of diethyl ether, a brown solid precipitated and is collected by filtration to give 2-methyl-2,3-dihydro-1H-isoindol-5-ylamine as a dihydrochloride salt (0.61 g, 55 %). MS (ES*): 149.3 (M+H)+ (4E>-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.20 g, 0.71 mmol) and 2-methyl-2,3-dihydro-1H-isoindol-5-ylamine»2 HCI (0.52 mg, 2.3 mmol) were stirred in N.N-dimethylformamide (5 mL) and triethylamine (0.83 mL) at 70 DC. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give a crude solid, which is then purified by reverse phase high performance liquid chromatography to provide (4z)6-bromo-4:-{I(2-methyl-2,3-dihydro-1H-isoindol-5-yl)amino]methylene}isoquinpline-1,3(2Hv,4H)-dione»trifluoroacetic acid (80 mg, 22 %). MS (ES): 396.1, 398.2 (M-H) (Formula Removed) Example 260 (4Z-6-Bromo-4-({[4-(1Wmida2ol-1-yl)phenyllam»no}methylene)isoquinoline- 1,3(2W,4W)-dione In a 20 mL vial were combined 4-fluoronitrobenzene (1.1 mL, 10 mmol), imidazole (0.68 g, 10 mmol), and sodium carbonate (1.1 g, 11 mmol) in N,N-dimethylformamide (5 mL). The mixture is shaken at 100 °C for 24 hours and then allowed to cool to room temperature and then diluted with water. Concentrated hydrochloric acid is added to bring the pH to 1, and then the mixture is extracted thrice with chloroform (10 mL). The acidic aqueous phase is then treated with 2.5 M sodium hydroxide solution to give a pH of 10. A light yellow solid is collected and washed with water to give 1-(4-nitrophenyl)-1 H-imidazole. MS (ES*): 190.2 ([M+H]+ A solution of 1-(4-nitrophenyl)-1 H-imidazole (0.38 g, 2.0 mmol) in ethanol (20 mL), water (3 mL), and concentrated hydrochloric acid (5 drops) is hydrogenated for overnight at atmospheric pressure over 10% Pd/C. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 4-(1H-imidazoM-yl)~benzenamine trihydrochloride as a gray powder. MS (ES+): 160.2 (M+H)+ (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (70 mg, 0.25 mmo!) and 4-(1 H-imidazol-1-yl)-benzenamine»3 HCI (70 mg, 0.25 mmoi) were stirred in N,N-dimethylformamide (1.5 mL) and triethylamine (0.15 mL) at 75 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then.dried under vacuum to give (4Z>6-bromo-4-({[4-{1H-irnidazol-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (95 mg, 93 %) MS (ES+): 409.0, 411.0 (M+Hf (Formula Removed) Example 261 (426-Bromo-4-{[(4-{methyl[2-(4-methylpipera2in-1-yI)ethyl]amino}phenyl)amino]methyJene}isoquinoIine-1,3(2H.4H)-dione To a solution of toluene-4-sulfonic acid 2-[methyl-(4-nitro-phenyl)-amino]-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 fiL) and N-methylpiperazine (70 µL, 0.63 mmol). The mixture is shaken in 70 °C block shaker overnight The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give methyl-[2-(4-methyl-piperazin-1-yl)-ethyrj-(4-nitro-phenyl)-amine as a tri-TFA salt (98 mg, 98 %). A solution of methyK2-(4-methyl-piperazin-1-yi)-ethyl]-(4-nitro-phenyl)-amine »3 TFA (98 mg) in ethanol/tetrahydrofuran (1:1, 5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-methyl-N-[2-(4-methyl-piperazin-1-yl)-ethyl3-benzene-1,4-diamine as a tri-TFA salt. (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-Methyl-N-[2-(4-methyl-plperazin-1-yl)-ethyl]-benzene-1,4-diamine «3 TFA (0.21 mmol maximum) were stirred in N.N-dimethylformamide (1 mL) and triethylamine (50 |uL) at 60 — 70 °C for 12 hours. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4Z)-6-bromc~4-{[(4-{methyl[2-(4-methylpiperazH> 1 - yI)ethyfJamino}phenyl)amino]methylene}isoquinoline-1,3(2/-/,4H)-dione as a tri-TFA salt. MS (ES*): 500.2 (M+H)+ (Formula Removed) Example 262 (42>6-Bromo-4-[({4-[methyl(2-rnorpholin-4-ylethyl)amino]phenyl>amino)methylene]isoquinoline-1,3(2H,4H)-dione To a solution of toluene-4-sulfonic acid 2-[methyl-(4-nitrc-phenyl)-amiho]-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 M.L) and morpholine (55 jU_, 0.63 mmol). The mixture is shaken in 70 °C block shaker overnight. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give methyl-(2-morpholin-4-yl-ethylH4-nitro-phenyl)-amine as a di-TFA salt (80 mg. 77 %). MS (ES+): 266.3 [M+H]+ A solution of methyl-(2-morpholin-4-yl-ethyl)-(4-nitro-phenyl)-amine»2 TFA (80 mg) in ethanol/tetrahydrofuran (1:1, 5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. Tpe reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-methyl-N-(2-morpholin-4-yl-ethyl)-benzene-1,4-diamine as a di-TFA salt. (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H.4H)-dione (59 mg, 0.21 mmol) and N-Methyl-N-(2-morpholin^-yl-ethyl)-benzene-1,4-diamine»2 TFA (0.21 mmol maximum) were stirred in N.N-dimettiylformamide (1 mL) and triethyiamine (50 nL) at 60 - 70 °C for 12 hoMrs. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4z)6-bromo-4-[({4-[methyl(2-morpholin-4-ylethyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione. MS (ES*): 587.2 (M+H)* (Formula Removed) Example 263 (4Z)-6-(4-Fluorophenyl)-4-({[4-(4-methylpipera2in-1-yl)phenyQamino}methylene)- isoquinoline-1,3(2H.4H)-dione Using the procedure described for the preparation of (4Z)-6^3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yrjphenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione, after purified by column chromatography over silica gel using 5% MeOH/CHCIa as eluent, 0.098 mg (47.3 % yield) of yellow solid is obtained from 0.20 g (0.45 mmol) of (42)-6-bromo-4-({t4-(4-methylpiperazin-1-yl)phenyl]amino>methylene)isoquinoline-1,3(2H,4H)-dione, 0.095 g (0.68 mmol)of 4-fluorophenylboronic acid, 0.041 g (0.05 mrnol) of tris(dibenzytdeneaacetone)-dipalladrum(O), 0.46 g (0.10 mmol) of 2-(di-t-butyl-phosphino)-biphenyl, and 0.48 g (0.90 mmol) of sodium carbonate: mp 228-229 °C; MS (ESI) m/z 455.2 (M+H)"1 (Formula Removed) Example 264 (4Z)-6-lodo-4-{[(4-{[(3R)-3-methoxypynrolidin-1-yf|methyl}phenyl)amino]methylene}isoquinoIine-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 300 mg (84 % yield) is obtained as a yellow solid from 300 mg (1.1 mmol) (4£}-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H.4H)-dione and 190.57 mg (1.1 mmol) of 4-{[(3R)-3-methoxypyrrolidin-1-yl]methyI}phenyl)amine, mp 160-161°C. MS (ESI) m/z 504.0 (M+1)+ (Formula Removed) Example 265 (4Z-6-(4-Fluorophenyl)-4-{[(4-{[(3S)-3-methoxypyrTO»idin-1-ylJmethylHhenyl)amirio]methylene}isoquinoline-1F3(2H,4H)-dione Using the procedure described for the preparation of '(4Z)-6-(4-fluorophenyl)-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}methyiene)isoquinoline-1,3(2H,4H>-dione, 100 mg of yellow solid (21 % yield) is obtained from 461 mg (1.01 mmol) (4z)6-bromo-4-({[4~(piperiain-1- ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2/-/,4H)-dione and 4-Flurophenyl boronic acid 353.38 mg, (2.53 mmol).; mp 145-146°C MS (ESI) m/z 472.2 ([M+H]+. (Formula Removed) Example 266 (4Z)-6-Bromo-4-{l(4-{I(3R)-a-methoxypyrroliclin-1-yl]methyl}phenyl)amlno]methyiene}isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of example 14, 800 mg (71 % yield) is obtained as a yellow solid from 700 mg (2.48 mmol) (4£)-6-bromo-4-(methoxymethylene)isoquinollne-l ,3(2H,4H)-dione and 514 mg (2.48 mmol) of 4-{[(3R)-3-methoxypyrrolidin-1-yl]methyl}phenyl)amJne, mp 132-133°C. MS (ESI) m/z 458.1 [M+1]+ (Formula Removed) Example 267 (4Z)-6^lcKlo-4-{[(4-difluoromethoxy-3-hydroxybenzy0amino)methylene}isoquinoline- 1.3(2H.4-dione An amount of 4-difluorornethoxy-3-hydroxy benzylamine hydrochloride (113 mg, 0.50 mmol), is dissolved in N.N-dimethylformamide (5 mL), triethylamine (50 µL 0.75 mmol) is added followed by (4E)-6-iodo-4-(methoxyrnethylene)isoquinoline-1,3(2H,4H)-dione (165 mg, 0.50 mmol). After the mixture is stirred at room temperature for 30 min, the solvent is removed in-vacuo and the residue dissolved in 7.5% methanol in chloroform and passed thai a short pad of Florisil eluting with 7.5% methanol in chloroform, the eluate is evaporated and the solid triturated with ether, filtered and washed several times with anhydrous ether to give 193 mg of (4Z)-6-lodo-4-{[(4-difluoromethoxy-3-hydroxybenzyl)amino)methytene}isoquinoline-1,3(2H,4-dione as a beige solid (79% yield); mp 254-5°C, MS data ES(-) 485.0 m/e. (Formula Removed) Example 268 6-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquino»irv-4(1 H)-ylidene)methyQamino}methvl)-2,2-dimethyl-1,3-benzodtoxol-4-yl acetate To a solution of (4Z)-6-bromo-4-({[(7-hydroxy-2,2-dimethyl-1,3-benzodioxol-5-yl)methyrjamino}methylene)isoquinoline-1,3(2H,4H)-dione (30 mg, 67 nmol) in N,N-dimethylformamide (0.5 mL) is added pyridine (12 µL, 0.17 mmol) and acetyl chloride (10 µL). The reaction mixture.is shaken overnight at room temperature and then purified by reverse-phase high performance liquid chromatography to give 6-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyQamino}methyl)-2,2-dimethyl-1,3-benzodioxol-4-yl acetate. (Formula Removed) Example 269 6-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dthydroisoquinolin-4(1 H- ylidene)methyl]amino}methyt)-2,2-dimethyl-1,3-benzodioxol-4-yl cydopropanecarboxylate To a solution of (4Z)-6-bromo-4-({l(7-hydroxy-2,2-dimethyl-1,3-benzodioxol-5-yl)methyamino}methylene)isoquinoline-1,3(2H,4H)-clione (30 mg, 67 nmol) in N.N-dimethyfformamide (0.5 mL) is added pyridine (12 µL, 0.17 mmol) and cyclopropanecarbonyl chloride (10 p.L). The reaction mixture is shaken overnight at room temperature and then purified by reverse-phase high performance liquid chromatography to give 6-{{[(2>(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H}-ylidene)methyl]amino}methyl)-2,2-dimethyl-1,3-benzodioxol-4-yl cydopropanecarboxylate. (Formula Removed) Example 270 (4Z)-6-Bromo-4-[({4-[3-(dimethylamino)propyl]phenyl}amino)rnethyJene]isoquJnoline-1,3(2W,4H)-dione N{4-(3-Oxo-propyl)-phenyl]-acetamide is prepared according to Bjomestedt, R.; Zhong, G.; Lerner, R.A.; Barbas, C.F. J Am Chem Soc. 118, 1996, 11720-11724. t To a suspension of N-[4-(3-Oxo-propyl)-phenyl]-acetamide (96 mg, 0.50 mmol), dimethylamine hydrochloride (82 mg, 1-0 mmol). and sodium acetate (66 mg, 0.80 mmol) in methanol (0.5 mL) is added sodium cyanoborohydride (47 mg, 0.75 mmol): Upon completion of the reaction, the solvent is evaporated under reduced pressure and the residue is partitioned between ethyl acetate and water. The aqueous phase is extracted with ethyl acetate. The combined extracts were concentrated to give N-[4-(3-dimethylamino-propyl)-phenyl]-acetamide (0.14 g, > 100%). MS (ESy. 221.3 (M+H]+ To a solution of N-[4-(3-dimethylamino-propyl)-phenyl]-acetamide (0.50 mmol maximum) in methanol (8 mL) is added 20 % aqueous hydrochloric acid solution. After 3 J4 hours of shaking at 56 °C, an additional 2 drops of concentrated hydrochloric acid is added and shaking is continued for 3 days. The mixture is concentrated to give 4-(3-dimethy!amino-propyl)-phenylamine hydrochloride, which is used without further purification in the following step. MS (ES+): 179.3 (M+H)+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (50 mg, 0.18 mmol) 4-(3-dSmethy!amino-propyt)-phenylamine hydrochloride (0.40 mmol) were stirred in N.N-dimethylformamide (1 mL) and triethylamine (140 pL) at 78 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with water, and then dried under vacuum to give {4Z)-6-bromo-4-[({4-[3-(dimethylamino)propyflphenyl}amino}methylene]isoquinoline-1,3(2H.4H)-dione (58 mg, 75 %) as a golden solid. MS (ES*): 428, 430 (M+H)+ (Formula Removed) Example 271 (4Z)-6-Bromo-4-[(quinolin-6-ylamino)methyJene]isoquinoline-1,3(2H,4H)-dione A mixture of 6-bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (141 mg, 0.5 mmol), 6-aminoquinoline (72.2 mg, 0.5 mmol) in 1 mL of N,N-dimethylformamlde is heated at 110°C for 0.5 h. After cooling in the refrigerator, the precipitate is collected, and washed with N.N-dimethylformamide (DMF) and ether to give 169 mg (85%) of yellow solid. MS (ESI) m/z 394.0, 396.0 (M+H)+1 (Formula Removed) Example 272 (4Z)-6-lodo-4-[(quinolin-6-ylamino)nTethylene]isoquinoline-1,3(2H,4H)-dione A mixture of 6-iodo-4-methoxymelhylene-4H-isoquinoline-1,3-dione (164.5 mg, 0.5 mmol), 6-aminoquinoline (72.2 mg, 0.5 mmol) in 1 mL of N.N-dimethylformamide is heated at 110°C for 0.5 h. After cooling in the refrigerator, the precipitate is collected, and washed with N.N-dimethylformamide(DMF) and ether to give 189 mg (85%) of yellow solid. MS (ESI) m/z442.0 (M+H)+1 (Formula Removed) Example 273 (4Z)-4-({[4-(1H-lmidazo)-1-ylmethyl)phenytJamino}methyJene>6-iodoisoquinoiine- 1,3(2H,4H)-d: 223.3 (M+H]+ A solution of 1-methyl-3-(4-nitrc-phenoxy)-pyrTolidineBA (0.34 g, 1.0 mmol) in ethanol (10 mL) is hydrogenated for one hour at atmospheric pressure over 10 % Pd/C. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 4-(1-methyl-pyrrolidin-3-yloxy)-phenylamine»TFA as a black solid. (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (52 mg, 0.18 mmol) and 4-(1-methyl-pyrrolidin-3-yloxy)-phenylamine»TFA (55 mg, 0.18 mmol) were stirred in N.N-dimethylformamide (1 mL) and triethylamine (100 jd_) at 75 °C. The reaction mixture is purified by reverse phase high performance liquid chromoatography to give (4Z)-6-bromo-4-[({4-[(1-methylpyrrolidin-3-yl)oxy]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione as its TFA salt. MS (ES*): 442.2, 444.2 (M+H)+ (Formula Removed) Example 277 2-Amin(2-4-[(6-bromo-1,3-dioxo-2,3-dihydro-1H-isoquJnolin-4-yHdenemethyl)- amino]-phenyl}-propionic acid A mixture of (4E)-6-bromo-4-(methoxymethylene)iscxuinoline-1,3(2H,4H)-dione (191 mg, 0.50 mmole), N,N-dimethylformamide (2 mL) and 2-Amino-2-(4-amino-phenyl)-propionic acid (90 mg, 0.50 mmole) is stirred and heated at 110°C for one hour, cooled in the refrigerator. The reaction mixture is diluted with ether, filtered, washed with acetonitrile and dried to give a dull yellow solid 71 mg (33%), mp 250-253°C; MS (ESI): m/z 428.2, 430.2 (M - H). (Formula Removed) Example 278 4-[(3-Hydroxy-^-propoxy-benzylamino)-methylene]-6-pyrrol-1-yl-4H-isoquinoline- 1,3-dione A mixture of 5-aminomethyl-2-propoxy-phenol hydrochloride (109 mg, 0.50 mmole), 4 mL of N.N-dimethylformamide and triethylamine (75 µL 0.54 mmole) is stirred for 15 minutes. Then (4-methoxymethylene-6-pyrrol-1-yl-4H-isoquinoline- 1,3-dione (134 mg, 0.50 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, taken up in 5% methanol in chloroform and passed through a short pad of Florisil eluting with 5% methanol in chloroform. The eluate is evaporated in vacuo and treated with acetonitrile, filtered and dried to give a beige solid, 94 mg, (45%), mp 2t5-216°C dec; MS (ES+): m/z 418.2(M + H). (Formula Removed) Example 279 4-^[3-(4-Methyl-piperazin-1-yl)-propylamino]-methylene}-6-pynrol-1-yl-4H- isoquinoiine-1,3-dione A mixture of 4-methoxymethylene-6-pynrol-1-yl-4H-isoquinoline-1,3-dione (134 mg, 0.50 mmole), N.N-dimethylformamide (2 mL) and 3-(4-methyl-piperazin-1-yl)-propylamine (79 mg, 0.50 mmole) is stirred at room temperature for one hour. The reaction mixture is evaporated to dryness, taken up in 2 mL of DMSO and purified by reversed phase HPLC. The fractions containing the product were combined and evaporated, the solid is triturated with ether, filtered and dried to give the product as a di-TFA salt, a grey solid 152 mg (49%), mp 207-210°C; MS (ES+): m/z 394.2 (M + H). Example 280 4-{[(Z)-(6-Bromo-1,3-dioxo-2.3-dihydroisoquinolin~4(1H)-ylidene)methyI]amino}- NN-dimethylbenzohydrazide . To a solution of 4-tert-butoxycarbonylarnino-ben2oic acid (0.10 g, 0.42 mmol) in N.N-dimethylformamide (2 mL) is added sequentially 1-hydroxybenzotriazole hydrate (0.11 g, 0.80 mmol), 1-(3-diemthylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.15 g, 0.80 mmol), N-methylmorphoHne (0.14 mL, 1.2 mmol), and N,N-dimethyIhydrazine (64 juL, 0.80 mmol). The mixture is stirred overnight at room temperature and then purified by reverse phase high performance liquid chromatography to give (4-tert-butoxycarbonylamino-phenyl)-N.N-dimethylbenzohydraade as its trifluoroacetate salt. MS (ES+): 280.3 (M+H]+ A 0 °C ethanolic hydrochloric acid solution (2.9 M, 3.5 mL, 10 mmol) is added (4-tert-butoxycarbonylamino-phenyl)-NIN-dimethylbenzohydra2ide»TFA. After 15 minutes, the reaction mixture is concentrated to give (4-amino-phenyl)-N,N-dimethylbenzohydrazide as its hydrochloride salt. MS (ES+): 180.3 (M+H]+ (4E)-6-Bromo-4-(methoxymethytene)isoquinoline-1,3(2H,4H)-dione (71 mg, 0,25 mmol) and(4-amino-phenyl)-N,N—dimethylbenzohydrazide»HCI (54 mg, 0.25 mmol) were stirred in N,N-dimethyiformamide (1.25 mL) and triethylamine (100 jiL) at 75 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give 4-{[(ZH6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyr|amino}-N,,N,-dimethylbenzohydrazide as its TFA salt. MS (ES*): 429.0, 431.1 (M+H]+ (Formula Removed) Example 281 (4Z)-6-Bromo-4-({[4-(1,3-thiazolidin-3-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H ,4H)-dione Using the procedure described for the preparation of example 14, 680 mg (86 % yield) is obtained as a yellow solid from 500 mg (1.77 mmol) (4E)-6-bromo-4-(methoxymethylene)isoquirtoline-1,3(2H,4H)-d»one and 688 mg (3.54 mmol) 4-thiazoiidin-3- ylmethyl)phenyl]amine; mp 224-225°C. Example 282 470 MS (ESI) m/z 446.0 (M+1+ (Formula Removed) (4Z4-({[4-(PyrroIidin-1-ylmethyl)phenyl]amino}methylene)-6-[4-(tnfIuoromethyf)phenyl]isoquinolJne-1,3(2H,4H)-dtone: Using the procedure described for the preparation of '(4Z)-6-(4-fJuoropheny))({[4-(piperidin-1-ylrnethyl)phenyl]amino}methyJene)isoqu»noline-1,3(2H,4H)-dione, 210 mg (36 %) of yellow solid is obtained from 500 mg (1.17mmol) of 42)-6-bromo-4-({[4-(pyrrolidin-1-ylrnethyl) phenyl}amino)methylene] isoquinolin-1,3(2H,4H)-dione and 4-fluorophenyl boronic acid 556.5 mg, (2.93 mmol); mp 176-177 °C. MS (ESI) m/z 492.2 (M+1). (Formula Removed) Example 283 2-(4-{[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 Hy ylidene)methyl]amino}phenyl)-H,Hdimethylacetohydraade A mixture of 4-nitrophenylacetic acid (0.27 g, 1.5 mmol) and di-ferf-butyldicarbonate (0.65 g, 3.0 mmol) in ethyl acetate (10 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth, and after concentration of the filtrate, the residue is taken up in dioxane/water (1:1, 10 mL). Aqueous sodium hydroxide solution (1 M, 3 mL) is added, followed by di-tert-butyldicarbonate (0.47 g, 2.1 mmol). After stirring for 3 hours at room temperature, the reaction is quenched by the addition of 5 % aqueous potassium hydrogen sulfate solution. The mixture is extracted thrice with dichloromethane, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to afford (4-tert-butoxycarbonylaminc-phenyl)-acetic acid, which is purified by reverse phase high performance liquid chromatography. MS (ES): 250.2 (M-H)' To a solution of (4-tert-butoxycarbonylamino-phenyl)-acetic acid (0.10 g, 0.40 mmol) in N,N-dimethylformamide (2 mL) is added sequentially 1-hydroxybenzotriazole hydrate (0.11 g, 0.84 mmol), 1-(3-diemthylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.16 g, 0.84 mmol), N-methylmorpholine (0.14 mL, 1.3 mmol), and N,N-dimethylhydrazine (64 nL, 0.84 mmol). The mixture is stirred overnight at room temperature and then purified by reverse phase high performance liquid chromatography to give (4-tert-butoxycarbonylamino-phenyl)-N,N-dimethylacetohyrazide as its trifluoroacetate salt. MS (ES+): 294.3 (M+H)+ A 0 °C ethanolic hydrochloric acid solution (2.9 M, 3.5 mL, 10 mmol) is added to (4-tert-butoxycarbonylamino-phenyl)-N,N-dimethylacetohyrazide»TFA. After 15 minutes, the reaction mixture is concentrated to give (4-amino-phenyl)-N.N-dimethylacetohydrazide as its hydrochloride salt. MS (ES+): 194.3 (M+H)+ (4E)-6-Bromo-4-{methoxymethylene)isoquinoline-1,3(2H,4H)-dione (71 mg, 0.25 mmol) and (4-amino-phenyl)-acetic acid N,N-dimethylhydrazide»HCI (57 mg, 0.25 mmol) were stirred in N.N-dimethylformamide (1.25 mL) and trietbylamine (100 jiL) at 75 °C. The reaction mixture is purified by reverse phase high performance liquid chromoatography to give 2-(4-(J(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}phenyl)-N',N*-dimethylacetohydrazide as its TFA salt. (Formula Removed) Example 284 Diethyl [(4Z)-4-({[4-(4-methylpiperaan-1-yl)phenyl]amino}methylene)-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-6-yl]phospnonate To a solution of (4Z)-6-bromo-4-({I4-{4-methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (67 mg, 0.15 mmol) in N.N-dimethylformamide (1 mL) is added diethyl phosphite (22 jiL) and tetrakis(triphenylphosphine)palladium(0) (9 mg, 8 jimol, 0.05 mol %). The mixture is heated in a 120 °C oil bath for 6 hour and then purified by reverse phase high performance liquid chromatography to give diethyl [(4Z)-4-({[4-(4-methylpiperazin-1 -yl)phenyfjamino}methylene)-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-6-yijphosphonate as its ditrifluoroacetate salt (8.8 mg, 3.1 %). MS (ES+): 499.2 (M+Hf (Formula Removed) Example 285 (4Z)-6-lodo-4-{[(4-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyi)phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of example 14, 150 mg (47% yield) is obtained as a yellow solid from 200 mg (0.61 mmol) (4£)-6-iodo-4-(methoxymethylene)isoqu»noline-1,3(2/-/,4H)-dione and 135.5 mg (0.61 mmol) of {t(4-{[(2S)-2-(methoxymethyl)pyrrolidin-1- yl}methyl}phenyl)amine; mp 1150-151 °C. MS (ESI) m/z 518.1 (M+1 )+ Example (4Z)^-Brorm)-4-({[4-(morpholin-4-ylmethyl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione: Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (24), 2.38 g (75.9 % yield) of light brown solid is obtained from 2.0 g (7.09 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione, and 1.63 g (8.5 mmol) of 4-Mopholin-4-ylmethyl-phenylamine mp 209-210°C; MS (ESI) m/z 442.1 (M+H)+1 (Formula Removed) (4Z)-6-Bromo-4-[({4-[(2-methylpyrrolidin-1-yl)methyl]phenyl}arnino)met)iytene]-isoquinolir»e-1,3(2H,4H)-dione (60) Using the procedure described for the preparation of 4Z)-6-bromo-4-({I4-(3,5-dimethylpiperazin-1-yl)pheny0amino}methylene)isoquinoIine-1,3(2H,4H)-dione, 5.11 g (81.9 % yield) of yellow solid is obtained from 4.0 g (14.18 mmol) of 4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3.24 g (17.0 mmol) of4-[(2-methylpyrroIidin-1-yl)methyrjphenyl}amine: mp 183-184 °C; MS (ESJ) m/z 440.0 (M+H)+1 Example 288 (4Z>6-Bromo-4-({I3-fluoro-4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)- isoquinoline-1,3(2H,4H)-dJone Using the procedure described for the preparation of4Z>6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione> 3.0 g (92.0 % yield ) of light brown solid is obtained from 2.0 g (7.09 mmol) of (4E)- 6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 1.63 g (7.8 mmol) of [3-fluoro-4-(4-methylpiperazin-1-yl)phenyl]amine and 25 mL of N,N-dimethylformamide: mp 206-207 °C; MS (ESI) m/z 459.0-461.0 (M+H)+1 (Formula Removed) Example 289 (4Z)-6-{4-Fluorc>phenyl)-4-[({4-[(2-rnethylpyrrolidin-1-yl)methyr]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of(4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpipera2in-1-yfJphenyr}amino)-methytene]isoquJnoline-1,3(2H,4H)-dione, 0.13 g (65. % yield ) of light brown solid is obtained from 0.20 (0.454 mmol) of (4Z)-6-brorno-4-[({4-[(2-rnethy1pyrrolidin-1-yl)methy|Jphenyl}amino)methylene]-isoquinoline-1,3(2H,4H)-dione. 0.095 g (0.681 mmol) of 4-fluorobenzylboronic acid, 0.043 g (0.045 mmol) of Pd(dba)3, 0.02 g (0.09 mmol) of t-Bu3P„ and 0.15 g (0.90 mrnol) of Na2C03: mp 165-166 °C; MS (ESI) m/z 456.2 (M+H]1 (Formula Removed) Example 290 (4Z)-4-({[3-Fluoro-4-(4-methy!piperazin-1-yl)phenyOamino}methylene)-6-(4-fluorophenyl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethyipiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione., 0.12 g (55. % yield ) of yellow solid is obtained from 0.21 (0.454 mmol) of (4Z)-4-({[3-fluoro-4-(4-methylpiperazin-1 -yl)phenyl]amino}methylene)-6-iodoisoquiroline-1,3(2H,4H)-dione, 0.095 g (0.681 mmol) of 4-fluorobenzylboronic acid, 0.043 g (0.045 mmol) of Pd(dba)3, 0.02 g (0.09 mmol) of t-Bu3P. and 0.15 g (0.90 mmol) of Na2C03: mp 166-167 "C; MS (ESI) m/z 475.2 (M+H)+1 (Formula Removed) Example 291 (4Z)-6-(3-Furyl)-4-[({4-[(2-methylpyn-olidin-1-yl)methyrjphenyl}amino)methylene]- isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of(4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4.5-trimethylpiperazin-1-yl3phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione, 0.041 g (21.6. % yield ) of light brown solid is obtained from 0.20 (0.454 mmol) of (4Z)-6-bromo-4-[({4-[(2-methylpyrrolidin-1-yl)methyl]phenyl}amino)methylene]-isoquinoline-1,3(2H,4H)-dione, 0.076 g (0.681 mmol) of 3-furanboronic acid, 0.043 g (0.045 mmol) of Pd(dba)3, 0.02 g (0.09 mmol) of t-Bu3P, and 0.15 g (0.90 mmol) of Na2C03: mp 165-166 °C; MS (ESI) m/z 428.2 (M+H)+1 (Formula Removed) Example 292 PEG5000thio-acetic acid 5-{[(6-iodo-1,3-dioxo-2,3-dihydro-1 H-lsoquinolin-4-ylidenemethyl)-amino]HTiethyl}-2-propoxy~phenyl ester To(4Z)-4-{[(3-hydroxy-4-propoxybenzyOamino]methy!ene}-6-iodoisoquinoline-1,3(2H,4H)-dione (40 mg, 0.084 mmol), mPEG5000SCH2CO2H (460 mg, 0.092 mmol), 1-(3-dimethylaminopropyl)-3-ethyJcarbodiimide hydrochloride (EDC) (26 mg, 0.138 mmol), 1-hydroxybenzotirazole hydrate (HOBT hydrate) (18.6 mg, 0.138 mmol) were added dimethylformamide (5 mL) and triethylamine (38 uL, 0.28 mmol). After 3h concentrate in vacuo and chromatograph on silica gel (CH2CI2/methanol). The desired compound is obtained as a solid (289 mg). Example 293 5-({T(Z)-(6-Iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyilamino}methyl)-2-propoxyphenyl chloroacetate To iodoacetic acid (242 mg, 1.3 mmol) in N.N-dimethylforrnamide (2 mL) at -20C is added N-methylmorpholine (142 uL, 1.3 mmol) and isobutyichloroforrnate (178 uL, 1.3 mmol). After 5 min (4Z)-4-{[(3-hydroxy-4- propoxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (250 mg, 0.52 mmol) is added. The reaction mixtue is allowed to warm to 25C. After 24h 15% aq. Citric acid is added. The resulting precipitate is filtered and washed with water to give a brown solid (352 mg). A portion of this material (50 mg) is chromatographed on silica gel (CH2CI2/MeOH) to give the title compound as a tan powder (23 mg). MS (ESI) m/z 555 (M+ H)+1 (Formula Removed) Example 294 tert-Butyl 4-(4-{[(ZM6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-yIidene)methyl]amino}phenyl)piperazine-1 -carboxylate A N,N-dimethylformamide solution (2.2 mL) of 6-bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (280 mg, 0.99 mmol), and tert-buty! 4-(4-aminophenyl)piperazine-1-carboxylate (300 mg, 1.08 mmol) is heated at 90°C for 0.5 h. After cooling in the refrigerator, the precipitate is collected, and washed with N.N-dimethylformamide and ether to give 222 mg (42%) of the title compound as a yellow solid. MS (ESI) m/z 527.529 (M+H)+1 (Formula Removed) Example 295 (4Z)-4-({[3-Fluoro-4-(4-methylpiperazin-1-yl)phenyfJamino}methylene)-6-rodoisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of4Z)-6-bromo-4-({[4-(3,5-dimeftylpiperaziri-1-yl)phenyl]arnino}rnethylene)isoquinollne-1.3(2H.4H)-dione, 0.27 g (90.0 % yield ) of light brown solid is obtained from 0.2 g (0.61 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1.3(2H,4H)-dione and 0.15 g (0.73 mmol) ofI3-fluoro-4-(4-methy1piperazin-1-yl)phenyl]amine: mp 211-212 °C; MS (ESI) rn/z 507.1 (M+H)+1 (Formula Removed) Example 296 (4Z)-6-lodo-4-({[4-(rnorpholin-4-yfmethyt)phenyrjamino}methylene)isoquinoline- 1.3(2H,4H)-dione: Using the procedure described for the preparation of 4Z)-6-bromo-4-<{[4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2Hf4H)-dione, 0.27 g (91.0 % yield) of tan solid is obtained from 0.20 g (0.608 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione, and 0.14 g (0.608 mmol) of 4-Mopholin-4-ylmethyl-phenylamine: mp 186-187 oC; MS (ESI) m/z 490.1 (M+H)+1 (Formula Removed) Example 297 (4Z)-4-({[3-FJuoro-4-(4-methylpiperazin-1-yl)phenyl]amino}rnethylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of(4Z)-6-(3-furyl)-4-[({4-{(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione. 0.32 g (65.8 % yield ) of light brown solid is obtained from 0.5 (1.09 mmol) of (4Z)-6-bromo-4-({t3-fluoro-4-(4-methylpiperazin-1-yl)phenyQamino}methylene)-isoquinoline-1,3(2H,4H)-dione, 0.2 g (1.78 mmol) of 3-furanboronic acid, 0.10 g (0.11 mmol) of Pd(dba)3, 0.05 g (0.24 mmol) of t-Bu3P, and 0.38 g (3.58 mmol) of lsla2C03: mp 203-204 °C; MS (ESI) m/z 447.2 (M+H)*1 (Formula Removed) Example 298 (42)-4-({4-(4-Methylplperan-1-yl)phenyl]amino}methylene)-6-[4-(trifluoromethoxy)phenyl]isoquinoline-1,3(2H,4H)-dione An amount of 6-bromo-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione (0.1 g, 0.2267 mmol) in 1 ml_ of N,N'-djmethylformamide is added to 4-(trifluoromethoxy)phenylboronic acid (0.07 g, 0.34 mmot), 0.032 g (0.034 mmol) of tris(dibenzylideneacetone)dipalladium(0), tri(t-butyl)phosphine (0.014 g, 0.068 mmol) and cesium carbonate (0.148 g, 0.4534 mmol). The reaction mixture is stirred at 130 oC under N2 for 15 min. Mass spectroscopy suggested the completion of the reaction. The mixture is diluted with chloroform and filtered through Celite. The filtrate is evaporated to dryness and purified by column chromatography using 5% methanol/methylene chloride as eluent to yield 85 mg (72% yield) of the title compound as orange solid. MS (ESI) m/z 523.2 (M+H)+1. (Formula Removed) Example 299 (4Z)-6-(4-FluorophenyI)-4-{[(4-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)aminoJmethylene}isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of '(4Z)-6-(4-fluorophenyl)-4-({I4-(piperidin-1-,ylmethyi)phenyrjamino}methylene)isoquinoline-1,3(2H,4H)-dione, 228 mg (44% yield) is obtained as a yellow solid from 500 mg (1.06 mmol) of (4Z)-6-bromo-4-{[(4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino)methyiene}isoquinoline-1,3(2H,4H-dione and 4-Flurophenyl boronic acid 372 mg, (2.65 mmol).; mp 162-163°C MS (ESI) m/z 486.2 (M+1)* Example 300 (4Z)-6-(4-lsopropoxyphenyl)-4-{[(4-{[(2R)-2-(methoxymethyl)pyrroIidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of {42)-6-(4-fluorophenyl)-4-({[4-(piperidirt-1-ylrnethyl)phenyl]amino}rnethylene)isoquinoline-1.3(2H,4H)-dione, 196 mg (44 % yield) rs obtained as a yellow solid from 400 mg (0.85 mmol) of (4Z)-6-bromo-4-{[(4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-y1]methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione-and 4-isopropoxyphenyl boronicacid 383 mg, (2.13 mmol).; mp 200-201 °C. MS (ESI) m/z 526.2 (M+l]+ (Formula Removed) Example 301 N-[4-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)-2-hydroxyphenylJacrylamide Following the acetylation and desilylation procedure employed for the preparation of H-{2-hydroxy-4-({[(2>(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]ben2amide,(4Z)-4-[({4-amino-3-[(triisoprapylsilyl)oxy]ben2ylamir)rnethytene)-6-brornoisoqulnoline-1,3(2H(4H-dione (54 mg, 0.10 mmol) Is reacted with acryloyl chloride (41 jiL, 0.50 mmol). Following desilylation, precipitation, and washing with methanol and diethyl ether, A/-[4-({[(Z-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)-2-hydroxyphenyl]acrylamide is obtained (8 mg, 18 %). MS (ES ): 440.3 (M-H)' (Formula Removed) Example 302 N-[4-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]-2,2-dichloroacetamide A suspension of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.10 g, 0.35 mmol) and 4-aminobenzylamine (43 mg, 0.35 mmol) in N,N-dimethylformamide (1 mL) is stirred overnight at room temperature and then diluted with water. The precipitate is collected by filtration, washed successively with diethyl ether, water, and methanol, and then dried under house vacuum to give (42-4-{[4-amino benzylamino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (0.11 g, 85 %). MS (ES): 370.1 (M-H)' To a O °C solution of (4Z)-4-{[4-amino benzyIamino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (37 mg, 0.10 mrnol) in N,N-dimethylformamide/dimethylsulfoxide (1:1, 2 mL) is added triethylamine (26 p.L, 0.20 mmol) followed by dichloroacetyl chloride (19 \iL, 0.20 mmol). After 30 minutes of stirring at 0 °C, additional volumes of triethylamine (26 \xL, 0.20 mmol) and dichloroacetyl chloride (50 jiL, 0.53 mmol) were added. After stirring at room temperature for 60 hours, the reaction mixture is quenched by the addition of water. The precipitated solid is collected, dissolved in dimethylsulfoxide, and purified by reverse phase HPLC to give N-[4-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2,2-dichloroacetamide (7 mg, 15 %). MS (ES+): 484.1 (M+H)+ (Formula Removed) Example 303 (4Z)-4-[({4-AmJno-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-bromoisoquinoline-1,3(2H,4H)-dione A solution of 4-nitro-3-[(triisopropylsilyl)oxy]benzaldehyde O-methyloxime (0.70 g, 2.0 mmol) in ethanol (13 mL) and tetrahydrofuran (3 mL) is degassed with solid carbon dioxide, then charged with 5 % palladium on carbon (100 mg) and 88 % formic acid (0.8 mL). The mixture is stirred under 1 atm hydrogen gas overnight. The mixture is then filtered through a pad of diatomaceous earth, and the filtrate is concentrated under reduced pressure to give {4-(aminomethyl)-2-t(triisopropylsilyl)oxy]phenyl}amine as its diformic acid salt. This material is used in the subsequent step without further purification. GC-MS (ES+): 294 (M+) To a mixture of {4-(aminomethyI)-2-[(triisopropylsilyl)oxy]phenyl}amine diformate (0.51 g, 1. 3 mmol) and triethylarnine (0.68 mL, 5.2 mmol) in N,N-dimethylformamide (6.5 mL) is added (4E)-6-bromo-4- (methoxymethylene)isoquinoIine-1,3(2H,4H)-dione (0.34 g, 1.2 mmol). The mixture is stirred overnight at room temperature arid then 1 mL of the reaction mixture is purified by reverse phase HPLC to give a Sample of (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)rTiethy!erie]-6-brornoisoquinoline-1,3(2H,4H)-dione as its trifiuoroacetate salt (10 mg). MS (ES+): 546.2 (M+H)+ (Formula Removed) Example. 304 (Z)-6-Bromo-4-((5-(dimethylamino)pentylaniino)methylene)isoquinollne-1,3(2H,4H)- dione: A mixture of 6-bromo-4-(methoxym^thyiene)-isoquinoline-1,3(2HF 4H)-dione (70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and N1,N1-dimethylpentane-1,5-diamine (32.6 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a light salmon solid, 61.1 mg, (64% yield) MS (ES+): 382.2, (M + H). (Formula Removed) Example 305 (Z)-6-Bromo-4-((4-(dirnethylamino)butylarnino)methylene)isoquinoline-1,3(2H,4H)- dione: A mixture of 6-bromo-4-(methoxymethylene)-isoqutnoline-1,3(2H, 4H)-dione {70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and N1,N1-dimethylbutane-1,4-diamine (29.1 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a light salmon solid, 65.5 mg, (73% yield) MS (ES+): 366.2, (M + H). (Formula Removed) Example 306 (Z)-6-Bromo-4-((3-(d»nriethvlamino)propylamino)methylene)isoquinoline-1,3(2H,4H)- dione: A mixture of 6-bromo-4-(methoxymethylene)-isoquinoline-1,3(2H, 4H)-dione (70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and N1,N1-dimethylpropane-1,3-diamine (25.6 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a light brown solid, 65.8 mg, (66% yield) MS (ES+): 352.2, (M + H). (Formula Removed) (Z)-6-Bromo-4-((2-(piperazin-1-yl)ethylamino)methylene)isoquinoline-1,3(2H,4H)- dione: A mixture of 6-bromo-4-(methoxymethylene)-isoquinoline-1,3(2H, 4H)-dione (70.5 mg, 0.25 mmole), dtmethylformamkte (2 mL) and 2-(piperazin-1-yl)ethanamine (32.3 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a light brown solid, 66.6 mg, (70% yield) MS (ES+): 379.2, (M + H). Example 308 -4-((4-(diethylamino)butylamino)methylene)isoquinoline-1.3(2H,4H)- dione: A mixture of 6-bromo-4-(methoxyrnethylene)-isoquinoline-1,3(2H, 4H)-dione (70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and N1,N1-diethylbutane-1,4-diamine (36.1 mg, 0.25 mmole) is stirred at room temperature for one hour. The eaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a light brown solid, 26.0 mg, (26% yield) MS (ES+): 394.2, (M + H). Example 309 (Formula Removed) (Z)-6-Bromo-4-((3-(pyrrolidin-1-yl)propylamino)methylene)isoquinoline-1,3(2H,4H)- dione: A mixture of 6-bromo-4-(methoxymethylene)-isoquinoline-1,3(2H, 4H)-dione (70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and 3-(pyrrolidin-1-yl)propan-1-amine (32.1 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a light brown solid, 73.3 mg, (77% yield) MS (ES+): 378.2, (M + H). (Formula Removed) Example 310 (Z)-6-Bromo-4-((3-morpholinopropylamino)methylene)isoquinoline-1,3(2H,4H)- dione: A mixture of 6-bromo-4-(methoxymethylene)-isoquinoline-1,3(2H, 4H)-dione (70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and 3-morpholinopropan-1-amine (36.1 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a cream solid, 53.6 mg, (54% yield) MS (ES+): 394.2. (M + H). (Formula Removed) Example 311 (Z)-6-Bronrio-4-((3-(2-oxopyrrolidin-1-yl)propylamino)methylene)isoquinoline- 1,3(2H,4H)-dione: A mixture of 6-bromo-4-(methoxymethylene)-isoquinoline-1,3(2H, 4H)-dione (70.5 mg, 0.25 mmole), dimethylformamide (2 mL) and 1-(3-aminopropyl)pyrrolidin-2-one (35.6 mg, 0.25 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with ether, filtered and washed with fresh ether and dried to give a beige solid, 63.5 rng, (65% yield) MS (ES+): 392.2, (M + H). (Formula Removed) Example 312 4-{[(5-Hydroxy-4-oxo-4H-pyran-2-ylmethyl)-amino]-methylene}-6-pyrrol-1-yl-4H- isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-hydroxy-pyran-4-one (106 mg, 0.75 mmole), 4 mL of N,N-dimethylformamide and 4-methoxymethylene-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione (201 mg, 0.80 mmole) is stirred for one hour at ambient temperature. The reaction mixture is evaporated to dryness, dissolved in 7.5% methanol in chloroform passed through Florisil eluting with 7.5% methanol in chloroform. The eluate is evaporated, treated with acetonitrile, the resulting solid filtered and dried to give a beige solid, 157 mg, (55%), mp 310-2°C dec; MS (ES+): m/z 378.1 (M + H). (Formula Removed) Example 313 6-Bromo-4-{[(5-hydroxy-4-oxo-4H-pyran-2-ylmethyl)-amino]-methylene}-4H- isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-hydroxy-pyran-4-one (106 mg, 0.75 mmole), 4 mL of N,N-dimethylformamide and 4-methoxymethylene-6-bromo-4H-isoquinoline-1,3-dione (212 mg, 0.75 mmole) is stirred for one hour at ambient temperature. The reaction mixture is evaporated to dryness, dissolved in 7.5% methanol in chloroform passed through Florisil eluting with 7.5% methanol in chloroform. The eluate is evaporated, treated with acetonitrile, the resulting solid filtered and dried to give an off white solid, 220 mg, (75%), mp 293-7°C dec; MS (ES+): m/z 391 (M + H). (Formula Removed) Example 314 (Z)-4-((6-Bromo-1 ,3-dioxo-2,3-dihydroiscx}u»noiin-4(1 H>-ylidene)methylamino)butanoicacid: A mixture of (E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (212 mg, 0.75 mmole), dirnethylformamide (5 mL), and 4-aminobutanoic acid (78 mg, 0.75 mmole) is stirred at room temperature for 1 hour. The reaction mixture is diluted with ether, filtered, washed with fresh ether and dried to give a salmon solid, 164 mg. (61%), mp260-2°C dec; MS (ES+): m/z 353.0 (M + H). (Formula Removed) Example 315 (Z)-4-((1,3-Dioxo-6-(1H-pyrrol-1-yl)-2,3-dihydroisoquinolin^(1 H)-ylidene)methylamino)butanoic acid: A mixture of (EM-(meth°xymethylene)-6-(1H-pyrroM-yl)isoquinoline-1,3(2H,4H)-dione (201 mg, 0.75 mmole), dimethylformamide (5 mL), and 4-aminobutanoic acid (78 mg, 0.75 mmole) is stirred at room temperature for 1 hour. The reaction mixture is diluted with ether, filtered, washed with fresh ether and dried to give a beige solid, 215 mg, (84%), mp 230-40°C dec; MS (ES+): m/z 338.1 (M + H). (Formula Removed) Example 316 6-Bromo(5-methoxy-4o-pyran-2-ylmethyl)-amino]-methylene}-4H- isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-methoxy-pyran-4-one (116 mg, 0.75 mmole), 4ML of N.N-dimethylformamide and 4-methoxymethylene-6-bromo-4H-isoquinoline-1,3-dione (212 mg, 0.75 mmole) is stirred for one hour at ambient temperature. The reaction mixture is evaporated to dryness, dissolved in 7.5% methanol in chloroform passed through Florisil eluting with 7.5% methanol in chloroform. The eluate is evaporated, treated with acetonitrile, the resulting solid filtered and dried to give a light pink solid, 152 mg, (50%), mp 259-61°C dec; MS (ES-): m/z 403 (M - H). (Formula Removed) Example 317 4-{[(5-Methoxy-4-oxo-4H-pyran-2-ylmethyl)-amino]-methytene}-6-pyrrol-1-yl-4H- isoquinoline^l ,3-dione A mixture of 2-aminomethyl-5-methoxy-pyran-4-one (116 mg, 0.75 mmole), 4 mL of N,N-dimethylformamide and 4-methoxymethylene-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione (201 mg, 0.80 mmole) is stirred for one hour at ambient temperature. The reaction mixture is evaporated to dryness, dissolved in 7.5% methanol in chloroform passed through Florisil eluting with 7.5% methanol in chloroform. The eluate is evaporated, treated with acetonitrile, the resulting solid filtered and dried to give a beige solid, 106 mg, (36%), mp 251-4°C dec; MS (ES-): m/z 390.1 (M-H). Example 318 (4Z)-6-Bromo-4-I({4-[(3R,5S)-3,5-dimethylpjperazin-1-yl]-3-fluorophenyl}amino)methylene)isoquinoline-1,3(2H ,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4~({[4-(3,5-dimethylpiperazin-1-yl)phenyrjamino}methylene)isoquinoline-1,3(2H,4H)-dione 1.28 g (76.6 % yield) of yellow solid is obtained from 1.00 g (3.50 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline'1,3(2H,4H)-dione, and 1.00 g (4.20 mmol) of{4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-fluorophenyl}amine: mp 168-169 °C; MS (ESI) mte 473.0 (M+H)*1 (Formula Removed) Example 319 (4Z)-4-[({4-[(3R,5S)-3,5-Dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene3-6-iodoisoquinoline-1,3(2H,4H)-dione (75) Using the procedure described for the preparation of4Z)-6-bromo-4-({[4-(3,5Klimeylpiperazin-1-yt)phenyl]aj7i)no}meWiylene)isoquinolJne-1,3(2H,4H)-dione, 0.21 g (65.6 % yield) of yellow solid is obtained from 0.2 g (0.60 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione, and 0.17 g (0.72 mmol) of{4-[(3R,5S)-3,5-dimethylpiperazin-1-yll-3-fluorophenyl}amine: mp 173-174 °C; MS (ESI) m/z 521.0 (M+H)1 (Formula Removed) Example 320 N-[4-({[(ZM6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 Hy yridene)methyl]arnino}rnethyl)-2-hydroxyphenyl]-2,2-dichloroacetamide Following the acetylation and desilylation procedure employed for the preparation of AJ-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]benzamide, (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-bromoisoquinoline-1.3(2HF4H)-dione (60 mg, 0.11 mmol) is reacted with dichloroacetyl chloride (110 pi., 1.1 mmol). Following desilylation and precipitation, N-[4-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydraisoquinolin-4(1H)-ylidene)methyl]amino}methyl)-2-hydroxyphenyll-2>2-dichloroacetamide is obtained 8.8 mg, 16 %). MS (ES): 498.0, 500.0 (M-H)" Example 321 N[4-({[(2H6-Bromo-1,3-dioxo-2,3-dihydroisoqumolin-4(1 H)-ylidene)methyl]amino}rnethyl)phenyf]propanamide To aO°C solution of (4Z)-4-{[4-amino benzylamino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-clione (35 mg, 0.10 mmol) in N,N-dimethylformarnide/dimethylsulfoxide (1:1,2 mL) is added triethylamine (26 µL, 0.20 mmol) followed by propionyl chloride (87 µL 1.0 mmol)- After stirring at room temperature for 30 minutes, the reaction mixture is quenched by the addition of water. The precipitated solid is collected, washed successively with water, diethyl ether, and methanol, and dried under house vacuum to give N-[4-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-yItdene)methyl]amino}methyl)phenyl]propanamide (38 mg, 88 %). Example 322 N-[4-({[CZH6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyrjamino}methyl)phenyl]acrylamide 496 MS (ES): 426.1, 428.2 (M-H)- (Formula Removed) To a 0 °C solution of (4Z)-4-{[4-amino benzylamino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dIone (35 mg, 0.10 mmol) in N,N-dimethylformamide/dimethylsulfoxide (1:1, 2 mL) is added triethylamine (26 u.L, 0.20 mmol) followed by acvryloyl chloride (81 nL, 1.0 mmol). After stirring at room temperature for 30 minutes, the reaction mixture is quenched by the addition of water. The precipitated solid is collected, washed successively with water, diethyl ether, and methanol, and dried under house vacuum to give A/-[4-({[(2>(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-yr«dene)methy!]amino}methyi)phenyfJpropanamide (25 mg, 58 %). MS (ES): 424.1 (M-H)- (Formula Removed) Example 323 (4Z)-4-[({4-Amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4/-/)-dione A mixture of 3-hydroxy-4-nitrobenzaldehyde (1.3 g, 7.5 mmol), and methoxylamine hydrochloride (0.7 g, 8.4 mmol) in pyridine (40 mL) is stirred overnight at room temperature. The solvent is then evaporated under reduced pressure, and the residue is partitioned between ethyl acetate and water. The organic layer is washed once with water and once with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, decanted, and concentrated under reduced pressure to give 3-hydroxy-4-nitrobenzaldehyde O-methyloxime as a yellow solid (1.5 g, 100 %). MS (ES): 195.2 (M-H)' To a solution of 3-hydroxy-4-nitrobenzaldehyde O-methyloxime (5.0 g, 25 mmol) in N,N-dimethylformamide (40 mL) is added imidazole (1.8 g, 27 mmol), followed by triisopropylsilyl chloride (6.0 mL, 28 mmol), and 4-(dimethylamino)pyridine (catalytic amount). After stirring overnight at room temperature, the reaction mixture is diluted with diethyl ether (200 mL) and then washed twice with water and once with saturated aqueous sodium chloride solution.. The organic phase is then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude solid is purified by flash chromatography (hexanes/ethyl acetate) to give 4-nitro-3-[(triisopropylsilyl)oxy]benzaldehyde O-methyloxime as a white solid (6.2 g, 70 %). TOF MS (ES+): 353.2 (M+Hf A solution of 4-nitro-3-[(triisopropylsilyl)oxy]benzaldehyde O-methyloxime (3.1 g, 9.S mmol) In ethanol (100 mL) and tetrahydrofuran (80 mL) is degassed with solid carbon dioxide, then charged with 10 % palladium on carbon (200 mg) and glacial acetic acid (1.3 mL). The mixture is shaked under 45 psl hydrogen gas for 36 hours. The mixture is then filtered through a pad of diatomaceous earth, and the filtrate is concentrated under reduced pressure to give {4-(aminomethyl)-2-[(triisopropylsilyl)oxy}phenyl}amine, a golden semi-solid, as its diacetic acid salt. This material is used in the subsequent step without further purification. GC-MS (ES+): 294 (M+) To a suspension of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.66 g, 2.0 mmol) and {4-(aminomethyl)-2~ [(triisopropylsilyl)oxy]phenyl}amine diacetic acid (0.84 g, 2.0 mmol) in tetrahydrofuran (20 mL) is added triethylamine (0.78 mL, 6.0 mmol). The mixture is stirred at room temperature for three hours and then concentrated under reduced pressure. The residue is triturated with water, and the resulting solid is collected by filtration and washed successively with water and diethyl ether. Following drying under house vacuum, (4Z)-4-{({4-amino-3- [(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4/-/)-dJone is obtained (0.97 g, 81 %). MS (ES*): 592.2 (M+H)* (Formula Removed) Example 324 (4Z)-4-I({4-[(3R,5S)-3,5-Dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene]-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[{{4-[(3R>5S)-3,4(5-trirnethylpiperazin-1-yr]phenyl}amino)-rnethylene]isoquinoline-1,3(2H,4H)-dione, 0.21 g (56.7 % yield ) of yellow solid is obtained from 0.40 (0.85 mmol) of 4Z)-6-bromo-4-[({4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-fluoropheny)}amino)methylene]isoquinoHne-1,3(2H,4H)-dione,"0.14 g (1.3 mmol) of 3-furanboronic acid, 0.08 g (0.085 mmol) of Pd(dba>3, 0.03 g (0.17 mmol) bf t-Bu3P, and 0.18 g (1.70 mmol) of Na2C03: mp 222-223 °C; MS (ESI) m/z 461.1 (M+H)*1 (Formula Removed) Example 325 (4Z)-4-[({4-[(3R,5S)-3,S-Dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(SR^SV-S^.S-trimethylpiperarfn-l-yflpheny^aminoy-methyleneJisoquinoiine-1,3(2H,4H)-dione, 0.18 g (45.0 % yield ) of yellow solid is obtained from 0.40 (0.85 mmol) of 4Z)-6-bromo-4-[({4-[(3R,5S)-3,5-dimethylpiperazin-1-yrj-3-fluorophenyl}amino)methylene)isoquinoline-1,3(2H,4H)-dione, 0.16 g (1.3 mmol) of 3-thiopheneboronic acid, 0.08 g (0.085 mmol) of Pd(dba)3, 0.03 g (0.17 mmol) of t-Bu3P, and 0.18 g (1.70 mmol) of Na2C03: mp 214-215 °C; MS (ES!) m/z 477.1 (M+H)+1 (Formula Removed) Example 326 (4Z)-4-[({44(3R,5S)-3r5-Dimethylpiperazin-1-yt]-3-fluorophenyl}amino)methylene]-6-(4-fluorophenyl)isoqulnoline-1,3(2H,4H)-dione (78) Using the procedure described for the preparation of(4Z)-6-(3-furylHH({4-[(3R,5B)-3,4t5-trimethylptperazin-1-yl]phenyl}amino)-rnethylene]isoquinolirie-1,3(2H,4H)-dione, 0.1B g (39.0 % yield ) of yellow solid is obtained from 0.40 (0.85 mmol) of 4Z>6-bromo-4-[({4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione, 0.18 g (1.3 mmol) of 4-fiubrophenylboronic acid, 0.08 g (0.085 mmol) of Pd(dba)a, 0.03 g (0.17 mmol) of t-Bu3P, and 0.18 g (1.70 mmol) of Na2C03: mp 182-183°C; MS (ESI) m/z 489.1 (M+H)+1 (Formula Removed) Example 327 (4Z)-4-({[4-(1-Methylpipeiidin-4-yI)phenyl}amino}methyiene)-6-thien-3-ylisqquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of(4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl}amino)-methyleneJisoquinoline-1,3(2H,4H)-dione, 0.041 g (21.6. % yield ) of yellow solid is obtained from 0.40 (0.68 mmol) of (4Z)-6-bromo-4-({[4-(1-methyIpiperidin-4- yl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione, 0.17 g (1.02 mmol) of 3-thiopheneboronic acid, 0.08 g (0.09 mmol) of Pd(dba)3, 0.03 g (0.15 mmol) of t-Bu3P, and 0.16 g (1.51 mmol) of Na2C03: mp 217-218 °C; MS (ESI) m/z 444.2 (M+H)+1 (Formula Removed) Example 328 (4Z)-4-({[3-Fluoro-4-(4~rnethylpiperazin-1 -yl)phenyl]amino}methylene)-6-(1 H- pyrrol- 1 -yl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethyipiperazin-1 -yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 0.28 g of tan solid is obtained from 0.2 g (0.746 mmol) of (4E)-4-(methoxy-8.42 g (methylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione and 0.187 g (0.895 mmol) of [3-fluoro-4-(4-methylpipera2in-1-yl)phenyl]amine: mp 206-207 °C; MS (ESI) m/z 446.2 (M+H)+1 (Formula Removed) Example 329 6-Bromo-4-[(4-pyridin-4-yl-phenylarnino)-rnethylene]-4H-isoquinoline-1,3- dione 4-Pyridin-4-yl-phenylamine (130 mg, 0.76 mmol) and 6-bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (200 mg, 0.71 mmol) is heated in N.N-dimethylforrnamide (10 mL) at 100 °C for 2 h. EtOAc (100 mL) and HzO (20 mL) is then added. The EtOAc layer is washed with H20 (3 X 20 mL) and brine (15 mL) and dried over MgS04. After removal of EtOAc, the predpitate is collected and washed with MeOH and Et20 and dried to provide the title compound (230 mg, 77%). 1H NMR (300 MHz, DMSO) δ 12.59 (1H. d, J = 12.9 Hz), 11.50 (1H. s), 9.0 (1H. d, J = 12.6 Hz), 8.53-8.64 (3H, m), 7.43-7.95 (8H, m). MS (ESI) m/z 420.0, 422.0 (M+H)+1; Anal. Cacl.for C21H14BrN302: C, 60.02; H, 3.36; N, 10.00; Found: C, 59.4; H, 3.26; N, 9.34. (Formula Removed) Example 330 (4Z)-6-(3-Furyl)-4-{[(4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(4-fluorophenyl)-4-({[4-(plperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 130 mg (33 % yield) is obtained as a yellow solid from 400 mg (0.85 mmol) of (4Z)-6-bromo-4-{[(4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione and 3-furan boronic acid 238 mg, (2.13 mmol).; rnp 130-131 °C MS (ESI) m/z 458.1 (M+1)+ (Formula Removed) Example 331 (4Z)-4-{[(4-{[(2R)-2-(Methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(4-f)uoropheny))-4-({[4-(piperidin-1-ylmethyl)phenyr)amino}methylene)isoquinoline-1,3(2H,4H)-dione, 90 mg (18 % yield) is obtained as a yellow solid from 500 mg (1.06 mmol) of (42)-6-bromo-4-{[(4-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amlno)methylene}isoquinoline-1,3(2H,4H-dtone and 3-thiophine boronic acid 340 mg, (2.65 mmol).; mp 95-96°C MS (ESI) m/z 474.1 (M+1)+ (Formula Removed) Example 332 6-Bromo-4-{[(4-hydroxy-5-methoxy-pyridin-2-ylmethyl)-amino]-methylene}-4H- isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-methoxy-pyridin-4-ol (123 mg, 0.80 mmole), 4 mL of N.N-dimethylformamide and 4-methoxymethylene-6-bromo-1-yl-4H-isoquinoline-1,3-dione (226 mg, 0.80 mmole) is added and the reaction mixture and stirred for one hour. The reaction mixture is filtered and washed with acetonitrile, the solid filtered and dried to give a white solid, 90 mg, (28%), mp 209-11°C dec; MS (ES+): m/z 402 (M + H). (Formula Removed) Example 333 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-pyrrol-1-yl-4H-rsoquinoline- 1,3-dione A mixture of 2-aminomethyl-5-methoxy-pyridin-4-ol (123 mg, 0.80 mmole), 4 mL of N.N-dimethylformamide and 4-methoxymethylene-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione (215 mg, 0.80 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness and treated with acetonitrile, the solid filtered and dried to give a white solid, 199 mg, (65%), mp 199-209°C dec; MS (ES+): m/z 391.1 (M + H). (Formula Removed) Example 334 N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-yIidene)methyl]amino}methyl)phenyl]benzamide To a solution of (42)-4-[({4-amino-3-[{triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (65 mg, 0.11 mmol) in tetrahydrofuran (6 mL) is added 4-methyJmorpholine (36 µL, 0.33 mmol), and the mixture is cooled to 0 °C in an ice-water bath. Benzoyl chloride (38 µL. 0.33 mmol) is added and the mixture is allowed to stir at room temperature for one hour. To the mixture is then added 1.0 M tetrabutylammonium fluoride solution in tetrahydrofuran (1 mL, 1 mmol). After heating for 10 minutes at 55 °C, water is added. The precipitated solid is collected by filtration, washed with water and acetonitrile, and dried under house vacuum to give N-{2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]benzamide (34 mg, 58 %). MS (ES): 538.2 (M-H)- (Formula Removed) Example 335 N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]-2-nnethyIpropanamide Following the acetylation and desilylation procedure employed for the preparation of N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]benzarnide, (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methyIene]-6-iodoisoquinoline-1,3(2H,4H)-dione (65 mg, 0.11 mmol) is reacted with isobutyryl chloride (38µL, 0.33 mmol). Following desilylation and precipitation, N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2-methylpropanamide is obtained (31 mg, 56 %). MS (ES): 504.2 (M-H)- (Formula Removed) Example 336 (2E)-N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]-2-methylbut-2-enamide General acylation, desilylation procedure B: To a suspension or solution of carboxylic add, in this case tiglic acid (0.11 g, 1.1 mmol) in anhydrous acetonitrile (3 mL) is added oxalyl chloride (neat, 100µL, 1.1 mmol). The mixture is shaken at 65 °C for 30 minutes and then reduced to half volume under reduced pressure. The resulting acetonitrile solution is then added to a solution of (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}arnino)methylene]-6-iodoisoquinoline-1,3(2H.4H)-dione (65 mg, 0.11 mmol) and diisopropylethyiamine (380 µL, 2.2 mmol) in tetrahydrofuran (3 mL) After stirring overnight at room temperature, the reaction mixture is concentrated to dryness under reduced pressure. Tetrabutylammonium fluoride solution (1.0 M, 2.0 mL, 2.0 mmol) is added and the mixture is shaken at 55 °C for 2 hours and then allowed to cool to room temperature. Following concentration, the residue is triturated with water and the resulting solid collected by filtration, washed with acetonitrile, and dried under house vacuum to give (2E)-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2-methylbut-2-enamide (12 mg, 21 %). MS (ES-): 516.1 (M-H)- (Formula Removed) Example 337 (2Z)-3-Chloro-N-[2-hydroxy-4-({[(2)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]acrylamide Following the acetylation and desilylation procedure employed for the preparation of (2E)-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methy1]amino}methyl)phenyl]-2-rnethylbut-2-enarnide,(4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (65 mg, 0.11 mmol) is reacted with acid chloride derived from cis-3-chloroacrylic acid (0.12 g, 1.1 mmol). Following desilylation and precipitation, (2Z)-3-chloro-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4( 1 H)-ylidene)methyl]amino}methyl)phenyl]acrylamide is obtained as a solid (10 mg, 17 %). MS (ES): 522.0 (M-H)- (Formula Removed) Example 338 2-[{Dimethylamino)rnethyl]-N-[2-hydroxy-4-({[(Z)-(6-iodo-1.3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)rnethyl]amino}methyl)phenyl]acrylamide Following the acetylation and desilylation procedure employed for the preparation of (2E)-N-{2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]-2-methylbut-2-enarnide,(4Z)-4-I({4-arnino-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-l,3(2H,4H)-dione (65 mg, 0.11 mmol) is reacted with acid chloride derived from 2-dimethylaminomethyl acrylic acid (Wissner, A.; Overbeek, E.; Reich, M. F.; Floyd, M. B.; Johnson, B. D.; Mamuya, N.; Rosfjord, E. C; Discafani, C.; Davis, R.; Shi, X.; Rabindran, S. K.; et al. J. Med. Chem. 46; 1; 2003; 49 - 63, 0.18 g, 1.1 mmol). Following desilylation and precipitation, 2-[(dimethylamino)methyl]-N-[2-hydroxy-4-({[(Z}-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- yiidene)methyl]amino}methyl)phenyI]acrylamide is obtained as a solid (19 mg, 32 %). MS (ES): 545.2 (M-H)- (Formula Removed) Example 339 N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dlhydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]but-2-ynamide Following the acetylation and desilylation procedure employed for the preparation of (2E)-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)rnethyl]amino}methyl)phenyl]-2-methylbut-2-enamide,(42)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl)amino)methylene]-6-iodoisoquinoline-1,3(2H.4H)-dione (65 mg, 0.11 mmol) is reacted with acid chloride derived from 2-butynoic acid (92 mg, 1.1 mmol). Following desilylation and precipitation, N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]but-2-ynamide is obtained as a solid (20 mg, 36 %). MS (ES): 500.0 (M-H)- (Formula Removed) Example 340 N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]prop-2-ynamide Following the acetylation and desilyiation procedure employed for the preparation of (2E)-N-[2-hydroxy-4-({{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2-methylbut-2-enamide(4Z)-4-[({4-amino-3-((triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (65 mg, 0.11 mmol) is reacted with acid chloride derived from propiolic acid (77 mg, 1.1 mmol). Following desilyiation and precipitation, N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]prop-2-ynamide is obtained as a solid (22 mg, 41 %). MS (ES): 486.0 (M-H)- (Formula Removed) Example 341 N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyrjpropanamide Following the acetylation and desilylation procedure employed for the preparation of N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyllben2amide, (Z)-4-{({4-amino-3-[(triisopropylsilyl)oxy]benzyl}annino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (75 mg, 0.13 mmol) is reacted with propionyl chloride (110 pi_, 1.3 mmol). Following desilylation and precipitation, N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroasoquinolin-4( 1 H)-ylidene)methyl]amino}methyi)phenyl]-2-methylpropanarrude is obtained (9.3 mg, 15 %). MS (ES): 490.1 (M-H)- (Formula Removed) Example 342 N-[2-Hydroxy-4-({[(2)-(6-iodo-1,3-dioxo-2,3-dihydroisoqulnolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]acryIamide A solution of 3-hydroxy-4-nitrobenzaldehyde O-methyloxime (5.9 g, 30 mmol) in ethanol (100 mL) and tetrahydrofuran (100 mL) is degassed with solid carbon dioxide, then charged with 10 % palladium on carbon (500 mg) and concentrated hydrochloric acid (5.5 mL). The mixture is shaken under 50 psi hydrogen gas until consumption of hydrogen had ceased. The mixture is then filtered through a pad of diatomaceous earth, and the filtrate is concentrated under reduced pressure to give 2-amino-5-(aminomethyI)phenol dihydrochloride (6.1 g, 97 %). 1H NMR (300 MHz, DMSO-d6) ppm 3.92 (d, J=5.58 Hz, 2 H), 6.99 (dd, J=8.10 Hz, 1H), 7.14 (d, J=1.4 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H). 8.52 (s, 3H). 10.0 (brs, 3H), 11.0 (s,1H). To a suspension of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (1.0 g, 3.0 mmol) and 2-amino-5-(aminomethyl)phenol dihydrochloride (0.64 g, 3.0 mmol) in N.N-dimethylformamide (15 mL) is added triethylamine (1.2 mL, 9.0 mmol). The mixture is stirred at room temperature for 60 hours and then concentrated to dryness under reduced pressure. The residue is then triturated with water, and the solid is collected by filtration, washed successively with diethyl ether and acetonitrile, and dried under house vacuum to provide (4Z)-4-{[(4-aminc-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione as a golden powder (1.3 g, 100 %). A solution of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline- 1,3(2H,4H)-dione (1.1 g, 2.3 mmol) in dimethylacetamide (12 mL) is cooled to 0 °C in an ice water bath. Acryloyl chloride (1.9 mL, 23 mmol) is added and the mixture Is stirred at 0 °C for 15 minutes. The reaction mixture is then concentrated under reduced pressure and combined with impure material from a previous batch. The material is adsorbed onto flash silica gel, which is then subjected to flash chromatography (methanol/chloroform) to give N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]acrylamide (1.6 g). MS (ES): 488.0 (M-H)- (Formula Removed) Example 343 2-[(2E)-But-2-enoylamino]-5-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl (2E)-but-2-enoate Following the acetylation and desiiylation procedure employed for the preparation of N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methylJamino}methyl)phenyl]benzamide, (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)rnethylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (65 mg. 0.11 mmol) is reacted with crotonic anhydride (49 µL, 0.33 mmol). Following desiiylation and precipitation, 2-[(2E)-but-2-enoytamino]-5-({(Z2)(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl (2E)-but-2-enoate is obtained (17 mg, 27 %). MS (ES): 570.1 (M-H)- (Formula Removed) Example 344 (4Z)-6-Bromo-4-({[4-(1-methylpiperidin-4-yl)phenyl]amino}methylene)lsoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}rnethylene)isoquinoline-1,3(2H,4H)-dione (24), 1.17 g (62.6 % yield ) of yellow solid is obtained from 1.2 g (4.25 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dioneand 0.97 g (5.10 mmol) of [4-(methylpiperidin-1-yl)phenyl]amine: mp 217-218 °C; MS (ESI) m/z 440.1-442.1 (M+H)+1 (Formula Removed) Example 345 (4Z)-4-[({4-[(3R,5S)-3,5-Dimethylpiperazin-1-yl]-3-fluorophenyl}annino)metriylene]-6-(4-methoxyphenyl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoqulnoline-1,3(2H,4H)-dione. 0.29 g (69.0 % yield ) of yellow solid is obtained from 0.40 (0.85 mmol) of (4Z)-6-bromo-4H;({4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-fluorophenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione, 0.18 g (1.3 mmol) of 4-methoxyphenylboronic acid, 0.08 g (0.085 mmol) of Pd(dba)3, 0.03 g (0.17 mmol) of t-Bu3P, and 0.18 g (1.70 mmol) of Na2C03: mp 227-228 °C; MS (ESI) m/z 501.2 (M+H)+1 (Formula Removed) Example 346 (4Z)-4-[({5-[(3R,5S)-3,5-Dimethylpiperazin-1-yl]pyridin-3-yl}amino)methylene]-6-(3- furyl)isoquinoline-1,3(2H.4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-({[6-{4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)isoquinollne-1,3(2H,4H)-dione 500 mg (47 % yield) is obtained as a yellow solid from 500 mg (1.09 mmol) of 4Z)-6-bromo-4-[({5-[(3R,5S)-3.5-dimethylpiperazin-1-yl]pyridin-3-yl}amino)methylene]isoquinoline-1,3(2H,4H)-dione and 3-furan boronic acid 245 mg, (2.19 mmol): mp 175-176°C; MS (ESI) m/z 444.1 (M+1)+ (Formula Removed) Example 347 (4Z)-4-({[4-(Dimethylarnino)-3-hydroxybenzyl]amino}methylene)-6-iodoisoquinoline- 1,3(2H,4H)-dione An amount of 300 mg (0.51 mmol) of (4Z)-4-[({4-amino-3-[(triisopropylsilyl)oxy]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione and formylaldehyde (45.9 mg, 1.53 mmol) were dissolved in tetrahydrofuran (3 mL) and methanol (2 mL). After stirring for ten minutes, a mixture of sodium cyanoborohydride (64.1 mg, 1.02mmol) and acetic acid (0.4 mL, 5.1 mmol) were added drop-wise. The mixture is allowed to stir for 2.5 hours. Tetrabutylammonium fluoride (2 mL) is added and stirred for additional 1 hour. The mixture is neutralized with 1NHCI solution and extracted with dichloromethane (200 ml), dried over sodium sulfate and evaporated. The desired final product is purified by column chromatography to afford 60 mg (26 % yield) of a light brown solid.; mp 198-199°C. MS (ESI) m/z 464.0 (M+1)+. (Formula Removed) Example 348 6-Bromo-4-{[4-(4-chloro-3,5-dimethyl-pyrazol-1-yl)-phenylamino]-methyLene}-4H-isoquinoline-1,3-dione The 4-(4-Chloro-3,5-dimethyl-pyrazol-1-yl)-phenylamine (130 mg, 0.58mmol) and 6-8romo-4-methoxymethylene-4H-isoquinoline-1,3-dione (120 mg, 0.43 mmol) is heated in N.N-dimethyiformamide (10 mL) at 100 °C for 4 h. EtOAc (1O0 mL) and H20 (20 mL) is then added. The EtOAc layer is washed with HzO (3 X 20 mL) and brine (15 mL) arid dried over MgS04. Upon removal of EtOAc, precipitate formed and the precipitate is collected and washed with MeOH and Et2O and dried to provide the title compound (64 mg. 32%). 1H NMR (400 MHz, DMSO) δ 12.56(1H, d, J = 12.4 Hz). 11.46 (1H. s), 8.98 (1H. d, J = 12,4 Hz), 8.50 (1H. s), 7.43-7.94 (6H, m), 2.30 (3H, s), 2.21 (3H, s); MP: 290-291 °C; Anal. Cacl. for C21H18BrCIN4O2: C, 53.47; H, 3.42; N, 11.88; Found: C, 51.49; H. 2.94; N, 11.31. (Formula Removed) Example 349 6-Bromo-4-[(4-pyridin-3-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione:(4Z)-6-bromo-4-{[(3-hydroxy-4propoxybenzyl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of 6-brorno-4-{(4-pyridin-4-yl-pheny!amino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-Pyridin-3-yl-phenylamine (100 mg, 0.59 mmol), 6-Bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (200 mg, 0.71 mmol) in 43% yield as a solid: 1H NMR (300 MHz, DMSO) δ 12.59 (1H, d, J = 12.6 Hz), 11.48 (1H, s), 8.95-9.03 (2H, m), 8.53-8.57 (2H, m), 8.13 (1H, d, J = 7.8 Hz). 7.73-7.94 (5 H. m), 7.43-7.51 (2H. m). MS (ESI) m/z 420.0, 422.0 (M+H)+1;. Anal. Cacl. for C21Hl4BrN302: C, 60.02; H, 3.36; N, 10.00; Found: C, 57.94; H, 2.81; N, 9.66. (Formula Removed) Example 350 (4Z)-6-Bromo-4-[({6-[(2R,6S)-2,6-dimethylpiperidin-4-yl]-5-methylpyridin-3-yl}amino)methylene]isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 900 mg (86 % yield) of solid is obtained from 630mg (2.23 mmol) of (4E)-6-bromo- 4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione, and 0.14 g (0.608 mmol) of 6-[(2R,6S)-2,6-dimethylpiperidin-4-yl]-5-methylpyridin-3-yl}amlne; mp: 194-195 °C; MS (ESI) m/z 470.1 (M-H)-1 (Formula Removed) Example 351 (42)-4-({[4-(1-Acetylpiperidin-4-yl)phenyl]amino}methylene)-6-(3-furyl)isoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene)isoquinoline-1,3(2H,4H)-dionef 0.21 g (72.4. % yield) of yellow solid is obtained from 0.30 (0.68 mmol) of (4Z)-4-({[4-(1-acetylpiperidin-4-yl)phenyl]amino}methylene)-6-bromoisoquinoline- 1,3(2H,4H)-dione, 0.11 g (0.98 mmol) of 3-furanboronic acid, 0.06 g (0.06 mmol) of Pd(dba)3, 0.026 g (0.13 mmol) of t-Bu3P, and 0.14 g (1.32 mmol) of Na2C03: mp 178-179 °C; MS (ESI) m/z 456.2 (M+H)+1 (Formula Removed) Example 352 5-({[(Z)-( 6-Bromo-1,3-dioxo-2.3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)-2-propoxybenzoic acid To a solution of 5-formylsalicylic acid (5.0 g, 30 mmol) in N,N-dimethylformamide (150 mL) is added potassium carbonate (25 g, 180 mmol). The mixture is heated in an 80 °C oil bath and 1-iodopropane (6.4 mL, 66 mmol) is added. The reaction mixture is stirred overnight in a 90 °C bath and then concentrated under reduced pressure. The residue is diluted with water and acidified with concentrated hydrochloric acid to pH 8. After extracting 3X with ethyl acetate, the combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, decanted, and concentrated under reduced pressure: The crude oil is purified is flash chromatography (hexanes/ethyl acetate) to give propyl 5-formyl-2-propoxybenzoate as a solid (5.1 g, 68 %). TOF MS(ES+): 251.1 (M+H)+ To a solution of propyl 5-formyl-2-propoxybenzoate (1.0 g, 4.0 mmol) in tetrahydrofuran/methanol/water (20 mL: 20 mL: 8 mL) is added 5 N sodium hydroxide solution (2 mL, 10 mmol). The mixture is heated in a 70 °C oil bath for three hours and then allowed to cool to room temperature. While acidifying to pH 1 with concentrated hydrochloric acid, a white solid precipitated, which is collected and discarded. The filtrate is concentrated under reduced pressure, and the solid residue is collected by filtration and washed with water to give 5-formyl-2-propoxybenzoic acid as flocculent white needles (0.79 g, 95 %). TOF MS (ES): 207.0 (M-H)- A mixture of 5-formyf-2-propoxybenzoic acid (1.4 g, 6.7 mmol) and methoxylamine hydrochloride (0.62 g, 7.4 mmol) in pyridine (36 mL) is stirred overnight at room temperature. After 30 minutes, the reaction mixture is concentrated under reduced pressure. The residue is taken up in ethyl acetate, washed thrice with water, dried over anhydrous sodium sulfate, decanted, and concentrated. The white crystalline product is washed with water and acetontrile and then dried under house vacuum to give 5-[(methoxyimino)methyl]-2-propoxybenzoic acid. TOF MS (ES): 236.1 (M-H)- To a solution of 5-[(methoxyimino)methyl]-2-propoxybenzoic acid (0.70 g, 2.9 mmol) in ethanol/tetrahydrofuran (1:1, 50 mL) is added concentrated hydrochloric acid (250µL). The mixture is degassed by the addition of a small piece of dry ice; then palladium on carbon (10%, 100 mg) is added. The incomplete reaction mixture is shaken for two hours under 45 psi hydrogen, filtered through a pad of diatomaceous earth, and concentrated under reduced pressure. The material is then redissolved In ethanol/tetrahydrofuran (1:1, 50 mL), degassed, and treated with a RaNi slurry (1 mL). The mixture is shaken overnight under 45 psi hydrogen. After passing the mixture through a pad of Celite and concentrated under reduced pressure, the residue is triturated with methanol to give a solid material, which is collected by filtration. The filtrate is purified by reverse phase HPLC to give 5-(aminomethyl)-2-propoxybenzoicacid trifluoroacetate (0.15 g, 16 %). MS(ES+): 210.3 (M+H)+ (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (67 mg, 0.24 mmol) and 5-(aminomethyl)-2-propoxybenzoic acid trifluoroacetate (50 mg, 0.1& mmol) were coupled in N,N-dimethylformamide (2 mL) and tetrahydrofuran (2 mL) with triethylamine (0.13 mL). The mixture is heated at 50 °C for 30 minutes and then at 65 °C overnight. Water is added and resulting mixture purified by reverse-phase HPLC to give a white solid material which is collected by filtration, washed with water, methanol, and diethyl ether and then dried under house vacuum to give 5-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)-2-propoxybenzoic acid (42 mg, 59 %). MS (ES-): 457.2, 459.2 (M-H)- (Formula Removed) Example 353 5-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyrjamino}methyl)-2-propoxybenzamide To a solution of 5-({[(Z)-{6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)-2-propoxybenzoic acid (30 mg, 65 µmol) in N.N-dimethylformamide(1 mL) is added 1-hydroxybenzotriazole hydrate (22 mg, 0.16 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (31 mg, 0.16 mmol), and 1-methyImorpholine (25µL, 0.23 mmol). After shaking at room temperature for 1 hour, to the reaction mixture is added 30 % aqueous ammonium hydroxide (5 drops). After 10 minutes of agitation, water is added to the mixture, precipitating a solid, which is collected by filtration, washed with water and methanol, and then dried under house vacuum to give 5-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)-2-propoxybenzamide (17 mg, 57 %). MS (ES-): 457.3 (M-H)- (Formula Removed) Example 354 6-lodo-4-{[4-(1-pyrrolidin-1-yl-ethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methyleneJ-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-(1-Fyrrolidin-1-yl-ethyl)-phenylamine (49 mg, 0.26 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoiine-1,3-dione (80 mg, 0.24 mmol) in 23% yield as a brown solid: 1H NMR (300 MHz. CDCI3) δ 12.27(1 H, d. J = 12.6 Hz), 8.33-8.43 (2H, m). 7.90-7.97 (2H, m), 7.46-7.62 (3H, m), 7.23 (2H, d, J = 8.4 Hz). 3.30 (1H, q, J = 5.7 Hz), 2.65 (2H, m), 2.48 (2H, m), 1.82 (4H, m). 1.47 (3H, d, J = 6.6 Hz). MS (ES pos): 488,417. Anal. Cacl. for C22H22IN302: C, 54.22; H, 4.55; N, 8.62; Found: C, 53.72; H, 4.04; N. 7.83. (Formula Removed) Example 355 (4Z)-4-[({6-{(3R,5S)-3,5-Dimethylpiperazin-1-yl]-5-methylpyridin-3-yl}amino)rnethylene]-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline- 1,3(2H,4H)-dione (41), 100 mg (47.0 % yield ) of yellow solid is obtained from 220mg (0.46 mmol) of , and 104 mg (0.94 mmol) of 3-furan boronic acid,: mp 195-196°C; MS (ESI) m/z 458.1 (M+H)+1 (Formula Removed) Example 356 (4Z)-4-[({6-[(3R,5S)-3,5-Dimethylpiperazin-1-yl]-5-methylpyridin-3-yl}amino)methylene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione (41), 120 mg (55.0 % yield ) of yellow solid is obtained from 220mg (0.46 mmol) of, and 120 mg (0.94 mmol) of 3-thiophine boronic acid; mp 219-220°C; MS (ESI) m/z 474.2 (M+H)+1 (Formula Removed) Example 357 (4Z)-4-[({6-[(3R,5S)-3,5-Dimethylpiperazin-1-yl]-5-methylpyridin-3-yl)amino)methylene]-6-(4-methoxyphenyl)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-ylJphenyl}amino)-methyIene]isoquinoline-1,3(2H,4H)-dione (41), 94 mg (41 % yield ) of yellow solid is obtained from 220 mg (0.46 mmol) of, and 140 mg (0.94 mmol) of 4-methoxyphenyl boronic acid: mp 213-214 °C; MS (ESI) m/z 498.2 (M+H) Example 358 (4Z)-6-(4-Methoxyphenyl)-4-[({4-[(2-methylpyrrolidin-1-yl)methyl]phenyl}amino)-methylene]-isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dlone, 0.23 g (6.4. % yield ) of light brown solid is obtained from 0.40 (0.91 mmol) of (4Z)-6-bromo-4-[({4-[(2-methylpyrrolidin-1-yl)methyllphenyl}amino)methylene]-isoquinoline-1,3(2H,4H)-dione, 0.2 g (1.31 mmol) of 4-methoxybenzylboronic acid, 0.086 g (0.90 mmol) of Pd(dba)3, 0.04 g (0.18 mmol) of t-Bu3P, and 0.30 g (1.8 mmol) of Na2C03: mp 232-233 °C; MS (ESI) m/z 466.2 (M+H)+1 (Formula Removed) Example 359 (2E)-4-(Dimethylamino)-N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoqurnolin-4(1H)-ylidene)methyl]amino}methyl)phenyl] but-2-enamide An amount of 8.3 g (50.6 mmol) of (E)-4-(dimethylamino)-2-butenioc acid is added excess of 2.0M oxalyl chloride (10 mL) and refluxed at 60°C until all the solid is in solution. To a separate flask is added 2.2g (5.06 mmol) of '2-(acetylamino)-5-({[(ZM6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H) -ylidene)methyl]amino}methyl)phenyl acetate, and N,N-dimthetylacetamide (5 mL) and placed in an ice bath for ten minutes. The mixture containing the acid chloride is cooled to room temperature and evaporated to dryness. Dichloromethane (5mL) is added and transferred to the flask in the ice bath slowly. The mixture is allowed to stir in the ice bath for 3 hours. It is evaporated and purified by column chromatography with 10% methanol: 80% dichloromethane: 1.5% ammonium hydroxide to give the desired product (1.2g 43% yield) as a light-brown solid.; mp 185-186°C MS (ESI) m/z 547.0 (M+1)+. (Formula Removed) Example 360 6-lodo-4-{[4-(4-methyl-piperazin-1-yl)-cyclohexylamino]-methylene}-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-rsoquinoline-1,3-dione, the title compound is obtained from 4-(4-Methyl-piperazin-1-yl)-cyclohexylamine (40 mg, 0.20 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (60 mg, 0.18 mmol) in 28% yield as a pale yellow solid: 1H NMR (400 MHz, CD30D) δ 8.44( 1H, s). 8.17 (1H, d, J = 1.2 Hz), 7.76 (1H, d, J = 8.4 Hz), 7.52 (1H, dd, J = 8.4 and 1.6 Hz), 2.76-3.51 (10H, m), 2.75 (3H, s), 2.05-2.20 (4H, m), 1.51-1.59 (4H, m). MS (ESI): 495 (M+1)+1. Anal. Cacl. for C21H27IN4O2: C, 51.02; H, 5.50; N, 11.33; Found: C, 39.87; H. 3.93; N. 7.41. (Formula Removed) Example 361 6-lodo-4-{[4-(1-methyl-pyrrolidin-2-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-y)-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-(1-MethyI-pyrrolidin-2-yl)-phenylamine(2.52 g, 90% pure, 12.8 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (4.0 g, 12.1 mmol) in 61% yield as a brown solid: 1H NMR (300 MHz. CDCI3) δ 12.29(1H. d, J = 12.6 Hz), 8.37-8.43 (2H, m). 7.91-7.97 (2H, m), 7.42-7.61 (3H, m), 7.22 (2H, d, J = 8.4 Hz), 3.24-3.29 (1H, m), 3.05-3.11 (1H, m), 2.19 (3H. s), 1.70-2.36 (5H, m). MS (ESI): 474 (M+1)*1. Anal. Cacl. for C21H2olN302: C, 53.29; H, 4.26; N, 8.88; Found: C, 53.23; H, 3.91; N, 8.54. (Formula Removed) Example 362 6-lodo-4-{[(4-hydroxy-5-methoxy-pyridin-2-ylmethyl)-amino3-methylene}-4H- isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-methoxy-pyridin-4-ol (116 mg, 0.75 mmole), 4 mL of N.N-dimethylformamide and 4-methoxymethylene-6-iodo-4H-isoquinoline-1,3-dione (247 mg, 0.75 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness and treated with acetonitrile, the solid filtered and dried to give a pink solid, 293 mg. (87%); MS (ES+): m/z 451.9 (M+H). (Formula Removed) Example 363 4-{[(4-Hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino-methylene}-6-pyrrol-1-yl-4H- isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-propoxy-pyridin-4-ol (137 mg. 0.75 mmole)IN 10 mL of N.N-dimethylformamide is stirred, then 4-methoxymethylene-6-pyrrol-1-yl-4H-isoquinoline-1,3-dione (201 mg, 0.75 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, triturated with 5% methanol in chlororform, filtered, washed with fresh 5% methanol in chloroform, washed with acetonitrile and dried to give a grey solid, 290 mg, (92%); MS (ES+): m/z 419.1 (M + H). (Formula Removed) Example 364 4-{[(4-Hydroxy-5-propoxy-pyridin-2-ylmethyI)-amino]-methylene}-6-iodo-4H- isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-propoxy-pyridin-4-ol (137 mg, 0.75 mmole) in 10 mL of N.N-dimethylformamide is stirred, then 4-methoxymethylene-6-iodo-4H-isoquinoline-1,3-dione (247 mg, 0.75 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, triturated with 5% methanol in chlororform, filtered washed with fresh 5% methanol in chloroform, washed with acetonitrile and dried to give a pink solid, 313 mg, (87%); MS (ES+): m/z479.9(M + H). (Formula Removed) Example 365 4-{[(4-Hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino}-methylene}-6-bromo-4H- isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-propoxy-pyridin-4-ol (137 mg, 0.75 mmole) in10 mL of N,N-dimethylformamide is stirred, then 4-methoxymethylene-6-bromo- 4H-isoquinoline-1,3-dione (212 mg, 0.75 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, triturated with 5% methanol in chlororform, filtered washed with fresh 5% methanol in chloroform, washed with acetonitrile and dried to give a beige solid, 303 mg, (93%); MS (ES+): m/z 432.0 (M + H). (Formula Removed) Example 366 (4Z)-4-({[3-Hydroxy-4-{propylamino)benzyl]amino}methylene)-6-iodoisoquinoline- 1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-4-({[4-(dimethylamino)-3-hydroxybenzyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione, 122 mg of yellow-brown solid (51 % yield) is obtained from 300 mg (1.01 mmol) of (4Z)-4-[({4-amino-3- [(triisopropylsilyl)oxy]benzyl}arnino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione and propylaldehyde 41 uL, (0.56 mmol).; mp 236-237°C MS (ESI) m/z 478.0 (M+1)+. (Formula Removed) (Formula Removed) Example 367 D-1 -{4-[(6-lodo-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-benzyl}-pyrrolidine-2-carboxylic add methyl ester Using the procedure described for the preparation of 6-Bromo-4-{(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from D-1-(4-Amino-benzyl)-pyrrolidine-2-carboxylic acid methyl ester (100 mg, 0.43 mmol), 6-iodo-4-methoxyrnethylene-4H-isoquinoline-1,3-dione (160 mg, 0.49 mmol) in 44% yield as a brown solid: 1H NMR (400 MHz, DMSO) δ 12.55 (1H, d, J = 12.8 Hz), 11.39 (1H, s), 8.93 (1H, d, J = 12.8 Hz). 8.59 (1H, s). 7.32-7.74 (6 H, m), 3.85 (1H, d, J = 12.8 Hz), 3.60 (3H, s), 3.53(1 H, d, J = 13.2 Hz), 3.26-3.30 (1H, m), 2.85-2.89 (1Ht m), 2.37-2.39 (1H, m), 1.72-2.10 (4H, m). MS (ESI): 532 (M+1)+1 Anal. Cad. for C23H22IN3O3: C, 51.99; H, 4.17; N. 7.91; Found: C, 51.37; H, 3.59; N, 7.64. (Formula Removed) Example 368 D-4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-mthylene}-6-iodo- 4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from D- [1-(4-Amino-benzyl)-pyrrolidin-2-yl]-methanol (2.36 g, 11.4 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (3.0 g, 9.1 mmol) in 76% yield as a brown solid: 1 HNMR (400 MHz, DMSO) δ 12.55 (1H, d, J = 12.4 Hz), 11.38 (1H, s), 8.93 (1H, d, J = 12.8 Hz), 8.59 (1H, s), 7.36-7.74 (6 H, m), 4.44 (1H, br), 4.06 (1H, d, J = 13.2 Hz), 3.31-3.48 (3H, m), 2.79 (1H, m), 2.5-2.6 (1H, m), 2.33 (1H, m), 1.88-1.90 (1H, m). 1.54-1.63 (3H, m). MS (ESI): 504.0 (M+1)+1. Anal. Cacl. for C22H22lN3O3: C, 52.50; H, 4.41; N, 8.35; Found: C. 52.46; H, 4.04; N, 8.15. (Formula Removed) Example 369 D-4-({4-[2-(1 -Hydroxy-1 -methyl-ethyl)-pyrrolidin-1 -ylmethyl]-phenylamino}-methylene)-6-iodo-4H-isoquino!ine-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methyleneJ-4H-isoquinoline-1,3-dione, the title compound is obtained from 2-[1-(4-Amino-benzyl)-pyrrolidin-2-yl]-propan-2-ol (70 mg, 0.30 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (110 mg, 0.33 mmol) in 35% yield as a brown solid: 1H NMR (400 MHz, DMSO) δ 12.53 (1H, d, J = 12.8 Hz), 11.38 (1H, s), 8.92 (1H, d, J = 13.2 Hz), 8.58 (1H, s), 7.40-7.74 (6H, m), 4.34(1H, d, J = 13.6 Hz). 4.08 (1H, br), 3.36( 1H, m), 2.78 (1H, m), 2.61 (1H, m), 2.19 (1H, m), 1.59-1.90 (4H, m), 1.14 (3H. s), 1.10 (3H. s). MS (ESI): 532 (M+1)+1. HRMS Cacl. for C24H27IN3O3: 532.10917; Found: 532.10965. (Formula Removed) Example 370 (4Z)-Bromo-4-[({3,5-difluoro-4-t(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1 H)-yl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenyGamino}methylene)isoquinoline-1,3(2H,4H)-dione, 1.87 g (72.2 % yield) of light brown solid is obtained from 1.45 g (5.14 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinofine-1,3(2H,4H)-dione, and 1.3 g (5.14 mmol) of {3,5-difluoro-4-[(8aS)-hexahydropyrrolo[1,2-a]pyrazn-2(1H)-yl]phenyl}amine: mp 190-191 °C; MS (ESI) m/z 503.1 (M+H)+1 (Formula Removed) Example 371 (4Z)-4-[({3,-Difluoro-4-[8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1 H)-yl]phenyl}amino)-methylenel-6-thien-3-ylisoquinoline-1,3(2H,4H)dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trirnethyliperazin-1-yrjphenyl}amino)-rnethylenelisoquinoline-1,3(2H,4H)-dione, 0.13 g (43.3 % yield ) of yellow solid is obtained from 0.3 (0.6 mmol) of (4Z)-6-bromo-4-[({3,5-difluoro-4-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin- 2(1H)-yl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione, 0.11 g (0.9 mmol) of 3-thiopheneboronic acid, 0.06 g (0.06 mmol) of Pd(dba)3, 0.024 g (0.12 mmol) of t-Bu3P, and 0.13 g (1.2 mmol) of NazC03: mp 190-191 °C; MS (ESI) m/z 507.1 (M+H)+1 (Formula Removed) Example 372 (4Z)-6-Bromo-4-({[4-[(3R,5S)-3.5-dimethylpiperazin-1-yl]-3-(trifluoromethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of 42)-6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, \2.28g (62 % yield) of yellow solid is obtained from 2.0g (7.0mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline 1,3(2H,4H)-dione, and 2.13 g (7.7 mmol) of 4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3- (trifluoromethyl)phenyl]amine; mp: 224-225 °C; MS (ESI) m/z 523.1 (M+H)+1 (Formula Removed) Example 373 (42)-4-[({4-[(3R.5S)-4-(N,N-Dimethylglycyl)-3,5-dlmethylpiperazin-1-yl]phenyl}amino)methylene]-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione (41), 150 mg (51 % yield ) of yellow solid is obtained from 300 mg (0.56 mmol) of (4Z)-6-bromo-4-[({4-{(3R,5S)-4-(N,N-dimethylglycyl)-3.5- dimethylpiperazin-1-yl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione (CATS-1265844), and 125 mg (1.12 mmol) of 3-furan boronic acid: mp 191-192°C; MS (ESI) m/z 528.1 (M+H) (Formula Removed) Example 374 4-({4-[2-(1-Hydroxy-ethyl)-pyrrolidin-1-ylmethyr|-phenylarnino}-methylene)-6-iodo- 4H-isoquinoIine-1,3-dione Using the procedure described for the preparation of 6-bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 1-[1-(4-Amino-benzyl)-pyrrolidin-2-yl]-ethanol (200 mg, 0.91 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (290 mg, 0.88 mmol) in 22% yield as a single diastereomen 1H NMR (400 MHz. DMSO) δ12.53 (1H. d, J = 12.8 Hz), 11.38 (1H, s), 8.93 (1H, d, J = 12.8 Hz), 8.59 (1H, s), 7.36-7.74 <6H. m), 4.47 (1H, br), 4.12(1H, d, J = 12.8 Hz). 3.69( 1H, m), 3.36-3.39 (1H, m), 2.81 (1H, m), 2.67 (1H, m), 2.22 (1H, m), 1.54-1.76 (4H, m), 1.05 (3H, d. J = 6.4 Hz). MS (ESI): 518.1 (M+1)+1. Anal. Cad. for C23H24IN3O3: C, 53.4; H, 4.68; N, 8.12; Found: C. 48.24; H, 4.18; N, 6.97. (Formula Removed) Example 375 6-lodo-4-({4-[2-(1-methoxy-ethyl)-pyrrolidin-1-ylmethyl]-phenylamino}-methy!ene)- 4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenyIamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-[2-(1-Methoxy-ethyl)-pyrroridin-1-ylmethyl]-phenylamine (200 mg, 0.85 mmol), 6-iodo-4-methoxymethylene-4H-isoquinolme-1,3-dione (325 mg, 0.99 mmol) in 33% yield as a brown solid: 1H NMR (300 MHz, CDCI3) δ12.28 (1H, d, J = 12.9 Hz), 8.53 (1H, br), 8.35 (1H, d, J = 12.9 Hz), 7.91-7.96 (2H. m), 7.57-7.60 (1H, m), 7.41 (2H, d, J = 8.1 Hz), 7.20 (2H, d, J = 8.4 Hz), 4.18 (1H. d, J = 13.5 Hz), 3.34-3.40 (2H, m), 3.38 (3H, s), 2.92 (1H, m), 2.72-2.76 (1H, m), 2.19 (1H, m), 1.61-1.83 (5H, m), 1.16 (3H, d, J = 6.0 Hz). MS (ESI): 532.1 (M+1)+1. Anal. Cacl. for C24H26lN3O3: C. 54.25; H. 4.93; N, 7.91; Found: C, 53.51; H, 4.41; N, 7.63. (Formula Removed) Example 376 L-4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-6-iodo-4H-isoquino!ine~1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from L- [1-(4-Amino-benzyl)-pyrrolidin-2-yl]-methanol (230 g, 1.14 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (200 mg, 0.61 mmol) in 72% yield as a brown solid: MS (ESI): 504.1 (M+1)+1. Anal. Cacl. for C22H22IN3O3: C, 52.50; H, 4.41; N, 8.35; Found: C, 52.07; H, 4.21; N, 8.11. (Formula Removed) Example 377 tert-Butyl 4-(4-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}phenyl)piperazine-1-carboxylate A N.N-dimethylformamide solution (2.2 mL) of 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (329 mg, 1 mmol), and tert-butyl 4-(4-aminophenyl)piperazine-1-carboxyiate (277 mg, 1 mmol) is heated at 90°C for 0.5 h. After cooling in the refrigerator, the precipitate is collected, and washed with N.N-dimethylformamide and ether to give 423 mg (74%) of the title compound as a yellow solid. MS (ESI) m/z 575.2 (M+H)+1 (Formula Removed) Example 378 (4Z)-6-lodo-4-{[(4-piperazin-1-ylphenyl)arnino]methylene}isoquinoline-1,3(2H,4H)- dione A N,N-dimethylformamide mixture (0.6 mL) of tert-butyl 4-(4-{[(Z)-(6-iodo-1,3-dioxo-2.3-dihydroisoquinolin-4(1 H)-yIidene)methyl]amino}phenyl)piperazine-1 -carboxylate (50 mg, 0.087 mmol) and concentrated phosphoric acid (0.6 mL) is heated at 60 C for 2 h. After evaporating to dryness, the residue is partitioned between methylene chloride and saturated sodium bicarbonate. The organic layer is washed with water, dried, and evaporated to yield 10 mg (24%) of the title compound as an orange solid. MS (ESI) m/z 475.2 (M+H)+1 (Formula Removed) Example 379 (Z)-4-(((6-Bromo-5-propoxypyridin-2-yl)methylamino)methylene)-6-iodoisoquinoline- 1,3(2H,4H)-dione: A mixture of (E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (173 mg. 0.40 mmole), dimethylformamide (4 mL), and mPEG-NCO1 (2.0 g, ~0.4 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with acetonitriie, filtered, washed with fresh acetonitriie and dried to give an off-white solid, 877 mg, (41%); MS (ESI): MW 5380. 5424. 5469. 5512. 5556, 5599, 5644, 5687. (Formula Removed) Example 380 (4Z)-4-[({4-[(3R,5S)-4-(N,N-Dimethylglycyl)-3,5-dimethylpiperazin-1 -yl]phenyl}amino)methylene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione (41), 130 mg (43 % yield ) of yellow solid is obtained from 300 mg (0.56 mmol) of (4Z)-6-bromo-4-[({4-[(3R.5S)-4-(N,N-dimethylglycyl)-3,5-dimethylpiperazin-1-yl]phenyl}amino)methylene]isoquinoline-1,3{2H,4H)-dione (CATS-1265844). and 143.4 mg (1.12 mmol) of 3-thiohpine boronic acid: mp 198-199°C; MS (ESI) m/z 545.2 (M+H) (Formula Removed) Example 381 (4Z)-6-Bromo-4-[({4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3,5-difluorophenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenyl]amino}rnethylene)isoquinoline-1.3(2H,4H)-dione 7.58 g (87.0 % yield) of tan solid is obtained from 5.0 g (17.7 mmol) of (4E)-6-bromo-4-(methoxymethyiene)isoquinoline-1,3(2H,4H)-dione, and 4.7 g (19.5 mmol) of{4-{(3R,5S)-3.5-dimethylpiperazin-1-yl]-3,5-difluorophenyl}amine: mp 187-188 °C; MS (ESI) m/z 491.1 (M+H)+1 (Formula Removed) Example 382 (4Z)-4-[({3-Fluoro-4-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1 H)- yl]phenyl}amino)-methylene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyi)-4-l({4-[(3R,5S)-3,4,5-trirnethylpiperazin-1-yl]phenyl}amino)-methylenelisoquinoline-1,3(2H,4H)-dione 0.38 g (76.0 % yield ) of yellow solid is obtained from 0.5 (1.03 mmol) of (4Z)-6-bromo-4-[({3-fluoro-4-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1 H)-yl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione, 0.2 g (1.55 mmol) of 3-thiopheneboronic acid, 0.10 g (0.10 mmol) of Pd(dba)3, 0.02 g (0.21 mmol) of t-Bu3P, and 0.22 g (2.06 mmol) of Na2C03: mp 208-209 °C; MS (ESI) m/z 489.2 (M+H)+1 (Formula Removed) Example 383 (4Z)-4-[({4-[(3R,5S)-3,5-Dimethylpiperazin-1-yl]-3,5-difluorophenyl}amino)ethylene]-6-thien-3-ylisoquinolme-1,3(2H,4H)-dione (83) Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl)phenyl}amino)-methylene]lsoqulnoline-1,3(2H,4H)-dione. 4.12 g (82.0 % yield ) of yellow solid is obtained from 5.0 (10.18 mmol) of (4Z)-6-bromo-4-[({4-[(3R,5S)-3,5-dimethyIpiperazin-1-yl]-3,5-difluorophenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione 1.95 g (15.27 mmol) of 3-thiopheneboronic acid, 0.93 g (1.02 mmol) of Pd(dba)3,0.02 g (2.04 mmol) of t-Bu3P, and 2.16 g (20.4 mmol) of Na2C03: mp 195-196 °C; MS (ESI) m/z 495.2 (M+H)+1 (Formula Removed) Example 384 (2E)-N-[(4Z)-4-({[4-(4-Methylpiperazin-1 -yl)phenyl]amfno}methylene)-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-6-yl]but-2-enamideFollowing the acetylation procedure employed for the preparation of N-[2-hydroxy-4-({[(Z)-(6-iodo-1 ,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl)amino}rnethyl)phenyl3acrylamide, a solution of (4Z)-6-amino-4-({[4-(4-methylpiperazin-1- yl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione in dimethyiacetamide (1 nnL) is cooled to 0 °C in an ice water bath. Trans-crotonyl chloride (110 p.L, 1.0 mmol) is added and the mixture is stirred at 0 °C for 5 minutes. The reaction mixture is then concentrated under reduced pressure and then purified by reverse phase HPLC to provide (2E)-N-[(4Z)-4-({[4-(4-methylpiperazin-1- yl)phenyl]amino}methylene)-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-6-yi]but-2-enamide trifluoroacetate (18 mg, 32 %). MS (ES): 443.4. 445.4 (M-H)- (Formula Removed) Example 385 N-[(4Z)-4-({[4-(4-Methylpiperazin-1-yl)phenyl]amino}methylene)-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-6-yl]acrylamide Following the acetylation procedure employed for the preparation of N-[2-hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)phenyl]acrylamide, a solution (4Z)-6-amino-4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione in dimethylacetamide (1 mL) is cooled to 0 °C in an ice water bath. Acryloyl chloride (82 µL, 1.0 mmol) is added and the mixture is stirred at 0 °C for 5 minutes. The reaction mixture is then concentrated under reduced pressure and then purified by reverse phase HPLC to provide N-[(4Z)-4-({[4-(4-rnethylpiperazin-1-yl)phenyl]amino}methylene)-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-6-yl]acrylarnide trifluoroacetate (18 mg, 33 %). MS (ES*): 432.3, 433.4 (M+H)+ (Formula Removed) Example 386 (4Z)-6-lodo-4-({[4-(4-isopropylpiperazin-1 - yl)phenyl]amino}methylene)isoq uinoline- 1,3(2H,4H)-dione (4Z)-6-iodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (23.7 mg, 0.05 mmol) is dissolved in N-methylpyrrolidinone (0.5 mL) and methylene chloride (0.15 mL), followed by addition of sodium triacetoxyborohydride (122 mg, 0.575 mmol), acetone (0.095 mL, 1.29 mmol) and acetic acid (0.075 mL, 1.31 mmol). After stirring at room temperature for 1 h, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 18.8 mg (73 %) of the title compound as a yellow solid. MS (ESI) m/z 517.0 (M+H)+1 (Formula Removed) Example 387 (4Z)-6-lodo-4-[({4-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]phenyl}amino)methylenelisoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved In N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), 1 -methyl-piperidin-4-one (0.318 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 45 mg (78 %) of the title compound as a yellow solid. MS (ESI) m/z 572.2 (M+H)+1. (Formula Removed) Example 388 (4Z)-6-lodo-4-({[4-(4-propylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium ' triacetoxyborohydride (244 mg, 1.15 mmol), propionaldehyde (0.186 mL, 2.6 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 36 mg (70 %) of the title compound as a yellow solid. MS (ESI) m/z 517 (M+H)+1. (Formula Removed) Example 389 (4Z)-4-[({4-[4-(2-Furylmethyl)piperazin-1-yI]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (42)-6-lodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL). followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), furan-2-carbaldehyde (0.214 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 49 mg (88 %) of the title compound as a yellow solid. MS (ESI) m/z 555.4 (M+H)+1. (Formula Removed) Example 390 (4Z)-4-[({4-[4-(3-Furylmethyl)piperazin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(4-piperazin-1-ylphenyl)amino}methylene}isoquinoline-1,3(2H.4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), furan-3-carbaldehyde (0.214 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 45 mg (81 %) of the title compound as an organge solid. MS (ESI) m/z 555.4 (M+H)+1. (Formula Removed) Example 391 (4Z)-4-[({4-[4-(Cyclopropylmethyl)piperazin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{t(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), cyclopropanecarbaldehyde (0.195 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 44 mg (83 %) of the title compound as a yellow solid. MS (ESI) m/z 529.4 (M+H)+1. (Formula Removed) Example 392 (4Z)-4-({[4-(4-Cyclobutylpipera2in-1-yl)phenyllamino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(4-piperazin-1 -ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), cyclobutanone (0.195 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 32 mg (60 %) of the title compound as a yellow solid. MS (ESI) m/z 529.4 (M+H)+1. (Formula Removed) Example 393 (4Z)-4-({[4-(4-Ethylpiperazin-1-yl)phenyrjamino}methylene)-6-iodoisoquinoline- 1.3(2H,4H)-dione (4Z)-6-lodo-4-{[(4-piperazin-1 -ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), acetaldehyde (0.15 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 33 mg (60 %) of the title compound as a yellow solid. MS (ESI) m/z 503.3 (M+H)+1. (Formula Removed) Example 394 (4Z)-6-lodo-4-[({4-{(4-methoxypiperidin-1-yl)methyI]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of example 14, 230 mg (73 % yield) is obtained as a yellow solid from 200 mg (0.61 mmol) (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 134.3 mg (0.61 mmol) of {4-[(4-methoxypiperidin-1-yl)rnethyl]phenyl}amine, mp 199-200°C. MS (ESI) m/z 518.0 (M+1)+ (Formula Removed) Example 395 (4Z)-6-(4-Fluorophenyl)-4-[({4-[(4-methoxypiperidin-1 -yl)methyl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-{4-fluorophenyl)-4-({[4-(piperidin-1-ylmethyl)phenyl]amino)methylene)isoquinoline-1,3(2H.4H)-dione, 380 mg (74 % yield) is obtained as a yellow solid from 500 mg (1.06 mmol) of (4Z)-6-bromo-4-[({4-[(4-methoxypiperidin-1-yl)methyl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione and 4-Flurophenyl boronic acid 296 mg, (2.13 mmol).; mp 188-189°C MS (ESI) m/z 486.1 (M+1)+ (Formula Removed) Example 396 (4Z)-4-({[6-(4-Methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-({[6-(4-methylpiperazin-1-yl)pyridin-3-,yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione. 600 mg (60 % yield) is obtained as a yellow solid from 1 .Og (2.26 mmol) of (4Z)-6-bromo-4-({[6-(4-methylpiperazin-1-yl)pyridin-3- yl]amino}methylene)isoquinoltne-1,3(2H,4H)-dione and 3-thiophine boronic acid 296 mg, (2.26 mmol).; mp 165-166°C MS (ESI) m/z 466.1 (M+1)+ (Formula Removed) Example 397 (4Z)-6-Bromo-4-[({4-[(4-methoxypiperidin-1-yl)methyl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of example 14, 1.14 g (68 % yield) is obtained as a yellow solid from 1.0 g (3.54 mmol) (4E)-6-bromo-4-(methoxymethylene)isoquinoline-l ,3(2H,4H)-dione and 781 mg (3.54 mmol) of {4-[(4-methoxypiperidin-1-yl)methyl]phenyl}amine, mp 176-177°C. MS (ESI) m/z 518.0 (M+1)+ (Formula Removed) Example 398 (4Z)-4-[({4-[4-(2-Hydroxy-1-methylethyl)pipera2in-1-yl]phenyl}amino)metriylene]-6- iodoisoquinoline-1,3(2H,4H)-dione (4Z)-4-({[4-(4-ethylpiperazin-1-yl)phenyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquino|ine-1.3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), 1-hydroxy-propan-2-one (0.177 mL, 2.58 mmol) and acetic acid (0.15 mL. 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 38 mg (71 %) of the title compound as a yellow solid. MS (ESI) m/z 533.4 (M+H)+1 (Formula Removed) Example 399 (4Z)-6-lodo-4-[({4-[4-(2-methoxy-1-methylethyl)piperazin-1-yl]phenyl}}amino)methylene]isoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolldinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), 1-methoxy-propan-2-one (0.232 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min. methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 39 mg (71 %) of the title compound as a yellow solid. MS (ESI) m/z 547.4 (M+H)+1. (Formula Removed) Example 400 (4Z)-4-{[(4-{4-[2-(Dimethylamino)-1 -methylethyl]piperazin-1 -yI}phenyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg. 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), 1-dimethylamino-propan-2-one (0.296 mL, 2.58 mmol) and acetic acid (0.15 mL, 2.6 mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 32 mg (57 %) of the title compound as a yellow solid. MS (ESI) m/z 560.4 (M+H)+1 (Formula Removed) Example 401 (4Z)-4-[({4-[4-(2-Hydroxyethyl)piperazin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{|,(4-piperazin-1-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (47.4 mg, 0.1 mmol) is dissolved in N-methylpyrrolidinone (1 mL) and methylene chloride (0.3 mL), followed by addition of sodium triacetoxyborohydride (244 mg, 1.15 mmol), glycoaldehyde (155 mg, 2.58 mmol) and acetic acid (0.15 mL, 2.6'mmol). After stirring at room temperature for 40 min, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 43 mg (83 %) of the title compound as a yellow solid. MS (ES!) m/z 519.2 (M+H)+1. (Formula Removed) Example 402 4-({4-[1-(4-Dimethylamino-but-2-enoyl)-pyrrolidin-2-yl]-phenylamino}-methylene)-6-iodo-4H-isoquinoline-1,3-dione 4-Dimethylamino-but-2-enoic acid hydrochloride salt (66 mg, 0.40 mmol) in N,N-dimethylformamide (1 mL) is treated with Et3N (0.06 mL) at 0 °C. To the mixture is then added lobutylchloroformate (0.05 mL). The mixture is then stirred at this.temperature for 30 min before addition of 6-lodo-4-[(4-pyrrolidin-2-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione (80 mg, 0.17 mmol) in N,N-dimethylformamide (3 mL) dropwisely and the reaction is allowed to stir at room temperature overnight After an aqueous workup, the final residue is purified with prep-TLC to afford the title compound (20 mg, 21%). 1H NMR (400 MHz, DMSO) δ12.52 (1H, d, J = 12.4 Hz), 11.39-11.41 (1H, m), 8.90-8.94 (1H, m)r 8.59 (1H, m), 7.21-7.75 (6H, m), 6.48-6.59 (1.4H, m). 6.01-6.05 (0.6H. m), 5.1-5.24 (1H, m), 3.57-3.91 (2H, m), 3.06-3.07 (1H. m), 2.82-2.84 (1H, m), 2.1-2.39 (2H, m), 2.18 (3H, s), 1.96 (3H, s), 1.77-1.95 (2H, m). MS (ESI): 571.0 (M+1)+1. (Formula Removed) Example 403 4-{[4-(4,5-Dihydro-3H-pyrrol-2-yl)-phenylamino]-methylene}-6-iodo-4H-isoqulnoiine-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-{(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-(4,5-Dihydro-3H-pyrrol-2-yl)-phenylamine (220 mg, 1.36 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (400 mg, 1.22 mmol) in 81% yield as a yellow solid: 1H NMR (400 MHz, CDCI3) δ 12.34 (1H, d, J = 12.4 Hz). 8.39 (1H, d, J = 12.4 Hz), 8.22 (1H, s), 7.92-8.01 (2H, m), 7.62-7.64 (1H, m), 7.24-7.30 (2H, m), 4.07-4.12 (2H, m). 2.88-2.98 (2H, m), 2.04-2.11 (2H, m). MS (ESI): 458.0 (M+1)+1 Anal. Cacl. for C20H16IN3O3: C. 52.53; H, 3.53; N, 9.19; Found: C, 51.87; H, 3.26; N, 9. (Formula Removed) Example 404 4-{[4-(1,2,3,6-Tetrahydro-pyridin-2-yl)-phenylamino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione 2-{4-[(1,3-Dioxo-6-thiophen-3-yl-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-3,6-dihydro-2H-pyridine-1 -carboxylic acid tert-butyl ester (230 mg, -60-70% pure, -0.26-0.31 mmol) is mixed with H3PO4 (1 mL) in CH2CI2 (1 mL) at room temperature. The resulting mixture is stirred until no starting material is detected by TLC. CH3CN and H20 and ice were then added to dilute the sample. The mixture is neutralized by NaOH and extracted with EtOAc. The EtOAc layer is washed with brine and dried. After removal of EtOAc, the residue is purified by flash chromatography to provide the title compound (80 mg, 78% for two steps). 1H NMR(400 MHZ, DMSO) δ 12.53 (1H, d, J = 12.8 Hz), 11.30 (1H, s), 9.02 (1H, d, J = 12.4 Hz), 8.34 (1H, s), 8.21 (1H, s), 8.05 (1H, d, J = 7.6 Hz), 7.44-7.85 (7H, m), 5.76-5.84 (2H, m). 3.77-3.81 (1H. m), 3.31-3.50 (2H, m). 2.09-2.21 (2H, m). MS (ESI): 428.1 (M+1)+1. (Formula Removed) Example 405 (4Z)-6-Bromo-4-({[3-fluoro-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]amino}-methylene)-isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenyI]amino}rnethy1ene)isoquinoline-1,3(2H,4H)-dione, 0.18 g (40.0 % yield) of brown solid is obtained from 0.25 g (0.89 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione, and 0.25 g (1.07 mmol) of [3-fluoro-4-(4-pyrroiidin-1-ylpiperidin-1-yl)phenyl]amine: mp 204-205 °C; MS (ESI) m/z 513.0 (M+H)+1 (Formula Removed) Example 406 (4Z)-4-({[3-Fluoro-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]amino}methylene)-6-thien-3-ylisoquinoline-1,3(2H ,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4.5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione, 0.092 g (61.3 % yield ) of light brown solid is obtained from 0.15 (0.29 mmol) of (4Z)-6-bromo-4-(([3-fluoro-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]amino}-methylene)-isoquinoline-1,3(2H,4H)-dione, 0.06 g (0.44 mmol) of 3-thiopheneboronic acid, 0.027 g (0.03 mmol) of Pd(dba)3, 0.006 g (0.06 mmol) of t-Bu3P, and 0.06 g (0.60 mmol) of Na2CO3. mp 200-201 °C; MS (ESI) m/z 517.1 (M+H)+1 (Formula Removed) Example 407 (4Z)-6-Bromo-4-({[6-(4-pyrrotidin-1-ylpiperidin-1-yl)pyridin-3-yl]amino)methylene)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpiperaan-1-yl)phenyl]amino)methylene)isoquinoline-1,3(2H,4H)-dione (24), 0.53g (86 % yield) of brown solid is obtained from 0.335g (1.24 mmol) of (4E)-6-bromo-4-(methoxymethylene)isoquinoline 1,3(2H,4H)-dione, and 0.30 g (1.24 mmol) of 6-(4-pyrrolidin-1-ylpiperidin-1-yl)pyridin-3- yljamine; mp: 214-215 °C; MS (ESI) m/z 498.1 (M+H)+1 (Formula Removed) .Example 408 (4Z)-4-[({4-[(3R.5S)-4-(N,N-Dimethylglycyl)-3,5-dimethylpiperazin-1-yl]phenyl}amino)methylene]-6-thien-3-ylisoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4^[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione (41), 50 mg (20 % yield ) of light brown solid is obtained from 250 mg (0.50 mmol) of (4Z)-6-bromo-4-({[6-(4-pyrrolidin-1-ylpiperidin-1-yl)pyridin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione and 128 mg (1.0 mmol) of 3-thiohpine boronic acid: mp 203-204°C; MS (ESI) m/z 500.7 (M+H) (Formula Removed) Example 409 tert-Butyl 4-(5-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}pyridin-2-yl)piperazine-1-carboxylate A N,N-dimethylformamide solution (1 mL) of 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (106.4 mg, 0.323 mmol), and tert-butyl 4-(5-aminopyridin-2-yl)piperazine-1-carboxylate (90 mg, 0.323 mmol) is heated at 90°C for 40 min. After cooling in the refrigerator, the precipitate is collected, and washed with N.N-dimethylformamide and ether to give 147 mg (79%) of the title compound as a yellow solid. MS (ESI) m/z 576.1 (M+H)-1 (Formula Removed) Example 410 (4Z)-6-lodo-4-{[(6-piperazin-1-ylpyridin-3-yl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione A N.N-dimethylformamide mixture (0.35 mL) of tert-butyl 4-(5-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}pyridin-2-yl)piperazine-1-carboxylate (100 mg, 0.1738 mmol) and concentrated phosphoric acid (1.1 mL) is heated at 60 C for 2 h. The reaction solution is then treated with an ice-cold aqueous solution of potassium carbonate (1.8 g), and filtered, the solid which is washed exhaustively with water yielded 70 mg (85%) of the title compound as a solid. MS (ESI) m/z 476.1 (M+H) 1 (Formula Removed) Example 411 4-{[4-(2-Ethoxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-5-iodo-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-(2-Ethoxymethyl-pyrrolidin-1-ylmethy!)-phenylamine (130 g, -85% pure, 0.47 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (100 mg, 0.30 mmol) in 63% yield as a yellow solid: 1H NMR (400 MHz, DMSO) δ12.54 (1H, d. J = 12.8 Hz), 11.38 (1H. S), 8.93 (1H. d, J = 12.8 Hz), 8.59 (1H, s), 7.34-7.74 (6H, m), 4.06 (1H, d, J = 9.6 Hz), 3.35-3.46 (4 H, m), 3.24-3.29 (1H, m), 2.67-2,78 (2H, m), 2.16-2.18 (1H, m), 1.84-1.89 (1H, m). 1.50-1.63 (3H, m), 1.10 (3H, t, J = 7.2 Hz). MS (ESI): 531.9 (M+1)+1. Anal. Cacl. for C24H26IN303: C, 54.25; H, 4.93; N, 7.91; Found: C. 55.03; H, 5.12; N. 7.61; HRMS Cacl. for C24H26IN303: 532.10917; Found: 532.11104, (M+1)+1. (Formula Removed) Example 412 4-{[4-(2-Dimethylaminomethyl-pyrrolidin-1 -yl)-3-fluoro-phenylam ino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methyJene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-(2-Dimethylaminomethyl-pyrrolidin-1-yl)-3-fluoro-phenylamine (65 mg, 0.27 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (60 mg, 0.18 mmol) in 64% yield as a brownish solid: 'H NMR (400 MHz, DMSO) δ 12.54 (1H, d, J = 12.8 Hz), 11.33 (1H, s), 8.80 (1H, d, J = 12.4 Hz), 8.56 (1H, s), 7.56-7.73 (3H, m), 7.19-7.22 (1H, m), 6.81 (1H, t, J = 9.2 Hz), 4.03(1 H, m), 3.49-3.51 (1H. m), 3.37 (2H, m, buried with water signal), 3.16 (1H, m), 2.19 (6H, s), 1.83-2.03 (4H, m). MS (ESI): 535.0'(M+1)+1 Anal. Cacl. for C23H24FIN4O2: C, 51.7; H, 4.53; N, 10.78; Found: C, 50.88; H, 3.93; N, 9.76. (Formula Removed) Example 413 (4Z)-6-lodo-4-({[6-(4-isopropylpiperazin-1-yl)pyridin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(6-piperazin-1-yipyridin-3-yl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (150 mg, 0.315 mmol) is dissolved in N-methylpyrrolidinone (3 mL) and methylene chloride (0.9 mL), followed by addition of sodium triacetoxyborohydride (0.77 mg, 3.63 mmol), acetone (0.6 mL, 8.14 mmol) and acetic acid (0.47 mL, 8.2 mmol). After stirring at room temperature for 4 h, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 105 mg (64 %) of the title compound as a yellow solid. MS (ESI) m/z 517.4 (M+H)+1 (Formula Removed) Example 414 (4Z)-4-({[6-(4-Ethylpipera2in-1-yl)pyridin-3-yl]amino}methylene)-6-iodoisoquinoline- 1,3(2H,4H)-dione (4Z)-6-lodo-4-{|(6-pipera2in-1-ylpyridin-3-yl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (150 mg, 0.315 mmol) is dissolved in N-methylpyrrolidinone (3 mL) and methylene chloride (0.9 mL), followed by addition of sodium triacetoxyborohydride (0.77 mg, 3.63 mmol), acetaldehyde (0.46 mL, 8.14 mmol) and acetic acid (0.47 mL, 8.2 mrnol). After stirring at room temperature for 1 h, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 110 mg (69 %) of the title compound as a brown solid. MS (ESI) m/z 504.2 (M+H)+1 (Formula Removed) Example 415 (4Z)-4-[({6-[4-(Cyclopropylmethyl)piperazin-1-yl]pyridin-3-yl}amino)methylene]-6- iodoisoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{[(6-piperazin-1-yIpyridin-3-yl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (150 mg, 0.315 mmol) is dissolved in N-methylpyrrolidinone (3 mL) and methylene chloride (0.9 mL), followed by addition of sodium triacetoxyborohydride (0.77 mg, 3.63 mmol), cyclopropanecarbaldehyde (0.61 mL, 8.14 mmol) and acetic acid (0.47 mL, 8.2 mmol). After stirring at room temperature for 1 h, methylene chloride and saturated sodium bicarbonate solution were added. The organic layer is separated and dried to give 110 mg (69 %) of the title compound as a brown solid. MS (ESI) m/z 530.4 (M+H)+1 (Formula Removed) Example 416 (4Z)-4-({[6-(4-Ethylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione (4Z)-4-({[6-(4-Ethylpiperazin-1-yl)pyridin-3-yl]amino}methyiene)-6-iodoisoquinoline-1,3(2H,4H)-dione (50.3 mg, 0.1 mmol) is mixed with 3-furanboronic acid (22 mg, 0.2 mmol), Pd2(dba)3 (13.7 mg, 0.015 mmol), and cesium carbonate (65 mg, 0.2 mmol). After the solids were degassed, N,N-dimethylformamide (0.7 mL) and P(t-Bu)3 (6 mg, 0.03 mmol) were added. The mixture is heated at 100 C for 10 min, diluted with methylene chloride, and filtered. The filtrate is evaporated to dryness and purified by column chromatography to yield 30 mg (67%) of the title compound as an orange solid. MS (ESI) m/z AAA (M+H)+1 (Formula Removed) Example 417 (4Z)-4-({I6-(4-isopropylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-{3-thienyl)isoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-{{[6-(4-isopropylpipera2in-1-yl)pyridin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (63 mg, 0.1218 mmol) is mixed with 3-furanboronic acid (32 mg, 0.224 mmol), Pd2(dba)3 (16.7 mg, 0.018 mmol), and cesium carbonate (80 mg, 0.24 mmol). After the solids were degassed, N,N-dimethylformamide (0.8 mL) and P(t-Bu)3 (7.4 mg, 0.037 mmol) were added. The mixture is heated at 100 C for 10 min, diluted with methylene chloride, and filtered. The filtrate is evaporated to dryness and purified by column chromatography to yield 33 mg (57%) of the title compound as a yellow solid. MS (ESI) m/z 474 (M+H)+1 (Formula Removed) Example 418 (4Z)-4-[({6-[4-(Cyclopropylmethyl)piperazin-1-yl}pyridin-3-yl}amino)methylene]-6-(3-thienyl)isoquinoline-1,3(2H,4H)-dione (4Z)-4-[({6-[4-(Cyclopropylmethyl)piperazin-1-yl]pyridin-3-yl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione (72 mg, 0.136 mmol) is mixed with 3-furanboronic acid (35 mg, 0.272 mmol), Pd2(dba)3 (18.7 mg, 0.02 mmol), and cesium carbonate (89 mg, 0.272 mmol). After the solids were degassed, N.N-dimethylformamide (0.8 mL) and P(t-Bu)3 (8.25 mg, 0.04 mmol) were added. The mixture is heated at 100 C for 10 min, diluted with methylene chloride, and filtered. The filtrate is evaporated to dryness and purified by column chromatography to yield 27 mg (41%) of the title compound as a yellow solid. MS (ESI) m/z 486 (M+H)+1 Example 419 4-{[4-(1-Allyl-pyrrolidin-2-yl)-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione. the title compound is obtained from 4-(1-Allyl-pyrrolidin-2-yl)-phenylamine (190 mg, 0.58 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (190 mg, 0.18 mmol) in 74% yield as a redish solid: MS (ESI): 500.0 (M+1)+1. (Formula Removed) Example 420 4-{[4-(1-Allyl-pyrrolidin-2-yl)-phenylaminol-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-nnethylene}-6-thiophen-3-yl-4H-tsoquinoline-1,3-dione, the title compound is obtained from 4-{[4-(1-Allyl-pyrrolidin-2-yl)-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione (100 mg, 0.20 mmol) in 42% yield as a yellow powder. MS (ESI): 456.2 (M+1 )+1. (Formula Removed) Example 421 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenyIarnino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione To a solution of 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-yfmethyl)-phenylamino]-methylene)-6-iodo-4H-isoquinoline-1,3-dione (200 mg. 0.40 mmol) in N,N-dimethylformamide (10 mL) were added 3-thienylboronic acid (120 mg, 0.94 mmol) and Na2C03 (216 mg, 2.0 mmol). Pd2(dba)3●CHCI3 (20 mg, 0.02 mmol) and P(tBu)3●HBF4 (19 mg, 0.06 mmol) were then added. The mixture is then degassed and heated at 100 °C for 1 h. The N,N-dimethylformamide is then evaporated under reduced pressure and the residue is taken up in EtOAc and H20. The EtOAc layer is dried and evaporated. The residue, which resulted, is subjected to chromatography to provide the desired product (90 mg, 49%). MS (ESI): 460.2 (M+1)+1 (Formula Removed) Example 422 (4Z)-4-[(4-{{3-(Dimethylamino)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of example 14, 230 mg (49 % yield) is obtained as a yellow solid from 300 mg (0.92 mmol) (4E)-6-iodo-4- (methoxymethylene)isoquinoline-1 ,3(2H,4H)-dione and 202 mg (0.92 mmol) of 3-(dimethylamino)pyrrolidin-1-yl]methyl}phenyl)amine; mp 134-135°C. MS (ESI) m/z 517.0 (M+1)+ (Formula Removed) Example 423 (4Z)-4[(4-{t3-(Dimethylamino)pyrrolidin-1-yl]methyl}phenyl)amino}methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 20 mg (5 % yield) is obtained as a yellow solid from 281.4 mg (0.92 mmol) (4E)-6-iodo-4-(methoxymethylene)isoquinoline-l ,3(2H,4H)-dione and 234 mg (0.85 mmol) of (2R)-2-[(dimethylamino)methyl]pyrrolidin-1-yl)methyl)phenyl]amine; mp 130-131 °C. MS (ESI) m/z 531.1 (M+1)+ (Formula Removed) Example 424 4-{[(5-Amino-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}-6-iodo-4H- isoquinoline-1,3-dione A mixture of 5-amino-2-aminomethyl-pyridin-4-ol (60 mg, 0.19 mmole as the dihydrobromide). 3 ml. of N,N-dimethylformamide and triethylamine (101uL, 0.72 mmole) were stirred for 15 mins, 4-methoxymethylene-6-iodo-4H-isoquinoline-1,3-dione (63 mg, 0.19 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, taken up in dimethylsulfoxide and purified by HPLC (acetonitrile-water with 0.2% trifluoroacetic acid). The product is isolated by evaporation in-vacuo to give a brown solid, 5.5 mg, (5%); MS (ES+): m/z 437.0 (M + H). (Formula Removed) Example 425 (4Z)-4-{[(4-{1-[3-(Dimethylamino)propyl]piperidin-4-yl}phenyl)amino]methylene}-6- iodoisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of 4Z)-6-bromo-4-({[4-(3,5-dimethylpiperazin-1-yl)phenylJamino}methvlene)isoquinoline-1,3(2H,4H)-dione, 0.079 g (73.1 % yield ) of greenish tan solid is obtained from 0.064 g (0.19 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 0.061 g (0.23 mmol)of (4-{1-[3-(dimethylamino)propyl]piperidin-4-yl}phenyl)amine: mp 139-140 °C; MS (ESI) m/z 559.0 (M+H)+1 (Formula Removed) Example 426 4-{[3-Fluoro-4-(2-hydroxymethyl-pyrrolidin-1-yl)-phenylamino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from [1-(4-Amino-2-fluoro-phenyl)-pyrrolidin-2-yl]-methanol (150 g, 0.71 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (100 mg, 0.30 mmol) in 98% yield as a redish solid: 1H NMR (400 MHz, DMSO)δ12.56 (1H, d, J = 12.8 Hz), 11.33 (1H, s), 8.80 (1H, d, J = 12.4 Hz), 8.56 (1H. s), 7.56-7.73 (3H. m), 7.17-7.20 (1H, m), 6.83 (1H. t, J = 9.2 Hz), 4.67 (1H, t, J = 5.6 Hz), 3.89 (1H, m), 3.43-3.55 (2H, m), 3.15-3.25 (2H, m), 1.84-1.98 (4H, m). MS (ESI): 507.9 (M+1)+1. Anal. Cacl. for C21H19FIN303: C, 49.72; H, 3.78; N. 8.28; Found: C, 49.62; H, 3.37; N, 8.13. (Formula Removed) Example 427 6-lodc-4-{[(5-oxo-pyrrolidin-2-ylrnethyl)-arnino]-methylene}-4H-isoquinoline-1,3- dione 5-Aminomethyl-pyrrolidin-2-one (140 mg, -80-90% pure, 1.04 mmol) is stirred with 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (150 mg, 0.46 mmol) in N.N-dlmethylformamide (5 mL) at room temperature. The suspension become clear in 10 minutes and further stirring gave a pale yellow precipitate. The precipitate is filtered and washed with MeOH, Et20 and dried to provide the title compound (110 mg. 58%). MS (ESI): 411.8 (M+1)+1. (Formula Removed) Example 428 N-(4-Hydroxy-6-{(6-iodo-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyi)-amino]-methyl}-pyridin-3-yl)-acrylamide A mixture of 4-{[(5-Amino-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoIine-1,3-dione (334 mg, 0.766 mmole), 20 mL of dimethylacetamide is stirred, acryoyl chloride (651 µL, 7.66 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, stirred overnight with a saturated aqueous sodium bicarbonate solution, filtered, washed well with water, and dried to give a green solid, 98 mg, (27%); MS (ES-): m/z 489 (M - H). (Formula Removed) Example 429 1-(4-{[(Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinoiin-4(1 H)-ylidene)methyl]amino}phenyl)N,N-dimethylpiperidine-4-carboxamide Dimethylamine (2.0 M solution in tetrahydrofuran, 2 mL) is added to 1-(4-nitrophenyl)piperidine-4-carboxylic acid chloride hydrochloride (0.15 g, 0.5 mmol). When the combined compounds fully reacted, the reaction mixture is concentrated under reduced pressure, then taken up in methanol. Water is added and the resulting solid is collected to give 1-(4-nitro-phenyl)-piperidine-4-carboxylic acid dimethylamide, which is used without further purification in the subsequent step. MS (ES+): 278.3 (M+H)+ A solution 1-(4-nitro-phenyl)-piperidine-4-carboxylicacid dimethylamide in ethanol/tetrahydrofuran and concentrated hydrochloric add is degassed with dry ice. Palladium on carbon (10 %, 50 mg) is added and the mixture is shaken for two hours under 50 psi of hydrogen. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 1-(4-amino-phenyl)-piperidine-4-carboxylic acid dimethylamide dihydrochloride, which is used in the next step without further purification. (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.14 g, 0.44 mmol) and 1-(4-amino-phenyl)-piperidine-4-carboxylic acid dimethylamide dihydrochloride (0.14 g, 0.44 mrnol) were coupled in N.N-dimethylformamide (2.5 mL) with triethylamine (0.57 mL). The mixture is heated in a 100 °C block shaker until complete. Water is added to precipitate the solid product. The solid is collected by filtration, purified by reverse phase HPLC to give 1-(4-{[(Z)-(6-iodu-1.3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyi]amino}phenyl)-N,N-dimethylpiperidine-4-carboxamide, trifluoroacetic acid salt (37 mg. 13 %). MS (ES+): 545.1 (M+H)+ (Formula Removed) Example 430 1-(4-{[(Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}phenyl)piperidine-4-carboxamide Three drops of triethylamine were added to a suspension of 1-(4-nitrophenyl)piperidine-4-carboxylic acid chloride hydrochloride (0.15 g, 0.5 mmol) in tetrahydrofuran (5 mL). Ammonia gas is bubbled into the mixture for 10 minutes. When completed, the reaction mixture is concentrated under reduced pressure. Water is added and the resulting solid is collected to give 1-(4-nitro-phenyl)-piperidine-4-carboxamide, which is used without further purification in the subsequent step. MS (ES+): 250.3 (M+H)+ A solution of 1-{4-nitro-phenyl)-piperidine-4-carboxamide in ethanol/tetrahydrofuran and concentrated hydrochloric acid is degassed with dry ice. Palladium on carbon (10%, 50 mg) is added and the mixture is shaken for two hours under 50 psi of hydrogen. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 1-(4-aminc-phenyl)-piperidine-4-carboxamide dihydrochloride, which is used the next step without further purification. (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.14 g, 0.44 mmol) and 1-(4-amino-phenyl)-piperidine-4-carboxamide dihydrochloride (0.13 g, 0.44 mmol) were coupled in N.N-dimethylformamide (2.5 mL) with triethylamine (0.57 mL). The mixture is heated in a 100 °C block shaker until complete. Water is added to precipitate the solid product. This solid is collected by filtration, then purified by reverse phase HPLC to give 1-(4-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}phenyl)piperidine-4-carboxamide, trifluoroacetic acid salt (11 mg, 4.0 %). MS (ES+): 517.3 (M+H)+ (Formula Removed) Example 431 1-(4-{[(Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}phenyl)piperidine-4-carboxylic acid To a suspension of isonipecotic acid (8.3 g, 64 mmol) in methanol (250 mL) is added tetrabutylammonium hydroxide (40% aqueous solution, 42 mL). Solvents were then removed under reduced pressure. Residual water is removed by azeotropic distillation with toluene. The semisolid tetrabutylammonium isonipecotate is dried under high vacuum. To a solution of tetrabutylammonium isonipecotate (64 mmol) in dimethylsulfoxide (150 mL) is added 4-fluoronitrobenzene (7.5 mL, 71 mmol) and potassium carbonate (9.6 g, 70 mmol). The reaction mixture is heated in a 75 °C oil bath for three hours and then allowed to cool to room temperature. Water is added, followed by concentrated hydrochloric acid to bring the mixture to pH 6. The precipitated material is collected by filtration, washed with acetonitrile, and dried under house vacuum to provide 1-(4-nitropheny1)piperidine-4-carboxylic acid as a yellow powder (14 g, 88 %). MS (ES+): 251.1 (M+H)+ In a 75-mL Parr bottle, 1-(4-nitrophenyl)piperidine-4-carboxylic acid (0.13 g, 0.52 mmol) is dissolved in ethanol/ethyl acetate (1:1, 30 mL). Concentrated hydrochloric acid (0.5 mL) is added. After degassing the mixture with dry ice, palladium on carbon (10%, 30 mg) is added. The reaction mixture is shaken overnight under 50 psi hydrogen, then filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 1-(4-aminophenyl)piperidine-4-carboxylic acid dihydrochloride. (4E)-6-iodo-4-(methoxymethylene)isoquJnoline-1,3(2H,4H)-dione (0.19 g, 0.58 mmol) and 1-(4-aminophenyl)piperidine-4-carboxylic acid dihydrochloride (0.17 g, 0.58 mmol) were coupled in N,N-dimethylformamide (2.5 mL) with triethylamine (760 µL), The mixture is heated in a 100 °C block shaker until complete. Water is added to precipitate the solid product. This solid is collected by filtration, then purified by reverse phase HPLC to give 1-(4-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)metiiyl]amino}phenyl)piperidine-4-carboxylic acid trifluoroacetate (3.4 mg, 0.9 %). MS (ES): 516.3 (M-H)- (Formula Removed) Example 432 1-{4-{[(Z)-(6-lodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}prrenyl)-A^memoxy-A^rnethylpiperidine-4-carboxamide A suspension of 1-(4-nitrophenyl)piperidine-4-carboxylic acid (0.76 g, 3.0 mmol) in dichloromethane (15 mL) is cooled to 0 °C in an ice-water bath. Carbonyldiimidazole (0.59 g, 3.6 mmol) is added and the mixture is allowed to warm to room temperature. An additional volume of dichloromethane (10 mL) is added and the mixture continued to stir for 30 minutes before the addition of A/.O-dimethylhydroxylamine hydrochloride (0.73 g, 7.5 mmol). After stirring overnight, the reaction mixture is filtered. The insoluble material is washed with diethyl ether, and the combined filtrate is washed with 5% aqueous potassium hydrogen carbonate solution, water, and saturated aqueous sodium chloride solution. The organic phase is dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give 1-(4-nitro-phenyl)-piperidine-4-carbbxylic acid methoxy-methyl-amide as a bright yellow powder (0.84 g, 95 %). MS (ES+): 294.3 (M+H)+ A solution of 1-(4-nitro-phenyl)-piperidine-4-carboxylic acid methoxy-methyl-amide (approximately 0.20 g, 0.8 mmol) in ethanol/ethyl acetate (1:1, 30 mL) and concentrated hydrochloric acid (1 mL) is degassed with dry ice. Palladium on carbon (10%, 35 mg) is added and the mixture is shaken for two hours under 40 psi of hydrogen. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 1-(4-amino-phenyl)-piperidine-4-carboxylic acid methoxy-methyl-amide dihydrochloride (0.30 g, > 100 %). MS (ES+): 264.3 (M+H)+ (4E)-6-iodo-4-(methoxymethylene)lsoquinoline-1.3(2H,4H)-dione (0.30 g, 0.89 mmol) and 1-(4-amino-phenyl)-piperidine-4-carboxylic acid methoxy-methyl-amide dihydrochloride (0.30 g, 0.89 mmol) were coupled in N,N-dimethylformamide (2.5 mL) with triethylamine (1.2 mL). The mixture is heated in a 100 °C block shaker until complete. Then water is added in order to precipitate the solid product. This solid is collected by filtration, then purified by reverse phase HPLC to give 1-(4-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}phenyl)-N-methoxy-N-methylpiperidine-4-carboxamide trifluoroacetate (6.5 mg, 1.1 %). MS (ES+): 561.1 (M+H)+ (Formula Removed) Example 433 N-[2-(Dimethylamino)ethyl]-1-(4-{[(2)-(6-ioclo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}phenyl)piperidine-4-carboxamIde To a suspension of 1-(4-nitrophenyl)piperidine-4-carboxylic acid (0.75 g, 3.0 mmol) in dichloromethane (15 mL) is added oxaiyl chloride (0.32 mL, 3.6 mmol) and then one drop of N,N-dimethylformamide. The reaction mixture is heated in a 60 °C oil bath under a nitrogen atmosphere for 30 minutes, concentrated under reduced pressure to provide 1-(4-nitrophenyl)piperidine-4-carboxylic acid chloride hydrochloride. N,N-dimethylethylenediamine (1.0 mmol) is added neat to 1-(4-nitrophenyl)piperidine-4-carboxylic acid chloride hydrochloride (0.15 g, 0.5 mmol). The resulting solid is purified by reverse-phase HPLC to provide 1-(4-nitro-phenyl)-piperidine-4-carboxylic acid (2-dimethylamino-ethyl)-amide trifluoroacetate. MS(ES+):321.4(M+H)+ A solution of 1-(4-nitro-phenyl)-piperidine-4-carboxyIic acid (2-dimethytamino-ethyl)-arnide trifluoroacetate in ethanol/tetrahydrofuran and concentrated hydrochloric acid is degassed with dry ice. Palladium on carbon (10 %, 50 mg) is added and the mixture is shaken for two hours under 50 psi of hydrogen. The mixture is filtered through a pad of dlatomaceous earth and concentrated under reduced pressure to give 1-(4-amino-phenyl)-piperidine-4-carboxylic acid (2-dimethylamino-ethyl)-amide trihydrochloride. (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.16 g, 0.50 mmol) and 1-(4-amino-phenyl)-piperidine-4-carboxylic acid (2-dimethylamino-ethyl)-amide trihydrochloride (0.20 g, 0.50 mmol) were coupled in N,N-dimethylformamide (2.5 mL) with trietnylamine (0.65 mL). The mixture is heated in a 100 °C block shaker until complete. Then water is added in order to precipitate the solid product. This solid is collected by filtration, then purified by reverse phase HPLC to give N-[2-(dimethylamino)ethyl]-1-(4-{[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}phenyI)piperidine-4-carboxamide ditrifluoroacetate (118 mg, 29 %). MS (ES+): 588.0 (M+H)+ (Formula Removed) Example 434 (4Z)-4-[({4-[4-(Hydroxyrnethyl)piperidin-1-yl]phenyI}arnino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione To a 0 °C solution of 1 -(4-nitrophenyl)piperidine-4-carboxylic acid (1.0 g, 4.0 mmol) in tetrahydrofuran (14 mL) is added borane-tetrahydrofuran complex (1.8 M, 7 mL, 13 mmol). After completion of the dropwise addition, the coolant is removed. The mixture is stirred overnight at room temperature and re-cooled to 0 °C in an ice-water bath. Sodium hydroxide solution (1M, 6 mL) is added dropwise. The basic mixture is neutralized by the addition of saturated aqueous ammonium chloride solution. The mixture is extracted 3x with ethyl acetate, and the combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give [ 1 -(4-nitro-phenyl)-piperiidin-4- yl]-methanol. MS (ES+): 237.3 (M+H)+ A solution of [1-(4-nitro-phenyl)-piperidin-4-yl]-methanol. (0.15 g, 0.64 mmol) in ethanol/tetrahydrofuran/water (2:2:1 mL) and concentrated hydrochloric acid (10 drops) is degassed with dry ice. Palladium on carbon (10 %, 50 mg) is added and the mixture is stirred overnight under 1 atm of hydrogen. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give [1-(4-amino-phenyl)-piperidin-4-yl]-methanol dihydrochloride (0.19 g,>100%). MS (ES+): 207.4 (M+H)+ (4E)-6-iodo-4-(methoxyrnethylene)isoquinoline-1,3(2H,4H)-dione (0.22 g, 0.68 mmol) and [1-(4-amino-phenyI)-piperidin-4-yl]-methanol dihydrochloride (0.19 g, 0.68 mmol) were coupled in N.N-dimethylformamide (2.5 mL) with triethylamine (0.89 mL). The mixture is heated in a 100 °C block shaker until complete. Water is added to precipitate the solid product. This solid is collected by filtration and purified by reverse phase HPLC to give (4Z)-4-[({4-[4-(hydroxymethyl)piperidin-1-yI]phenyl}amino)methylene|-6-iodoisoquinoline-1,3(2H,4H)-dionetrifluoroacetate (28 mg, 6.7 %). MS (ES+): 504.3 (M+H)+ (Formula Removed) Example 435 (4Z)-6-lodo-4-[({4-[4-(methoxymethyl)plperidin-1-yl}phenyl}amino)methylene]isoquinoline-1.3(2H,4H)-dione To a 0 °C mixture of t1-(4-nitro-phenyl)-piperidin-4-yl]-methanol and iodomethane (0.25 mL, 4.0 mmol) in N.N-dimethylformamide (3 mL) is added sodium hydride (60 % dispersion in mineral oil, 80 mg, 2.0 mmol). The cooling bath is removed and the mixture is stirred at room temperature for five hours before it is re-cooled to 0 °C and quenched by the addition of saturated aqueous sodium hydrogen carbonate solution. The precipitated solid is collected by Buchner filtration, washed with water, and dried under house vacuum to give 4-methoxymethyl-1-(4-nitro-phenyl)-piperidine as pale yellow crystals (0.15 g, 60 %). MS (ES+). 251.4 (M+H)+ A solution of 4-methoxymethyl-1-(4-nitro-phenyl)-piperidine (0.15 g, 0.60 mmol) in ethanol/tetrahydrofuran/water (2:2:1 mL) and concentrated hydrochloric acid (10 drops) is degassed with dry ice. Palladium on carbon (10 %, 50 mg) is added and the mixture is stirred for seven hours under 1 atm of hydrogen. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 4-rnethoxymethyl-1-(4-amino-phenyl)-piperidine dihydrochloride (0.18 g, 100 %). MS (ES+): 221.4 (M+H)+ (4E)-6-iodo-4-(methoxymethyIene)isoquinoline-1,3(2H.4H)-dione (0.20 g, 0.61 mmol) and 4-methoxymethyl-1-(4-amino-phenyI)-piperidine dihydrochloride (0.18 g, 0.61 mmol) were coupled in N.N-dimethylformamide (2.5 mL) with triethylamine (0.80 mL). The mixture is heated in a 100 °C block shaker until complete. Water is added in to precipitate the solid product. The solid is collected by filtration and purified by reverse phase HPLC to give (4Z)-6-iodo-4-[({4-[4-(rnethoxymethyl)piperidin-1-yl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione trifluoroacetate (37 mg, 9.6 %). MS (ES): 516.6 (M-H)- (Formula Removed) Example 436 4-{[4-(2-Ethyl-pyrroIidin-1-ylmethyl)-phenylamino]-methytene}-6H'odo-4H-isoquinoline-1,3-dlone Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-(2-Ethyl-pyrrolidin-1-ylmethyl)-phenylamine (85 mg, 0.41 mmol), 6- iodo-4-methoxymethylene-4H-isoquinoltne-1,3-dione (95 mg, 0.29 mmol) in 48% yield as a yellow solid: MS (ESI): 502.1 (M+1)+1. (Formula Removed) Example 437 6-Bromo-4-{[4-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from [1-(4-Amino-benzyl)-pyrrolidrn-2-yl]-methanol (1.3 g, 6.3 mmol), 6-bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (1.4 g, 5.0 mmol) in 73% yield as a brown solid: MS (ESI): 456.1, 458.1 (M+1)+1 (Formula Removed) Example 438 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-6-thiophen-2-yl-4H-isoquinoline-1,3-dione To a mixture of 6-Bromo-4-{[4-(2-hydroxymethyl-pyrrolidin-1 -ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione (100 mg, 0.2 mmol) in N,N-dimethylformamide (1 mL) is added Pd2(dba)3●CHCl3(10 mg, 0.01 mmol) and P(tBu)3 (20 µL, 1 M solution in N.N-dimethylformamide, 0.02 mmol). After degassing the mixture, 2-thienyl zinc chloride (2.2 mL, 0.5 M solution in THF, 1.1 mmol) is then added and the resulting mixture is stirred for 2 h. N,N-dimethylformamide is then removed and the residue is purified through chromatography to provide the title compound (35 mg, 38%). MS (ESI): 460.1 (M+1)+1. (Formula Removed) Example 439 (4Z)-4-{[(4-{[2-(Hydroxymethyl)piperidin-1-yl]methyl}phenyl)amino]methylene}-6-iodoisoquinoline-1,3(2H ,4H)-dione: Using the procedure described for the preparation of example 14, 68 mg (14 % yield) is obtained as a orange solid from 300 mg (0.91 mmol) (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 200 mg (0.91 mmol) of 2-(hydroxymethyl)piperidin-1-yl]methyl}phenyl)amino; mp 205-206°C. MS (ESI) m/z 518.1 (M+1)+ (Formula Removed) Example 440 (4Z)-4-[({4-[(4-Hydroxypiperidin-1 -yl)methyl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of example 1 (4Z)-4-[({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}amino)methylene]isoquinoIine-1,3(2H,4H)-dione 450 mg (89 % yield) of an orange solid is obtained from 330 mg (1.0 mmol) of 4E)-6-iodo-4(methoxymethyiene)isoquinoline-1.3(2H,4H)-dione and 206.3 mg, (1.0 mmol) of 1-(4-aminobenzyl)piperidin-4-ol mp 255-256°C. MS (ESI) m/z 504.1 (M+1). (Formula Removed) Example 441 6-(5-Chloro-thiophen-2-yl)-4-{[4-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene)-4H-isoquinoline-1,3-dione: Using the procedure described for the preparation of 4-{[4-(2-Hydroxymethyl-pyrroridin-1-ylmethyl)-phenylamino]-methylene}-6-thiophen-2-yl-4H-isoquinoline-1,3-dione, the title compound is obtained from 6-Bromo-4-{[4-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione (200 mg, 0.4 mmol). 5~chloro-2-thienyl zinc chloride (4.4 mL, 0.5 M solution in THF, 2.2 mmol) in 48% yield as a yellow solid: MS (ESI): 494.1 (M+1)+1 (Formula Removed) Example 442 (4Z)-6-Bromo-4-({[5-(4-methyIpiperazin-1-yl)pyridin-2-yl]amino}methyIene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 1.2 g (75 % yield) is obtained as a orange solid from 1.0 g (3.54 mmol) (4E)-6-bromo-4-(methoxymethyIene)isoquinoline-1,3(2H,4H)-dione and 670 mg (3.54 mmol) of 5-(4-methylpiperazin-1-yl)pyridin-2-yl]amine; mp 191-192°C. MS (ESI) m/z 444.0 (M+1)+ (Formula Removed) Example 443 (4Z)-6-(3-Furyl)-4-({[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-({[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione 1.2g (63 % yield) is obtained as a yellow solid from 2.0g (4.52 mmol) (4Z)-6-bromo-4-({[5-(4-methylpiperazin-1-y!)pyridin-2-yl)amino}methylene)isoquinoline-1,3(2H,4H)-dione and 3-furan boronic acid 1.3 g, (11.3 mmol).; mp 262-263°C MS (ESI) m/z 430.1 (M+1)+ (Formula Removed) Example 444 (Z)-4-((5-Bromopyridin-2-y)amtno)methylene)-6-(1H-pyrrol-1-yl)isoquinoline- 1.3(2H,4H)-dione: A mixture of (E)-4-(methoxymethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione (268 mg, 1.0 mmole), dimethylformamide (8 mL). and 5-bromopyridin-2-amine (173 mg, 1.0 mmole) is heated at 125°C for four hours. The reaction mixture is cooled, diluted with ether, filtered, washed with fresh ether and dried to give a salmon solid. 176 mg, (43%), mp 317-8°C dec; MS (ES-): m/z 407.0 (M - H). (Formula Removed) Example 445 (42)-4-({[2-Fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione . Into a suspension of 2,6-dichloro-3-nitropyridine (13 g, 68 mmol) in ethanol (65 mL) is bubbled anhydrous ammonia gas for 20 minutes. The mixture is allowed to stir at room temperature for 64 hours and then the volume is reduced by 50% under reduced pressure. Water is added to the suspension, and the solid is collected by Buchner filtration, washed with water and methanol, and dried under house vacuum to give 6-chloro-3-nitropyridin-2-amine as a yellow powder (10 g, 85 %). MS (ES-): 172.2 (M-H)- To a suspension of 6-chloro-3-nitropyridin-2-amine (1.7 g, 9.8 mmol) in methanol (17 mL) is added N-methylpiperazone (1.6 mL, 15 mmol). The mixture is stirred at room temperature overnight and then concentrated to dryness under reduced pressure. The solid material is collected by Buchner filtration, washed with methanol, and dried under house vacuum to give 6-(4-methylpiperazin-1-yl)-3-nitropyridin-2-amine as a yellow powder (10 g, 85 %). MS (ES+): 238.3 (M+H)+ A solution of 6-(4-methylpiperazin-1-yl)-3-nitropyridin-2-amine (1.2 g, 5.0 mmol) in hydrogen fluoride-pyridine (15 mL) is cooled to 0 °C in an ice-water bath. Sodium nitrite (0.36 g. 5.2 mmol) is added in a single portion, and the mixture is stirred for 30 minutes at 0 "C. The bath is removed and the mixture is heated for 15 minutes in an oil bath on a 70 °C hot plate. After cooling to room temperature, the reaction mixture is poured onto ice (50 g), neutralized with saturated aqueous sodium hydrogen carbonate solution, and basified with 10 N sodium hydroxide solution. The mixture is extracted 3x with dichloromethane, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Eighty-percent of the crude residue is purified by reverse-phase HPLC to give 1-(6-fluoro-5-nitropyridin-2-yl)-4-methylpiperazine● trifluoroacetic acid salt (0.40 g. 29%). MS (ES+): 241.3 (M+H)+ To a suspension of 1-(6-fluoro-5-nitropyridin-2-yl)-4-methylpiperazine« trifluoroacetic acid salt (0.38 g, 1.1 mmol) in ethanol (30 mL) is added triethylamine dropwise with agitation until all of the solid had dissolved. The mixture is then degassed with dry ice and treated with an aqueous slurry of Raney nickel (approx 1.5 mL). After shaking under 50 psi of hydrogen, the reaction mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 2-fluoro-6-(4-methyl-piperazin-1-yl)-pyridin-3-ylamine (contaminated with triethylammonium trifluoroacetate) as a red wine colored solid. MS(ES+):211.3(M+H)+ (4E)-6-liodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.26 g, 0.80 mmol), 2-fluoro-6-(4-methyl-piperazin-1-yl)-pyridin-3-ylamine (contaminated with triethylammonium trifluoroacetate, approximately 0.80 mmol) were coupled in N.N-dimethylformamide (10 mL) with triethyiamine (0.66 mL). The mixture is heated in a 100 °C oil bath for one hour. The reaction mixture is purified by reverse phase HPLC and then flash silica gel chromatography (methanol/chloroform) to give(4Z)-4-({[2-fluoro-6-(4-rnethylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione (0.20 g, 49 %). MS (ES+): 508.1 (M+H)+ (Formula Removed) Example 446 (4Z)-4-[({4-[4-({[2-(Dimethylamino)ethyl]amino}methyl)piperidin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione To a mixture of 1-{4-aminophenyl)plperidine-4-carboxy)ic acid dihydrochloride (2.1 g, 7.2 mmol) in 50 % aqueous dioxane (34 mL) is added sodium hydroxide (1.0 g, 25 mmol), followed by di-tert-butyldicarbonate (1.9 g, 8.6 mmol). After stirring overnight at room temperature, the mixture is acidified to pH 3 with 5 % aqueous potassium hydrogen sulfate solution. The mixture is extracted 3x with dichloromethane. The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give 1-{4-[(tert-butoxycarbonyl)amino]phenyl}piperidine-4-carboxy!ic acid as a light tan solid (1.3g.57%). MS (ES+): 321.3 (M+H)+ To a suspension of 1-{4-[(tert-butoxycarbonyl)amino]phenyl}piperidine-4-carboxylic acid (1.3 g, 4.1 mmol) in dichloromethane (40 mL) is added carbonyldiimidazole (0.79 g, 4.9 mmol) and the mixture is stirred at room temperature for 30 minutes before N,O-dimethylhydroxylamine hydrochloride (1.0 g, 10 mmol) is added. After stirring for 30 minutes, the reaction mixture is concentrated under reduced pressure. The residue is partitioned between diethyl ether and water. The ethereal phase is washed 2x with water and once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to provide tert-butyl [4-(4-{[methoxy(methyl)amino]carbonyl}piperidin-1-yl)phenyl]carbamate as a pale yellow solid (1.5 g, 100%). MS (ES+): 364.4 (M+H)+ A solution of tert-butyl [4-(4-{[methoxy(methyl)amino]carbonyl}piperidin-1-yl)phenyl]carbamate (1.4 g, 3.9 mmol) in tetrahydrofuran (15 mL) is cooled to 0 °C in an ice-water bath. Lithium aluminum hydride (0.21 g, 5.4 mmol) is added in several portions to the solution. The reaction mixture is allowed to warm to room temperature where it stirred for 30 minutes. It is cooled to 0 °C and quenched with 5 % aqueous potassium hydrogen-sulfate solution. The insoluble material is removed via filtration. The filtrate is concentrated under reduced pressure and taken up in ethyl acetate. The organic liquor is washed once with water and once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to tert-butyl [4-(4-formyl-piperidin-1-yl)-phenyl]carbamate as an off-white solid (0.90 g, 75 %). MS (ES+): 305.3 (M+H)+ To a suspension of tert-butyl [4-(4-formyl-piperidin-1-yl)-phenyl]carbamate (0.30 g, 1.0 mmol) in methanol (5 mL) is added N,N-dimethylethylenediarnine (0.18 g, 2.0 mmol). The reaction mixture is stirred for 10 minutes and then a mixture of zinc chloride (82 mg, 0.6 mmol) and sodium cyanoborohydride (75 mg, 1.2 mmol) in methanol (2 mL) is added in a dropwise fashion. After stirring for two hours at room temperature, the reaction mixture is diluted with water and extracted 3x with ethyl acetate. The combined extracts were washed once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give tert-butyl {4-[4-({[2- (dimethylamino)ethyl]amino}methyl)piperidin-1-yl]phenyl}carbamate as a white foam (0.4 g, 100%). MS (ES+): 377.4 (M+H)+ To a sample of tert-butyl {4-[4-({[2-(dimethylamino)ethyl]amino}methyl)piperidin-1-yl]phenyl}carbamate (approximately 1.0 mmol) is added hydrogen chloride solution (4 N in dioxane (10 mL). After stirring overnight at room temperature, the solvent is evaporated under reduced pressure. The solid material is collected, washed with diethyl ether, and dried under house vacuum to give the intermediate N-[1-(4-amino-phenyl)-piperidin-4-ylmethyl]-N,N-dimethyl-ethane-1,2-diamine tetrahydrochlorlde (0.29 g, 69 %), which is used in the following step without further purification. (4E)-6-lodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.23 g, 0.69 mmol), N-[1-(4-amino-phenyl)-piperidin-4-ylmethyl]-N,N-dimethyl-ethane-1,2-diamine tetrahydrochloride (0.29 g, 0.69 mmol) were coupled in N,N-dimethylformamide (5 mL) with triethylamine (1.0 mL). The mixture is heated in a 100 °C block shaker for three hours. Then water is added in order to precipitate the solid product. This solid is collected by filtration, then a portion thereof is purified by reverse phase HPLC to give (4Z)-4-[({4-[4-({[2-(dimethylamino)ethyl]amino}methyl)piperidin-1-yl]phenyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione tritrifluoroacetate (44 mg). MS (ES+): 574.2 (M+H)+ (Formula Removed) Example 447 (4Z)-4-({[2-Hydroxy-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione A solution of 6-(4-methylpiperazin-1-yl)-3-nitropyridin-2-amine (1.2 g, 5.0 mmol) in hydrogen fluoride●pyridine (15 mL) is cooled to 0 °C in an ice-water bath. Sodium nitrite (0.36 g, 5.2 mmol) is added in a single portion, and the mixture is stirred for 30 minutes at 0 °C. The bath Is removed and the mixture is heated for 15 minutes in an oil bath on a 70 °C hot plate. After cooling to room temperature, the reaction mixture is poured onto ice (50 g), neutralized with saturated aqueous sodium hydrogen carbonate solution, and basified with 10 N sodium hydroxide solution. The mixture is extracted 3x with dichloromethane, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Eighty-percent of the crude residue is purified by reverse-phase HPLC to give 6-(4-methylpiperazin-1-yl)-3-nitropyridin-2-ol● trifluoroacetic acid salt (0.18 g, 7.8 %). MS (ES+): 239.3 (M+H)+ To a suspension 6-(4-methylpiperazin-1-yl)-3-nitropyridin-2-ol● trifluoroacetic acid salt (0.17 g, 0.48 mmol) in ethanol (25 mL) is added triethylamine dropwise with agitation until all of the solid had dissolved. The mixture is then degassed with dry ice and treated with an aqueous slurry of Raney nickel (approx 1 mL). After shaking under 50 psi of hydrogen, the reaction mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 3-amino-6-(4-methyl-piperazin-1-yl)-pyridin-2-ol (0.15 g, contaminated with triethylammonium trifluoroacetate) as a blue solid. MS (ES+): 209.3 (M+H)+ (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1.3(2H,4H)-dione (0.12 g, 0.35 mmol), 3-amino-6-(4-methyl-piperazin-1-yl)-pyridin-2-ol (0.15 g, contaminated with triethylammonium trifluoroacetate) were coupled in N.N-dimethylformamide (3 mL) with triethylamine (0.27 mL). The mixture is heated in a 100 °C oil bath for three hours. The reaction mixture is purified by reverse phase HPLC to give (4Z)-4-({[2-hydroxy-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methy1ene)-6-iodoisoquinoline-1,3(2H,4H)-dione●2 trifluoroacetic acid salt (18 mg, 7.0 %). MS (ES+): 506.2 (M+H)+ (Formula Removed) Example 448 4-[(4Z)-4-({[5-(4-Methylpiperazin-1-yl)pyridin-2-yl]amino}methylene)-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-2-furaldehyde: Using the procedure described for the preparation of '(4Z)-6-(3-furyl)-4-{{[6-(4-rnethylpiperazin-1-yl)pyridin-3-'yl]arnino}rnethylene)isoquinoline-1,3(2H,4H)-dione, 170 mg (27 % yield) is obtained as a orange solid from 600 mg (1.36 mmol) of (4Z)-6-bromo-4-({[5-(4-methylpiperazin-1 -yl)pyridin-2- yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione and 5-formyl-3-furyl boronic acid (L27615-102) 563 mg, (4.08 mmol).; mp 183-184°C MS (ESI) m/z458.1 (M+1)+ (Formula Removed) Example 449 (4Z)-4-({[5-(4-Methylpiperazin-1-yl)pyridin-2-yl]amino}methylene)-6-[5- (pyrrolidin-1-ylmethyl)-3-furyl]isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-4-({[4-(dimethylamino)-3-hydroxybenzylJamino}methylene)-6-iodotsoquinoline-1,3(2H,4H)-dione, 30 mg (45 % yield) is obtained as a yellow solid, from 60 mg (1.36 mmol) of 4-[(4Z)-4-({[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino)methylene)-1,3-dioxo- 1,2f3,4-tetrahydroisoquinolin-6-yl]-2-furaldehyde and pyrrolidine 0.11 mL, (1.3 mmol).; mp 194-195°C MS (ESI) m/z 271.1 (M+2H)+ (Formula Removed) Example 450 4-{[4-(1-Methyl-pyrrolidin-2-yl)-phenylamino]-methylene}-6-thiophen-2-yl-4H- isoquinoline-1,3-dione Using the procedure described for the preparation of 4-{[4-(2-Hydroxyrnethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methy1ene}-6-thiophen-2-yl-4H-isoquinoline-1,3-dione, the title compound is obtained from lodo-4-{[4-(1-methyl-pyrrolidin-2-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione (150 mg, 0.3 mmol), 2-thienyl zinc chloride (2.0 mL, 0.5 M solution in THF, 1.0 mmol) in 69% yield as a yellow solid: MS (ESI): 430.1 (M+1 )+1. (Formula Removed) Example 451 6-Furan-3-yl-4-{[4-(1-rnethyl-pyrrolidin-2-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 4-{[4-(2-Hydroxymethyl-pyn-olidin-1-ylmethyl)-phenylarnino]-methylene)-6-thiophen-3-yl-4H-isoquinoline-1,3-dione the title compound is obtained from 6-lodo-4-{[4-(1-methyl-pyrrolidin-2-yl)-phenylaminol-methylene}-4H-isoquinoline-1,3-dione (200 mg, 0.42 mmol), 3-furyl boronic acid (100 mg, 0.78 mmol) in 24% yield as a yellow solid: MS (ESI): 414.1 (M+1)+1. (Formula Removed) Example 452 6-Bromo-1,1 -dimethyl-4-{[4-(4-methyI-piperazin-1 -yl)-phenylamino]-methylene}-1,4-dihydro-2H-isoquinoIin-3-one: 6-Bromo-1,1-dimethyt-1,4-dihydro-2H-isoquinolin-3-one (210 mg, 0.83 mmol) and dimethoxymethyl-dimethyl-amine (250 mg, 2.1 mmol) in (N,N-dimethylformamide) DMF (4 mL) is heated at 100 °C for 1 hour. After which the DMF is evaporated and toluene (6 mL) is added. This solution is then mixed with a solution of 4-(4-Methyl-piperazin-1-yl)-pbenylamine (450 mg, 2.4 mmol) in toluene (4 mL) and the mixture is heated at reflux for 6 hours. The mixture is then allowed to cool to room temperature, upon cooling, precipitates formed. The precipitate is collected and further purified through chromatography to provide the title compound (120 mg, 31%). MS (ESI): 455.1, 457.1 (M+1)+1. (Formula Removed) Example 453 (4Z)-6-lodo-4-({[(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione To a solution of methyl isonicotinate (5.0 g, 36 mmol) in benzene (165 mL) is added iodomethane (4.5 mL, 72 mmol). The mixture is heated in a 110 °C oil bath for two hours and then allowed to cool to room temperature.. The solid is collected by BOchner filtration, washed with hexanes and diethyl ether, and dried under house vacuum to give 4-methoxycarbonyl-1-methylpyridinium iodide (4.6 g, 46 %). MS (ES+): 152.3 (M+-l)+ 1-Methyl-2-oxo-1,2-dihydropyridine-4-carboxylic acid is prepared according to the procedure of Fronk, M.H. and Mosher, H.S. JOC. 24. 1959, 196-198. MS (ES-): 152.1 (M-H)- 1-Methy1-2-oxo-1,2-dihydropyridine-4-carboxamide is prepared according to a procedure modified from Fronk, M.H. and Mosher, H.S. JOC. 24, 1959, 196-198. MS (ES+): 153.3 (M+H)+ 4-Aminomethyl-1-methyl-1H-pyridin-2-one is prepared in two steps from 1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamide from WO 03/051868A1. MS (ES+): 139.3 (M+H)+ (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (130 mg, 0.40 mmol), 4-aminomethyl-1-methyl-1H-pyridin-2-one (55 mg, 0.40 mol) were coupled in N,N-dimethylformamide (2 mL) at room temperature. The reaction mixture is diluted with water and the precipitate is collected by Buchner filtration and then dried under house vacuum to give (4Z)-6-iodo-4-{{[(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline-1,3{2H,4H)-d\one as an orange solid (0.15 g. 88 %). MS (ES+): 436.2 (M+H)+ (Formula Removed) Example 454 (4Z)-4-{[(4-{4-[(Dimethylamjno)methyl}piperidin-1-yl}phenyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4h)-dione To a suspension of tert-butyl [4-(4-formyl-piperidin-1-yl)-phenyl]carbamate (0.20 g, 0.66 mmol) in methanol (5 mL) is added dimethylamine (2.0 M solution in tetrahydrofuran, 0.66 mL, 1.3 mmol). The reaction mixture is stirred for 20 minutes and then a mixture of zinc chloride (53 mg) and sodium cyanoborohydride (50 mg) in methanol (2 mL) is added in a dropwise fashion. After stirring overnight at room temperature, the reaction mixture is diluted with water and extracted 3x with ethyl acetate. The combined extracts were washed once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give tert-butyl [4-(4-dimethylaminomethyl-piperidin-1-yl)-phenyl]-carbamate as a white foam (0.33 g, >100 %). MS (ES+): 333.4 (M+H)+ Tert-butyl {4-(4-dimethylaminomethy1-piperidin-l-yl)-phenyrj-carbamate (approximately 0.66 mmol) in dichloromethane (5 mL) is treated with trifluoroacetic acid (1 mL). After being stirred overnight at room temperature, the reaction mixture is concentrated under reduced pressure to afford 4-(4-dimethylaminomethyl-piperidin-1-yl)-phenylamine●3 trifluoroacetic acid, which is subsequently used without further purification. (4E)-6-lodo-4~(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.17 g, 0.50 mmol), 4-(4-dimethylaminomethyl-piperidin-1-yl)-phenylamine●3 trifluoroacetic acid (0.50 mmol) were coupled in N,N-dimethylformamide (2 mL) with triethylamine (0.5 mL). The mixture is heated in a 100 °C oil bath overnight. The reaction mixture is purified by reverse phase HPLC to give (4Z)-4-{[(4-{4-[(dimethylamino)methyl)pipericlin-1-yl}phenyI)arnino]rnethylene}-6-iocloisoquinoline-1,3(2H,4H)-dione●2 trifluoroacetic acid (45 mg, 12 %). MS(ES+):531.2(M+H)+ (Formula Removed) Example 455 (4Z)-6-lodo-4-({[4-(4-{[methyl(1-methylpyrrolidin-3-yl)amino]methyl}piperidin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione To a suspension of tert-butyl [4-(4-formyl-piperidin-1-yI)-phenyl]carbamate (0.20 g, 0.66 mmol) in methanol (5 mL) is added N,N-dimethyl-3-aminopyrrolidine (0.15 g, 1.3 mmol). The reaction mixture is stirred for 20 minutes and then a mixture of zinc chloride (53 mg) and sodium cyanoborohydride (50 mg) in methanol (2 mL) is added in a dropwise fashion. After stirring overnight at room temperature, the reaction mixture is diluted with water and extracted 3x with ethyl acetate. The combined extracts were washed once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give tert-butyl [4-(4-{[methyl-(1-methyl-pyrrolidin-3-yl)-amino]-methyl}-piperidin-1-yl)-phenyl]-carbamate as a foam (0.27 g, 100 %). MS (ES*): 403.5 (M+H)+ Tert-butyl [4-(4-{[methyl-(1-methyl-pyrrolidin-3-yl)-amino]-methyl}-piperidin-1-yl)-phenyl]-carbamate (0.66 mmol) in dichloromethane (5 mL) is treated with trifluoroacetic acid (1mL). After being stirred overnight at room temperature, the reaction mixture is concentrated under reduced pressure to afford [1-(4-amino- phenyl)-piperidin-4-ylmethyl]-methyl-(1-rnethyl-pyrrolidin-3-yl)-amine●4 trifluoroacetic acid, which is subsequently used without further purification. (4E)-6-liodo-4-(methoxyrnethylene)isoquinoline-1,3(2H,4H)-dione (0.17 g, 0.50 mmol), [1 -(4-amino-phenyl)-piperidin-4-ylmethyl]-methyl-(1 -methyl-pyrrolidin-3-yl)-amine»4 trifluoroacetic acid (0.50 mmol) were coupled in N,N-dimethylformamide (2 mL) with triethylamine (0.5 mL). The mixture is heated in a 100 °C oil bath overnight. The reaction mixture is purified by reverse phase HPLC to give (4Z)-6-iodo-4-({[4-(4-{[methyl(1 -methylpyrrolidin-3-yl)amino]methyl}piperidin-1-yl)phenyflarnino}rnethylene)isoquinoline-1,3(2H,4H)-dione●3 trifluoroacetic acid (41 mg, 4.4 %). MS (ES+): 600.3 (M+H)+ (Formula Removed) Example 456 (4Z)-4-{[(4-{4-[(Ethylamino)methyl]piperidin-1-yl}phenyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione To a suspension of tert-butyl [4-(4-formyl-piperidin-1-yl)-phenyl]carbamate (0.20 g, 0.66 mmol) in methanol (5 mL) is added ethylamine (2.0 M solution in tetrahydrofuan, 0.66 mL, 1.3 mmol). The reaction mixture is stirred for 20 minutes and then a mixture of zinc chloride (53 mg) and sodium cyanoborohydride (50 mg) in methanol (2 mL) is added in a dropwise fashion. After stirring overnight at room temperature, the reaction mixture is diluted with water and extracted 3x with ethyl acetate. The combined extracts were washed once with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give tert-butyl [4-(4-ethylaminomethyl-piperidin-1-yl)-phenyll-carbamate as a foam (0.27 g, >100 %). MS (ES+): 334.4 (M+H)+ Tert-butyl [4-(4-ethylaminomethyl-piperidin-1 -yl)-phenyl]-carbamate (approximately 0.B6 mmol) in dichloromethane (5 mL) is treated with trifluoroacetic acid (1mL). After being stirred overnight at room temperature, the reaction mixture is concentrated under reduced pressure to afford 4-(4-ethylaminomethyl-piperidin-1-yl)-phenylamine»3 trifluoroacetic acid, which is subsequently used without further purification. (4E)-6-lodo-4-(methoxymethylene)isoquinoIine-1l3(2H,4H)-dione (0.17 g, 0.50 mmol), 4-(4-ethylaminomethyl-piperidin-1-yl)-phenylamine-3 trifluoroacetic acid (0.50 mmol) were coupled in N,N-dirnethylformamide (2 mL) with triethylamine (0.5 mL). The mixture is heated in a 100 °C oil bath overnight. The reaction mixture is purified by reverse phase HPLC to give (42)-4-{[[(4-{4-[(ethylamino)methyl]piperidin-1-yl}phenyl)amino]methylene}-6-iodoisoquinoline-1,3(2H,4H)-dione»2 trifluoroacetic acid (45 mg, 12 %). MS (ES+): 531.3 (M+H)+1 Example 457 (4Z)-4-({[2-Fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}rnethylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione (Formula Removed) Example 458 6-Furan-3-yl-1,1-dimethyl-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-1,4-dihydro-2H-isoquinolin-3-one Using the procedure described for the preparation of 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione, the title compound is obtained from 6-Bromo-4-{[4-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-rnethylene}-4H-isoquinoline-1,3-dione {100 mg, 0.22 mmol), 3-furyl boronic acid (50 mg, 0.39 mmol) in 21% yield as a yellow solid: MS (ESI): 443.2 (M+1)+1. (Formula Removed) Example 459 (Z)-4-((5-Bromopyridin-2-ylamino)rnethylene)-6-(1H-pyrrol-1-yl)isoquinoline- 1,3(2H,4H)-dione: A mixture of (E)-4-(methoxymethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione (189 mg, 0.705 mmole), dimethylformamide (5 mL), and 5-(1-methylpyrrolidin-2-yl)pyridin-2-amine (125 mg, 0.705 mmole) is heated at 125°C for four hours. The reaction mixture is cooled, diluted with ether, filtered, washed with fresh ether and dried to give a red solid, 15 mg. (5%), mp 186-96°C dec; MS (ES+): m/z 414.1 (M + H). (Formula Removed) Example 460 (2)-6-lodc-4-((5-(1-methylpyrrolidin-2-yl)pyridin-2-ylamino)methylene)isoquinoline- 1,3(2H,4H)-dione: A mixture of (E)-6-iodo-4-(methoxymethyIene)isoquinoline-1,3(2H,4H)-dione (696 mg, 2.12 mmole), dirnethylforrnarnide (15 mL), and 5-(1-methylpyrrolidin-2-yl)pyridin-2-amine (375 mg, 2.12 mmole) is heated at 125°C for four hours. The reaction mixture is cooled, diluted with ether, filtered, washed with fresh ether and dried to give a yellow solid, 580 mg, (58%), mp 174-206°C dec; MS (ES+): m/z 475.0 (M + H). (Formula Removed) Example 461 2-{4-[(6-lodo-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyt)-amino]-phenyl}-pyrrolidine-1-carboxylic acid tert-butyl ester Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoiine-1,3-dione, the title compound is obtained from 2-(4-Amino-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 3.82 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (1.0 g, 3.03 mmol) in 59% yield as a yellow solid: 1H NMR (400 MHz, DMSO) δ12.55-12.57 (1H, M), 11.38 (1h. S), 8.93 (1H. d, J = 12.4 Hz). 8.59 (1H. s). 7.73 (1H, d. J = 8.4 Hz), 7.54-7.61 (3H, m), 7.22 (2H, d, J = 7.2 Hz), 4.73-4.87 (1H, m), 3.42-3.57 (2H, m), 2.29 (1H, m), 1.70-1.83 (3H, m), 1.40 (4H. s). 1.14 (5H, s). [Two rotamers exist in the NMR.] MS (ESI): 560.1 (M+1)+1 Anal. Cacl. for C25H26IN3O4 C, 53.68; H, 4.68; N, 7.51; Found: C, 53.42; H, 4.94; N, 7.42. (Formula Removed) Example 462 6-lodo-4-[(4-pyrrolidin-2-yl-phenylamino)-methylene]-4H-isoquinoline-1,3- dione Using the procedure described for the preparation of 4-{[4-(1,2,3,6-Tetrahydro-pyridin-2-yl)-phenylamino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione, the title compound is obtained from 2-{4-[(6-lodo-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-arnino]-phenyl}-pynrolidine-1-carboxyHc acid tert-butyl ester (0.9 g, 1.61 mmol) in 74% yield as a yellow solid: 1H NMR (400 MHz. DMSO) δ 12.55 (1H. d, J = 13.2 Hz), 11.40 (1H, or), 8.93 (1H, d. J = 11.6 Hz), 8.59 (1H, s), 7.73 (1H, d, J = 8.4 Hz), 7.42-7.61 (5H, m). 4.1 (1H, t, J = 8.4Hz), 3.03-3.12 (1H, m). 2.90-2.97 (1H, m), 2.12-2.17 (1H. m). 1.75-2.00 (2H, m), 1.51-1.57 (1H, m). MS (ESI): 460.0 (M+1)+1. Anal. Cacl. for C20H18IN3O2: C, 52.3; H, 3.95; N, 5.15; Found: C, 46.16; H, 4.31; N. 7.88. HRMS Cacl. for C20H19IN3O2: 460.05154; Found: 460.05165, (M+1)+1. (Formula Removed) Example 463 6-Furan-3-yl-4-{[4-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 4-{[4-(2-HydroxymethyI-pyrrolidin-1-ylmethyl)-phenylamino]-metriylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione,, the title compound is obtained from 6-Bromo-4-{[4-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylannino]-rnethylene}-4H-isoquinoline-1,3-dione (200 rng, 0.4 rnmol), 3-furyl boronic acid (120 mg, 0.94 mmol) in 99% yield as a yellow solid: MS (ESI): 444.1 (M+1)+1 (Formula Removed) Example 464 4-({4-[1-(2-Hydrbxy-ethyl)-pyrrolidin-2-yl]-phenylamino}-methylene)-6-iodo-4H-isoquinoline-1,3-dione 6-lodo-4-[(4-pyrrolidin-2-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione (250 mg, 0.54 mmol) and Na2C03 (2.0 g, 18.9 mmol) in THF (10 mL) is heated to reflux and bromoethanol (0.15 mL) is added every 45 min for 4 hours. The resulting mixture is then allowed to reflux overnight. After TLC suggested no starting material left, the THF is removed and after an aqueous work up, the desired product is isolated through chromatography (75 mg, 28%). MS (ESI): 504.0 (M+1)+1. (Formula Removed) Example 465 4-{[4-(1-Ethyl-pyrrolidin-2-yl)-phenylamino]-methyiene}-6-iodo-4H-isoquinoline-1,3-dione 6-lodo-4-[(4-pyrrolidin-2-yl-phenylarnino)-methylene]-4H-isoquinoline-1,3-dione (250 mg, 0.54 mmol) and K2C03 (170 mg, 1.23 mmol) and Etl (155 mg, 0.99 mmol) in N,N-dimethytformamide (5 mL) were stirred at room temperature for 2 hours. After TLC suggested no starting material left, the N.N-dimethylforrnamide is removed through an aqueous work up, and the desired product is isolated through chromatography (125 mg, 48%). MS (ESI): 488.0 (M+1)+1. (Formula Removed) Example 466 6-Furan-2-yl-4-(I4.-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione 6-Bromo-4-{[4-(2-hydrpxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione (130 mg. 0.26 mmol) and 2-furyltriburyltin (270 mg, 0.76 mmol) and PdCI2(PPh3)2 (30 mg) is mixed in N,N-dimethylforrnarnide (4 mL) and degassed. The solution resulted is heated at 100 °C for 1 hour. After the mixture cooled to room temperature, the N,N-dimethylformamide is removed and the residue is purified through chromatography to afford the title compound (68 mg, 59%). MS (ESI): 444.1 (M+1)+1. (Formula Removed) Example 467 (4Z)-6-(2-Furyl)-4-{I(4-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}isoquinollne-1,3(2H ,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-tr!methylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione, 136 mg (77 % yield ) of yellow solid is obtained from 200 mg (0.39 mmol) of (4Z)-6-bromo-4-{[(4-{[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}phenyl)amino)methytene}isoquinoline-1,3(2H,4H-dione, 0.4 mL (1.17 mmol) of 2-(tributyltsannyyl)furan and 40 mg (0.059mmol) of trans-Dichlorobis(triphenylphosphine)palladium(ll): mp 159-160ºC; MS (ESI) m/z 458.1 (M+H). (Formula Removed) Example 468 (4Z)-4-[({5-[(3R,5S)-3,5-Dimethylpiperazin-1-yl]pyridin-2-yl}amino)methylene]-6-(3- furyl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-({[6-(4-methylpipera2in-1-yl)pyridin-3-,yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 500 mg (47 % yield) is obtained as a yellow solid from 500 mg (1.09 mmol) of (4Z)-6-bromo-4-[({5-[(3R,5S)-3,5-dimethylpiperazin-1 -yl]pyridin-2-yl}amino)methylene]isoquinoline-1,3(2H,4H)-dione and 3-furan boronic add 245 mg, (2.19 mmol).; mp 230-231 °C MS (ESI) m/c 444.0 (M+1)+ (Formula Removed) Example 469 (4Z)-6-Bromo-4-[({5-[(3R,5S)-3,5-dimethylpiperazin-1-yripyridin-2-yl}amino)methyleneJisoquinollne-1,3(2H,4H)-dione: Using the procedure described for the preparation of example 14, 1.1 mg (58 % yield) is obtained as a brown solid from 1.2g (4.25 mmol) (4E)-6-bromo-4-(methoxymethylene)isoquinoiine-1,3(2H,4H)-diorte and 880.0 mg (4.25 mmol) of 5-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridin-2- yl}amine; mp 245-246oC. MS (ESI) m/z 456.0 (M+1)+ (Formula Removed) Example 470 N-(4-Hydroxy-6-{[(6-iodo-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidene methyl)-amino]-methyl}-pyridin-3-yl)-propionamide A mixture of 4-{[(5-Amino-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1.3-dione (332 mg, 0.761 mmole), 6 mL of dimethylacetamide is stirred, then propiortyl chloride (705 mg, 7.61 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, and then stirred overnight with a saturated aqueous sodium bicarbonate solution, the solid is filtered, washed well with water and dried to give a yellow solid, 46 mg. (11%); m.p. 210-18 °C dec; MS (ES+): m/z 492.9 (M + H). (Formula Removed) Example 471 6-lodo-4-{[(1 -methyl-4-oxo-5-propoxy-1,4-dlhydro-pyridin-2-ylmethyl)-amino]-methylene}-4H-isoqulnoline-1,3-dione A mixture of 2-aminomethyl-1-methyl-5-propoxy-1H-pyridin-4-one (196 mg, 1.0 mmole), 10 mL of N,N-dimethylformamide is stirred, 4-methoxymethylene-6-iodo-4H-isoquinoline-1,3-dione (329 mg, 1.0 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, triturated with 5% methanol in chlororform, filtered washed with fresh 5% methanol in chloroform, washed with acetonitrile and dried to give an off-white solid. 124 mg, (24%); m.p. 176-96 °C dec; MS (ES+): m/z 494.0 (M + H). Example 472 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-6-thiazol-2-yl-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-y)methyl)-phenylaminoJ-methylene}-6-thiophen-2-yl-4H-isoquinoline-1,3-dlone„ the title compound is obtained from6-Bromo-4-{1l4-(2-hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isdquinoline-1,3-dione (166 mg, 0.33 mmol), 2-thiazolyl zinc chloride (3.6 mL, 0.5 M solution in THF, 1.8 mmol) in 21% yield as a yellow solid: MS (ESI): 461.1 (M+1)+1. (Formula Removed) 4-{[4-(1-Ethyl-pyrrolidin-2-yl)-phenylamino]-methylene}-6-furan-3-yl-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 4-{[4-(2-Hydroxymethyl-pynrolidin-1-ylmethyl)-phenyJamino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-{[4-(1-Ethyl-pyrrolidin-2-yl)-phenylamino]-methylene}-6-iodo-4H-isoquinoIine-1,3-dione (90 mg, 0.18 mmol), 3-furyl boronic acid (90 mg, 0.70 mmol) in 65% yield as a yellow solid: MS (ESI): 428.1 (M+1)+1. (Formula Removed) Example 474 (42)-4-({[6-(4-Methylpiperazin-1 -yl)pyridin-3-yl]amino}methylene)-6-(1 -methyl- 1H-pyrrol-2-yl)isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-[({4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]phenyl}amino)-methylene]isoquinoline-1,3(2H,4H)-dione (41), 79 mg (40 % yield ) of yellow solid is obtained from 200 mg (0.45 mmol) of (4Z)-6-bromo-4-({I6-(4-methylpiperazin-1-yl)pyridin-3-y]amino}methylene)isoquinoline-1,3(2H,4H)-dione 330 mg (0.45 mmol), 2-(tributyltsannyl) thiazole and 50 mg (0.90 mmol) of trans- Dichlorobis(triphenylphosphine)palladium(ll): mp 216-217°C; MS (ESI) m/z 443.1 (M+H). (Formula Removed) Example 475 (4Z)-6-lodo-4-(([2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione A N,N-dimethylformamide solution (1.6 mL) of 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (254 mg, 0.77 mmol), and 2-(4-methyl-piperazin-1-yl)- pyrimidin-5-ylamine (157 mg, 0.813 mmol) is heated at 90°C for 40 min. After cooling in the refrigerator, the precipitate is collected, and washed with N,N-dimethylformamide and ether to give 259 mg (65%) of the title compound as a yellow solid. MS (ESI) m/z 491 (M+H)+1 (Formula Removed) Example 476 (4Z)-6-(3-Furyl)-4-({(6-(4-methylpiperazin-1-yl)pyridazin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H}-dione Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-({[6-(4-methylpipera2in-1-yl)pyridin-3-'yl]arnino}methylene)isoquinoline-1,3(2H.4H)-dione, 90 mg (23 % yield) is obtained as yellow solid from 400 mg (0.9 mmol) of (4Z)-6-brorno-4-({[6-(4-methylpiperazin-1-yl)pyridazin-3- yr]amino}methylene)isoquinoline-1,3(2H,4H)-dione and furan boronic acid 252 mg, (2.25 mmol).; mp 275-276°C MS (ESI) m/z 431.1 (M+1)+ (Formula Removed) Example 477 (4Z)-6-Bromo-4-({[6-(4-methylpiperazin-1-yl)pyridazin-3-yl]amino}methy/ene)isoquinoline-1,3(2H ,4H)-dione Using the procedure described for the preparation of example 14, 700 mg (89 % yield) is obtained as a yellow solid from 500 g (1.77 rnmol) (4E)-6-bromo-4- (methoxymethylene)isoqulnoline-1,3(2H,4H)-dione and 342.o mg (1.77 mmol) of [6-(4-methylpiperazin-1-yl)pyridazin-3- yl]amine; mp 245-246°C. MS (ESI) m/z 445.0 (M+1)+ (Formula Removed) Example 478 (4Z)-6-lodo-4-{I(5-{[(2S)-2-(rnethoxymethyl)pyrrolidin-1-yl]methyl}pyridin-2-yl)amino]methylene)isoquinoIine-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 30 mg (11 % yield) is obtained as a yellow solid from 170 g (0.52 mmol) (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 137.2 mg (0.62 mmol) of (5-{I(2S)-2-(nrethoxymethyl)pyrrolidin-1-yl]methyl}pyridin-2- yl)amine; mp 185-186°C. MS (ESI) m/z 519.0 (M+1 )+ (Formula Removed) 4-{[(4-Hydroxy-5-methoxy-pyrimidin-2-ylmethyl)-amino]-methylene}-6-iodo-4H- isoquinoline-1,3-dione 2-Aminomethyl-5-methoxy-pyrimidin-4-ol (10 mg, 0.064 mmol) and 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (50 mg, 0.15 mmol) in N,N-dimethylformamide (3 mL) is stirred at room temperature for 1Hour. The N,N-dimethylformarnide is then removed and residue purified to provide the title compound (10 mg, 34%). MS (ESI): 453 (M+1)+ (Formula Removed) Example 480 (4Z)-4-{[(4-{(4-(2-Hydroxyethyl)piperidin-1-yl]methyl}pheny))amino]methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14,135 mg (42 % yield) is obtained as a yellow solid from 200 g (0.61 mmol) (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 145 mg (0.61 mmol) of 4-(2-hydroxyethyl)piperidin-1-yl]methyl}phenyl)amine; mp 223-224°C. MS (ESI) m/z 532.0 (M+1)+ (Formula Removed) Example 481 (4Z)-4-({[5-(4-Ethylpiperazin-1-yl)pyridin-2-yl]amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of '(4Z)-6-(3-furyl)-4-({[6-(4-methylpiperazin-1-yl)pyridin-3-yr]amino}methylene)isoqu!noline-1,3(2H,4H)-dione, 220 mg (45 % yield) is obtained as a yellow solid from 500 mg (1.1 mmol) of (4Z)-6-bromo-4-({[5-(4-ethylpiperazin-1 -yl)pyridin-2- yljamino}methylene)isoquinoline-1,3(2H,4H)-dione and furan boronic acid 246 mg, (2.2 mmol).; mp 256-257°C MS (ESI) m/z 444.1 (M+1)+ (Formula Removed) Example 482 (4Z)-6-(4-Fluorophenyl)-4-{[(4-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of '(4Z)-6-(4-fluorophenyl)-4-({I4-(piperidin-1-ylmethyl)phenyl}amino}methylene)isoquinoline-1,3(2H,4H)-dione, 141 mg (27 % yield) is obtained as a yellow solid from 500 mg (1.03 mmol) of (4Z)-6-bromo-4-{[(4-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H,4H}-dione and 4-Flurophenyl boronic add 289 mg, (2.06 mmol).; mp 202-203°C Example 483 608 MS (ESI) m/z 500. (M+1 )+ (Formula Removed) 4-{[4-(1,1 -Dioxo-1 -thiomorpholin-4-yimethyl)-phenylamrnoI-methylene}-6-iodo-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 6-Bromo-4-[(4-pyridin-4-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-(4-Amino-benzyl)-thiomorpholine 1,1-dioxide (85 mg, 0.35 mmol), 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (102 mg, 0.31 mmol) in 82% yield as a yellow solid: MS (ESI): 535.9 (M-1)-1. (Formula Removed) Example 484 (4Z)-6-(3-Furyl)-4-({[2-(4-methylpipera2rn-1-yl)pyrimidin-5-yI]amino}methylene)isoquinoline-1,3(2H,4H)-dione (4Z)-6-lodo-4-({|2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (73.5 mg, 0.15 mmol) is mixed with 3-furanboronic acid (33 mg, 0.3 mmol), Pd2(dba)3 (20.6 mg, 0.022 mmol), and cesium carbonate (98 mg, 0.3 mmol). After the solids were degassed, N,N-dimethylformamide (1.05 mL) and P(t-Bu)3 (9.1 mg, 0.045 mmol) were added. The mixture is heated at 100 C for 55 min, diluted with methylene chloride, and filtered. The filtrate is evaporated to dryness and purified by column chromatography to yield 36 mg (55%) of the title compound as a yellow solid. MS (ESI) m/z 431 (M+H)+1 (Formula Removed) Example 485 (4Z)-6-(3-Furyl)-4-{[(3-hydroxy-4-propoxybenzyl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione (4Z)-6-Bromo-4-{I(3-hydroxy-4-propoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (110mg, 0.255 mmol) is mixed with 3-furanboronic acid (58 mg, 0.51 mmol), Pd2(dba)3 (35 mg, 0.038 mmol), and cesium carbonate (166 mg, 0.51 mmol). After the solids were degassed, N,N-dimethylformamide (1.7 mL) and P(t-Bu)a (15.5 mg, 0.077 mmol) were added. The mixture is heated at 100 C for 1H, diluted with methylene chloride, and filtered. The filtrate is evaporated to dryness and purified by column chromatography to yield 8.5 rng (8%) of the title compound as a white solid. MS (ESI) m/z AM, 419 (M+H)1 (Formula Removed) Example 486 (4Z)-6-Bromo-4-({[5-(4-isoprcpylpiperazin-1-yl)pyridin-2-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14, 650 mg (65 % yield) is obtained as a brown solid from 600 mg (2.13 mmol) (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H.4H)-dione and 468 mg (2.13 mmol) of [5-(4-isopropylpiperazin-1-yl)pyridin-2- yljamine; mp 223-224°C. MS (ESI) m/z 472.0 (M+1)+ (Formula Removed) Example 487 (4Z)-4-[({6-[(3R,5S)-3,5-Dimethylpipera2in-1-yl]pyridin-3-yl}amino)methylene]-6-[5-(hydroxymethyl)-2-furylJisoquin6line-1,3(2H,4H)-dione: An amount of 100 mg (0.22 mmol) of (4Z)-4-[({6-{(3R,5S)-3,5-dimethylpiperazin-1-yrjpyridin-3-yl}amino)methylene)-6-)-[2-furanaldehyde]isoquinoline-1,3(2H,4H)-dione and 10% Pd/C were dissolved in 1:1 mathanol:N,N-dimethylformamide (20 mL) and hydrogenated at 40 psi for 2 hours. After filtering the palladium, the mixture is evaporated and crystallized the desired product from acetonitrite to give 60 mg (60 % yield) of yellow solid.; mp 253-254°C Example 488 (4Z)-6-(3-Furyl)-4-({I5-(4-isopropylpiperazin-1-yl)pyridin-2-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione: MS (ESI) m/z 474.1 (M+1)+ (Formula Removed) Using the procedure described for the preparation of (4Z)-6-(3-furyl)-4-({[6-(4-methylpipera2in-1-yl)pyridin-3-'yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 260 mg (67 % yield) is obtained as a yellow solid from 400 mg (0.85 mmol) of (4Z)-4-({[5-(4-ethylpiperazin-1 -yl)pyridin-2-yl]amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dion and furan boronic acid 190.2 mg, (1.7 mmol).; mp 278-279°C MS (ESI) m/z 458.1 (M+1)+ & (Formula Removed) Example 489 (4Z)-6-Bromo-4-{[(4-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}phenyl)aminoJmethylene}isoquinoline-1,3(2H,4H)-dione: Using the procedure described for the preparation of example 14, 950 mg (92 % yield) is obtained as a yellow solid from 600 g (2.13 mmol) (4E)-6-bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 500 mg (2.13 mmol) of 4-(2-hydroxyethyl)piperidin-1-yIJmethyl}phenyl)amine; mp 200-201°C. Example 490 612 MS (ESI) m/z 486.2 (M+1)+ (Formula Removed) 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3- dione 4-Aminomethyl-biphenyl-2-ol (80 mg, 0.4 mmol) and 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dlone (110 mg, 0.34 mmol) is stirred in N,N-dimethyJformamide (5 mL). After which N,N-dimethylformamide is removed under vacuum and the residue is triturated with MeOH. The precipitate thus formed is collected and washed with MeOH and dried to provide the title compound (151 mg, 89%). MS (ESI):: 495.1 (M-1)'1. (Formula Removed) Example 491 (4Z)-6-(3-Furyl)-4-{I(4-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of '(4Z)-6-(4-fluorophenyl)-4-({[4-(plperidin-1-,ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 210 mg (43 % yield) is obtained as a yellow solid from 500 mg (1.03 mmol) of (4Z)-6-bromo-4-{l(4-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}pheny!)amino]methylene)isoquinoline-1,3(2H,4H)-dione and 3-furan boronic acid 288 mg, (2.6 mmol).; mp 152-153°C MS (ESI) m/z 456.1 (M+1)+ (Formula Removed) Example 492 5-[(42)-1,3-Dioxo-4-({l4-(piperidin-1 -ylmethyl)phenyl]amino}methylene)-1.2,3,4-tetrahydroisoquinolin-6-yl]-2-furaidehyde Using the procedure described for the preparation of (4Z)-6-(4-fluorophenyl)-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 310 mg (43 % yield) is obtained as a yellow solid from 720 mg (1.64 mmol) of 4Z)-6-bromo-4-({[4-(piperidin-1- ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione and 5-formyl-2-furylboronic acid 459 mg, (3.28 mmol).; mp 173-174°C MS (ESI) m/z 472.0 (M+1)+ (Formula Removed) (Z)-4-(((6-Brprnc-5-propoxypyridin-2-yl)memyiarnino)methyJene)-6-iodoisoquinoline- 1.3(2H,4H)-dione: A mixture of (E)-6-iodo-4-(methoxymethylene)lsoquinoline-1,3(2H,4H)-dione (329 mg, 1.0 mmole), dimethylformamide (8 mL), and (6-bromo-5-propoxypyridin-2-yl)methanamine (245 mg, 1.0 mmole) is stirred at room temperature for one hour. The reaction mixture is diluted with acetonitrile, filtered, washed with fresh acetonitrile and dried to give a yellow solid, 434 mg, (80%), mp 251-3°C dec; MS (ES-): m/z 540.2 (M - H). (Formula Removed) Example 6-Furan-3-yl-4-{[(2-hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-4H-isoquinoline-1,3-dione Using the procedure described for the preparation of 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylrriethyl)-phenylamino]-methylene}-6-thiophen-3-y1-4H-isoquinoline-1,3-dione, the title compound is obtained from 4-{[(2-Hydroxy-biphenyl-4-yfmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione (75 mg, 0.15 mmol) and 3-furylboronic acid (50 mg, 0.39 mmol) as a yellow solid in 76% yield. MS (ESI): 435.3 (M-1)-1 (Formula Removed) Example 495 4-[(4-Butyl-3-hydroxy-benzylamino)-methylehe]-6-iodo-4H-isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-iodo-4-methoxymetnytene-4H-isoquinoline-1,3-dlone (85 mg, 0.26 mmol) and 5-Aminomethyl-2-butyl-phenol (54 mg, 0.3 mmol) in 65% yield: MS (ESI): 475.2 (M-1 )-1 (Formula Removed) 4-[(5-Hydroxy-2-iodo-benzylamino)-methylene]-6-iodo-4H-isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino}-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (100 mg, 0.30 mmol) and 3-Aminomethyl-4-iodo-phenol (80 mg. 0.32 mmol) in 73% yield: MS (ESI): 545.0 (M-1)"1. (Formula Removed) Example 497 (4Z)-4-({[2-Fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione A suspension of (4Z)-4-({[2-fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-iodoisoquinoIine-1,3(2H,4H)-dione (0.10 g, 0.20 mmol), 3-furanboronic acid (55 mg, 0.50 mmol), tris(dibenzylideneacetone)dipalladium(0) (27 mg, 0.03 mmol) and cesium carbonate (0.13 g) in N,N-dimethylformamide (2 mL) is heated in a 120 °C oil bath for 10 minutes. Tri-tert-butylphosphine (20 mg/mL solution in N,N-dimethylformamide, 0.50 mL, 10 mg, 0.05 mmol) is added, and the mixture continued to stir in the oil bath for one hour. After cooling to room temperature, the reaction mixture is diluted with chloroform and washed with saturated aqueous sodium hydrogen carbonate solution. The organic layer is concentrated under reduced pressure and purified via reverse phase HPLC to provide (4Z)-4-({[2-fluoro-6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)-6-(3-furyl)isoquinoline-1,3(2H,4H)-dione•3 trifluoroacetic acid salt (53 mg. 34 %). MS (ES+): 448.3 (M+H)+ Example 498 As you said Examples 497 and 498 have the same way. The only difference is their batch #. Since the second batch is purer than the first batch, please use the biological data from the second batch. (Formula Removed) Example 4-[(2-Furan-2-yl-5-hydroxy-benzylamino)-methylene]-6-iodo-4H-isoquinoline-1,3- dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (100 mg, 0.30 mmol) and 3-Aminomethyl-4-furan-2-yl-phenol (crude material from the previous reaction in 56% yield: MS (ESI): 485.1 (M-1)-1. (Formula Removed) Example 500 4-{|[(4,-Fluoro-2-hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H- isoquinoline-1,3-dione: Example 501 Following the same procedure for the preparation of 4-{[((2-Hydroxy-biphenyl-4-ytmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione-2, the title compound is prepared from 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (90 mg, 0.27 mmol) and 4-Aminomethyl-4,-fiuoro-biphenyl-2-ol (66 mg, 0.3 mmol) in 60% yield: MS (ESI): 513.1 (M-1 )-1 (Formula Removed) 4-{[(4'-Fluoro-2-hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-furan-2-yl-4H- isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-Furan-2-yl-4-methoxymethylene-4H-isoquinoline-1,3-dione (40 mg, 0.15 mmol) and 4-Aminomethyl-4,-fluoro-biphenyl-2-ol (33 mg, 0.15 mmol) in 62% yield: MS (ESI): 453.2 (M-1)-1 (Formula Removed) Example 502 6-Furan-2-yl-4-{[(4-hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino]-methylene}-4H- isoquinoline-1,3-dione A mixture of 2-amtnomethyl-5-propoxy-pyridin-4-ol (73 mg, 0.40 mmole), 5 mL of N,N-dimethylformamide is stirred, then 4-methoxymethylene-6-(furan-2-yl)-4H-isoquinoline-1,3-dione (108 mg, 0.40 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, triturated with 5% methanol in chlororform, filtered washed with fresh 5% methanol in chloroform, washed with acetonitrile and dried to give a pale yellow solid, 139 mg, (83%); m.p. 288-90 °C dec; MS (ES+): m/z 420.2 (M + H). (Formula Removed) 6-Furan-2-yl-4-[(5-hydroxy-2-iodo-benzylamino)-methylene]-4H-isoquinoline-1,3- dione Following the same procedure for the preparation of 4-{((2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-Furan-2-yl-4-methoxymethylene-4H-isoquinoline-1,3-dione (400 mg, 1.5 mmol) and 3-Aminomethyl-4-iodo-phenol (400 mg, 1.61 mmol) in 77% yield: MS (ESI): 485.1 (M-1)-1 (Formula Removed) Example 504 44(3-Hydroxy-4-iodo-benzylamino)-methylene]-6-iodo-4H-isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-ydroxy-biphenyl-4-ylmethyly-aminol-methylene^e-iodo^H-isoquinoline-1,3-dione, the title compound is prepared from 6-Furan-2-yl-4-methoxymethylene-4H-isoquinoline-1,3-dione (60 mg, 0.22 mmol) and 5-Aminomethyl-2-iodo-phenol (58 mg, 0.23 mmol) in 80% yield: MS (ESI): 485.1 (M-1)-1. Example 505 4-[(4-Furan-2-yl-3-hydroxy-benzylamino)-methylenel-6-iodo-4H-isoquinoline-1,3- dione Example 506 621 Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-iodo-4-rnethoxymethy)ene-4H-isoquinoline-1,3-dione (80 mg, 0.24 mmol) and 5-Aminomethyl-2-furan-3-yl-phenol (50 mg, 0.26 mmol) in 53% yield: MS (ESI): 485.1 (M-1)-1 (Formula Removed) 4-[(4-Furan-3-yl-3-hydroxy-benzylamino)-methiylene]-6-iodo-4H-isoquinoline-1,3- dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (85 mg, 0.26 mmol) and 5-Aminomethyl-2-furan-3-yl-phenol in 56% yield: MS (ESI): 487.1 (M+1)+1. (Formula Removed) Example 507 (4Z)-6-lodo-4-({[5-(4-methylpiperazin-1 -yl)pyrazin-2-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of example 14. 280 mg (57 % yield) is obtained as a brown solid from 330 g (1.03 mmol) (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 200 mg (1.03 mmol) of [5-(4-methylpiperazin-1-yl)pyrazin-2- yl]amine; mp 238-239°C. Example 508 (4Z)-6-(3-Furyl)-4-({[5-(4-methylpiperazin-1-yl)pyrazin-2-yl]amino}methylene)isoquinoiine-1,3(2H,4H)-dione: MS (ESI) m/z 491.1 (M+1)+ (Formula Removed) Using the procedure described for the preparation of '(4Z)-6-(3-furyl)-4-({[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione , 40 mg (23 % yield) is obtained as a yellow solid from 500 mg (0.41 mmol) of (4Z)-6-iodo-4-({[5-(4-methylpiperazin-1-yl)pyra2in-2-yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione and furan boronic acid 114 mg, (1.02 mmol).; mp 226 -227°C MS (ESI) m/z 431.1 (M+1)+ (Formula Removed) Example 509 4-[(3-Hydroxy-4-pyridirv-2-yl-benzylamino)-methylene]-6-iodo-4H-isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-blphenyl-4-ylmethyl)-aminoJ-methylene}-6-iodo-4H-isoquinollne-1,3-dione, the title compound is prepared from 6-iodo-4-nnethoxymethylene-4H-isoquinoline-1,3-dione (98 mg, 0.30 mmol) and 5-Aminomethyl-2-pyridin-2-yl-phenol (60 mg, 0.30 mmol) in 57% yield: MS (ESI): 498.1 (M+1)+1. (Formula Removed) Example 510 4-{[(6-Hydroxy-5-propoxy-pyridin-2-ylmethyl)-arnino]-methylene}-6-iodo-4H- isoquinoline-1,3-dione A mixture of 6-aminomethyl-3-propoxy-pyridin-2-ol (91 mg, 0.50 mmole), 7 mL of N,N-dimethylformamide is stirred, then 4-methoxymethylene-6-iodo-4H-isoquinoline-1,3-dione (165 mg, 0.50 mmole) is added and the reaction mixture stirred for 4 hours. The reaction mixture is evaporated to dryness, triturated with 5% methanol in chlororform, filtered washed with fresh 5% methanol in chloroform, washed with acetonitnle and drfed to give a beige solid, 152 mg, (63%);m.p. 275-81 °C dec; MS (ES+): m/z 478.1 (M + H). (Formula Removed) Example 511 4-[(3-Hydroxy-4-pyridin-4-yl-berizylamino)-methylene]-6-iodo-4H-isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (50 mg, 0.15 mmol) and 5-Aminomethyl-2-pyridIn-2-yl-phenol (40 mg, 0.20 mmol) in 40% yield: MS (ESI): 498.1 (M+1)+1. (Formula Removed) Example 512 (4Z)-4-{[(4-{I3-(Dimethylamrno)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}-6-(4-fluorophenyl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of '(4Z)-6-(3-furyl)-4-({[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino}niethylene)isoquinoline-1,3(2H,4H)-dione, 65 mg (16 % yield) is obtained as a yellow solid from 400 mg (0.85 mmol) of (4Z)-4-{[(4-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}-6-bromoisoquinoline-1,3(2H,4H)-dione and 4-flurophenyl boronic acid 298 mg, (2.13 mmol).; mp 95-96°C MS (ESI) m/z 485.3 (M+1)+ (Formula Removed) Example 513 (4Z)-4-{((H[3-(Dimethylamino)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}-6-(3- furyl)isoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of '(4Z)-6-(3-fury1)-4-({[6-(4-methylpiperazin-1-yl)pyridin-3-,yl]amino}methylene)isoquinoline-1,3(2H,4H)-dione, 90 mg (19 % yield) is obtained as a yellow solid from 500 mg (1.07 mmol) of (4Z)-4-{[(4-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}phenyl)amino]methylene}-6-bromoisoquinoline-1,3(2H,4H)-dione and 3-furan boronic acid 305 mg, (2.9 mmol). MS (ESI) m/z 457.0 (M+1)+ (Formula Removed) Example 514 (4Z)-4-({[3-Hydroxy-4-(1H-pyrrol-1 -yl)benzyl]amino}methylene)-6-iodoisoquinoline- 1,3(2H,4H)-dione A mixture of (4Z)-4-{[(4--amino-3-hydroxyberzyl)amino]fmethylene}-6-iodoisoquinoline-1,3(2H,4H)-dion (300 mg, 0.67 mmol), 2,5-dimethoxytctrahydrofuran (182.2 mg 1.4 mmol), and 4-chloropyridine hydrochloride (101mg, 0.67 mmol) were placed in a flask and N,N-dimethylformamide (5 mL) is added. The mixture is then placed in a pre-heated oil bath at 80°C for 2 hours. After cooling, all the solvent is evaporated. The brown solid is stirred in water and washed with ether to give the product as a brown solid 85 mg (25 % yield).; mp 230-231°C. MS (ESI) m/z 484.1 (M-1). (Formula Removed) Example 515 4-[(3-Hydroxy-4-pyridin-3-yl-benzylamino)-methylenel-6-iodo-4H-isoquinoline-1,3- dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-iodc-4-methoxymethylene-4H-isoquinoline-1,3-dione (50 mg. 0.15 mmol) and 5-Aminomethyl-2-pyridin-2-yl-phenol (53 mg, 0.27 mmol) in 76% yield: MS (ESI): 498.0 (M+1)-1 (Formula Removed) Example 516 N-[2-Hydroxy-4-({[(Z)-(6-iodo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)phenyl]-2-furamide Using the procedure described for the preparation of (example 69), 120 mg (50 % yield) of brown solid is obtained from 150 mg (0.46 mmol) of (4Z)-4-{[(4-amino-3-hydroxybenzyl)amino]methylene}-6-iodoisoquinoline- 1,3(2H,4H)-dion and 2-furoyl chloride 600 mg (4.6 mmol); mp 229-230°C MS (ESI) m/z 528.1 (M-1) (Formula Removed) Example 517 (4Z)-6-lodo-4-({[(2-oxo-1 -phenyl-1,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione To a solution of 4-aminomethyl-1H-pyridin-2-one hydrochloride in 50 % aqueous dioxane (100 mt.) is added sodium hydroxide (2.8 g, 69 mmol), followed by di-tert-butyldicarbonate (5.0 g, 23 mmol). After stirring overnight at room temperature, the mixture is neutralized with 5 % aqueous potassium hydrogen sulfate solution. The mixture is extracted four times with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. A sample of crude material is purified by reverse-phase HPLC to give tert-butyl (2-oxo-1,2-dihydro-pyridin-4-ylmethyl)-carbamate as a straw colored foam. MS (ES+): 225.3 (M+H)+ To a solution of tert-butyl (2-oxo-1 ,2-dihydro-pyridin-4-ylmethyl)-carbarnate (0.13 g, 0.58 mmol) in dichloromethane (5 mL) is added tiimethylphenylstannane (210 µL, 1.2 mmol), followed successively by copper (II) acetate (0.12 g. 0.64 mmol) and tetra-n-butylammonium fluoride (1.0 M solution in tetrahydrofuran, 1.2 mL). The reaction mixture is stirred for 2 days at room temperature and then is quenched by the addition of methanolic ammonia (2 M, 4 mL). The reaction mixture is concentrated and then purified by flash silica gel chromatography (methanol/chloroform) to give tert-butyl (2-oxo-1-phenyl-1,2-dihydropyridin-4-ylmethyl)-carbamate (88 mg, 52 %). MS (ES+): 301.3 (M+H)+ Tert-butyl (2-oxo-1 -phenyl- 1,2-dihydropyridin-4-ylmethyl)-carbamate (83 mg, 0.28 mmol) is treated with 4N hydrogen chloride in dioxane in order to remove the Boc protecting group. The hydrochloride salt of 4-aminomethyl-1-phenyl-1H-pyridin-2-one, obtained after concentration of the reaction mixture, is dissolved in N,N-dimethylforrnarnide (5mL) and is coupled to (4E)-6-iodo-4-(methoxymethylene)isoquinoline-l ,3(2H,4H)-dione (92 mg, 0.28 mmol) in the presence of triethylamine (200 µL). After one hour, the reaction mixture is concentrated under reduced pressure and purified by flash silica gel chromatography (methanol/chloroform) to provide (4Z)-6-iodo-4-({[(2-oxo-1-phenyl-1,2dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione as a pale yellow solid (8.8 mg, 6.3 %). MS (ES+): 498.2 (M+H)+ (Formula Removed) Example 518 (4Z)-6-lodo-4-({[(2-oxo-1 -phenyl-1,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione To a solution of 4-aminomethyl-1H-pyridin-2-one hydrochloride in 50 % aqueous dioxane (100 mL) is added sodium hydroxide (2.8 g. 69 mmol), followed by di-tert-butyldicarbonate (5.0 g, 23 mmol). After stirring overnight at room temperature, the mixture is neutralized with 5 % aqueous potassium hydrogen sulfate solution. The mixture is extracted four times with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. A sample of crude material is purified by reverse-phase HPLC to give tert-butyl (2-oxo-1,2-dihydro-pyridin-4-ylmethyl)-carbamate as a straw colored foam. MS (ES+): 225.3 (M+H)+ To a solution of tort-butyl (2-oxo-1,2-dihydro-pyridin-4-yimethyl)-carbamate (0.13 g, 0.58 mmol) in dichloromethane (5 mL) is added trimethylphenylstannane (210 µL, 1.2 mmol), followed successively by copper (II) acetate (0.12 g, 0.64 mmol) and tetra-n-butylammonium fluoride (1.0 M solution in tetrahydrofuran, 1.2 mL). The reaction mixture is stirred for 2 days at room temperature and then is quenched by the addition of methanolic ammonia (2M, 4 mL). The reaction mixture is concentrated and then purified by flash silica gel chromatography (methanol/chloroform) to give tert-butyl (2-oxo-1-phenyl-1,2-dihydropyridin-4-ylmethyl)-carbamate (88 mg, 52 %). MS (ES+): 301.3 (M+H)+ Tert-butyl (2-oxo-1-phenyl-1,2-dihydropyridin-4-ylmethyl)-carbamate (83 mg, 0.28 mmol) is treated with 4N hydrogen chloride in dioxane in order to remove the Boc protecting group. The hydrochloride salt of 4-aminomethyl-1-phenyl-1H-pyridin-2-one, obtained after concentration of the reaction mixture, is dissolved in N,N-dimethylformamide (5 mL) and is coupled to (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (92 mg, 0.28 mmol) in the presence of triethylamine (200 µL). After one hour, the reaction mixture is concentrated under reduced pressure and purified by flash silica gel chromatography (methanol/chtoroform) to provide (4Z)-6-iodo-4-({[(2-oxo-1-phenyl-1,2dihydropyridin-4-yl)methylJamino}methylene)isoquinoline-1,3(2H,4H)-dione as a pale yellow solid (8.8 mg, 6.3 %). MS (ES+): 498.2 (M+H)+ (Formula Removed) Example 519 4-{[(3-Dimethylaminomethyl-2-hydroxy-biphenyl-4-ylmethyl)-arninol-methylene}-6- iodo-4H-isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-bipheny l-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound (purified through chromatography) is prepared from 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (50 mg, 0.15 mmol) and 4-aminomethyl-3'-dimethylaminomethyl-biphenyl-2-oi (50 mg, 0.1 B mmol) in 24% yield: MS (ESI): 554.0 (M+1)+1 (Formula Removed) Example 520 4-[(2-Fluoro-4-furan-3-yl-5-hydroxy-benzylamino)-methylene]-6-iodo-4H- isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinolrne-1,3-dione, the title compound is prepared from 6-iodo-4-methoxymethylene-4H-isoquinoline-1,3-dione (40 mg, 0.12 mmol) and 4-Aminomethyl-3*-dimethylaminomethyl-biphenyl-2-ol (26 mg, 0.13 mmol) in 55% yield: MS (ESI): 503.0 (M-1)-1 (Formula Removed) (4Z)-4-({[3-Hydroxy-4-(4-methylpiperazin-1-yl)benzyl]amino}methylene)-6-iodoisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (example 69), 100 mg (64 % yield) is obtained as an orange soild from 100 mg (0.46 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 13-hydroxy-4-(4-methylpiperazin-1-yl)benzyflamine 221.3 mg (1.0 mmol).; mp 180-181°C MS (ESI) m/z 519.1 (M+1). (Formula Removed) Example 522 4-({[4-Hydroxy-5-(2-pyrrolidin-1-yl-ethoxy)-pyridin-2-ylmethyl]-amino}-methylene)-6- iodo-4H-isoquinoline-1,3-dione A mixture of 2-aminomethyl-5-(2-pyrrolidih-1-yl-ethoxy)-pyridin-4-ol (237 mg, 1.0 mmole), 3 ml_ of N,N-dimethylforrnamide is stirred, then 4-methoxymethylene- 6-iodo-4H-isoquinbline-1,3-dione (329 mg, 1.0 mmole) is added and the reaction mixture stirred for one hour. The reaction mixture is evaporated to dryness, taken up in methanol and purified by HPLC (acetonitrile/water without trifluoroacetic acid); the fractions belonging to the product peak (as determined by MS) were evaporated and still had impurities. This is re-purified by HPLC (acetonitrile water with 0.2% trifluoroacetic acid). The product is isolated by evaporation in-vacuo to give a yellow-orange solid assumed to be the bis trifluoroacetic acid salt, 30 mg, (4%); MS (ES+): m/z 535.1 (M + H). (Formula Removed) Example 523 (4Z)-4-[({3-Hydroxy-4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]benzyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione Using the procedure described for the preparation of (example 69), 45 mg (28 % yield) is obtained as a purple solid from 100 mg (0.46 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione and 3-hydroxy-4-[(2S)-2-(methoxymethyl)pyrrolidin-l- yl]benzyl}amine (excess).; mp 120-121 °C MS (ESI) m/z 534.1 (M+1). (Formula Removed) Example 524 (4Z)-{[(4-Hydroxy-5-phenyJ-pyridin-2-ylmethyl)-amino]-methylene}-6-iodo-4H- isoquinoline-1,3-dione An amount of 64 mg (0.33 mmol) of 2-aminomethyl-5-phenyl-pyridin-4-ol, is slurried in N,N-dimethylformamide (3 mL), followed by the addition of 110 mg (0.33 mmol) of (4E)-6-iodo-4-(metnoxymethylene)lsoquinoline-1,3{2H,4H)-dione. After the mixture is stirred at room temperature for 6 hours, the solid is filtered and washed several times with N,N-dimethylformamide, then ether and dried to give 89mg of example 524 as a light beige solid (53% yield); mp 292-3°C dec, MS data ES(+) 498.1 m/e. (Formula Removed) Example 525 (42)-4-[({[1 -(3-Furyl)-2-oxo-1,2-dihydropyridin-4-yl]methyl}amino)methylene]-6-iodoisoquinoiine-1,3(2H,4H)-dione A mixture of 2-hydroxy-4-methylpyridine (0.66 g, 6.0 mmol), 3-bromofuran (1.7 g, 12 mmol), copper (I) iodide (0.11g, 0.60 mmol), and potassium carbonate (0.84 g, 6.0 mmol) in N,N-dimethylformamide (12 mL) were heated at 180 °C for 2 hours in a 300 W microwave reactor. The completed reaction mixture is. diluted with 10 % aqueous ammonium hydroxide solution and extracted 3x with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 1-furan-3-yi-4-methyl-1H-pyridin-2-one (0.65 g. 62 %). LC/MS (ES+): 176.1 (M+H)+ A mixture of 1-furan-3-yl-4-methyl-1H-pyridin-2-one (3.7 g, 21 mmol), tert-butoxybis{dimethylamino)methane (11 g, 63 mmol), and N,N-dimethylformamide (4 mL) is heated in a 150 °C oil bath for 2 14 hours and then concentrated to dryness under reduced pressure. A quantitative yield of 4-(2-dimethylamino-vinyl)-1 -furan-3-yl-1H-pyridin-2-one is assumed, and the material is carried on without further purification. MS (ES+): 231.3 (M+H)+ To a solution of 4-(2-dimethylamino-vinyl)-1-furan-3-yl-1H-pyridin-2-one (21 mmol) in 50 % aqueous tetrahydrofuran (700 mL) is added sodium periodate (13 g, 63 mmol). After six hours of stirring at room temperature, the reaction mixture is filtered. The filtrate is washed 3x with saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to provide 1-furan-3-yl-2-oxo-1,2-dihydro-pyridine-4-carbaldehyde as a yellow powder (2.1 g, 53 % over 2 steps). MS (ES+): 190.3 (M+H)+ A solution of 1-furan-3-yl-2-oxo-1,2-dihydro-pyridine-4-carbaldehyde (1.4 g, 7.4 mmol) in pyridine (40 mL) is treated with methoxylamine hydrochloride (0.68 g, 8.1 mmol). After bring stirred overnight at room temperature, the reaction mixture is concentrated under reduced pressure. The residue is partitioned between ethyl acetate and water. The organic phase is washed twice with water and once with saturated aqueous sodium chloride solution, dried, and concentrated under reduced pressure to provide 1-furan-3-yl-2-oxo-1,2-dihydro-pyridine-4-carbaldehyde O-methyl-oxime, which is used in the following step without further purification. MS (ES+): 219.3 (M+H)+ To a mixture of the crude 1-furan-3-yl-2-oxo-1,2-dihydro-pyridine-4-carbaldehyde O-methyl-oxime (approximately 7.4 mmol) and glacial acetic acid (77 mL) is added zinc powder (3.1 g). The reaction mixture is heated for 45 minutes in a 100 °C oil bath and then allowed to cool to room temperatre. After filtration of the mixture through a pad of diatomaceous earth and consontration the residue is purified by reverse-phase HPLC to give 4-aminomethyl-1-ethyl-3-yI-1H-pyridin-2-one*trifluoroacetic acid (contaminated with zinc salts, 2.3 g). MS (ES+): 191.3 (M+H)+ To a solution of 4-aminomethyl-1-furan-3-yl-1H-pyridin-2-one»trifluoroacetic acid (contaminated with zinc salts, 2.3 g) in 50 % aqueous dioxane (20 mL) is added sodium hydroxide (approximately 800 mg), followed by an additional volume of aqueous dioxane (20 mL) and then the addition of di-tert-butyldicarbonate (600 µL). When complete, the reaction mixture is filtered. The filtrate is neutralized with 5 % aqueous potassium hydrogen sulfate solution and extracted 3x with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried, and concentrated under reduced pressure to provide tert-butyl (1-furan-3-yl-2-oxo-1,2-dihydro-pyridin-4-ylmethyl)-carbamate (0.18 g, 0.62 mmol). MS (ES+): 291.3 (M+H)+ tert-Butyl (1-furan-3-yl-2-oxo-1,2-dihydro-pyridin-4-ylmethyl)-carbamate (0.18 g, 0.62 mmol) is treated with 4N hydrogen chloride in dioxane in order to remove the Boc protecting group. The hydrochloride salt of 4-aminomethyl-1-furan-3-yi-1H-pyridin-2-one, obtained after concentration of the reaction mixture, is dissolved in N,N-dimethylformamide (4 mL) and is coupled to (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.20 g, 0.62 mmol) in the presence of triethyiamine (400 µL). After three hours, the reaction mixture is concentrated under reduced pressure, and the residue is triturated with acetoniblle to provide (4Z)-4-[({[1 -(3-furyl)-2-oxo-1,2-dihydropyridin-4-yl]methyl}amino)methylene]-6-iodoisoquinoline-1,3(2H,4H)-dione as a brown powder (0.12 g, 40 %). MS (ES+): 488.1 (M+H)+ (Formula Removed) Example 526 N1-[2-Hydroxy-4-({[(Z)-(6-iodo-l,3-dioxo-2,3-dihydroisoquinolin-4{1H)-ylidene)methyl]amino}methyl)phenyl]-N2,N2-dimethylglycinamide 4-1(4- Amino-3-hydroxy-benzylarnlno)-methylene]-6-lodo-4H-lsoquinoline-1,3-dione (89 mg, 0.20 mmol) is dissolved in N,N-dimethylformamide (3.56 mL), followed by addition of triethylamine (0.236 mL, 1.69 mmol), dimethylamino-acetic acid (30.58 mg, 0.30 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodimide hydrochloride (42.6 mg, 0.22 mmol) and 1-hydroxybenzotriazole (13.8 mg, 0.10 mmol). It is stirred at room temperature overnight. It is then evaporated to dryness, and the residue is washed with ether, and then acetonitnle to yield 21 mg (20%) of the title compound as a solid. MS (ESI) m/z 521 (M+H)+1 (Formula Removed) Example 527 (4Z)-{{(5-Furan-3-yl-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}-6-iodo-4H- isoquinoline-1,3-dione An amount of 64 mg (0.33 mmol) of 2-aminomethyJ-5-furan-3-yl-pyridin-4-ol, is slurried in N,N-dimethylformamide (3 mL), followed by the addition of 110 mg (0.33 mmol) of (4E)-6-iodo-4-(methoxymethylene)isoquino!ine-1,3(2H,4H)-dione. After the mixture is stirred at room temperature for 6 hours, the solid is filtered and washed several times with N,N-dimethylformamide, then ether and dried to give 109 mg of the title compound as a light beige solid (67% yield); mp 213-228°C dec, MS data ES(+) 488.0 m/e. (Formula Removed) Example 528 6-tert-Butyl-4-[(2-furan-3-yl-5-hydroxy-benzylamino)-methylene]-4H-isoquinoline- 1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-arninol-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound (purified through chromatography) is prepared from 6-tert-Butyl-4-methoxymethylene-4H-isoquinoline-1,3-dione (-15 mg, 0.058 mmol) and 3-Amfnomethyl-4-furan-3-yl-phenol (40 mg. 0.21 mmol) in 50% yield: MS (ESI): 415.1 (M-1)'1. (Formula Removed) Example 528 6-tert-Butyl-4-[(4-furan-3-yl-3-hydroxy-benzylamino)-methylene]-4H-isoquinoline- 1,3-dione Following the same procedure for the preparation of 4-{[[(2-Hydroxy-biphenyl-4-ylmethyl)-aminol-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound (purified through chromatography) is prepared from 6-tert-Butyl-4-methoxymethylene-4H-isoquinoline-1,3-dione (--15 mg, 0.058 mmol)and 5-Aminomethyl-2-furan-3-yl-phenol (40 mg, 0.21 mmol) in 50% yield: MS (ESI): 415.1 (M-1)-1. (Formula Removed) Example 529 (4Z)-6-lodo-4-({[( 1 -butyl-2-oxo-1,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione 4-Aminomethyl-1-buty1-1H-pyridin-2-one trifiuoroacetate is prepared in two steps from 1-butyl-2-oxo-1,2-dihydropyridine-4-carboxamide in a manner analogous to the preparation of 4-aminomethyl-1-methyl-1H-pyridin-2-one. Purification of 4-aminomethyl-1-butyHH-pyridin-2-one is accomplished via semi-preparative HPLC (Prodigy ODS3 column, 5 % acetonitrile/95 % water/0.01 % trifluoroacetic acid to 100 % acetonitnle at 10 mL/min). MS (ES+): 181.4 (M+H)+ A mixture of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (170 mg, 0.51 mmol) and 4-aminomethyl-1-butyl-1H-pyridin-2-one trifluoroacetate (150 mg, 0.51 mol) is stirred in dimethylformamide (2.7 mL) at room temperature in the presence of triethylamine (0.33 mL) for 18 hours. The reaction mixture is concentrated under reduced pressure. The residue is purified via semi-preparative HPLC (Prodigy ODS3 column, 5 % acetonitrile/95 % water/0.01 % trifluoroacetic acid to 100 % acetonitnle at 10 mL/min) to give (4Z)-6-iodo-4-({[(1-butyl-2-oxo-1,2-dihydropyridin-4-yl)methyl]amino}methylene)isoquinorme-1,3(2H,4H)-dione as an peach colored solid (25 mg, 10 % due to substantial loss of material during HPLC malfunction). MS (ES+): 478.0 (M+H)+ (Formula Removed) Example 530 6-tert-Butyl-4-{[(4-hydroxy-5-propoxy-pyridin-2-ylmethyl)-amino]-methylene}-4H- isoquinoline-1,3-dione An amount of 50.0 mg (0.193 mmol) of (4E)-6-tert-butyl-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione, is dissolved in N,N-dimethylformamide (3 mL), followed by the addition of 35 mg (0.193 mmol) of 2- aminomethyl-5-propoxy-pyridin-4-ol. All solids dissolved and after the mixture is stirred at room temperature for 2 hours, the solution is evaporated to dryness in vacuo, treated with acetonitnle, filtered and washed several times with fresh acetonitnle and dried to give 52 mg of the title compound as a light pink solid (66% yield); mp 162-178°C dec, MS data ES(+) 410.4 m/e. (Formula Removed) Example 531 6-tert-Butyl-4-{[(4-hydroxy-5-phenyl-pyridin-2-ylmethyl)-amino]-methylene}-4H- isoquinoline-1,3-dione An amount of 40.0 mg (0.154 mmol) of (4E)-6- t-butyl-4-(rnethoxymethylene)isoquinoline-1,3(2H,4H)-dione (based on a sample that is 39% pure by weight), is dissolved in N,N-dimethylformarnide (3 mL), followed by the addition of 31 mg (0.154 mmol) of 2-aminomethyl-5-phenyl-pyridin-4-ol. All solids dissolved and after the mixture is stirred at room temperature for 2 hours, the solution is evaporated to dryness in vacuo, treated with acetonitnle, filtered and washed several times with fresh acetonitrile and dried to give 44 mg of the title compound as a pink solid (66% yield); mp 195-218°C dec, MS data ES(+) 428.4 m/e. (Formula Removed) Example 532 6-tert-Butyl-4-([(5-furan-3-yl-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}-4H- isoquinoline-1,3-dione Example 533 An amount of 40.0 mg (0.154 mmole) of (4E)-6-tert-butyl-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (based on a sample that is 39% pure by weight), is dissolved in N,N-dimethylformarnide (3 mL), followed by the addition of 29 mg (0.154 mmole) of 2-aminomethyl-5-furan-3-yl-pyridin-4-ol. All solids dissolved and after the mixture is stirred at room temperature for 2 hours, the solution is evaporated to dryness in vacuo, treated with acetonitrile, filtered and washed several times with fresh acetonitrile and dried to give 41 mg of the title compound as a pink solid (64% yield); mp 215-230°C dec, MS data ES(+) 418.3 m/e. (Formula Removed) (42)-6-tert-Butyl-4-[({[1 -(3-furyl)-2-oxo-1,2-dihydropyrldin-4-yl]methyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione A mixture of (4E)-6-tert-buty l-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (50 mg, 0.19 mmol), 4-aminomethyl-1-furan-3-yl-1H-pyridin-2-one hydrochloride (43 mg, 0.19 mmol), and triethylamine (150 µL, 1.1 mmol) in N,N-dimethylformamide (2 mL) is stirred overnight at room temperature. The reaction mixture is concentrated under reduced pressure, and the residue is triturated with chloroform to provide (4Z)-6-tert-butyl-4-[({[1 -(3-furyl)-2-oxo-1,2-dihydropyridin-4- yl]methyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione as a white solid (34 mg, 43 %). MS (ES): 416.2 (M-H)" (Formula Removed) Example 534 6-tert-Butyl-4-[(2-fluoo-4-furan-3-yl-5-hydroxy-benzy1amino)-methylene]-4H- isoquinoline-1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-5-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-tert-Butyl-4-methoxymethylene-4H-isoquinoline-1,3-dione (11 mg, 0.042 mmol) and 5-AminorhethyI-4-fluoro-2-furan-3-yl-phenol (12 mg, 0.058 mmol) in 60% yield: MS (ESI): 433.2 (M-1)-1 Example 535 6-tert-Butyl-4-[(4-furan-3-y)-3-hydroxy-benzylarrtino)-methylenel-4H-isoquinoline- 1,3-dione Following the same procedure for the preparation of 4-{[(2-Hydroxy-biphenyl-4-ylmethyl>-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound is prepared from 6-tert-Buryl-4-methoxymethylene-4H-isoquinoline-1,3-dione (84 mg, 0.32 mmol) and 5-Aminomethyl-2-furan-3-yl-phenol (95 mg, 0.5 mmol) in 56% yield: MS (ESI): 415.4 (M-1)-1 (Formula Removed) Example 536 6-Cyclopenty(-4-[(4-furan-3-yl-3-hydroxy-benzylamino)-methylene]-4H-isoquinoIine- 1,3-dione: Following the same procedure for the preparation of 4-{[(2-hydroxy-biphenyl-4-ylmethyl)-amino]-methylene}-6-iodo-4H-isoquinoline-1,3-dione, the title compound (purified through chromatography) is prepared from 6-cyclopentyf-4-methoxymethylene-4H-isoquinoline-1,3-dione (108 mg, 0.398 mmol) and 5-Aminomethyl-2-furan-3-yl-phenol (109 mg, 0.57 mmol) in 78% yield: MS (ESI): 427.1 (M-1)-1. (Formula Removed) Example 537 6-Cyclopentyl-4-{I(5-furan-3-yl-4-hydroxy-pyridin-2-ylmethyl)-amino]-methylene}- 4H-tsoquinoline-1,3-dione An amount of 77 mg (0.405 mmol) of 2-aminomethyl-5-furan-3-yl-pyridin-4-ol, is slurried in N,N-dimethylformamide (4 mL), followed by the addition of 110 mg (0.405 mmol) of 6-cycIopentyl-4-methoxymethylene-4H-isoquinoline-1,3-dione. After the mixture is stirred at room temperature overnight. The reaction mixture is evaporated in-vacuo and the residue treated with acetonitrile, the solid is filtered and washed several times with acetonitrile and dried to give 152 mg of the title compound as a pink solid (87% yield); mp 279-283°C dec, MS data ES(+) 430.1 m/e. Example 538 6-Cyclopentyl-4-{[(4-hydroxy-5-propoxy-pyridin-2-ylmethy1)-amino]-methylene}-4H- isoquinoline-1,3-dione An amount of 74 mg (0.405 mmole) of 2-arninornethy(-5-phenyl-3-yl-pyridin-4-ol, is slurried in N,N-dimethylformamide (4 mL), followed by the addition of 110 mg (0.405 mmole) of 6-cyclopentyl-4-methoxymethylene-4H-isoquinoline-1,3-dione. After the mixture is stirred at room temperature overnight. The reaction mixture is filtered, washed with N,N-dimethylformamide, then several times with ether and dried to give 162 mg of the title compound as a pink solid (94% yield); mp 263-6°C dec; MS (ESI): m/z 422.2 (M + H). (Formula Removed) Example 539 (4Z)-6-lodo-4-[({[2-oxo-1-(3.thienyl)-1,2-dihydropyridin-4-yl]methyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione A mixture of 2-hydroxy-4-methylpyridine (1.5 g, 14 mmol). 3-bromothiophene (4.5 g. 28 mmol), copper (I) iodide (0.27g, 1.4 mmol), and potassium carbonate (1.9 g, 14 mmol) in N,N-dimethylformamide (30 mL) is heated in a 150 °C oil bath for 6 hours. After cooling to room temperature, the reaction mixture is diluted with 20 % aqueous ammonium hydroxide solution and extracted 3x with diethyl ether. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude oil, which is purified by flash chromatography (ethyl acetate/hexanes) to give 4-methyl-1-(3-thienyl)pyridin-2(1H)-one (0.79 g, 29 %). MS (ES+): 192.1 (M+H)+ A mixture of 4-methyl-1-(3-thienyl)pyridin-2(1H)-one (0.73 g, 3.8 mmol), tert-butoxybis(dimethylamino)methane (3 mL, 15 mmol), and N,N-dimethylformamide (4 mL) is heated in a 100 oC oil bath for 3 hours and then concentrated to dryness under reduced pressure. A quantitative yield of 4-(2-dimethylamino-vinyl)-1-thiophen-3-yl-1H-pyridin-2-one is carried on without further purification. MS (ES+): 247.3 (M+H)+ To a solution of 4-(2-dimethylamino-vinyl)-1-thiophen-3-yl-1H-pyridin-2-one (3.8 mmol) in 50 % aqueous tetrahydrofuran (130 mL) is added sodium periodate (2.4 g, 11 mmol). After 17 hours of stirring at room temperature, the reaction mixture is filtered. The filtrate is washed 3x with saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to provide 1-thiophen-3-yl-2-oxo-1,2-dihydro-pyridine-4-carbaldehyde as a yellow powder (0.27 g, 34 % over 2 steps). MS (ES+): 206.2 (M+H)+ A solution of 1-thiophen-3-yl-2-oxo-1,2-dihydro-pyridine-4-carbaldehyde (0.27 g, 1.3 mmol) in methanol (20 mL) is cooled to 0 °C in an ice-water bath and then treated with sodium borohydride (50 mg, 1.3 mmol). After stirring at 0 °C for two hours, the reaction mixture is quenched by the addition of 10 % aqueous hydrochloric acid. The mixture is extracted with ethyl acetate. The combined organic extracts were washed once with saturated aqueous sodium chloride solution, dried, and concentrated under reduced pressure to provide 4- hydroxymethyl-1-thiophen-3-yl-1H-pyridin-2-one (0.18 g, 67 %), which is used in the following step without further purification. MS (ES+): 208.3 (M+H)+ To a 0 °C mixture of the crude 4-hydroxymethyl-1-thiophen-3-yl-1H-pyridin-2-one (0.18 g, 0.87 mmol) and triethylamine (250 µL) in dichloromethane (5 mL) is added methanesulfonyl chloride (125 µL). The reaction mixture is stirred at 0 °C for 30 minutes and then allowed to warm to room temperature, where it stirred for one hour. The mixture is concentrated to dryness under reduced pressure and is then taken up in N,N-dimethylformamide. To the resulting suspension is added sodium azide (150 mg). After stirring for two hours at room temperature, the mixture is poured onto ice and then extracted from the aqueous mixture with diethyl ether. The oarganic extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to provide 4-azidomethyl-1-thiophen-3-yl-1H-pyridin-2-one (assumed 0.87 mmol). MS (ES+): 233.2 (M+H)+ To a solution of crude 4-azidomethyl-1 -thiophen-3-yl-1H-pyridin-2-one in tetrahydrofuran (2 mL) is added triphenylphosphine (0.19 g). The mixture is stirred for 10 minutes before the addition of water (200 µL). After stirring for 16 hours at room temperature, the mixture is purified by reverse-phase high performance liquid chromatography (5 % acetonitrile/95 % water to 75 % acetonitrile/25 % water over 45 minutes) to provide 4-aminomethyl-1-thiophen-3-yl-1H-pyridin-2-one (60 mg, 34 % over 2 steps). MS (ES+): 207.3 (M+H)+ A mixture of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (97 mg, 0.30 mmol), 4-aminomethyl-1-thiophen-3-yl-1H-pyridin-2-one (61 mg, 0.30 mmol), and triethylamine (77 µL. 0.59 mmol) in N,N-dimethylformamide (2 mL) is stirred overnight at room temperature. The reaction mixture is concentrated under reduced pressure, and the residue is triturated with acetonitrile to provide (4Z)-6-iodo-4-[({[2-oxo-1 -(3-thienyl)-1,2-dihydropyridin-4- yl]methyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione as a mauve powder (65 mg, 43 %). MS (ES): 502.1 (M-H)-1 (Formula Removed) Example 539 (4Z)-6-lodo-4-[({{2-oxo-1 -(3-thienyl)-1 ,2-dihydropyridin-4-yl]methyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione A mixture of 2-hydroxy-4-methylpyridine (1.5 g, 14 mmol), 3-bromothiophene (4.5 g, 28 mmol), copper (I) iodide (0.27g, 1.4 mmol), and potassium carbonate (1.9 g, 14 mmol) in N,N-dimethylforrnamide (30 mL) is heated in a 150 °C oil bath for 6 hours. After cooling to room temperature, the reaction mixture is diluted with 20 % aqueous ammonium hydroxide solution and extracted 3x with diethyl ether. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a crude oil, which is purified by flash chromatography (ethyl acetate/hexanes) to give 4-methyl-1-(3-thienyl)pyridin-2(1H)-one (0.79 g, 29 %). MS (ES+): 192.1 (M+H)+ A mixture of 4-methyl-1-(3-thienyl)pyridin-2(1H)-one (0.73 g, 3.8 mmol), tert-butoxybis(dimethylamino)methane (3 mL, 15 mmol), and N,N-dimethylformarnide (4 mL) is heated in a 100 °C oil bath for 3 hours and then concentrated to dryness under reduced pressure. A quantitative yield of 4-(2-dimethylamino-vinyl)-1- thiophen-3-yl-1H-pyridin-2-one is assumed, and the material is carried on without further purification. MS (ES+): 247.3 (M+H)+ To a solution of 4-(2-dimethylamino-vinyl)-1-thiophen-3-yl-1H-pyridin-2-one (3.8 mmol) in 50 % aqueous tetrahydrofuran (130 mL) is added sodium periodate (2.4 g, 11 mmol). After 17 hours of stirring at room temperature, the reaction mixture is filtered. The filtrate is washed 3x with saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to provide 1-thiophen-3-yl-2-oxo-1,2-dihydro-pyridine-4-carbaldehyde as a yellow powder (0.27 g, 34 % over 2 steps). MS (ES+): 206.2 (M+H)+ A solution of 1 -thiophen-3-yl-2-oxo-1,2-dihydro-pyridine-4-carbaldehyde (0.27 g, 1.3 mmol) in methanol (20 mL) is cooled to 0 °C in an ice-water bath and then treated with sodium borohydride (50 mg, 1.3 mmol). After bring stirred at that temperature for two hours, the reaction mixture is quenched by the addition of 10 % aqueous hydrochloric acid. The mixture is extracted with ethyl acetate. The combined organic extracts were washed once with saturated aqueous sodium chloride solution, dried, and concentrated under reduced pressure to provide 4-hydroxymethyl-1-thiophen-3-yl-1H-pyridin-2-one (0.18 g, 67 %), which is used in the following step without further purification. MS (ES+): 208.3 (M+H)+ To a 0 °C mixture of the crude 4-hydroxymethyl-1-thiophen-3-yl-1H-pyridin-2-one (0.18 g, 0.87 mmol) and triethylamine (250 µ) in dichloromethane (5 mL) is added methanesulfonyl chloride (125 µL). The reaction mixture is stirred at O °C for 30 minutes and then allowed to warm to room temperature, where it stirred for one hour. The mixture is concentrated to dryness under reduced pressure and is then taken up in N,N-dimethylformamide. To the resulting suspension is added sodium azide (150 mg). After stirring for two hours at room temperature, the mixture is poured onto ice and then extracted from the aqueous mixture with diethyl ether. The organic extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to provide 4-azidomethyl-1-thiophen-3-yl-1H-pyridin-2-one (assumed 0.87 mmol). MS (ES+): 233.2 (M+H)+ To a solution of crude 4-azidomethyl-1-thiophen-3-yl-1H-pyridin-2-one in tetrahydrofuran (2 mL) is added triphenylphosphine (0.19 g). The mixture is stirred for 10 minutes before the addition of water (200 µL). After stirring for 16 hours at room temperature, the mixture is purified by reverse-phase high performance liquid chromatography (5% acetonitrile/95% water to 75% acetonitrile/25% water over 45 minutes) to provide 4-aminomethyl-1-thiophen-3-yl-1H-pyridin-2-one (60 mg, 34 % over 2 steps). MS (ES+): 207.3 (M+H)+ A mixture of (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (97 mg, 0.30 mmol), 4-aminomethyl-1-thiophen-3-yl-1H-pyridin-2-one (61 mg, 0.30 mmol), and triethylamine (77 µL, 0.59 mmol) in N,N-dimethylformamide (2 mL) is stirred overnight at room temperature. The reaction mixture is concentrated under reduced pressure, and the residue is triturated with acetonitrile to provide (4Z)-6-iodo-4-[({[2-oxo-1 -(3-thienyl)-1,2-dihydropyridin-4- yl]methyl}arnino)methylene)isoquinoline-1,3(2H,4H)-dione as a mauve powder (65 mg, 43 %). MS (ES): 502.1 (M-H)- Exampie 540 4-{[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-aminoJ-methyl}- benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 541 4-[(2-Trifluoromethoxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione This compound Is prepared using appropriate starting materials according to the procedure of Example 550. Example 542 3-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 543 N-{2-Diethylaminc-ethyl)-4-[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-benzamide This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 544 4-{[2-(3,4-Dihydroxy-phenyl)-ethyIamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 545 4-[(4-Amino-phenylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 546 N-{4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}- oxaiamic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 547 4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-benzamidine This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 548 {4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenylsulfanyl}- acetic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 549 4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-N-(5-methyl-[1,3,4]thiadiazol-2-yl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 550. (Formula Removed) Example 550 4-[(3,4-Dihydroxy-benzylamino)-metbylene]-4H-isoquinoline-1,3-dione Step 1: To a suspension of 4H-isoquinoline-1,3-dione (1.5 g. 9.3 mmol) in 22.5 mL of a 4:1 mixture of acetic anhydride and N,N-dimethylformamide, respectively, is added trimethylorthoformate (2.0 mL, 18.6 mmol). The reaction mixture is shaken in a heating block at 125°C for 1Hour, at which point a beige precipitate formed, product. Upon cooling to room temperature, more product precipitated out. The precipitate is then filtered off, rinsed with copious amounts of ether, and dried to yield 1.47 g of 4-Methoxymethylene-4H-isoquinoline-1,3-dione. Step 2: To a suspension of 4-Methoxymethylene-4H-isoquinoline-1,3-dione (20.3 mg, 0.1 mmol) in N,N-dimethylforrnamide (250 µL) is added 3,4-dihydroxybenzylamine hydrobromide (22 mg, 0.1 mmol), followed by 21 pL of triethylamine. The reaction mixture is shaken at 115°C for 1.5 hours. The reaction mixture is diluted to 2 mL with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The product peak is collected based on UV absorption, the pure fractions were combined and concentrated to yield Example 550 (28.4 mg). Example 551 4-{[2-(1H-Benzoimidazol-2-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 552 3-[N-(1,5-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-hydrazinol-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 553 N-(4,5-Dimethyl-oxazol-2-yl)-4-[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-aminoj-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 554 N-{4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-N- methyl-acetamide This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 555 {4-[(1,3-Dioxc-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}- acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 556 4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-N-(5-methyl-isoxazol-3-yl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 557 3-{4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-pheny1}-acrylic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 558 4-{4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-butyric acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 559 4-[(4-Hydroxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 560 4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-2-hydroxy- benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 561 4-[(3-Hydroxy-4-methoxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 562 2-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-5-hydroxy- benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 563 5-[(1,3-Droxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-2-hydroxy- benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 564 4-{{2-(3,4-Dihydroxy-phenyl)-2-hydroxy-ethyiaminol-methylene}-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 565 4-[(2,6-Dihydroxy-pheny1amlno)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 566 3-(3,4-Dihydroxy-phenyl)-2-[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-propionic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 567 3-(3,4-Dihydroxy-phenyl)-2-[(1,3-dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-propionic acid This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 568 4-[(2,4-Dihydroxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 569 4-[(8-Hydroxy-quinoiin-5-ylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 570 4-[(5-Chloro-2-hydroxy-4-nitro-phenylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 571 4-({4-[4-(2-Morpholin-4-yl-ethyl)-piperazin-1-yl]-phenylamino}-methylene)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 572 4-({4-[4-(2-Pyrrolidin-1-yl-ethyl)-piperazin-1-yl]-phenylamino}-methylene)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 573 4-[(3-Amino-benzylamino)-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 574 4-[(4-Diethylaminomethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 576. Example 575 4-({4-[(Cyclopropylmethyl-propyl-amino)-methyl)-phenylamino}-methylene)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 576. (Formula Removed) Example 576 4-[(4-Pyrrolidin-1 -ylmethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione Step 1: To a suspension of 4-Methoxymethylene-4H-isoquinoline-1,3-dione (203 mg, 1.0 mmol) in N,N-dimethylfonmamide (2.5 mL) is added 4-aminobenzyl alcohol (123.2 mg, 1.0 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. Upon cooling to ambient temperature, product precipitated out of solution. The product is recovered by filtration, rinsing with diethyl ether, and drying to yield 263.3 mg 4-[(4-Hydroxymethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione. Step 2: To a suspension of 4-[(4rHydroxymethyl-phenylamino)-methyleneJ-4H-isoquinoline-1,3-dione (294 mg, 1 mmol) in N,N-dimethylformamide (10 mL) is added methanesulfonyl chloride (0.77 mL, 10 mmol) and triethylamine (2.79 mL, 20 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. The crude product, methanesulfonic acid 4-[(1,3-dioxo-2,3-dihydro-1H-isoquinoiin-4-ylidenemethyl)-amino]-benzyl ester (304 mg), thus obtained is used as such for the next reaction. Step 3: To a suspension of crude methanesulfonic acid 4-[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-benzyl ester (72 mg, 0.23 mmol) in N,N-dimethylforrnamide (2 mL) is added pyrrolidine (21 µL, 0.25 mmol). The reaction mixture is shaken at ambient temperature for 16 hours. The reaction mixture is diluted to 2 mL with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield the title compound (3.0 mg). Example 577 4-{{4-[(Cydohexyl-methyl-amino)-methyg-phenylamino}-methylene)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 576. Example 578 4-[(3-Aminomethyl-benzylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 550. Example 579 Thiophene-2-sulfonic acid (3-{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 580 Propane-2-sulfonic acid (3-{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 581 N-(3-{[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}- phenyl)-methanesulfonarnide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 582 2,2,2-Trifluoro-ethanesulfonic acid (3-{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-arnide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 583 Ethanesulfonic acid (3-{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl}- amino]-methyl}-phenyl)-amide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 584 Propane-1-sulfonic acid (3-{[(1,3-dioxo-2,3-dihydro-1H-isoquinoiin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 585 N-(3-{[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}- phenyl)-acetamide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 586 Cyclopropanecarboxylic acid (3-{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-amide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 587 Cyclobutanecarboxylic acid (3-{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methy1}-phenyl)-amide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 588 Thiophene-2-sulfonic acid (4-{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-arnide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 589 N-(4[(1,3-Dioxo-2»3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}- phenyl)-methanesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 590 N-(4{[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-aminoI-methyl}-phenyl)-C-phenyl-rnethanesulfonarnide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 591 2,2,2-Trifluoro-ethanesutfonic acid (4{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-phenyl)-arnide This compound is prepared using appropriate starting materials according to the procedure of Example 593. Example 592 Propane-1-sulfonic acid (4{[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-methyl}-phenyl)-amide This compound is prepared using appropriate starting materials according to the procedure of Example 593. (Formula Removed) Example 593 N-{4{{(1,3-Dioxc-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}- phenyl)-3-methyl-butyrarnide Step 1: To a suspension of 4-Methoxymethylene-4H-isoquinoline-1,3-dione (406 mg, 2.0 mmol) in N,N-dimethylformamide (250 µL) is added 4-aminobenzylamine (244 mg, 2.0 mmol). The reaction mixture is shaken at ambient temperature for 1.5 hours, then concentrated. Ethyl acetate is added to the solid residue that remained and the solid is recovered by filtration, rinsing with diethyl ether, and drying to yield 555.5 mg of 4-[(4-Amino-benzylamino)-methyleneJ-4H-isoquinoIine-1,3-dione. Step 2: To a suspension of 4-[(4-Amino-benzylamino)-methylene*|-4H-isoquinoline-1,3-dione (29.3 mg, 0.1 mmol) in pyridine (250 µL) is added isovaleryl chloride (26 pL, 0.2 mmol)- The reaction mixture is shaken at room temperature for 1Hour. The reaction mixture is diluted to 2 mL with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield the title compound (37.2 mg). (Formula Removed) Example 594 4-[(3,4-Dihydroxy-phenylamino)-methylene]-4H-isoquinoline-1,3-dione Step 1: To a solution of 4-nitrocatechol (310 mg, 2.0 mmol) in methanol (20 mL) is added hydrazine (200 µL) and a catalytic amount of Raney-Nickel (50 mg). The reaction mixture is left to stir at ambient temperature for 16 hours. The solution is then filtered over celite to remove Raney-Nickel and the filtrate evaporated to dryness. The 3,4-dihydroxyaniIine thus produced is used as such for the next reaction. Step 2: To a suspension of 4-Methoxymethylene-4H-isoquinoline-1,3-dione (40.6 mg, 0.2 mmol) in N,N-dimethylfonnamide (0.5 mL) is added 3,4-dihydroxyaniline (25 mg, 0.2 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. The reaction mixture is diluted to 2 mL with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield the title compound (15.6 mg). Example 595 4-{[4-(4-Ethyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 596 (4-{4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}- piperazin-1 -yl)-acetonitrile Stepl. To a suspension of 4-Methoxymethylene-4H-isoquinoline-1,3-dione (203 mg, 1.0 mmol) in N,N-dimethylformamide (2.5 mL) is added 1,4-phenylenediamine (108 mg, 1.0 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. Upon cooling to ambient temperature, product precipitated out of solution. The product is recovered by filtration, rinsing with diethyl ether, and drying to yield 205.9 mg 4-[(4-Amino-phenylamino)-methylene]-4H-isoquinoline-1,3-dione. Step 2: A dry mixture of 4-[(4-Amino-phenylamino)-methylene]-4H-isoquinoline-1,3-dione (140 mg, 0.5 mmol) and bis(chloroethyl)amine hydrochloride (90 mg, 0.5 mmol) is placed in a microwave at 900 W for 10 minutes. The crude product, 4-[(4-Piperazin-1 -yl-phenylamrno)-methylene]-4H-isoquinoline-1,3-dione hydrochloride (192 mg), thus obtained is used as such for the next reaction. Step 3: To a suspension of crude 4-[(4-Piperazin-1-yl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione hydrochloride (34.8 mg, 0.1 mmol) in N,N-dimethylformamide (250 µL) is added bromoacetonitrile (7 µL, 0.1 mmol) and triethylamine (42 µL). The reaction mixture is shaken at ambient temperature for 16 hours. The reaction mixture is diluted to 2 mL with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield Example 596 (12.0 mg). Example 597 4-{I4-(4-Allyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1l3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 598 4-({4-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-phenylamino}-methylene)-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 599 4-{{4-[4-(2-Diethylamino-ethyl)-piperazin-1-yl]-phenylamino}-methylene)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 600 4-{[4-(4-lsopropyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3- diorie This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 601 4-{[4-(4-Cyclopentyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 602 4-{[4-(4-CycJobutylmethyl-piperazin-1-yl)-phenylarnino]-methylene}-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 596. Example 603 4-{[3-(2,2,2-Trifluoro-ethylamino)-benzylaminoJ-methylene}-4H-tsoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 604. (Formula Removed) Example 604 4-[(4-Methylamino-benzylamlno)-methylene]-4H-isoquinoline-1,3-dione Step 1: To a suspension of 4-Methoxymethylene-4H-isoquinoline-1,3-dione (406 mg, 2.0 mmol) in N,N-dimethylformamide (250 µL) is added 4-aminoben2ylamine (244 mg, 2.0 mmol). The reaction mixture is shaken at 115°C for 1.5 hours, then concentrated. Ethyl acetate is added to the solid residue that remained and the solid is recovered by filtration, rinsing with diethyl ether, and drying to yield 555.5 mg of 4-[(4-Amino-benzylamino)-methylenel-4H-isoquinoline-1,3-dione. Step 2: To a suspension of 4-[(4-Amino-benzylamino)-methylene]-4H-isoquinoline-1,3-dione (29.3 mg, 0.1 mmol) in N,N-dimethylformamide (400 µL) is added triethylamine (100 µL) and iodomethane (6.2 pL, 0.2 mmol). The reaction mixture is shaken at 80°C for 18 hours. The reaction mixture is diluted to 2 mL with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield Example 604 (5 mg). Example 605 2,2,2-Trifluoro-ethanesulfonic acid 4-[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethy1)-aminol-benzylamide (Formula Removed) Example 606 This compound is prepared using appropriate starting materials according to the procedure of Example 613. 4-{[{1.3-Dioxo-2,3-dihydro-1H-isoquino!in-4-ylidenemethyl)-arnino]-methyl}-N-ethyl- benzenesulfonamide To a suspension of 4-Methoxymethylene-4H-isoquinoIine-1,3-dione (507 mg, 2.5 mmol) in N,N-dimethylformate (250 µL) is added 4-amlnoethylbenzene sulfonylamlde hydrochloride (556 mg, 2.5 mmol) and triethylamine (525 µL). The reaction mixture is shaken at 115°C for 1.5 hours, then concentrated. Ethyl acetate is added to the solid residue that remained and the solid is recovered by filtration, rinsing with diethyl ether, and drying to yield 660.8 mg of 4-{[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl} benzenesulfonamide. Step 2: To a suspension of 4-{[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-benzenesuifonamide (35.7 mg, 0.1 mmol) in Trifluoroacetic acid (250 µL) is added acetaldehyde (16.3 µL, 0.3 mmol) and sodium borohydride (11.4 mg, 0.3 mmol). The reaction mixture is shaken at ambient temperature for 18 hours. The reaction mixture is diluted to 2 mL with N,N-dimethylformarnide and purified by C18 reverse phase HPLC. Example 607 4-{[(1.3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-N-pyridin-3-ylmethyl-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 606. Example 608 6-Diethylamino-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 609. (Formula Removed) Example 609 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-pyrrolidin-1-yl-4H-isoquinoline-1,3- dione Step 1: To a solution of 6-Amino-4H-isoquinoline-1,3-dione (17.6 mg, 0.1 mmol) in trifluoroacetic acid (250 µL) is added 2,5-dirnethoxytetrahydrofuran (15 µL, 0.11 mmol). The reaction mixture is shaKen for 5 minutes at ambient temperature, followed by addition of sodium borohydride (9 mg, 0.22 mmol). After shaking at ambient temperature for 15 minutes, gas evolution had ceased and the reaction mixture is quenched with saturated bicarbonate solution. Upon quenching, a precipitate formed. The precipitate is filtered off, rinsed with water, and dried to yield 19.5 mg of 6-Pyrrolidin-1-yl-4H-isoquinoline-1,3-dione. Step 2: To a suspension of 6-Pyrrolidin-1-yl-4H-isoquinoline-1.3-dione (19.5 mg, 0.09 mmol) in 250 µL of a 4:1 mixture of acetic anhydride and N,N-dimethylformamide, respectively, is added trimethylorthoformate (22 µL, 0.2 mmol). The reaction mixture is shaken in a heating block at 125°C for 1Hour. The reaction mixture is then dried under a stream of nitrogen and the crude product, 4-Methoxymethylene-6-pyrrolidin-1-yl-4H-isoquinoline-1,3-dione, is used as such for the next reaction. Step 3: To a solution of crude 4-Methoxymethylene-6-pyrrolidin-1-yl-4H-isoquinoline-1,3-dione in N,N-dimethylformamide {250 µL) is added 3.4-dihydroxybenzylamine hydrobromide (22 mg, 0.1 mmol), followed by 21 µL of triethylamjne. The reaction mixture is shaken at 115°C for 1.5 hours. The reaction mixture is diluted to 2 mL with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield Example 609 (8.8 mg). Example 610 6-(1,3-Dihydro-isoindol-2-yl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H- isoquinoiine-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 609. Example 611 6-[Bis-(3,3,3-trifluoro-propyl)-amino]-4-{(3,4-dihydroxy-benzylamino)-methylene]- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 609. Example 612 N-{4-[(1,3-Dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-benzyl}- methanesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 613. (Formula Removed) Example 613 Ethanesulfonic acid 4-[(1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- aminoj-benzylamide Step 1: To a solution of 4-nitro-benzylamine (47.2 mg, 0.25 mmol) in THF (250 µL) is added triethylamine (89 µL) and ethyl sulfonyl chloride (24 pL, 0.25 mmol). The reaction mixture is shaken at ambient temperature for 16 hours. The reaction mixture is then concentrated, methanol is added followed by Novabiochem AM resin to remove unreacted amine. This is then shaken for two hours, filtered, concentrated to yield ethanesulfonic acid 4-nitro-benzylamide, which is used as such for the subsequent reaction. Step 2: To the residue of the product from step 1 (0.25 mmol) is added methanol (350 µL), hydrazine (33 µL), and Raney-Nickel (10 mg). The reaction mixture is shaken at room temperature for 16 hours, then filtered and the solution concentrated to yield ethanesulfonic acid 4-amino-benzylamide, which is used as such for the subsequent reaction. Step 3: To a suspension of 4-Methoxymetbylene-4H-isoquinoline-1,3-dione (20.3 mg, 0.1 mmol) in N,N-dimethylformarnide (250 µL) is added ethanesulfonic acid 4-amino-benzylamide (21.4 mg, 0.1 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. Upon cooling to ambient temperature, product precipitated out of solution. The product is recovered by filtration, rinsing with diethyl ether, and drying to yield Example 613 (15.0 mg). Example 614 4-t(4-Dipropylaminomethyl-phenylamino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 616. Example 615 4-{T.4-(3-Hydroxy-piperidin-1-ylmethyl)-phenylamino3-methylene}-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 61 (Formula Removed) Example 616 4-[(4-{[(2-Methoxyethyl)-methyl-amino]-methyl}-phenylamino)-methylene]-4H- isoquinoline-1,3-dione Step 1: To a solution of 1-bromometrryl-4-nitro-benzene (86.4 mg, 0.4 mmol) in tetrahydrofuran (800 µL) is added triethylamine (200 µL) and 2- (methoxyethyl)methylamine (43 µL, 0.4 mmol). The reaction mixture is shaken at 50°C for 5 hours. To the reaction mixture is then added 500 µL each of tetrahydrofuran and methanol followed by 350 mg of PS-Ph3P resin to remove unreacted alkyl bromide and shaken for 1H. The resin is filtered off, rinsed with dichloromethane and the filtrate concentrated. To the residue is added 500 pl¬each of tetrahydrofuran and methanol followed by 350 mg of PS-TsOH resin to remove unreacted amine. This is then shaken for two hours, filtered, washed with dichloromethane, and concentrated to yield (2-methoxy-ethyl)-methyl-(4-nitro-benzyl)-amine, which is used as such for the subsequent reaction. Step 2: To a solution of (2-methoxy-ethyl)-methyl-(4-nitro-benzyl)-amine, from step 1, (56 mg, 0.25 mmol) is added methanol (1 mL), hydrazine (33 µL), and Raney-Nickel (10 mg). The reaction mixture is shaken at room temperature for 16 hours, then filtered and the solution concentrated to yield 4-{[(2-Methoxy-ethyl)-methyl-amino]-methyl}-phenylamine, which is used as such for the subsequent reaction. Step 3: To a suspension of 4-Methoxymethylene-4H-isoquinoline-1,3-dione (20.3 mg, 0.1 mmol) in N,N-dimethylformamide (250 µL) is added 4-{[(2-methoxy-ethyl)-methyl-arnino]-methyl}-phenylamine (19.4 mg, 0.1 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. Upon cooling to ambient temperature, product precipitated out of solution. The product is recovered by filtration, rinsing with diethyl ether, and drying to yield Example 616 (11.0 mg). Example 617 4-{[4-(2-Methyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 616. Example 618 4-(Pyridin-4-ylaminomethylene)-4H-isoquinollne-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 619. (Formula Removed) Example 619 4-[(5-Hydroxy-naphthalen-1 -ylamino)-methylene]-4H-isoquinoline-1,3-dione To a suspension of 4-Methoxymethylene-4H-isoquinoline-1,3-dione (20.3 mg, 0.1 mmol) in N,N-dimethylformamide (250 µL) is added 5-amino-1-naphthol (13.5 mg, 0.1 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. Upon cooling to ambient temperature, product precipitated out of solution. The product is recovered by filtration, rinsing with diethyl ether, and drying to yield Example 619 (7.0 mg). Example 620 4-[(3.4-Dihydroxy-berizylamino)-methylene]-6-phenyl-4H-lsoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 621 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-furan-2-yI-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 622 5-(3-Phenyl-propenyl)-4-[(4-pyrrolidin-1-ylmethyl-phenylamino)-methylene]-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 623 {4-[(6-Naphthalen-1 -yl-1 ,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-phenyl}-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 624 {4-[(6-Naphthalen-2-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-phenyl}-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 625 {4-[(1,3-Dioxo-6-quinolin-8-yl-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]- phenyl}-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 626 {4-[(6-Benzofuran-2-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-phenyl}-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 627 {4-[(6-Benzo[b]thiophen-2-yH,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-phenyl}-acetonitri!e This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 628 {4-[(6-Benzo[b}thiophen-3-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino]-phenyl}-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 629 (4-{[6-(1H-lndol-5-yl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}- phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 630 (4-{[1,3-Dioxo-6-(1H-pyrrol-2-yl)-2,3-dihydro-1H-isoquinoIin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 631 (4-{[1,3-Dioxo-6-(1H-pyrrol-3-yl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 632 4-{[(6-Naphthalen-2-yl-1,3-dioxc-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 633 4-{[(1,3-Dioxo-6-quinolin-8-yl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]- methyl}-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 634 4-{[(6-Benzofuran-2-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}-benzehesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 635 4-{[(6-Benzo[b]thlophen-2-yl-1,3-dioxo-2,3-dihydro-1H-isoquinorin-4-ylidenemethyl)- amino]-methyl}-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 636 4-{((6-Benzo[b]thiophen-3-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-yiidenemethyl)- amino]-methyl}-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 637 4-({[6-(1H-lndol-5-yl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}- methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 638 4-({[1,3-Dioxo-6-(1H-pyrrol-2-yl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 639 4-({[1,3-Dioxo-6-(1H-pyrrol-3-yl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 640 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-naphthalen-1-yl-4H-isoquinoline-1.3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 641 4-[(3,4-Dihydroxy-ben2ylarru'no)-methylenel-6-naphthalen-2-yl-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 642 4-[(3,4-Dihydroxy-bervzylarnino)-methylene]-6-quinolin-8-yl-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 643 6-Benzofuran-2-yl-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 644 6-Benzo[b]thiophen-2-yl-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 645 6-Benzo{b]thiophen-3-yl-4-{(3,4-dihydroxy-benzylamino)-methylenel-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 646 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(1H-indol-.5-yl)-4H-isoquinoltne-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 647 4-[{3,4-Dihydroxy-ben2ylamino)-methylene]-6-(1H-pyrrol-2-yl)-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 648 (44[1,3-Dioxo^-(2-pyridirv-2-yi-vinyl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 649 (4-{{1,3-Dioxo-6-(2-pyridin-4-yl-vinyl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitriie This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 650 {4-[(1,3-Dioxo-6-styryl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}- acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 651 (4-[J6-(2-lmidazol-1 -yl-vinyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)- amino}-phenyl)-acetonitrite This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 652 4-({[1,3-Dioxo-6-(2-pyridin-2-yl-vinyl)-2,3-dihydro-1H-iSoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonarnide Example 653 4-({[1,3-Dioxo-6-(2-pyridin-4-yl-vinyl)-2,3-dihydro-1H-lsoquinolin-4-ylidenemethyr]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 654 4-{[(1,3-Dioxo-6-styryl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-methyl}- benzenesutfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 655 4-({[1,3-Dioxo-6-(2-pyrazin-2-yl-vinyl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyr|-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 656 4-({[6-(2-Cyclohexyl-vinyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 657 4-({[6-(3-lmidazol-1 -yl-propenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 658 4-({[6-(2-lmkJazol-1-yl-vinyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 659 4-[({6-[2-(4-Methyl-thiazol-5-yl)-vinyll-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl}-amino)-methyl]-ben2enesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 660 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-phenyl-propenyl)-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 661 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-naphthalen-2-yl-vinyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 662 4-[(3,4-Dihydroxy-benzylamino)-rnethylene]-6-(2-pyrid»n-2-yl-vinyl)-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. (Formula Removed) Example 663 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-pyridin-4-yl-vinyl)-4H-isoquinoline- 1,3-dione Step 1: To a suspension of 6-Bromo-4H-isoquinoline-1,3-dione (4.8 g, 20 mmol) in 50 mL of a 4:1 mixture of acetic anhydride and N,N-dimethylformamide, respectively, is added trimethylorthoformate (4.4 mL, 40 mmol). The reaction mixture is shaken in a heating block at 125°C for 1Hour. Upon cooling to room temperature, the product precipitated out. The precipitate is then filtered off, rinsed with copious amounts of ether, and dried to yield 4.8 g of 6-Bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione. Step 2: To a suspension of crude 6-Bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (846 mg, 3 mmol) in N,N-dimethylformamide (7.5 mL) is added 3.4-dihydroxy benzylamine hydrobromide (660 mg, 3 mmol) and triethylamine (630 µL, 4.5 mmol). The reaction mixture is shaken at 115°C for 1.5 hours. Upon cooling to room temperature, the product precipitated out. The precipitate is then filtered off, rinsed with copious amounts of ether, and dried to yield 1.38 g of 6-Bromo-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3-dione hydrobromide. Step 3: To a mixture of cesium carbonate (39 mg, 0.12 mmol), tetrabutyl ammonium bromide (32.2 mg, 0.1 mmol), tri-o-tolylphosphine (30.4 mg, 0.1 mmol) and palladium acetate (9 rng, 0.04 mmol) in N,N-dimethylformamide (1.2 mL) is added 6-Bromo-4-{(3,4-dihydroxy-benzylaminoJ-methylene]-4H-isoquinoline-1,3-dione hydrobromide (47 mg, 0.1 mmol) and 4-vinylpyridine (16.2 µL, 0.15 mmol). The reaction mixture is subjected to microwave heating at 200°C for 120 seconds. The reaction mixture is then diluted to 2 mL with N,N-dimethylformamide and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield Example 663 (9.4 mg). Example 664 6-(2-Cyclohexyl-vrnyl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 665 4-[(3,4-Dihydroxy-ben2ylamino)-methylene]-6-(3-imidazol-1-yl-propenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 666 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-pipera2in-1-yl-propenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 667 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-imidazol-1-yl-vinyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 668 4-{l4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-naphthalen-2-yl-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 669 6-Benzofuran-2-yI-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 670 6-Benzo[b]thiophen-2-yl-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 671 6-(1H-lndol-5-yl)-4-{[4-{4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 672 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(1H-pyrrol-2-yl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 673 4-{(4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-6-(1H-pyrrol-3-yl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 674 4-{[4-(4-methyl-pipera2in-1-yl)-phenylaminoJ-methylene}-6-(2-naphthalen-2-yl- vinyl)-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 675 4-{4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(2-pyridin-2-yl-vinyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 676 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(2-pyridin-4-yl-vinyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 677 4^4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-styryl-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 678 4-{[4-{4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(2-pyrazin-2-yl-vinyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 679 6-(3-lmidazol-1-yl-propenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 680 6-(2-imidazol-1 -yl-vinyl)-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 681 4--{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-[2-(4-methyl-thiazol-5- yl)-vinyl]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 682 6-(4-Methoxy-phenyl)-4-{[4-{4-methyl-piperazin-1-yl)-phenylaminoJ-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 683 6-(2-Methoxy-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 684 6-(2-Fluoro-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoJine-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 685 4-(4-{[4-(4-Methyl-piperazin-1-yl)-pheny!amino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 686 3-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2.3,4-tetrahydro-isoq uinolin-6-yl)-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 687 4-{[4-(4-Methyl-piperazin-1-yl)-pbenylamino]-methylene}-6-(4-trifluoromethyl-phenyl)-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 688 6-(4-Acetyl-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 689 6-(4-Chloro-phenyl)-4-fJ[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 690 6-(3-Chloro-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamtno]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 691 6-(2-Chloro-phenyl)-4-{[4-(4-nnethyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 692 4--{[4-(4-Methyl-piperazin-1-yl)-phenylarnino]-methylene}-6-p-tolyl-4H-isc)quinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 693 4-{[4-{4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-m-tolyl-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 694 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino3-rnethylene}-6-o-tolyl-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 695 3-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydrc-isoquinolin-6-yl)-benzonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 696 6-Biphenyl-4-yW-{[4-(4-methyl-piperazin-1-yl)-phenylarnino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 697 6-Biphenyl-3-yl-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 698 3-[4-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-phenyl]-acrylic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 699 3-[3-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-phenyl]-acrylic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 700 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(4-methylsulfanyl-phenyl)-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 701 (4-{[6-(4-Methoxy-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 702 (4-{[6-(3-Methoxy-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 703 (4-{[6-(2-Methoxy-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 704 (4-{[6-(4-Fluorc-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl3- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 705 {4-{[6-(3-Fluoro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 706 (4-{[6-(2-Fluoro-phenyl)-1,3-dioxo-2.3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 707 4-{4-[(4-Cyanomethyl-phenylamino)-methylene]-1,3-dioxo-l ,2,3,4-tetrahydro- isoquinolin-6-yl}-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 708 3-{4-{(4-Cyanomethyl-phenylarnino)-methylene]-1,3-dioxo-l ,2,3,4-tetrahydro- isoquinolin-6-yl}-benzoic add This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 709 (4-{[1 ,3-Dioxo-6-(4-trifluoromethyl-phenyl)-2,3-dihydro-1H-isoqulnolin-4-ylidenemethylJ-amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 710 (4-{[6-{4-Acetyl-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 711 (4-{[6-(2-Acetyl-phenyl)-1,3-dioxo-2,3-dihydro-1 H-isoquinoiin-4-yiidenemethyr]- amino}-phenyl)-acetonitriIe This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 712 (4-{[6-(4-Chloro-phenyl)-1,3-dioxc-2,3-dihydro-1H-isoquinolin-4-ylidenernethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 713 (4-{[6-(3-Chloro-phenyl)-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 714 (4-{[6-(2-Chloro-phenyl)-1,3dlioxo-2,3dihydro-1H-isoquino!in-4-ylidenemethyl]- amino}-phenyl)acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 715 {4-[{1,3-Dioxo-6-p~tolyl-2.3dihydro-1H-isoquinolin-4-ylldenemethyl)-amino]-phenyl)- acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 716 {4-[(1,3-Dioxo-6-m-tolyl-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyI)-amino]- phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 717 {4-[(1,3-Dioxo-6-o-totyl-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}- acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 718 4-{4-[(4-Cyanomethyl-phenylamino)-methylene]-1 ,3-dioxo-1,2,3,4-tetrahydro- isoquinolin-6-yl]-benzonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 719 3-{4-{(4-Cyanomethyl-phenylamino)-methyIene]-1,3-dioxo-1,2,3,4-tetrahydro- isoquinolin-6-yl}-benzonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 720 {4-[{6-Biphenyl-4-yl-1 ,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-aminol- phenyl]-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 721 {4-[(6-Biphenyl-3-yl-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenernethyl}-amino]- phenyl}-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 722 (4-[[6-(4-lsopropyl-phenyl)-1 „3-dioxo-2,3-dihydro-1 H-isoquinolin~4-ylidenemethyl]- amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 723 (4-{[6H-(4-Methylsulfanyl-phenyl)-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-phenyl)-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 724 6-(3-Hydroxy-propenyl)-4[[4-(4-methyl-piperazin-1-yl)-phenylamino]-rnethylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 725 6-[2-(4-Amino-phenyl)-vinyl]-4-{[4-{4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 726 6-[2-(4-Chloro-phenyl)-vinyl]-4-{[4-(4-methyl-piperazin-1-yl)-phenylarnino]-methylene}-4H-ispquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 727 4-[2-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino3-methylene}-1,3-dioxo-1,2.3,4-tetrahydro-isoquinolin-6-yl)-vinyl]-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 728 4-{2-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-vinyl3-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 729 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-[2-(4-trifluoromethyl-phenyl)-vinyl]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 730 6-(3,4-Dihydroxy-but-1-enyl)-4-{l4-(4-methyl-piperazin-1-yl}-phenylarninol-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according 3 the procedure of Example 663. Example 731 6-[2-(4-Fluoro-phenyl)-vinyl]-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinollne-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 732 6-[2-(4-Methoxy-phenyl)-vnyl]-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 733 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-{2-imidazol-1-yl-vinyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 734 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-(2-imidazol-1-yl-vinyl)-4H- isoquinoline-1,3-dione Example 735 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-(2-pyridin-2-yl-vinyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 736 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-[2-(4-dimethylaminomethyl-phenyl)- vinyl]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 737 4-({[6-(3-Methoxy-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 738 4-{{6-(4-Fluoro-phenyl)-1,3-dloxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide o This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 739 4-({[6-(3-Fluoro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-Denzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 740 4-({6-(2-Fluoro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-rnethyl)-benzenesulfbnamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 741 4-{1,3-Dioxo-4-[(4-suIfamoyl-benzylamino)-methylene]-1,2.3,4-tetrahydro-isoquinolin-6-yI}-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 742 3-{1,3-Dioxo-4-[(4-sulfamoyl-benzylamino)-methylene]-1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 743 4-({[1,3-Dioxo-6-(4-trifluoromethyl-phenyl)-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-a mino}-methyl}-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 744 4-({[1.3-Dioxo-6-(3-trifluoromethyl-phenyl)-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 745 4-({[1,3-Dloxo-6-(2-trifluoromethyl-phenyl)-2.3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 746 4-({[6-(4-Acetyl-phenyl)-1,3-dioxo-2,3-dibydro-1H-isoquinoiin-4-ylidenernethyl]-amino}-methyl)-benzenesulfonarnide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 747 4-({[6-(3-Acetyl-phenyl)-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 748 4-{{[6-(2-Acetyl-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 749 4-({[6-(4-Chloro-phenyl}-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 750 4-({6-(3-Chloro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoqulnolin-4-ylidenernethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 751 4-({[6-(2-Chloro-phenyl)-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-yBdenemethyl]-amino}-methyl)-benzenesuifonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 752 4-{[(1,3-Dioxo-6-p-tolyl-2,3dihydro-1H-isoquinolin-4-ylidenemethyl)-mino}-methyl}- benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 753 4-{[(1,3-Dioxo-6-m-tolyl-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amtno]- methyl}-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 754 4{[(1,3-Dioxo-6-o-tolyl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-arnino]-methyl}- benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 755 4-({[6-(4-Cyano-phenyl)-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 756 4-({[6-(3-Cyano-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 757 4-{[(6-Biphenyl-4-yl-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]- methyl}-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 758 4-{[(6-Biphenyl-3-yl-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl)-amino]- methyI}-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 759 3-(4-{1,3-Dioxo-4-[(4-sulfamoyl-benzylamino)-methylenel]-1,2,3,4-tetrahydro-isoquinolin-6-yl}-phenyl)-acrylic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 760 3-(3-{1,3-Dioxo-4-[(4-sulfamoyl-benzylamino)-methylene]-1,2,3,4-tetrahydro-isoquinolin-6-yl}-phenyl)-acrylic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 761 4-{{[6-(4-lsopropyl-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-amino}-rnethyl)-benzenesulfonarnide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 762 4-({[6-(3-lsopropyl-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl]-aminopmethyO-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 763 4-({[6-(4-Methylsulfanyl-phenyl)-1,3-dioxo-2,3-dihydro-1 H-isoquinolin-4-ylidenemethyl]-amino}-methyl)-benzenesulfonamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 764 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(4-methoxy-phenyl)-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 765 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-{3-rnethoxy-phenyl)-4H-isoquinoline- 1.3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 766 4-[(3,4-Dihydroxy-ben2ylamino)-methylene]-6-{2-methoxy-phenyl)-4H-isoquinoline- 1,3-dtone This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 767 4-[(3,4-Dihydroxy-benzylamino)-methylene dione This compound is prepared using appropriate starting materials according to the procedure of Example 759, Example 768 4~[(3,4-Dihydroxy4>enzylarYurm}-methylene dione This compound is prepared using appropriate starting materials according to the procedure of Exampie 169. Example 7S9 4-[{3,4~Dihydroxy-benzylaminomethylene]-6-(2-fluoro-phenyl)-4H-isoquinoline-1.3- dione This compound is prepared using appropriate starting materials according to the procedure of Exampie 169. Example 770 4-(4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo~1,2,3,4-tetrahydro- isoquinolin-6-yl]benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 771 3-{4-[(3,4-dihydroxy-benzylamino)-methylene}-1,3-dioxo-1,2,3,4-tetrahydro- isoquinlin-6-yl}-benzoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 772 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(4-trifluoromethyl-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 773 4-[(3,4-Dihydroxy-ben2ylamino)-methylene}-6-(3-trifluoromethyl-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 774 4-[(3.4-Dihydroxy-benzylamino)-methylene]-6-(2-trifluoromethyl-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 775 6-(4-Acetyl-phenyl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 776 6-(3-Acetyl-phenyl)-4-I(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinolin6-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 777 6-(2-Acetyl-phenyl)-4[(3,4-dihydroxy-ben2ylamino)-rnethylene]-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 778 6-(4-Chloro-phenyl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 779 6-(3-Chloro-phenyl)-4-[(3,4dihydroxy-oenzylamino)-methylene]-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 780 6-(2-Chloro-phenyl)-4-[(3,4~dihydroxy-benzylamino)-methylene}-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 781 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-p-tolyl-4H-isoq uinotine-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 782 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-m-tolyl-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 783 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-o-tolyl-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 784 4-{4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1f2,3,4-tetrahydro- isoquinotin-6-yl}-benzonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 785 3-{4-[{3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro- isoq uinolin-6-yl}-benzonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 786 6-Bipheny)-4-yl-4-[(3,4-dihydroxy-benzylamino)-rnethyIene]-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 787 6-Biphenyl-3-yl-4-[{3,4-dihydroxy-benzylamino)-methytene]-4H-isoquinoline-1,3- dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 788 3-(4-{4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-phenyl)-acrylic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 789 3-(3-{4-l(3,4-Dihydroxy-benzylamino)-methyleneh1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-phenyl}-acrylic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 790 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(4-isopropyl-phenyl)-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 791 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-isopropyl-phenyl)-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 792 4-[(3,4-Dihydroxy-benzylamino)-methyIene}-6-(4-methylsulfanyl-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 793 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2-methylsulfanyl-phenyl)-4H- isoquinoline-1,3-dione This compound Is prepared using appropriate starting materials according to the procedure of Example 169. Example 794 6-[2-2-Diethylamino-ethoxy)-vinyl]-4-{{4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 795 5-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-pent-4-enoic acid This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 796 6-(4-Hydroxy-but-1-enyl)--{[4-(4-methyl-piperazin-1-yl)-phenyIarnino]-methylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 797 6-(5-Hydroxy-pent-1 -enyl)-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 798 6-(6-Hydroxy-hex-1-enyl)-4-{[4-(4-methyl-piperazin-1-yI)-phenylamino]-methylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 799 6-I3-(2-Hydroxy-ethoxy)-propenyl]-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 800 6-[3-(2,4-Dioxo-imidazolidin-1-yl)-propenyl]-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 801 6-[3-(2-Hydroxy-phenyl)-propenyl]-4-{(4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 802 2-Methyl-3-(4-{[4-(4-methyi-piperazin-1-yl)-phenylamino]-methylene)-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-but-2-enenitrile This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 803 {4-{2-(4~{[4-{4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxc-1,2,3,4-tetrahydro-isoquinolin-6-yl)-vinyl]-phenyl}-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 804 4-[(3,4-Dihydroxy-benzylamino)-methylene)-6-[3-(2-hydroxy-3-methoxy-phenyl)-propenyl]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 805 [4-(2-{4-[(3,4-Dihydroxy-ben2ylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-vinyl)-phenyl]-acetonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 806 6-Benzo[1,3]dioxol-5-yl-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 807 6-(4-Dimethylamino-phenyl)-4-{[4-{4-methyl-pipera2in-1-yl)-phenylamino]-methylene)-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 808 6-(4-Hydroxymethyl-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 809 3-[4-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-phenyl]-propionic acid This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 810 6-(3-Amino-phenyl)-4-{{4-(4-rnethyl-piperazin-1-yl)-phenylarnino]-methylene}-4H- isoquinoiine-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 811 6-(2,4-Dichloro-phenyl)-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 812 6-Ben20[1,3]dioxol-5-yl-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 813 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3,4-dimethoxy-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169.. Example 814 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(2,4-dimethoxy-phenyl)-4H- isoquinofine-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 815 4-[(3,4-Dihydroxy-ben2yiamino)-methylene]-6-(3,4,5-trimethoxy-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 816 4-[(3,4-Dihydroxy-ben2ylamino)-methylene]-6-(4tdimethyiamino-phenyl)-4H- isoquinoline-1,3-dlone This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 817 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(4-hydroxymethyl-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 818 4-[(3,4-Dlhydroxy-benzylamino)-methylene]-6-(4-trifluoromethoxy-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 819 3-(4-{4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinofin-6-yl}-phenyl)-propionic acld This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 820 4-[(3,4-Dihydroxy-benzylamino)-methylene]-6-(3-nitro-phenyl)-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 821 6-(3-Amino-phenyl)-4-[{3,4-dihydroxy-benzylamino)-methylene]-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 822 N-(3-{4-[(3,4-Dihydroxy-benzylamino)-methylene]-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl}-phenyl)-acetamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 823 6-(2,4-Dichloro-phenyl)-4-[(3,4-dihydroxy-benzylamino)-methylene]-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 824 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-(2-pyridin-4-yl-vinyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 825 4-f(3-Hydroxy-4-Mnethoxy-benzylamino)-methylene]-6-styryl-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 826 6-[3-(2,4Dioxo-imidazolidin-1-yl)-propenyl)-4-[(3-hydroxy-4-methoxy-benzy!amino)-methylene]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 827 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-[3-(2-hydroxy-3-methoxy-phenyl)-propenyl]-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 828 6-Cyclopentylidenemethyl-4-{[4-(4-methyl-pipera2in-1-yJ)-phenylamino]-methylene}- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 829 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-6-[2-(4-nitro-phenyl)-vinyl]- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 663. Example 830 6-Furan-2-yl-4-{[4-(4-methyl-piperazin-1 -yl)-phenyIamino]-methylene}-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 831 4-{[4-(4-Methyl-piperazin-1-yl)-phenylamimo]-methylene}-6-phenyl-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 832 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylenel]-6-phenyl-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 833 4-{(3-Hydroxy-4-methoxy-ben2ylamino)-methylene]-6-(4-methoxy-phenyl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 834 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-naphthalen-2-yl-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 835 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-(1H-indol-5-yl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 836 4-[(3-Hydroxy-4-methoxy-benzylamino)-methylene]-6-(1H-pyrrol-2-yl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 837 6-Furan-2-yl-4-[(3-hydroxy-4-methoxy-benzylamino)-methylene}-4H-isoquinoline- 1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 838 4-[(4-Pyrrolidin-1-ylmethyl-phenylamino)-methylene]-6-(1l-H-byrrol-2-yl)-4H- isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 839 4-{1,3-Dioxo-4-[(4-pyrrolidin-1-ylmethyl-phenylamino)-methylene]-1,2,3,4-tetrahydro-isoquinolin-6-yl}-benzonitrile This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 840 6-(4-Hydroxymethyl-pheny))-4-[(4-pyrrolidin-1-ylmethyl-phenylamino)-methy)ene]- 4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 841 7-Bromr-4-[(4-methoxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one Stepl: A mixture of 4-bromo-phenylacetonitrile (0.196 mg, 1 mmol), paraformaldehyde (33 mg, 1.1 mmol) and pyrophosphoric acid (2 g) is treated in a microwave at 160°C for 10 min. The reaction mixture is poured into ice-water, neutralized with K2CO3, and then extracted with ethyl acetate. The extract is washed with 10% K2C03 and water, dried over MgSO4. filtered and evaporated to give of 7-Bromo-1,4-dihydro-2H-isoquinolin-3-one (167.8 mg). Step 2: To a suspension of 7-bromo-1,4-dihydro-2H-isoquinolin-3-one (450 mg, 2 mmol) in 1 mL of N,N-dimethylformamide is added N,N-dimethylformamide dimethylacetal (954 mg, 8 mmol). The reaction mixture is heated in a microwave at 100°C for 10 min. The reaction mixture is then filtered and washed with N,N-dimethylformamide to give 356 mg of 7-bromo-4-dimethylamlnomethylene-1,4-dihydro-2H-isoquinolin-3-one. Step 3: To a suspension of crude 7-bromo-4-dimethylaminomethylene-1,4-dihydro-2H-isoquinolin-3-one (56 rng, 0.2 mmol) in N,N-dimethylformamide (250 mL) is added N,N-dimethy1-1,4-phenylenediamine (41.8 mg, 0.2 mmol). The reaction mixture is shaken at 115°C for 3 hours, then purified by Prep. HPLC. The pure fractions were combined and concentrated to yield Example 841 (10.2 mg). Example 842 7-Bromo-4-{I4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-1,4-dihydro-2H- isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 841. Example 843 6-[1-(2-Methoxy-ethyl)-1H-pyrrol-3-yl]-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 853. Example 844 6-Bromo-4-[(4-methooxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one & 8-Bromo-4-[(4-methoxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3- one This compound is prepared using appropriate starting materials according to the procedure of Example 845 (Formula Removed) Example 845 6-Bromo-4-{[4-(4-methyi-pipera2in-1-yl)-phenylamino]-methylene}-1,4-dihydro-2H-isoquinolin-3-one & 8-Bromo-4-{[4-(4-methyl-pipera2in-1-yl)-pheny)amino]- methylene}-1,4-dihydro-2H-isoquinolin-3-one Stepl: A mixture of 3-bromo-phenylacetonitrile (2 mmol, 0.392 g), paraformaldehyde (2.2 mmol, 0.066 g) and pyrophosphorfc acid (4 g) is heated in a microwave at 160°C for 10 min. The reaction mixture is poured into ice-water, neutralized with K2CO3, and then extracted with ethyl acetate. The extract is washed with 10% K2CO3 and water, dried over MgSO4, filtered and evaporated to give a mixture of 6(and 8)-bromo-1,4-dihydro-2H-isoquinolin-3-one (0.47 g). Step 2: To a suspension of 6(and 8)-bromo-1,4-dihydro-2H-isoquinolin-3-one (0.204 g, 0.8 mmol) in 0.5 mL of N.N-dimethylformamide is added N.N-dimethylforrnamide dimethyiacetal (0.4 g, 3.4 mmol). The reaction mixture is heated in a microwave at 100°C for 10 min, then evaporated to dryness. The residue is applied on a C18 column and eluted with 25% ACN (30 ml) and 40% ACN (100 mL). The fractions which contained product were combined and evaporated to give 0.321 g of 6(and 8)-brormo-4-dimethylaminomethylene-1,4-dihydro-2H-isoquinoiin-3-one. Step 3: To a suspension of crude 6(and 8)-bromo-4-dimethylaminomethylene-1,4-dihydro-2H-isoquinolin-3-one (28 mg, 0.1 mmol) in N.N-dimethylformamide (250 ml) is added 4-(4-methyl-piperazin-1-yl)-phenylamine (19 mg, 0.1 mmol). The reaction mixture is shaken at 115°C for 1.5 hours, then purified by Prep. HPLC. The pure fractions were combined and concentrated to yield Example 845 (17.4 mg). Example 846 6-Bromo-4-[(4-pyrrolidin-1-ylmethyl-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one & 8-Brorno-4-[(4-pyrro!idin-1 -ylmethyl-phenylamino)-methylene]- 1 „4-dihydro-2H-isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 845. Example 847 7-Bromo-4-[(4-pyrrolidin-1-ylmethyl-phenylamino)-methylenel]-1,4-dihydro-2H- isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 841. Example 848 4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-7-thiophen-2-yl-1,4- dihydro-2H-isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 849. (Formula Removed) Example 849 4-[(4-Methoxy-phenylamino)-methylene]-7-(1 H-pyrrol-2-yl)-1,4-dihydro-2H- isoquinolin-3-one Stepl: A mixture of 4-bromo-phenylacetonitrile (0.196 mg, 1 mmol), paraformaldehyde (33 mg, 1.1 mmol) and pyrophosphoric acid (2 g) is heated in a microwave at 160°C for 10 min. The reaction mixture is poured into ice-water, neutralized with K2CO3 and then extracted with ethyl acetate. The extract is washed with 10% K2CO3 and water, dried over MgSO4, filtered and evaporated to give 7-bromo-1,4-dihydro-2H-isoquinolin-3-one (167.8 mg). Step 2:To a suspension of 7-bromo-1,4-dihydro-2H-isoquinolin-3-one (450 mg, 2 mmol) in 1 mL of N,N-dimethylforrnamide is added N,N-dimethylformamide dimethylacetal (954 mg, 8 mmol). The reaction mixture is heated in a microwave at 100°C for 10 min. The reaction mixture is then filtered and washed with N,N-dimethylforrnamide to give 356 mg of 7-bromo-4-dimethylaminomethylene-1,4-dihydro-2H-isoquinolin-3-one. Step 3: To a suspension of crude 7-bromo-4-dimethy!aminomethylene-1,4-dihydro-2H-isoquinolin-3-one (400 mg, 1.43 mmol) in N.N-dimethylforrnamide (250 mL) is added 4-anisidine (193 mg, 1.57 mmol). The reaction mixture is shaken at 115DC for 1.5 hours. The reaction mixture is filtered and the filtrate is purified by Prep. HPLC. The pure fractions were combined and concentrated to yield 114 mg of 7-Bromo-4-[(4-methoxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one. Step 4: To a suspension of 7-bromo-4-{(4-methoxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one (36 mg, 0.1 mmol) in N.N-dimethylforrnamide (1 mL) is add l-(t-butoxycarbonyl) pyrrole-2-boroic acid (25.3 mg, 0.12 mmol), 2 M aqueous solution of cesium carbonate (300 µL) and tetrakis(triphenylphosphine)-palladium (0) (30 mg). The reaction mixture is heated in a microwave at 180°C for 5 min. The reaction mixture is then filtered and the filtrate Is purified by Prep. HPLC. The pure fractions were combined and concentrated to yield the title compound (12.8 mg). Example 850 4-[(4-Methoxy-phenylamino)-methylene]-7-(1 H-pyrrol-3-yl)-1,4-dihydro-2H- isoquinoiin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 845. Example 851 2-[5-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-indol-1-yl]-acetamide This compound is prepared using appropriate starting materials according to the procedure of Example 169. Example 852 6-[ 1-(2-Diethylamino-ethyl)-1 H-indol-5-yl]-4-{[4-(4-methyl-piperazin-1 -yl)-pheny1amino]-methylene}-4H-isoquinotine-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 853. (Formula Removed) Example 853 2-[3-(4-{[4-(4-Methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-pyrrol-1 -yl]-acetamide Step 1: To a suspension of 6-bromo-4H-isoquinoline-1,3-dione (2.4 g, 10 mmol) in 25 mL of a 4:1 mixture of acetic anhydride and N,N-dimethylformamide, respectively, is added trimethylorthoformate (2.2 mL, 20 mmol). The reaction mixture is shaken in a heating block at 125°C for 1 hour. Upon cooling to room temperature, the product precipitated out. The precipitate is then filtered off, rinsed with copious amounts of ether, and dried to yield 2.4 g of 6-bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione. Step 2: To a suspension of crude 6-bromo-4-methoxymethylene-4H-isoquinoline-1,3-dione (846 mg, 3 mmol) in N,N-dimethylformamide (7.5 L) is added 4-(4-methyl-piperazin-1-yl)-phenylamine (573 mg. 3 mmol). The reaction mixture is shaken at 115°C for 1.5 hours, then evaporated to dryness and triturated with ether. The precipitate is then filtered off, rinsed with copious amounts of ether, and dried to yield 1.23 g of 6-bromo-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione. Step 3: To a suspension of 6-bromo-4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methyIene}-4H-isoquinoline-1,3-dione (0.2 g, 0.45 mmol) in N.N-dimethylformamide (5 mL) is added N-triisopropylsilyl- 3-pyrrole boronic acid (0.16 g, 0.54 mmol), followed by 300 uL of 2M aqueous cesium carbonate and tetrakis triphenylphosphine palladium (30 mg, 0.025 mmol). The reaction mixture is subjected to microwave heating at 180°C for 300 seconds. The reaction mixture is then divided into 3 fractions and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield 60 mg of 4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene)-6-(1H-pyrrol-3-yl)-4H-isoquinoline-1,3-dione. Step 4: To a solution of 4-{[4-(4-methyl-piperazin-1-yl)-phenylamino]-methylene}-6-(1H-pyrrol-3-yl)-4H-isoquinoline-1,3-dlone (42 mg, 0.1 mmol) in acetone (3 mL) and N.N-dimethylformamide (1 mL) is added potassium carbonate (27 mg, 0:2 mmol) and shaken at room temperature for 2 hours. This is followed by addition of sodium iodide (30 mg, 0.2 mmol) and 2-brornoacetamide (17 mg, 0.12 mmol) and further shaking at room temperature overnight. The reaction mixture is then divided into 2 fractions and purified by C18 reverse phase HPLC. The pure fractions were combined and concentrated to yield the title compound (8.4 mg). Example 854 6-[1 -(2-Diethylamino-ethyl)-1 H-pyrrol-3-yl]-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}-4H-isoquinoline-1,3-dione This compound is prepared using appropriate starting materials according to the procedure of Example 853. Example 855 4-[3-(4-{[4-(4-Methyl-piperazin-1-yl)-phenylamino]-methylene}-1,3-dioxo-1,2,3,4-tetrahydro-isoquinolin-6-yl)-pyrrol-1-yl]-butyronitrile This compound is prepared using appropriate starting materials according to the procedure of Example 853. Example 856 7-Chloro-4-[(3-hydroxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 841. Example 857 4-[(7-Chloro-3-oxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]- benzamidine This compound is prepared using appropriate starting materials according to the procedure of Example 841. Example 858 7-Methyl-4-[(4-morpholln-4-yl-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin- 3-one This compound is prepared using appropriate starting materials according to the procedure of Example 841. Example 859 4-[(3-Hydroxy-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 841.. Example 860 4-[(4-Piperidin-1-yl-phenylamino)-methylenel-1.4-dihydro-2H-isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 841. Example 861 4-[(7-Bromo-3-oxo-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]- benzamidine This compound is prepared using appropriate starting materials according to the procedure of Example 841. Example 862 7-Bromo-4-[(3-hydroxy-4-methoxy-phenylamino)-methylene]-1,4-dihydro-2H- isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 841. Example 863 7-Bromo-4{[4-(2-hydroxy-ethyl)-phenylamino]-methylene}-1,4-dihydro-2H- isoquinolin-3-one This compound is prepared using appropriate starting materials according to the procedure of Example 841. (Formula Removed) Example 864 (4Z)-6-Bromo-4-[({4-[methyl(2-pyrrolidin-1-ylethyl)amino]phenyl}amino)methylene}isoquinoline-1,3(2H,4H)-dione To a solution of 2-(methyl-4-nitroanilino)ethanol (2.9 g, 15 mrnol) in pyridine (75 mL) is added p-toluenesulfonyi chloride (3.1 g, 1.6 mmol) and 4-(dimethylamino)pyridine (1.8 g, 15 mmol). After stirring for three days at room temperature, the reaction is quenched by the addition of saturated aqueous sodium chtoride solution and then extracted 3x with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a viscous brown oil, which is purified by reverse phase high performance liquid chromatography to give toluene-4-sulfonic acid 2-[methyl-(4-nitro-phenyl)-arnino]~ethyl ester as a trifluoroacetic acid salt (0.52 g, 9.8 %). LC/MS (ES+): 351.0 (M+H)+ To a solution of toluene-4-sulfonic acid 2-[methyl-(4-nitro-phenyl)-amino]-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 u.L) and pyrrolidine (53 µL, 0.63 mmol). The mixture is shaken in 70 °C block shaker overnight. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give methyl-(4-nitro-phenylM2-pyrrolidin-1-yl-ethyl)-amine as a di-TFA salt (85 mg). A solution of methyl-(4-nitro-phenyl)-(2-pyrrolidin-1-yl-ethyl)-amine.2 TFA (85 mg) in ethanol/tetrahydrofuran (1:1,5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-methyl-N-(2-pyrrolidin-1 -yl-ethyl)-benzene-1,4-diamine as a di-TFA salt. (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-methyl-N-(2-pynrolidin-1-yl-ethyl)-benzene-1,4-diamine.2 TFA (0.21 mmol maximum) were stirred in dimethylfonmamide (1 mL) and triethylamine (50 µl_) at 60 — 70 °C for 12 hours.. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4Z)-6-bromo-4-[({4-[methyl(2-pyrrolidin-1-ylethyl)amino]phenyl}amino)methylene}isoquinoline-1,3(2H,4H)-dione. MS (ES+): 469.2, 471.2 (M+H)+ (Formula Removed) Example 865 (42)-B-bromo-4-[({4-[methyl(2-piperidin-1 -ylethyl)amino]phenyl)amino)methylene]isoquinoline-1,3(2H,4H)-dione To a solution of toluene-4-sulfonic acid-2-[methyl-(4-nitro-phenyl)-amino]-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 µL) and piperidine (62 µL, 0.63 mmol). The mixture is shaken in 70 °C block shaker overnight.. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give methyl-(4-nitro-phenylM2-piperadin-1-yl-ethyl)-amine as a di-TFA salt (74 mg). MS (ES+): 264.3 (M+H)+ A solution of methyl-(4-nitro-phenyl)-(2-piperidin-1-yl-ethyl)-amine-2 TFA (74 mg) in ethanol/tetrahydrofuran (1:1, 5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-methyl-N-(2-piperidin-1-yl-ethyl)-benzene-1,4-diamine as a di-TFA salt. (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-methyl-N-(2-piperidin-1-yl-ethyl)-benzene-1,4-diamine.2TFA (0.21 mmol maximum) were stirred in dimethyiformamide (1 mL) and triethyiamine (50 µL) at 60 — 70 °C for 12 hours. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4Z)-6-bromo-4-[({4-[methyl(2-piperidin-1-ylethyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione. MS (ES+): 483.2 (M+H)+ (Formula Removed) Example 866 (4Z)-6-Bromo-4-[({4-[{2-[butyl(methyl)amino]ethyl}(methyl)amino]phenyl}amino)methylene]isoquinoline- 1,3(2H,4H)-dione To a solution of toluene-4-sulfonic acid 2-[methyl-(4-nitro-phenyl)-amino]-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethyiamine (50 µL) and N-methylbutylamine (75 µL, 0.63 mmol). The mixture is shaken in 70 °C block shaker overnight. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give N-butyl-N,N*-dimethyl-N'-(4-nitro-phenyl)-ethane-1,2-diamine as a di-TFA salt (71 mg, 68 %). A solution of N-butyl-N,N'-dimethyl-N-(4-nitro-phenyl)-ethane-1 ,2-diamine.2 TFA (71 mg) in ethanol/tetrahydrofuran (1:1, 5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-[2-(butyl-methyl-amino)-ethyl]-N-methyl-benzene-1,4-diarnine as a di-TFA salt. (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-[2-(butyl-methyl-amino)-ethyl]-N-methyl-ben2ene-1,4-diamine.2 TFA (0.21 mmol maximum) were stirred in dimethylformamide (1 mL) and tnethylamine (50 µL) at 60 — 70 °C for 12 hours. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4Z)-6-bromo-4-[({4-[{2- [butyl(methyl)amino]ethyl}(methyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H.4H)-dione. MS (ES+): 487.3 (M+H)+ (Formula Removed) Example 867 (4Z)-6-Bromo-4-[({4-[2-(dimethylamino)ethoxy]phenyl}annino)methylene]isoquinoline-1,3(2H,4H)-dione Dimethyl-[2-(4-nitro-phenoxy)-ethyl]-amine is prepared according to Hunter, D.H.; Ponce, Y.Z.; Brown, G.W.; Chamberlain, M.J.; Driedger, A.A.; Morrissey, G. Can J Chem. 62, 2015-2019, 1984. MS (ES+): 211.3 (M+H)* A solution of dimethyl-[2-(4-nitro-phenoxy)-ethyl]-amine hydrochloride (0.29 g, 1.2 mmol) in ethanol (20 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give 4-(2-dimethylamino-ethoxy)-phenylamine hydrochloride (0.24 g, 96 %). MS (ES+): 181.3 (M+H)+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (70 mg, 0.25 mmol) and 4-(2-dimethylamino-ethoxy)-phenylamine hydrochloride (50 mg-, 0.23 mmol) were stirred in dimethylformamide (1 mL) and triethylamine (50µL) at 70 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-bromo-4-[({4-[2- (dimethylamino)ethoxy]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione (81 mg, 82 %). Example 868 744 MS (ES+): 430.0, 432.0 (M+H)+ (Formula Removed) (4Z)-6-Bromo-4-{[(2-methyl-2,3-dihydro-1H-isoindol-5-yl)aminoJmethylene}isoquinoIine-1,3(2H,4H)-dione The methylation of 4-nitrophthalimide to give 2-methyl-5-nitro-isoindole-1,3-dione (0.93 g, 43 %) is accomplished via the procedure of Billman, J.H. and Cash, V. J Am Chem Soc. 75(10), 1953, 2499-2501. A solution of give 2-methyl-5-nitro-isoindole-1,3-dione (1.1 g, 5.3 mmol) in ethanol/tetrahydrofuran (1:1, 50 mL) is hydrogenated at 45 psi over Raney nickel catalyst The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give 5-amino-2-methyl-isoindole-1,3-dione as a yellow cottony solid (0.85 g, 91 %). 1H NMR (300 MHz, DMSO-d6) d ppm 2.94 (s, 3 H), 6.44 (s, 2 H), 6.77 (dd, J=8.2 Hz, 1H), 6.91 (d, J=2.0 Hz, 1H), 7.47 (d, J=8.2 Hz, 1H). To a suspension of lithium aluminum hydride (0.55 g, 14 mmol) in tetrahydrofuran (7 mL) is added solid 5-amino-2-methyl-isoindole-1,3-dione (0.85 g, 4.8 mmol). The resulting suspension is heated at reflux for 15 minutes and is then cooled to 0 °C. At this temperature, the reaction is quenched by the addition of ethanol and then water. The resulting slurry is filtered, through a pad of diatomaceous earth, and the filtrate is concentrated under reduced pressure to give a brown solid. The crude solid is dissolved in absolute ethanol and acidified with concentrated ethanolic hydrochloric acid. With the addition of diethyl ether, a brown solid precipitated and is collected by filtration to give 2-methyl-2,3-dihydro-1H-isoindol-5-ylamine as a dihydrochloride salt (0.61 g, 55 %). MS (ES+): 149.3 (M+H)+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.20 g, 0.71 mmol) and 2-methyl-2,3-dihydro-1H-isoindol-5-ylamine.2 HCI (0.52 mg, 2.3 mmol) were stirred in dimethylformamide (5 mL) and triethylamine (0.83 mL) at 70 °C. The reaction- mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give a crude solid, which is then purified by reverse phase high performance liquid chromatography to provide (4Z)-6-bromo-4-{[(2-rnethyl-2,3- dihydro-1 H-isoindol-5-yl)amlno]methylene}isoquinoline-1,3(2H,4H)-dione-trifiuoroacetic acid (80 mg, 22 %). MS (ES): 396.1, 398.2 (M-H) Example 869 (4Z)-6-Bromo-4-({[4-(1 H-imidazol-1 -yl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione In a 20 mL vial were combined 4-fiuoronitrobenzene (1.1 mL, 10 mmol), imidazole (0.68 g, 10 mmol), and sodium carbonate (1.1 g, 11 mmol) in dimethyiformamide (5 mL). The mixture is shaken at 100 °C for 24 hours and then allowed to cool to room temperature and then diluted with water. Concentrated hydrochloric acid is added to bring the pH to 1, and then the mixture is extracted thrice with chloroform (10 mL). The acidic aqueous phase is then treated with 2.5 M sodium hydroxide solution to give a pH of 10. A light yellow solid is collected and washed with water to give 1-(4-nitrophenyl)-1H-imidazole. MS (ES+): 190.2 (M+H)+ A solution of 1-(4-nitrophenyl)-1H-imidazole (0.38 g, 2.0 mmol) in ethanol (20 mL), water (3 mL), and concentrated hydrochloric acid (5 drops) is hydrogenated for overnight at atmospheric pressure over 10 % Pd/C. The mixture is Filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give 4-(1 H-imidazol-1 -yl)-benzenamine trihydrochloride as a gray powder. MS (ES+): 160.2 (M+H)+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (70 mg, 0.25 mmol) and 4-(1 H-imidazol-1 -yl)-benzenamine.3 HCI (70 mg, 0.25 mmol) were stirred in dimethyiformamide (1.5 mL) and triethylamine (0.15 mL) at 75 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-bromo-4-({[4-(1H-imidazol-1-yl)phenyl]amino}rnethylene)isoquinoline-1,3(2H,4H)-dione (95 mg, 93 %) MS (ES+): 4O9.0,411.0 (M+H)+ (Formula Removed) Example 870 (4Z)-6-Bromo-4-{[(4-{methyl[2-(4-methylpiperazin-1-yl)ethyl]amino}phenyl)amino]methylene}lsoquinoline-1,3(2H,4H)-dione To a solution of toluene-4-sulfonic acid 2-[methyl-(4-nltro-phenyl)-amino]-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 µL) and N-methylpiperazine (70 µL, 0.63 mmol). The mixture is shaken in 70 °C block shaker overnight. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give methyl-[2-(4-methyl-piperazin-1-yl)-ethyl]-(4-nitro-phenyl)-amine as a tri-TFA salt (98 mg, 98 %). A solution of methyl-[2-(4-methyl-piperazin-1-yl)-ethyl]-(4-nitro-phenyl)-amine .3 TFA (98 mg) in ethanol/tetrahydrofuran (1:1, 5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-methyl-N-[2-(4-methyl-piperazin-1-yl)-ethyl]-benzene-1,4-diamine as a tri-TFA salt.(4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-Methyl-N-[2-(4-methyl-piperazin-1-yl)-ethylJ-ben2ene-1,4-diamine »3 TFA (0.21 mmol maximum) were stirred in dimethylformamide (1 mL) and triethylamine (50 µL) at 60 - 70 °C for 12 hours. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4Z)-6-bromc-4-{[(4-{methyl[2-(4-methylpiperazin-1- yl)ethyl]amino}phenyl)amino]methylene}isoqujnoline-1,3(2H,4H)-dione as a tri-TFA salt. MS (ES+): 500.2 (M+H)+ (Formula Removed) Example 871 (4Z)-6-Bromo-4-[({4-[methyl(2-morpholin-4-ylethyl)amino]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione To a solution of toluene-4-sulfonic acid 2-{methyl-(4-nitro-phenyl)-amino]-ethyl ester TFA salt (74 mg, 0.21 mmol) in toluene (1 mL) is added triethylamine (50 µL.) and morpholine (55 µL, 0.63 mmol). The mixture Is shaken In 70 °C block shaker overnight. The reaction mixture is concentrated and purified by reverse phase high performance liquid chromatography to give methyl-(2-morpholin-4-yl-ethyl)-(4-nitro-phenyl)-amine as a di-TFA salt (80 mg, 77 %). MS (ES+): 266.3 (M+H)+ A solution of methyl-(2-morpholin-4-yl-ethyl)-(4-nitro-phenyl)-amine.2 TFA (80 mg) in ethanol/tetrahydrofuran (1:1, 5 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N~methyl-N-(2-morpholin-4-yl-ethyl)-benzene-1,4-diamine as a di-TFA salt (4E)-6-Bromo-4-(methoxymethylene)isoquinoIine-1,3(2H,4H)-dione (59 mg, 0.21 mmol) and N-Methyl-N-(2-morpholin-4-yl-ethyl)-benzene-1,4-dlamine.2 TFA (0.21 mmol maximum) were stirred in dimetbylfomnamide (1 mL) and triethylamine (50 µL) at 60 — 70 °C for 12 hours. The reaction mixture is purified by reverse phase high performance liquid chromatography to give (4Z)-6-bromo-4-[({4- [methyl(2-morpholin-4-ylethyl)amino]phenyl}amino)methylene]isoquinoline- 1,3(2H,4H)-dione. MS (ES+): 587.2 (M+H)+ (Formula Removed) Example 872 6-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)-2,2-dimethyl-1,3-benzodioxol-4-y1 acetate Example 873 To a solution of (4Z)-6-bromo-4-({[(7-hydroxy-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]amino}methylene)isoquinoline-1,3(2H.4H)-dione (30 mg, 67 µmol) in dimethylformamide (0.5 mL) is added pyridine (12 µL, 0.17 mmol) and acetyl chloride (10 µl.). The reaction mixture is shaken overnight at room temperature and then purified by reverse-phase high performance liquid chromatography to give 6-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}methyl)-2,2-dimethyl-1,3-benzodioxol-4-yl acetate. (Formula Removed) 6-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)- ylidene)methyl]amino}methyl)-2,2-dimethyl-1,3-benzodioxol-4-yl cyclopropanecarboxylate To a solution of (4Z)-6-bromo-4-({[(7-hydroxy-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione (30 mg, 67 µmol) in dimethylformamide (0.5 mL) is added pyridine (12 µL, 0.17 mmol) and cyclopropanecarbonyl chloride (10 µL). The reaction mixture is shaken overnight at room temperature and then purified by reverse-phase high performance liquid chromatography to give 6-({[(Z)-(6-bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyrjamino}methyl)-2,2-dimethyl-1,3-benzodioxol-4-yl cyclopropanecarboxylate. (Formula Removed) Example 874 (4Z)-6-Bromo-4-[({4-[3-(dimethylamino)propyl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione N-[4-(3-Oxo-propyl)-phenyl]-acetamide is prepared according to Bjomestedt, R.; Zhong, G.; Lerner, R.A.; Barbas, C.F. J Am Chem Soc. 118, 1996, 11720-11724. To a suspension of N-[4-(3-Oxo-propyl)-phenyl]-acetamide (96 mg, 0.50 mmol). dimethylamine hydrochloride (82 mg, 1.0 mmol), and sodium acetate (66 mg, 0.80 mmol) in methanol (0.5 mL) is added sodium cyanoborohydride (47 mg, 0.75 mmol). Upon completion of the reaction, the solvent is evaporated under reduced pressure and the residue is partitioned between ethyl acetate and water. The aqueous phase is extracted with ethyl acetate. The combined extracts were concentrated to give N-[4-(3-dimethylamino-propyl)-phenyl]-acetamide (0.14 g, > 100 %). MS (ES+): 221.3 (M+H)+ To a solution of N-[4-(3-dimethylamino-propyl)-phenyl]-acetamide (0.50 mmol maximum) in methanol (8 mL) is added 20 % aqueous hydrochloric acid solution. After 3 1/2 hours of shaking at 56 °C, an additional 2 drops of concentrated hydrochloric acid is added and shaking is continued for 3 days. The mixture is concentrated to give 4-(3-dimethylamino-propyl)-phenylamine hydrochloride, which is used without further purification in the following step. MS (ES+): 179.3 (M+H)+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (50 mg, 0.18 mmol)4-(3-dimethylamino-propyl)-phenylamine hydrochloride (0.40 mmol) were stirred in dimethylformamide (1 mL) and triethylamine (140 µL) at 78 °C. The reaction mixture is quenched by the addition of water. The solid material is then coHected, washed with water, and then dried under vacuum to give (4Z)-6-bromo-4-[({4-[3-(dimethylamino)propyl]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione (58 mg, 75 %) as a golden solid. MS (ES+): 428. 430 (M+H)+ (Formula Removed) Example 875 (Methoxyamino)propyi]phenyl)amino)methylene]isoquinoline-1,3(2H,4H)-dione 3-(4'-Acetamidophenyl)propanal is prepared according to Bjomestedt, R.; Zhong, G.; Lerner, R. A.; Barbas, C. F. JACS (1996), 118(47), 11720-11724. LC/MS(ES+): 192.7 (M+H)+ A mixture of 3-(4-acetamidophenyl)propanal (96 mg, 0.50 mmol), methoxylamine hydrochloride (92 mg, 1.1 mmol), and pyridine (110µL) in methanol (0.7 mL) is heated in a 70 °C oil bath for 18 hours and then allowed to cool to room temperature. Methanol (1 mL) is added and the mixture is cooled to 0 °C in an ice-water bath. Borane.pyridine complex (0.11 mL, 1.1 mmol) is added, followed by the dropwise addition of 10 % aqueous hydrochloric acid. The mixture is allowed to warm to room temperature and then concentrated under reduced pressure. The residue is purified by reverse-phase HPLC to give N-[4-(3-rnethoxyamino-propyl)-phenyl]-acetamide. MS(ES+): 223.3 (M+H)+ A mixture of N-[4-(3-methoxyamino-propyl)-phenyl]-acetamide (0.50 mmol) and- 20 % aqueous hydrochloric acid (2 mL) in methanol (8 mL) is heated for 18 hours at 60 °C and then concentrated under reduced pressure to give N-[3-(4-amino-phenyl)-propyl]-O-methyl-hydroxylamine dihydrochloride (62 mg, 0.24 mmol) and is used in the following step without further purification. MS(ES+): 181.3 (M+H)+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (69 mg, 0.24 mmol) and N-[3-(4-amino-phenyl)-propyl]-O-methyl-hydroxylamine dihydrochloride (62 mg, 0.24 mmol) were coupled in dimethylformamide (1.4 mL) with triethylamine (0.15 mL). The mixture is heated at 75 °C for one hour and then cooled to 0 °C in an ice-water bath. Water is added and resulting solid is collected and then purified by reverse-phase HPLC to give (4Z)-6-bromo-4-[({4-{3-(methoxyamino)propyl]phenyl}amino)methyIene]isoquinoline-1,3(2H,4H)-dione as its trifluoroacetate salt (30 mg, 23 %). LC/MS (ES-): 428.4, 430.4 (M-H)- (Formula Removed) Example 876 (42)-6-Bromo-4-[({4-[[3-(dirnethylamino)propyl](rnethyl)arnino]phenyl}amino)methylene]isoquinoline- 1,3(2H,4H)-dione To a suspension of potassium hydroxide (1.4 g, 25 mmol) in dimethylsulfoxide (13 mL) is added N.N,N'-trimethyl-1,3-propanediamine (1.8 mL. 12 mmol). While stirring vigorously and while heating to 65 °C, 4-fluoronitrobenzene (1.1 mL, 10 mmol) is added dropwise. After stirring at this temperature for 6 hours, the mixture is allowed to cool to room temperature. Water is added and the mixture is acidified to pH 1 with concentrated hydrochloric acid and then extracted thrice with chloroform (3 x 30 mL). The acidic phase is then basified to pH 11 with 2.5 M sodium hydroxide solution. The basic phase is extracted thrice with chloroform (3 x. 30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give an orange-red oil, which is purified by reverse phase high performance liquid chromatography to give N.N.N'-trimethyl-N'-(4-nitrophenyl)propane-1,3-diamine as its ditrifluoroacetate salt. MS (ES+): 238.1 (M+H)+ A solution of give N,N,N'-trimethyl-N,-(4-nitrophenyl)propane-1,3-diamine.2 TFA (0.57 g, 1.2 mmol) in ethanol/tetrahydrofuran (1:1. 20 mL) is hydrogenated at atmospheric pressure over 10 % palladium on carbon. The reaction mixture is filtered through a pad of diatomaceous earth and concentrated to give N-(3-dimethylamino-propyl)-N-methyl-benzene-1,4-diamine.2 TFA as a dark oil. MS (ES+): 208.4 (M+H)+ (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (52 mg, 0.18 mmol) and N-(3-dimethylamino-propyl)-N-methyl-benzene-1,4-diamine.2TFA (80 mg, 0.18 mmol) were stirred in dimethylformamlde (1 mL) and triethylamine (100 µL) at 75 °C. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-bromo-4-[({4-[[3-(dimethylamino)propy|](methyl)aminolphenyl}amino)methylene]isoquinoline-1.3(2H.4H)-dione-2 TFA (43 mg. 35 %). MS (ES+): 457.1,459.1 (M+H)+ Example 877 (4Z)-6-Bromo-4-I({4-[( 1 -methylpyrrolidin-3-yl)oxy]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione To a suspension of sodium hydride (60 % dispersion in mineral oil, 0.65 g, 16 mmol) in tetrahydrofuran (50 mL) is added 1-methyl-3-pyrrolidinol (0.50 g, 4.9 mmol) as a solution in tetrahydrofuran (100 mL). After 2 1/2 hours of stirring at room temperature, a solution of 4-fluoronitrobenzene (0.73 mL, 6.9 mmol) in tetrahydrofuran (30 mL) is added to the mixture. After stirring overnight, the mixture is quenched with water and extracted 3X with diethyl ether. The combined extracts were washed with water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The crude product is purified by reverse phase high performance liquid chromatography to give 1-methyl-3-(4-nitro-phenoxy)-pyrrolidine.TFA as a colorless oil which solidified upon standing. MS (ES+): 223.3 (M+H)+ A solution of 1-methyl-3-(4-nitro-phenoxy)-pyrrolidine.TFA (0.34 g, 1.0 .mmol) in ethanol (10 mL) is hydrogenated for one hour at atmospheric pressure over 10 % Pd/C. The mixture is filtered through a pad of diatomaceous earth and concentrated under reduced pressure to give4-(1-methyl-pyrrolidin-3-yloxy)-phenylamine-TFA as a black solid. (4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (52 mg, 0.18 mmol) and 4-(1-methyl-pyrrolidin-3-yloxy)-phenylamine.TFA (55 mg, 0.18 mmol) were stirred in N.N-dimethylforrnamide (1 mL) and triethylamine (100 µL) at 75 °C. The reaction mixture is purified by reverse phase high performance liquid chromoatography to give (4Z)-6-bromo-4-[({4-[(1-methylpyrrolidin-3-yi)oxy]phenyl}amino)methylene]isoquinoline-1,3(2H,4H)-dione as its TFA salt. MS (ES+): 442.2, 444.2 (M+H)+ (Formula Removed) Example 878 6-Bromo-1,1 -dimethyl-4-{[4-(4-methyl-piperazin-1 -yl)-phenylamino]-methylene}-1,4- dihydro-2H-isoquinolin-3-one 6-Bromo-1,1-dimethyl-1,4-dihydro-2H-isoquinolin-3-one (210 mg, 0.83 mmol) and dimethoxymethyl-dimethyl-amine (250 mg, 2.1 mmol) in DMF (4 mL) is heated at 100 °C for 1 hour. After which the DMF is evaporated and toluene (6 mL) is added. This solution is then mixed with a solution of 4-(4-Methyl-piperazin-1-yl)-phenylamine (450 mg, 2.4 mmol) in toluene (4 mL) and the mixture is heated at reflux for 6 hours. The mixture is then allowed to cool to room temperature, upon cooling, precipitates formed. The precipitate is collected and further purified through chromatography to provide the title compound (120 mg, 31%). MS (ESI): 455.1,457.1 (M+1)+1. 1H NMR (400 MHz, CHLOROFORM-D) D ppm 1.53 (s, 6 H) 2.35 - 2.44 (m. 3 H) 2.63 (d, J=4.53 Hz, 4 H) 3.07 - 3.32 (m, 4 H) 6.90 - 6.97 (m, 2 H) 6.99 - 7.03 (m, 1 H) 7.03 - 7.09 (m, 2 H) 7.19 (dd, J=8.31, 1.76 Hz, 1 H) 7.44 (d, J=2.01 Hz. 1 H) 7.72 (d, J=12.34 Hz, 1 H) 11.26 (d, J=12.34 Hz, 1 H) Anal. (C23H27BrN4O.0.7H2O) C, H, N. Calcd: C, 59.13; H, 6.13; N, 12.00 Found: C, 59.40; H, 5.90; N, 11.91. (Formula Removed) Example 879 6-Furan-3-yl-1,1 -dimethyl-4-{[4-(4-methyl-ptperazin-1 -yl)phenylarnino]-methylene}- 1,4-dihydro-2H-isoquinolin-3-one Using the procedure described for the preparation of 4-{[4-(2-Hydroxymethyl-pyrrolidin-1-ylmethyl)-phenylamino]-methylene}-6-thiophen-3-yl-4H-isoquinoline-1,3-dione , the title compound rs obtained from 6-Bromo-4-{[4-(2-hydroxymethyl-pynrolidin-1-ylmethyl)-phenylarnino]-methylene}-4H-isoquinoline-1.3-dione (100 mg, 0.22 mmol), 3-furyl boronic acid (50 mg, 0.39 mmol) in 21% yield as a yellow solid: MS (ESI): 443.2 (M+1)+1. 1H NMR (400 MHz, DMSO-D6) D ppm 0.97 - 1.25 (m, 6 H) 1.40 (s, 4 H) 1.62 - 1.90 (m. 3 H) 2.29 (s, 1 H) 3.37 - 3.63 (m, 2 H) 4.59 - 4.96 (m, 1 H) 7.22 (d, J=7.55 Hz, 2 H) 7.55 (d, J=6.30 Hz, 2 H) 7.60 (d, J=8.31 Hz. 1 H) 7.73 (d, J=8.31 Hz, 1 H) 8.59 (s, 1 H) 8.93 ( (Formula Removed) Example 880 (4Z)-1,2-Diacetyl-4-{[(3-hydroxy-4-methoxybenzyl)amino]methy!ene}-1,4- dihydrocinnolin-3(2H)-one To a solution of (Z)-1,1,-(4-{methoxymethyIene)-3-oxo-3,4-dihydrocinnoline-1,2-diyl)diethanone (0.18 g, 0.66 mmol) in tetrahydrofuran (5 mL) is added 3-hydroxy-4-methoxybenzylamine hydrochloride (0.13 g, 0.66 mmol). The suspension is treated with triethylamine (0.21 mL) and dimethylformamide (1 mL). The mixture is stirred at room temperature until LC/MS analysis revealed the consumption of the starting materials. Following concentration under reduced pressure, the crude mixture is purified by semi-preparative reverse-phase HPLC, employing a gradient elution from 40 % acetonitrile in water with 0.1 % trifluoroacetic acid to 70 % acetonitrile in water over 60 minutes. The desired fractions were concentrated under reduced pressure to afford 0.14 g of (4Z)-1,2-diacetyl-4-{[(3-hydroxy-4-methoxybenzyl)amino]methyfene}-1 4- dihydrocinnolin-3(2H)-one. Calculated [M+H]+ = 396.15540 HRMS(ES+): 396.15482 observed Calculated [M+H]+ = 396.15540 HRMS(ES+): 396.15482 observed (Table Removed) Table 1: LCMS Data: Molecular ion and retention time (continued) (Table Removed) Standard Pharmacological Test Procedures Evaluation of representative compounds of this invention in several standard pharmacological test procedures indicated that the compounds of this invention possess significant antiproliferative activity. Based on the activity, which includes protein kinase activity, shown in the standard pharmacological test procedures, the compounds of this invention are therefore useful as antineoplastic agents. The compounds of this invention are useful in the the treatment of cancer in mammals. In particular, these compounds are useful in treating, inhibiting the growth of, or eradicating neoplasms such as those of the breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, lung, pancreas, liver, prostate and skin. The standard pharmacological test procedures and the results obtained for representative examples of the invention are shown in the following tables.BIOLOGICAL DATA CDK1. CDK2. CDK4 and CDK6 MATERIALS AND METHODS: 1. High-binding ELISA microtiter plates (Costar) were coated with 40 µl of the kinase substrate (GST fusion of C-terminal fragment of the retinoblastoma susceptibility gene product) diluted to 10 µg/ml in tris-buffered saline (TBS), overnight at 4°C. 2. Non-specific binding sites were blocked for 1 hour at 4°C with Superblock in TBS (Pierce), and the plates rinsed with water. 3. For the screen, 1.5 µl of test compound (200 µg/ml stock in 20% DMSO / 20 mM HEPES, pH 7.5) was added to each well. Final dose of the test compound in the assay was 10ug/ml. For IC50 analysis, compounds were tested at 5 doses (10-fold increments). 4. The kinase reaction (30 uJ) was dispensed into each well. Reactions contained 200 µM ATP, 0.5 mg/ml bovine serum albumin (BSA; Sigma), and 0.5 µl partially purified cyclin D1/cdk 4 enzyme*. The enzyme complex is expressed in insect cells (Sf9) infected with recombinant baculovirus and partially purified using ammonium sulfate fractionation. Reaction volumes were adjusted to 30 µl with kinase assay buffer (50 mM HEPES, pH 7.5, 10 mM MgCI 2, 5% glycerol, .10 mM 2-mercaptoethanol). *: For CDK2 assay, 1.0 uJ cyclin E/CDK2 enzyme (diluted 1:1000 in kinase assay buffer) was used. The enzyme is isolated from insect cells (Sf9) infected with recombinant baculovirus and partially purified using ammonium sulfate fractionation.. For CDK1 assay, 0.08 µl cyclin B/CDK1 enzyme [New England BioLabs; the enzyme is isolated from insect cells (Sf9) infected with recombinant baculovirus carrying human cdc 2 and human cyclin B] was used. Reference: Hunter, T. and Pines, J. Cyclins and Cancer II: Cyclin D and CDK come of age. Cell 79, 573-582 (1994). Rao, R.N. Targets for cancer therapy in the cell cycle pathway. Curr. Opinion in Oncol. 8, 516-524 (1996). 5. Plates were incubated at 30°C for 1 hour. 6. The reaction mixture was removed by aspiration and replaced with 250 µl TBS containing 0.1% Tween-20 and 5% nonfat dry milk (blocking buffer). The plates were incubated at 4° C for 1 hour. 7. The blocking buffer was removed and replaced with 50 µl of the primary antibody [anti-phospho-Rb ser 795 (New England BioLabs) diluted 1:1000 in blocking buffer]. Incubation was at 4° C for 16-20 hours. 8. The wells were rinsed 3 times with 250 µl of TBS containing 0.1% Tween-20 followed by the addition of 50 µl of secondary antibody [anti-rabbit lgG conjugated to horseradish peroxidase (Amersham Life Science) diluted 1:1000 in blocking buffer]. 9. After a 1 hour incubation at room temperature, the wells were rinsed 3 times with 250 µl of TBS/0.1% Tween 20. 10. TMB (3,3',5,5'-tetramethylbenzidine dihydrochloride) substrate solution (100 µl; Pierce) was added to each well and the color development reaction allowed to proceed 5-10 minutes at room temperature with shaking. The reaction was stopped by the addition of 2N sulfuric acid (100 µl) and the absorbance values read at 450 nm in a microplate reader (Molecular Devices). ANALYSIS OF RESULTS: 1. The percentage of the absorbance value in wells containing the test compound relative to control wells (no test agent) was determined. 2. IC50 values of selected compounds were determined from inhibition curves, after subtracting background values (no substrate).Table II: In Vitro Enzyme Assays CDK1, CDK2, CDK4 Activity (Table Removed) Table II: In Vitro Enzyme Assays CDK1, CDK2, CDK4 Activity (continued) CELLULAR ASSAY METHODS - IC50 STUDIES ON CDK 4 INHIBITORS Cell Lines: BT474, HCT-116, LoVo and MCF-7 were maintained under 7% CO2 in RPMI 1640 medium supplemented with 10% fetal bovine serum and 50‫g/ml gentamicin. Cytotoxicity Assay. Cells were plated in 96-well microliter dishes (12000cells/well for BT474, 4000cells/well for HCT-116, 6000cells/well for L0V0 and 6000cells/well for MCF-7) in RPMI 1640 medium containing 5% fetal bovine serum and 50‫g/ml gentamicin. The cells were allowed to incubate overnight at 37°C, 7% CO2. Compound dilutions were prepared using the same medium. HCT-116, LoVo and MCF-7 cells were cultured for three days and BT474 cells were cultured for 6 days, in the presence of each compound dilution. Untreated cells were included as controls. The percentage of surviving cells was determined using a protein binding dye (sulforhodamineB, SRB) assay. Cellular protein was precipitated in each well by the addition of 0.05ml of 50% cold trichloroacetic acid (TCA). After 1 hour, the plates were washed extensively in dH20 and dried. The sulforhodamineB dye solution (0.08 mL of 0.4% SRB in 1% acetic acid) was added to each well, kept at room temperature for ten minutes, then washed in 1 % acetic acid and dried. The dye was dissolved in 10mM Tris-HCI (150uL) and the absorbency read at 540nm. The concentration of compound that caused a 50% inhibition of growth (ICso) was determined. Table III: In Vitro Cellular Activity Table III: In Vitro Cellular Activity (continued) (Table Removed) CYCLIN D1/CDK6 ELISA . Cyclin D1/CDK6 was expressed in insect cells (Sf9) infected with recombinant baculovirus and partially purified using ammonium sulfate fractionation. Test compounds were diluted in 20% DMSO/20 mM HEPES, pH 7.5 and serial dilutions were prepared (5 concentrations; 0.005-50 aM). High-binding ELISA microtiter plates (Costar) were coated with the kinase substrate (glutathione¬s-transferase (GST) fusion of C-terminal fragment of the retinoblastoma susceptibility gene product (Rb). Non-specific binding sites were blocked with Superblock in Tris-buffered saline (TBS; Pierce). Kinase reactions contained the test inhibitor, 200 µM ATP, 0.5 mg/ml bovine serum albumin (BSA; Sigma), and 0.1 µl cyclin D1/cdk 6. Reaction volumes were adjusted to 30 µl with kinase assay buffer (50 mM HEPES, pH 7.5.10 mM MgCI 2, 5% glycerol, 10 mM 2-mercaptoethanol), and plates were incubated at 30°C for 1 hour. Reactions were terminated by aspiration, and non-specific sites were blocked with blocking buffer (TBS containing 0.1% Tween-20 and 5% nonfat dry milk). Phoshporylation of the substrate was detected using phospho-Rb specific antibodies (ser-795) (Cell Signalling Technologies) and anti-rabbit IgG/horseradish peroxidase conjugates (Amersham Life Science) using TMB as substrate. Colourimetric reactions were stopped with 2N sulphuric acid and the absorbance was measured at 450 nm (Molecualr Devices). IC50 values were determined from inhibition plots.Table IV: In Vitro Cellular Assays CDK 6 Activity (Table Removed) GEL KINASE ASSAY Compounds were diluted in 20% DMSO/20 mM HEPES, pH 7.5 and serial dilutions were prepared. Kinase reactions contained the test inhibitor, 200 µM ATP. 0.5 mg/ml bovine serum albumin (BSA; Sigma), 0.1-0.5 µl partially purified cyclin D1/cdk 4 enzyme and 5 ug of the substrate (GST-RB fusion protein). Reaction volumes were adjusted to 30 µl with kinase assay buffer (50 mM HEPES, pH 7.5,10 mM MgCI 2, 5% glycerol; 10 mM 2-mercaptoethanol). Reactions were incubated at 30°C for 30 minutes, stopped with sodium-dodecyl sulphate (SDS)-sample buffer, and analysed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and protern immunobloting. Phosphorylation of the substrate was detected using phospho-Rb-specific antibodies (ser-795), and anti rabbit IgG/HRP conjugates using enhanced luminescence (ECL, Amersham). Blots were scanned and quantified using the FluorS multiimage analyser (BioRad). IC50swere determined from inhibition plots (Kaleidagraph). RB PHOSPHORYLATION IN CELLS MCF-7 cells were treated overnight with various concentrations of the compounds. Cell lysates were prepared in lysis buffer (250 mM Tris, pH 7.5, 150 mM sodium chloride, 1% Nonidet P-40, 0.5% sodium deoxycholate, 2 mM phenylmethylsulfonyl fluoride, 100 mM sodium fluoride, 1 mM sodium vanadate, 5 mM DTT). Lysates were fractionated by SDS-PAGE and transferred to nitrocellulose. Phosphorylation of Rb was detected using phospho-RB specific antibodies (Ser-807/811) and anti rabbit IgG/HRP conjugates using enhanced luminescence (ECL, Amersham). Blots were scanned and quantified using the FluorS multiimage analyser (BioRad). IC50s were determined from inhibition plots (Kaleidagraph). Table V: Soluti on Assay (Table Removed) What is claimed is: 1. A compound having the Formula (I) (Formula Removed) or a pharmaceutically acceptable salt thereof, A1 is CO, C(S), NCOR100, NH, or C(R1)(R2): A2 is H, OH, CH2OH, C1-6 alkyl, alkoxy, benzyloxy, arylalkyl, benzyl, aryl. acyl, -C(O)R, -OC(O)O-PEG. -CH2OC(O)O-PEG, -OC(O)NH-PEG, -CH2OC(O)NH-PEG, OC(O)OH, CH2O(C(O)OH, OC(O)halogen, CH2OC(O)halogen, OC(O)CH2halogen, OC(O)CH2S(CH2)mO-PEG wherein the aryl or benzyl is optionally substituted with PEG is -(OCH2CH2)rOCH3; Y1 is CR3 or N, provided that when Y1 is N, then Y2 is NR,; Y2 is NR,, N(R1)N(R1), NHC(O) or NHNHC(O); L1 is C(R7)(R8); R1 and R2are each independently H, C-1-6 alkyl, aryl, or benzyl, or R1 and R2when taken together with the carbon atom to which they are attached form a 3-6 membered spirocyclic ring; R is C1-6 alkyl, aryl, or pyndyl; Ra is H, aryl, C1-6 alkyl, OR1 NR10R11 or -O-, provided that when R3 is OR or -NR10R11, that e and f are 0 when Z is H; R4, is selected from the group consisting of H, aryl, or C1-6 alkyl, halogen, -CN, -OCF3, -NO2. -COOH, -CF3, OH. SH, N3. -C(O)H, heteroaryl, C1-6alkoxy, heterocycloalkyl, C2-6 alkenyl, C2-6 alkynyl, -COR100, -Oaryl, -OR100, -NHaryl, -S(O)mR100, -C(O)Q, C(O)OR100, -NR100aryl. -OR100arylp -SR10oaryl, - NHR102OH, -NHR102OR100, -NHR102NHR100, -NR100R102OH, -NHR102Q, -NR100R102NH2. -NR100R102NHR100. -NR100R102OR100, -NR100R102Q. -OR102OH, -OR102OR100. -OR102NH2, -OR102NHR100, -OR102Q, -OCOR100, -OR100COR100, -NHCOR100, -NHCONH2, -NHCONHR100. -NHR100COR100, -NHR102NH2, -NHOH, -NHOR100, -CONR10R11, -NHSO2R100, NR10,R11. -NHC(O)-heteroaryl,-NHC(O)R102-heteroaryl, OC(O)CH2halogen, -OC(O)CH2S(CH).,0-PEG, OC(O)NH-PEG, -N(R10)(R11). -NHC(O)R102-aryl, and -NHG(O)NH-heterocycloalkyl that is optionally substituted with up to three C1-3 alkyl groups; wherein said aryl, said heteroaryl, and said heterocycloalkyl are each optionally substituted with up to four independently selected R12 groups; wherein said C2-6 alkenyl, said C1-6 alkyl, C1-6alkoxy, and said C2-6 alkynyl are each optionally substituted with up to three independently selected R13 groups; R5 is selected from the group consisting of C1-6 alkyl or alkenyl, wherein the alkyl or alkenyl are optionally substituted with OH, OR1 NR10R11. C1-6 alkyl; R7 and R8 are selected from the group consisting of H, H alkyl, OR100, OH, C(O)H or COOH; R10 and R11 are selected from the group consisting of H, C1-6 alkyl, C2-6alkenyl, C1-6 acyl, -S(O)2aryl, -C(O)C2-6 alkenyl, C2-6 alkynyl, aryl or heteroaryl, wherein said C1-6 alkyl is optionally substituted with up to three halogen atoms, wherein said aryl and said heteroaryl are optionally substituted with up to three R12 groups, wherein R10 and R11 may be taken together with the N to which they are attached to form a 3-8 membered heterocylic ring, wherein said heterocyclic ring may contain additional atoms selected from the group N, O, and -SCO),,, and said heterocyclic ring may be additionally substituted with 1 to 4 substjtuents selected from the group consisting of C1-6alkyl. OH, -OC1-6alkyl, -OC3-6cycloalkyl, -(CH2)nOH, -{CH2)nOC1-6alkyl, -(CH2)nOC3-Bcycloalkyl, -NR10R11. -(CH2)R11R10R11, and =0; R12 is independently selected from the group consisting of aryloxy, halogen, OH, -COOH, -C(O)H, -C(O)R1 -C13 perhaloalkyl, -OCF3, C1-6 acyl, -CN, -NO2, aryl, heteroaryl, -S-C1-6 alkyl, -NHCOC1-6alkyl, -N(R15)(R16), C1-3 perhaloalkoxy, C1-6 alkyl, C2-6 alkenyl, -CONH2, -CF3, SH, N3, heterocycloalkyl, -C(O)R100, -OR100, -NHaryl, -S(O)R100 -C(O)Q, C(O)OR100, -C(O)NHR100, -NR100aryl, -N(R100) R102aryl, - OR102aryl, - SR102aryl, -NHS(O)2-R100, - NHR102OH, -NHR102OR100, -NHR102NHR100, -N(R100)R102OH, -NHR102Q, -N{R100)R102NH2. -N(R100)R102NHR100. -N(R100)R102OR100. -N(R100)R102Q. -OR102OH, -OR102R100. -OR102NH2, -OR102NHR100, -OR102Q. -OC(O)R100, - OR102C(O)R100, -NHC(O)R100, -NHCONH2, -NHCONHR100, - NHR102C(O)R100. -NHR102NH2, -NHS(O)2-aryl, -NHOH, -NHC(O)aryl, -NHOR100, -NHC(O)-heteroaryl, -NHC(O)R102-heteroaryl, -C(O)N(R10)(R11), -N(R10)(R11), NHC(O)R102aryl, and NHC(O)NH-heterocycloalkyl that is optionally substituted with up to three C1-3 alkyl groups, wherein said C2-6 alkenyl, said C1-6 alkyl, and said C2-6 alkynyl are each optionally substituted with up to three independently selected R13 groups and -N(R15)(R16); R13 is independently selected from the group consisting of arylalkyl, aryl, heteroaryl, C1-6 alkyl, C3-6 cycloalkyt, heterocycle, heterocycloalkyl, heterocyctoalkyloxy, CN, OH, C1-6 alkoxy, halogen and -COOH. -SH, -COH, -COR100, -CONH2, -CONHR100, -COQ, -OCOR100, -OCONH2, -OCONHR100, -OCOQ, -OR102OH, -OR102NR15R18. and (Formula Removed) wherein said aryl, heteroaryl, and heterocycloalkyl are optionally substituted with up to three independently selected R18 groups; R15 and R16 are selected from the group consisting of H, C1-6 alkyl, and C1-6 acyl; and wherein said R15 and R16 groups taken together with the nitrogen to which they are attached may form a heterocylic ring of 3 to 8 atoms with 1 or 2 additional heteroatoms selected from the group N, O, and -S(O)m, the heterocyclic ring may be substituted with groups consisting of OH, -OCMcycloalkyl, -OC alkyl, -(CH2)nOH, -(CH2)OC1-6alkyl, -NR10R11, -(CH2)nNR10R11 and -(CH2)nOC3-6cycloalkyl; R16 is independently selected from the group consisting of OH, halogen, -NO2, dialkylamino, -N(R16)(R16), -COOH, -S(O)2NH2. C1-3 perhaloalkyl, -OCF3, C1-3 alkoxy, C^ alkyl, CN, C1-8 cyanoalkyl and C4-8 cycloalkenyl, wherein said cycloalkenyl is optionally substituted with up to three groups independently selected from OH and C1-3 alkoxy, and wherein said C1-6 alkyl is optionally substituted with -N(R15)(R18); R20 is selected from the group consisting of C1-6 alkyl, C3-6 cycloalkyl and C2-6 alkenyl, wherein said C1-6 alkyl is optionally substituted with up to three halogen atoms or a group of formula —{(CH2)(Q")]kCH3; R21 is selected from the group consisting of C1-6alkyl and cycloalkyl; R22 is selected from the group consisting of heteroaryl, aryi, arylalkyl and C1-6 alkyl, wherein said C1-6 alkyl is optionally substituted up to three halogen atoms; R23 is selected from the group consisting of aryl, heteroaryl and C1-6 alkyl, wherein said aryl and said heteroaryl is optionally substituted with up to three C1-3 alkyl groups, and said C1-6 alkyl is optionally substituted with up to three halogen atoms; R24 is selected from the group consisting of H, -COOH, C3-6 cycloalkyl, -OCHF2, -OCHCI2, C1-3 perhaloalkyl, C1-6 alkoxy, heteroaryl, heterocycloalkyl, C2-6 alkynyl, C1-6 alkyl, C2-6 alkenyl, and aryl, wherein said C1-6 alkyl is optionally substituted with up to three groups independently selected from halogen and C3-6 cycloalkyl, said C2-6 alkenyl optionally substituted with up to three groups independently selected from halogen and N(R27)(R28), said aryl is optionally substituted with up to three OH groups, and said heterocycloalkyl is optionally substituted with up to three independently selected C1-6 alkyl groups, -{CH2)mcycloalkyl, -(CH2)nOH, -(CH2)nOR, -(CH)2NR10R11, -COR5, and Q; R25 is OH, oR11R10R11; R27 and R28 are independently selected from the group consisting of C1-6 alkyl, C3-6 cycloalkyl, heterocycloalkyl, C2-6 alkenyl, H, aryl, Q, -C(O) C3-6alkyl(cycloalkyl), -COalkyt, -COalkenyl, -COalkynyl, -COaryl, -COheteroaryl, -COcycloalkyt, C1-6 acyl, -C(O)C(O)OH, halogen, -COC1-6halogen, C1-3alkoxy, and arylalkyi, wherein said C1-6 alkyl, aryl, acyl, and heterocycloalkyl are optionally substituted with up to three R52 groups; or R27 and R28 together with the nitrogen atom to which they are attached can form a 5 or 6 membered saturated heterocyclic ring that can include one additional O, N, or S ring atom, said saturated heterocyclic ring optionally substituted with a carboxylate or C1-3 alkyl groups; R31 is selected from the group consisting of trialkylsilyl. C1-6 alkoxycarbonyl, C1-6 alkyl, C2-6 alkenyl, heteroarylalkyi, heterocycloalkyl and arylalkyi, wherein said C1-6 alkyl, said arylalkyi and said heteroarylalkyi are each optionally substituted with up to three independently selected R53 groups, and said heterocycloalkyl is optionally substituted with up to three C1-6 alkyl groups; R32 is selected from the group consisting of H, C1-6 acyl, heteroaryl and C1-6 alkyl, wherein said heteroaryl is optionally substituted with up to three C1-3 alkyl groups, and said C1-6 alkyl is optionally substituted with up to three heteroaryl or R52 groups; R33 is selected from the group consisting of heterocycloalkyl, aryl, C1-3 perhaloalkyl, -N(R27)(R28) and C1-6 alkyl, wherein said aryl. C1-6 alkyl, heterocycloalkyl, are optionally substituted with up to three groups selected from halogen, C1-6 alkyl, aryl, OH and -N(R27)(R28); R34 is selected from the group consisting of aryloxy, C1-8 alkyl, aryl and alkoxy. wherein said aryl is optionally substituted with COOH, and said alkoxy is optionally substituted with -N(R27)(R28); R35 is selected from the group consisting of dialkylamino, or C1-6 alkyt that is optionally substituted with -COOH or with -N(R27)(R28); R41 is selected from the group consisting of -R100, -R102R100, -R102OR100, -R102OH, and -R102Q; R50 is selected from the group consisting of heterocycloalkyi, (N=H), NH2, -NHCOC1-3 alkyl, C1-3 alkyl, -NHCOC1-3 cycloalkyi, -NHCOC1-3 heterocycloalkyi, -OH, -CN, -COOH, -N(R27)(R28), -S02N(R27)(R28), halogen, heteroaryl and ary), wherein said aryl, heteroaryl, or heterocycloalkyi are optionally substituted with a group selected from C1.3 alkyl, C(O)H, C1-4 alkoxy. and -CONHN(R21)2, and up to three groups selected from halogen, and NH2; R52 is independently selected from the group consisting of COH, OH, CN, NH2, -NHR21, -N(R21)2, C1-8 alkyl, aryl, -COaryl, heterocycloalkyi, halogen, C1-3 perhaloalkyl, and -C3-6, cycloalkyi, wherein the aryl can be substituted with COOH; R53 is selected from the group consisting of OH, C1-6 alkyl, arylalkyloxy, heterocycloalkyi, C1-3 alkoxy, halogen and C3-6 cycloalkyi; R100 is selected from the group consisting of C1-12alkyl, C3-6 cycloalkyi aryl, heteroaryl, C2-6alkenyl, and C2-6alkynyl; R102 is a divalent C1-6alkyl, R200 is selected from the group consisting of-(CR201 R201)qR203. -N(R201)C(O)(CH2)qR203, N(R201)q(R203 and -IMHC(O)NH-R203; R201 is selected from the group consisting of H and C1-6 alkyl; R203 is selected from the group consisting of dialkylamino and a 5-7 membered heterocycloalkyi ring having up to three ring hetero atoms selected from O, N and S, said heterocycloalkyi ring being optionally substituted with up to three independently selected R204 groups; R204 is selected from the group consisting of OH, COOH, C1-6 alkyl, alkoxycarbonyl, arylalkyl, heteroaryiaikyl, C2-6 alkenyl, C3-6 cycloalkyl, aryl, C1-6 alkoxy, C2-6 acyl, heterocycloalkyl, -C(O)N(R300)(R300), -NHC(O)R300, -N(R201)(R201). and -NHC(=0)N(R201)(R201). wherein said C1-6 alkyl is optionally substituted with up to three independently selected R207 groups, wherein said arylalkyl and said heteroaryiaikyl are each optionally substituted with up to three independently selected R206 groups, wherein said C2-6 acyl may optionally contain one double bond, and may optionally be substituted with -NR10R11. wherein said heterocycloalkyl is optionally substituted with up to three independently selected C1-6 alkyl groups; R206 is independently C1-6 alkyl or C(O)NH2; R207 is independently selected from the group consisting of CN, heterocycloalkyl, CM alkoxy, OH, N(R27)(R28) and C3-6 cycloalkyl; R209 is R211. R212C=C-, or (R212)2C=C(R212) ; R210 is C1-6 alkyl, or C1-6 alkoxy; R211 is aryl and heteroaryl wherein said aryl and said heteroaryl, are each optionally substituted with up to four independently selected R12 groups; R212 is C1-6 alkyl, aryl, and heteroaryl, wherein said C1-6 alkyl is optionally substituted with up to three independently selected R13 groups wherein said aryl and said heteroaryl, are each optionally substituted with up to four independently selected R12 groups; R214 is R41, or R211", R300 is selected from the group consisting of H, C1-3 alkoxy and C1-6 alkyl wherein said C1-6 alkyl is optionally substituted with a dialkylamino group; e is 0 or 1 provided that when R3 is OR or NRR then e is 0, f is 0-5; k'is 1-6; m fs 0, 1, or 2; n is 1-4; q is 1-3; r is 2-1800; v is 1 or 2; G1, G2, G3 and G4 are each independently selected from the group consisting of H, halogen, -CN, -OCF3, -NO2, -COOH, -CONH2, -CF3, OH, SH, N3, -C(O)H, heteroaryl, C1-6alkoxy, heterocyctoalkyi, aryl, C3cycioalkyl, C1-12 alkyl, C2-6 alkenyl, C2-6 alkynyl, -COR100, -OC3-10cyc!oalkyl, -Oaryl, -OR100, R209 R211. Q, -OS(O)2NH2, OS(O)2R22, -S(O)mR100. -C(O)Q. C(O)OR100, -NHR100, -NR100aryl, -OR102aryl, -SR102aryl, - NHR102OH, -NHR102OR100, -NHR102NHR100. -NR100R102OH, -NHR102Q, -NR100R102NH2 -NR100R102NHR100.-NR100R102OR100. -NR100R0102Q. -OR102OH, -OR102R100, -OR102NH2, -OR102NHR100, -OR102Q, -OCOR100, -OR102COR100, -NHCOR100. -NHCONH2, -NHCONHR100, -NHR102COR100. -NHR102NH2, -NHOH,-NHOR100, -CONR10R11, -NHSO2R100, -NHC(O)-heteroaryl, -NHC(O)R102-heteroaryl, OC(O)CH2halogen, OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG, NHC(O)R102-aryl, and NHC(O)NH-heterocycloalkyl optionally substituted with up to three C1-3 alkyl groups; wherein said aryl, said heteroaryl, and said heterocycfoalkyl are each optionally substituted with up to four independently selected R12 groups; wherein said C2-6 alkenyl, said C1-6 alkyl, C1-6alkoxy, and said C2-6 alkynyl are each optionally substituted with up to three independently selected R13 groups; Q is —NR100R100 optionally the R100 groups taken together with the nitrogen to which they are attached form a heterocylic ring of 3 to 8 atoms with 1 or 2 additional heteroatoms selected from the group N, O, and S, said heterocydic ring may optionally be substituted with groups consisting of OH, OC1-6 alkyl, (CH2)nOH, (CH2)nOC1-6alkyl, NR10R11 (CH2)nNR10R11, and C1-6 alkyl; Q" is selected from the group consisting of O, S, and NH; Z may be absent or is selected from the group consisting of H, aryl, heteroaryl, cycloalkyl, dialkylamino, COOH, heterocyde, pyridone, C1-12 alkyl, wherein said alkyl is optionally substituted with up to 3 groups selected from an OH group, Q, NHQ, COOH, and a 5-10 member heteroaryl ring system having one or two rings with up to four ring heteroatoms independently selected from O, N and S, wherein said aryl, said pyridone, said cycloalkyl, said heteroaryl, and said heterocyde are each optionally substituted with up to ftve substituents independently selected from the group consisting of R210 R41. R209. R211, R214, OR41, (=0), OH, COOR100, C1-6 alkyl, C1-6 alkoxy. C1-3 perhaloalkyl, halogen, C1-3 perhaloalkoxy, (=NH), NH2,-NO2, C(O)H, -C(O)OH,-C(O)NH2, CN, Q, heterocyde, heteroaryl, S-C1-3 alkyl, S-C1 3 perhaloalkyl, S-heteroaryl, aryl, C2-8 alkynyl, C(NH)NH2, heterocydoalkyl, C2-6 alkenyl, - O-C(O)-R20. -O-C(O)OR21, -NHS(O)R22. -R102NHS(O)2R23, -NHC(O)R24, R102NHC(O)R24, -NHC(O)(CH2)mR25, -CH2N(R27)(R2a), -OC(O)N(R27)(R28), -N(R27)(R28), - OR31, -S(O)2NHR32, -S(O)2R33, -C(O)R34. -CH2C(O)OH, -C(O)NHR35, R200, - CH2NHS(O)2R21, OC(O)CH2halogen, OC(O)R100 -OC(O)CH2S(CH2)mO-PEG, - OC(O)NH-PEG, H, -CN, -OCF3. -CF3, SH, N3, -C(O)H, -COR100, -OR100. -Saryl, -C(O)Q, C(O)OR100. -C(O)NHR100, -NR100aryl, -OR102aryl, -SR102aryl, -NHSC(O)R100, - NHR102OH, -NHR102OR100, -NHR102NHR100, -NR100R102OH. -NHR102Q, -NR100R102NH2, NR100R102NHR100. -NR100R1D2OR100, -NR100R102Q, -OR102OH, -OR102OR100. -OR102NH2, - OR102NHR100, -OR102Q, -OCOR100. -OR102COR102OR102COR1o0, OR1o2COR102OR102OR100. -NHCOR100, -NHCONH2, -NHCONHR100, -NHR102COR100. -NHR102NH2, -NHS(O)2-aryl, -NHOH, -NHC(O)aryl, - -NHOR100, -NHC(O)-heteroaryl, - NHC(O)R102-het.eroaryl, OC(O)CH2halogen, OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG. OS(O)2NH2, OS(O)2R22, -N(R10)(R11). NHC(O)R102-aryl, and NHC(O)NH-heterocycle that is optionally substituted with up to three C1-3 alkyl groups, wherein said C2-6 alkenyl, said C1-6 alkyl, and said C2-6 alkynyl are each optionally substituted with up to three independently selected R13 groups, wherein said C1-8 alkyl. said -S-C1-6 alkyl, and C1-6 alkoxy are each optionally substituted with up to three independently selected R50, groups, wherein said aryl is optionally substituted with up to three groups independently selected from OH and NH2, wherein said heteroaryl and said S-heteroaryl, heterocycle, and said heterocycloalkyi, are each optionally substituted with up to three independently selected R51 groups, wherein said C2-6 alkenyl is optionally substituted with COOH, wherein any two adjacent carbon atoms of said aryl, heteroaryl or heterocycloalkyi can optionally be joined together by a group of the formula -OC(Ra)(Rb)-O- wherein Ra and Rb are independently H, C1-3 alkyl, phenyl or alkoxycarbonyl; and C1-3 alkoxy and C1-3 perhaloalkyi, wherein said aryl can be substituted with COOH. 2 The compound according to claim 1, wherein A1 is CO or C(R1 )(R2) or a pharmaceutical salt thereof. 3. The compound of claim 1, wherein e is 1, f is 0, Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two nngs, and having up to four ringiheteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of -CH2N(R27)(R2B). -NHR102NHR100. -NHR102Q, -NR100R102NH2. -NR100R102NHR100, -NR100R102Q, -OR102NH2, -OR102NHR10D, -OR102Q. and -NHR102NH2; or a pharmaceutically acceptable salt thereof. 4. The compound of claim 1, wherein e is 1; f is 0; A1 is C=O; A2 is H; Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of aryl. heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of -CH2N(R27)(R28), -NHR102NHR100. -NHR102Q. -NR100R102NH2, -NR100R102NHR100. -NR100R102Q, -OR102NH2, -OR102NHR100l -OR102Q, and -NHR102NH2; or a pharmaceutically acceptable salt thereof. 5. The compound of claim 1, wherein e is 1; f is 0; A1 is CH2; A2 is H; Y1 is CR3; Y2isNR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two rings, having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryt, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of-CH2N(R27)(R28), -NHR102NHR10o, -NHR102Q, -NR100R102NH2, -NR100R102NHR100. -NR100R102Q, -OR102NH2, -OR102NHR100, -OR102Q. and -NHR102NH2; or a pharmaceutically acceptable salt thereof. 6. The compound of claim 1, wherein e is 1; f is O; A1 is CR1R2; A2 is H; Y1 is CR3; Y2is NR1 Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two rings, having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of -CH2N(R27)(R28), -NHR102NHR100, -NHR102Q, -NR100R102NH2, -NR100R102NHR100. -NR100R100Q102 -OR102NH2. -OR102NHR100, -OR102Q, and -NHR102NH2; or a pharmaceutically acceptable salt thereof. 7. The compound according to claims 3-6, wherein Z is selected from a six membered aryl, heteroaryl or heterocyclic ring and further providing that the independently selected substituent on Z is at the para position of said six membered ring; or a pharmaceutically acceptable salt thereof. 8. The compound according to claim 1 wherein: e is 1 Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of aryl, heteroaryl, bicydic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two rings, having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, S-C1-3 alkyl, C2-6 alkynyl, and C2-6 alkenyl wherein said alkyl is substituted with OR102NR15R19, NH2 or N(R27)(R28). alkenyl and alkynyl are substituted with OR102NR15R16and wherein said S-alkyl and alkoxy are substituted with NH2 or N(R27)(R28). or a pharmaceutically acceptable salt thereof. 9 The compound according to claim 1, wherein e is 1; A1 is 0=0; A2 is H; Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicychic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, S-C1-3 alkyl, C2-6 alkynyl, and C2-6 alkenyl wherein said alkyl is substituted with -OR102NR15R16. NH2 or -N(R27)(R28), alkenyl and alkynyi are substituted with -OR102NR15R16and wherein said S-alkyl and alkoxy are substituted with NH2 or -N(R27R28). or a pharmaceutically acceptable salt thereof. 10. The compound according to claim 1, wherein e is 1; A1 is CH2; A2 is H; Y' is CR3; Y2isNR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl. said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, S-C1-6 alkyl, C2-6 alkynyi, and C2-6 alkenyl wherein said alkyl is substituted with -OR102NR15R16 NH2 or -N(R27)(R28), alkenyl and alkynyi are substituted with -OR102NR15R16and wherein said S-alkyl and alkoxy are substituted with NH2 or -N(R27)(R28). or a pharmaceutically acceptable salt thereof. 11. The compound according to claim 1, wherein e is 1; A1 is CR1R2; A2 is H; Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic heteroaryl, heterocycle, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, said bicyclic heteroaryl, and said heterocycle are each optionally substituted with up to five substituents independently selected from the group consisting of C1-6 alkyl, C1-6alkoxy, S-C1-3 alkyl, C2-6 alkynyl, and C2-6 alkenyl wherein said alkyl is substituted with OR102NR15R16. NH2 or N(R27)(R28), alkenyl and alkynyl are substituted with OR102NR15R16and wherein, said S-alkyl and alkoxy are substituted with NH2 or N(R27)(R28). or a pharmaceutical^ acceptable salt thereof. 12. The compound according to claim 1, wherein e is 1; f is 0; Y1 is N; Y2 is NR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, bicyclic and heteroaryl, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, and said bicyclic heteroaryl, are each optionally substituted with up to five substituents independently selected from the group consisting of-CH2N(R27)(R28), -NHR102NHR100. -NHR102Q, -NR100R102NH2, -NR100R102NHR100. -NR100R102Q, -OR102NH2, -OR102NHR100. -OR102Q. and -NHR102NH2; or a pharmaoeutically acceptable salt thereof. 13. The compound according to claim 1, wherein e is 1; f is0; A1 is C=O; A2 is H; Y' isN; Y2 is NR1; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, and bicyclic heteroaryl, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl, and said bicyclic heteroaryl, are each optionally substituted with up to five substituents independently selected from the group consisting of -NHR102NHR100. -NHR102Q, -NR100R102NH2. -NR100R102NHR100, -NR100R102Q, -OR102NH2, -OR102NHR100, -OR102Q, and -NHR102NH2; or a pharmaceutically acceptable salt thereof. 14. The compound according to claim 1, wherein e is 1, f is0; A1 is CH2; A2 is H; Y1 is N; Y2 is NR-,; Z is selected from the group consisting of aryl, heteroaryl, bicyclic aryl, and bicyclic heteroaryl, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicyclic aryl. and said bicyclic heteroaryl, are each optionally substituted with up to five substituents independently selected from the group consisting of -NHR102NHR100 -NHR102Q, -NR100R102NH2. -NR100R102NHR100. -NR100R102Q. -OR102NH2, -OR102NHR100, -OR102Q, and -NHR102NH2; or a pharmaceutically acceptable salt thereof. 15. The compound according to claim 1, wherein: e is 1, f is 0; A1 is CR1,R2; A2 is H; Y1 is N; Y2 is NR1 Z is selected from the group consisting of aryl, heteroaryl, bicydic aryl, and bicydic heteroaryl, and a 5-10 member heteroaryl ring system having one or two rings, and having up to four ring heteroatoms selected from O, N and S, wherein said aryl, said heteroaryl, said bicydic aryl, and said bicydic heteroaryl, are each optionally substituted with up to five substituents independently selected from the group consisting of -NHR102NHR100. -NHR102Q, -NR100R102NH2. -NR100R102NHR100. -NR100R102Q, -OR102NH2, -OR102NHR100, -OR102Q, and -NHR102NH2; or a pharmaceutically acceptable salt thereof. 16. The compound of daim 1, wherein e is 1; f is 0; Y1isCR3; Y2 is NR1; Z is selected from the group consisting of aryl, or heteroaryl wherein said aryl, and said heteroaryl, are each optionally substituted with up to three substituents independently selected from the group consisting of R210, R41, R209. R211. R214, OR41. OH, C1-6 alkyl, C1-6 alkoxy. C1-6 perhaloalkyl, halogen, C1-3perhaloalkoxy, NH2, Q, heterocycle, heteroaryl, S-C1-6 alkyl. S-C„ perhaloalkyl, S-heteroaryl, aryl, -O-(O-R20 -NHC(O)R24 -NHC(O)(CH2)mR25 -OC(O)N(R27)(R28), -N(R27)(R28. -OR31, R200, OC(O)R100, -OC(O)CH2S(CH2)mO-PEG, -0C(O)NH-PEG, -OCF3, -CF3, SH, -OR100, -Saryl, NR100aryl, -OR102aryl, -SR102aryl, -NHR102OH, - NHRl02OR100. -NR100R102OH, -NHR102Q, -NR100R1020R100- -NR100R102Q, -OR102OH. -OR102OR100. -OR102Q, -OCOR100, OR1o2COR102OR102OR100. -NHC(O)aryl, -NHC(O)-heteroaryl, -NHC(O)R102-heteroaryl, OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG. -N(R10)(R11), and NHC(O)R102-aryl, or a pharmaceutically acceptable salt thereof. 17. The compound of claim 1, wherein e is 1; f is 0; A' is C=0; A2 is H; Y1 is CR3; Y2 is NRi; Z is selected from the group consisting of aryl, or heteroaryl wherein said aryl, and said heteroaryl, are each optionally substituted with up to three substituents independently selected from the group consisting of R210, R41, R209, R211, R214, OR41OH, C1-6 alkyl, C1-6 alkoxy, C1-3 perhaloalkyl, halogen, C1-5perhaloalkoxy, NH2. Q. heterocycle, heteroaryl, S-C1-3 alkyl, S-C1-3 pemaldalkyl, S-heteroaryl, aryl, -O-C(O)R20, -NHC(O)R24, -NHC(O)(CH2)mR25, -OC(O)N(R27){R23), -N(R27)(R28). -OR31, R200. OC(O)R100. -OC(O)CH2S(CH2)mO-PEG. -OC(O)NH-PEG, -OCF3, -CF3, SH. -OR100. -Saryl. NR100aryl, -OR102aryl, -SR102aryl, -NHR102OH, - NHR102OR100. -NR100R102OH, -NHR102Q, -NR100R102OR100, -NR100R102Q, -OR102OH, -OR102OR100, -OR102Q, -OCOR100. OR1o2COR1o20R1o2OR100, -NHC(O)aryl, -NHC(O)-heteroaryl, -NHC(O)R102-heteroaryl, OC(O)CH2S(CH)mO-PEG. OC(O)NH-PEG, -N(R10)(Ri,). and NHC(O)R102-aryl, or a pharmaceutically acceptable salt thereof. 18. The compound of claim 1, wherein e is 1; f is0; A1 is CH2; A2 is H; Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of aryl, or heteroaryl wherein said aryl, and said heteroaryl, are each optionally substituted with up to three substrtuents independently selected from the group consisting of R210, R41, R209. R211, R214, OR41, OH, C1-6 alkyl, C1-6 alkoxy, C1-3 perfialoalkyl, halogen, C1-6 perhaloalkoxy, NH2, Q, heterocycle, heteroaryl, S-C,_3 alkyl, S-CM perhaloalkyl, S-heteroaryl, aryl, -O-C(O)-R20, -NHC(O)R24, -NHC(OXCH2)mR2s, -OCiOWRzrXRv), -N(R27)(R28), -OR3„ RKK,. OC(O)R100, -0C(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -CF3, SH, -OR100, -Saryl, NR100aryl, -OR102aryl, -SR102aryl, -NHR102OH, - NHR102OR100, -NR100R102OH, -NHR102Q, -NR100RlO2OR100, -NR^R-^Q. -OR102OH, -OR102OR1c.o, -OR102Q, -OCOR100, OR102CORlo20R102OR100, -NHC(O)aryl, -NHC(O)-heteroaryl, -NHC(O)R102-heteroaryl, OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG, -N(R1DKR)i), and NHC{O)R102-aryl, or a pharmaceutical^ acceptable salt thereof. 19. The compound of claim 1, wherein e is 1; f isO; A1 is CR1R2, A2 is H; Y1 is CR3; Y2is NR1; 2 is selected from the group consisting of aryl, or heteroaryl wherein said aryl, and said heteroaryl, are each optionally substituted with up to three substituents independently selected from the group consisting of R210 R41 R209, R211, R214, OR41, OH, C1-6 alkyl, C1-6 alkoxy, C1-3 perhaloalkyl, halogen, C1-3 perhaloalkoxy, NH2, Q, heterocycle, heteroaryl, S-C1-3 alkyl, S-C1-3 perhaloalkyl, S-heteroaryl, aryl, -O-CCOJ-RJO. -NHC(O)R24, -NHC(O)(CH2)raR25, -OC(O)N(R27)(R28), -{R27)(R28), -OR31, R200, OC(O)R100, -OC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -CF3, SH. -OR100, -Saryl, NR100aryl, -OR102aryi, -SR102aryl, -NHR102OH, - NHR102OR100, -NR100R102OH, -NHR102Q. -NR100R1020R100, -NR100R102Q, -OR102OH, -OR102OR100, -OR102Q, -OCOR100, OR102COR102OR1020R100, -NHC(O)aryl, -NHC(O)heteroaryl, -NHC(O)R102-heteroaryt, OC(O)CH2S(CH)mO-PEG, 0C(O)NH-PEG, -N(R10)(R11). and NHC(O)R102-aryl, or a pharmaceuticaily acceptable salt thereof. 20. The compound according to claims 18-21 wherein Z is selected from moieties of the formulae (Formula Removed) optionally substituted with up to 3 independently selected substituents: or a pharmaceutically acceptable salt thereof. 21. The compound of claim 1, wherein e is 1; f is 1, Y1 is CR3; Y2 is NR1; Z is selected from a moiety of the formula (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R11, R211, R214, C1-6 alkyl, C1-3 perhaloalkyl, heterocycle, heteroaryl, aryl, and heterocycloalkyl or a pharmaceutically acceptable salt thereof. 22. The compound of claim 1, wherein e is 1; fis 1; A1 is C=0; A2 is H; Y' isCR3; Y^isNR1; Z is selected from 3 moiety of the formula (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R41 R211, R214, C1-6 alkyl, C1-3 perhaloalkyl, heterocycle, heteroaryl, aryl, and heterocycloalkyl or a pharmaceutically acceptable salt thereof. 23. The compound of claim 1, wherein e is 1; f is 1; A1 is CH2; A2 is H; Y1 is CR3; Y2is NR1; Z is selected from a moiety of the formula (Formula Removed) wherein said Z is optbnally substituted with a substituent selected from the group consisting of R41, R211, R214. C1-6 alkyl, C1-3 perfialoalkyl, heterocycle, heteroaryl, aryl, and heterocydoalkyl or a pharmaceutically acceptable salt thereof. 24 The compound of claim 1, wherein e is 1; f is 1; A1 is CR1R2; A2 is H; Y1 is CR3; Y2 is NR1; Z is selected from a moiety of the formula (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R210, R41. R211, R214, C1-6 alkyl, C1-3 perhaloalkyl, heterocycle, heteroaryl, aryl, and heterocycloalkyl or a pharmaceutically acceptable salt thereof. 25. The compound of claim 1, wherein e is 1; f is 1 ; Y1 isCR3; Y2isNR1; Z is selected from the group consisting of R201-- (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R211, OR41 OH, C1-6 alkoxy. C1-6 perhaloalkoxy, heteroaryl, S-C,1-3 alkyl, S-C,1-3 perhaloalkyl, S-heteroaryl, aryl, -O-C(O)-R20, -0-C(O)OR21. OC(O)N(R27)(R28). -OR3i, OC(O)R100) -OC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -OR100, -Saryl, - OR102aryl, -SR102aryl, -OR102OH, -OR102OR100, -OR102Q, -OCOR100. OR102COR102OR102OR100. OC(O)CH2S(CH)mO-PEG. and OC(O)NH-PEG, or a pharmaceutically acceptable salt thereof. 26. The compound of claim 1, wherein e is 1; f is 1; A1 is C=0; A2 is H; Y1 isCR3; Y^ is NR1; Z is selected from the group consisting of(Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R211. OR41 OH, C1-6 alkoxy, C1-6 perhaloalkoxy, heteroaryl, S-C1-3 alkyl, S-C1-3 perhaloalkyi, S-heteroaryl, aryl, -O-C(O)-R20. -0-C(O)OR21, OC(O)NCR27)(R), -OR31, OC(O)R100. -OC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3. -OR100, -Saryl, - OR102aryl, -SR102aryl, -OR102OH, -OR102OR100 -OR102Q, -OCOR100, OR102COR102OR102OR100, OC(O)CH2S(CH)mO-PEG, and 0C(O)NH-PEG, or a pharmaceutically acceptable salt thereof. 7. The compound of claim 1, wherein e is 1; f is 1, A1 is CH2; A2 is H; Y1 is CR3; Y2 is NR1; Z is selected from the group consisting of (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R211, OR4,, OH, Cm alkoxy. C1-3 perhaloalkoxy, heteroaryt, S-C1-3 alkyl, S-C1-3 perhaloalkyi, S-heteroaryl, aryl, -O-C(O)-R20, -O-C(O)OR21, OC(O)N(R27)(R28), -OR31. OC(O)R100, -OC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -OR100, -Saryl, - OR102aryl, -SR102aryl, -OR102OH, -OR102OR100. -OR102Q. -OCOR100. OR102COR102OR102OR100, OC(O)CH2S(CH)mO-PEG, and OC(O)NH-PEG. or a pharmaceutically acceptable salt thereof. 28. The compound of claim 1, wherein e is 1; f is 1, A1 is CRiR2; AJ is H; Y1 isCRa; Y2 is NR1; Z is selected from the group consisting of (Formula Removed) wherein said Z is optionally substituted with a substituent selected from the group consisting of R211, OR41, OH, C1-6 alkoxy, C1-3 pertialoalkoxy, heteroaryl, S-C1-3 alkyl, S-C1-3 perhaloalkyi, S-heteroaryl, aryl, -O-C(O)-R20, -O-C(O)OR21, OC(O)N(R27)(R28). -OR31, OC(O)R100, -OC(O)CH2S(CH2)mO-PEG, -OC(O)NH-PEG, -OCF3, -OR100, -Saryl, - OR102aryl, -SR102aryl, -OR102OH, -OR102OR100, and -OR102Q, -OCORim, OR102COR102OR102OR100, OC(O)CH2S(CH)mO-PEG, OC(O)NH-PEG, or a pharmaceutically acceptable salt thereof. 29. The compound of claim 1, wherein G1, G3, and G4 = H; G2 is selected from the group consisting of halogen, heteroaryl, heterocycloalkyi, aryl, G3-10cycloalkyl, C1-12 alkyl, C2-6 alkenyl, C2^ alkynyl, -Oaryl, NHaryl, and (Formula Removed) or a pharmaceutically acceptable salt thereof. 30. The compound according to claim 1, wherein the compound is selected from the group (4Z)-4-{[(4-Methoxyphenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({f4-(4-Methy1-1-piperazinyl)phenyr)amino}methylene)-1,4-dihydro-3(2H)-isoquinolinone; (4Z)-4-({I4-(1H-lmidazol-4-yt)phenyl]amino}methylerie)-1,4-dihydro-3(2H) isoquinolinone; (4Z)-4-({[4-(4-Methylpiperazin-1 -yl)phenyl]aR11ino}methylene)isoquinoline 1,3(2H,4H)-dione; (4Z)-4-({I4-(2-Pyrrolidin-1 -ylethyl)phenyl]amino}methylehe)isoquinoline- 1,3(2H,4H)-dione; (4Z)-4-{[{4-Morpholin-4-ylphenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[(1H-lndazol-6-ylamino)methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-(Quinolin-6-ylamino)methylene]isoquinoline-1,3(2H,4H)-dione; (4E)-4-[4-(dimethylamino)benzylidene]isoquinoline-1,3(2H,4H)-dione - (4Z)-4-[4-(dimethylamino)benzylidene]Jsoquinoline-1,3(2H,4H)-dione (1:1); (4E)-4-(4-hydroxybenzylidene)isoquinorme-1,3(2H,4H)-dione; (4Z)-4-({[4-(Piperldin-1-ylmethyl)pheny1]aR11ino}methylene)isoquinoline-1,3(2H,4H>dione; (4Z-4-[{3-Chloro-4[( 1-methy)-1 H-imidazole-2-uy)thio]phenyl}amio)methylene]isoquinoline-1,3(2H,4H)-dione; (4Z)-4-[({3-Chloro-4-(4chlorobenzyl)oxy]phenyl}aR11ino)R11ethylene]isoquinoline-1,3(2H,4H-dione; (4Z)4-({[3-(Piperidin-1-ylmethyl)phenyl]amino}methylene)isoquR11oline-1,3(2H,4H)-dione) (1b); (4Z)-4-({[3-(Azepan-1-ylmethyl)phenyfJamino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-({[3-(Pyrrolidin-1-ylmethyl)phenyl]amino}methylene)tsoquinoline-1,3(2H,4H)-dione) (1c); (4Z)-4-{I4-(Morhpolin-4-ylmethyl)phenyl]aR11ino}methylene)isoquinoline-1,3(2H,4H)-dione (3); (4ZM-H{4-[(4-Methylpiperazin-1-y1)methynphenytamino)R11athylene]isoquilin-1,3(2H,4H)-dione (4); (4Z)-4-[(1,1'-Biphenyl-4-ylamino)methylene]isoquinoline-1,3(2H, 4H)-dione; (4Z)-4-({[3-(2-Pyrrolidin-1-ylethyl)pheny)]amino}methylene)isoquinoline-1,3(2H, 4H)- dione; (4Z)-4-[({4-[(4-Hydroxypiperidin-1-yl)methyl]phenyl}amino)methylene]isoquinolin- 1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-piperidin-1-ylmethyl)phenyl}amino}methyleneisoquinoline-1,3(2H, 4H)-dione; (4Z)-4-[({4[(Dimethylamino)methyl]phenyl}amino)methy)ene]isoquino)in-1,3{2H,4H)- dione; (4Z)-4-({[4-(Azepan-1-ylmethyl)phenyl]amino}methylene)iscxiuinoline-1,3(2H,4H)-dione) (1d); (4Z)-6-Bromo-4-({[4-(4-methylpiperazin-1-yl)phenyl}amino}methytene)isoquinoline- 1,3(2H, 4H)-dione; (4Z)-6-Bromo-4-{[(4-hydroxy-3-methoxybenzyl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione(3a); N-(4-{[(Z)-(1,3-Dioxo-2,3-dihydroisoquinolin-4(1 H)-ylidene)methyl]amino}phenyl)-1,3(2H, 4H)-dione N-Methyi-2-piperidin-1-ylacetamide; (4Z)-6-Bromo-4-{[(pyridin-3-ylmethyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(pyridin-4-ylmethyl)amino]methylene}isoquinoline-1,l3{2H,4H)-dione; (4Z)-6-N)tro-4-({[4-(4-methylpiperazin-1-yl)phenyI}amino}methy)ene)iscxiuinoJin©-1,3(2H, 4H)-dione; tert-Butyl 4-(4-{[(Z)-1,3-dioxo-2,3-dihydroisoquinolin-4(1 H)- ylidene)methyl]amino}piperazine-1-carboxylate; (4Z)-6,7-Dimethoxy-4-({[4-(-methylpiperazin-1 -yl) phenyl}amino)methylene] isoquinolin- 1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-{[(2s)-2-(methoxymethyl)pyrrolidin-1- yl]methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-6-Bromo-4-{[(4-{[(2R)-2-(methoxymethyl)pyrrolidin-1- yl}methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-6-Bromo-4-{t(3.4-dihydroxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-({[2-(piperid in-1 -ytmethyl)phenyi}amino)methylene]isoquino!in- 1,3(2H,4H)-dione; (4Z)-6-Nitro-4-{[(4-piperidin-1-ylmethy1)phenyl]amino}methyleneisoquinoline-1,3(2H> 4H)- dione; (4Z)-6-Bromo-4-({[2-(1H-indol-3-yl)ethyl]amino}methylene)isoquinoline-1,3(2H,4H)- dione; (4Z)-7-Bromo-4-({[4-(Piperidin-1-ylmethyl)phenyl]amino}methylene)soquinoline- 1-3(2H,4H)-dtone; (4Z)-7-Bromo-4-({[4-(4-methylPiperzin-1-yl)phenyr)amino}methylene)isoquinoline- 1,3(2H.4H)-dione; (4Z)-6-Bromo-4-{[(3-hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4-dtone; 2-(Acetyloxy)-4-({[(Z)-(1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}- methyl)phenyl acetate; N-[(4Z)-1,3-Dioxo-4-({[4-piperidin-1 -ylmethyl)phenyl]amirvo}methylene)-1,2,3,4- tetrahydroisoquinolin-6-yl]acetamide; (4Z)-2-Methyl-{[(4-piperidin-1-y)R11ethyl)phenyl]amino}R11ethyleneisoquinoline-1,3(2H, 4H)-dione; (4Z)-6-Brormo-4-{[(3-hydroxy-4-R11ethoxybenzyl)amino)methylene}isoquinoline- 1,3(2H,4H-dione; (4Z}-4-({[4-(4-Me thylptperazin-1-y{)phenyl]amino}methytene)-1,3-dioxo-1,2,3,4- tetrahydroisoquino!ine-6-carboxylic acid; (4Z)-4-{[(3-Aminobenzyl)amino]methylene}-6-bromoisoquinoline-1,3(2H 4H)-dione; (4Z)-6-Bromo-4--{[(4-ch)orobenzyl)amino)methy)ene}isoquincline-1,3(2H,4H)-dione; 2-(Acetyloxy)-({[(Z)-(6-bromo-1,3-dioxo-2.3-dihydroisoquinolin-4(1H)-ylidene)methyl]- amino}methyl)phenyl acetate; (4Z)-6-Chloro-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}methytene)isoquinotine- 1,3(2H.4H)-dione; 4-({[(Z)-(6-Bromo-1,3-dioxo-2,3-didroisoquinolin-4(1 H)- ylidene)methyl]amino)methyl)benzenesulfonamide; 5-({[(Z)-(6-Bromo-1,3-dioxo2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)- 2-methoxyphenyl acetate; 5-{[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-y!iderie)methyl]amino}-2- hydroxybenzoic acid; (4Z)-6-Bromo-4-({[4-(pyrrolidin-1-ylR11ethyl)phenyl]amino}methylene)isoquinoline- 1-3{2H,4H)-dione, (4Z)-4-({[4-(4-Methylpiperazin-1-yl)phenyl]amino}methylene)-6-(1H-pyrrol-1- yl)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-{[(4-Hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-6-Bromo-4-{[(4-hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-4-{[(3-Hydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-6-Bromo-4-{I(3,5-dihydroxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-N,N-Dimethyl-4-({I4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)-1,3-dioxo- 1,2,3,4-tetrahydroisoquinotine-6-carboxamide; (4Z)-N,N-Dimethyl-1,3-dioxo-4-({[4-(piperidinylrr)ethyl)phenyl]amino}methylene)-1,2,3,4- tetrahydroisoquinoline-6-carboxamide; (4Z)-6-Chloro-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-Fluoro-4{[(3-hydroxy-4-methoxybenzyl)amino)methylene}isoquinoline-1,3(2H,4H- dione; Acetic acid 3-acetoxy-5-{[(6-bromo1,3-dioxo-2,3-dihydro-1H-isoquinolin-4- ylidenemethyl)-amino]-methy)}-pheny1 ester; (4Z>-6-Fluoro-4-({[4-(4-methylPiperzin-1-yl)phenyl]amino}methylene)isoquinoline- (j, 1,3(2H,4H)-d'one; \j (4Z)-6-Fluoro-4-{[(3-hydroxy-4-methoxybenzyl)anr)ino)methylene}-6-(1H-pyrro!-1- yl)isoquinoline-1,3(2H,4H-dione; (4Z)-^({[4-PyrroIidin-1-ylmethyl)phenyr)atTiino}methylene)}-6-(1H-pyrrol-1- yl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{I(4-{[(4- [(dimethylamino)methyJ)methyl}phenyl)amino)methylene}isoquinoline-1,3(2H,4H-dione; (4Z)-4-({[4 -Piperidin-1-ylmethyl)pheny1]amino}methylene)}-6-{1H-pyrrol-1- yl)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Bromo-4-{[(4-[(4-hydroxypiperidin-1- yl)methyl}pheny))amino)methylene}isoquinoline-1,3(2H,4H-dione; Carbonic acid 5-{[(6-bromo-1,3-dioxo-2,3-dihydrc-1H-isoquinolin-4-ylidenemethyl)- amino]-methy1}-2-methoxycarbonyloxy-phenyl ester methyl ester; 5-({[(Z)-(6-Bromo-1,3KJioxC1-62,3Klihydroisoquinolin-4(1H)-yiidene)methyl]amino)methyl)- 2,3-dimethoxyphenyl acetate; (4Z)-6-Bromo-4-{[(3-hydroxy-4,5-dimethoxybenzyl)amino)methylene}isoquinoline- 1,3(2H,4H-dione; (4Z)-6-Bromo-{[(3,4,5-tnhydroxybenzyl)amino)methylene}isoquiR10line-1,3(2H,4H- dione; (4Z)-6-lodo-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)- dione (5c); (4Z)-6-lodCM4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline- 1-3(2H.4H)-dione(11c; (4Z)-6-lodo-4-({{4-(piperidin-1-y1methyl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione(11a); 5-({[(Z)-(6-Bromo-1,3-dioxo-2,3-dihydroisoquinolin-4(1H)-ylidene)methyl]amino}methyl)- 2-methoxypheny( methyl carbonate (8b); (4Z)-5^Bromo-4-{[(3-hydroxy-4-methoxybenzyl)amino]methylene}isoquinoline-1, 3(2H, 4H)-dione; (4Z)^^[(3-Hydroxy-4,5-dimethoxybenzyl)aR11ino)methylene}-6-thien-3-ylisoquinoline- 1,3(2H,4H-dione; (4Z)-4-{[(3-Hydroxy-4,5-dimethoxybenzyl)amino)methylene}-6-phenytisoquinoline- 1,3(2H(4H-dione; (4Z)-6-(3-Furyl)-4-[(3-hydroxy-4,5-diR11ethoxybenzyl)aR11ino)methylene}iscxiuinoline- 1,3(2H,4H-dione; (4Z)-4-{[(3-Hydroxy-4-methoxybenzyl)amino]methylene}-6-thien-3-yiisoquinoline- 1,3{2H,4H)-dione(5b); (4Z)-6-lodo-4-[{3-hydroxy-4,5-dimethoxybenzyl)amino)rriethy!ene}isoquinoline- 1,3(2H,4H)-dione; 4-[(3-hydroxy-4-methoxy-benzylamino)-methylene]-6-methoxy-4H-isoquinoline-1,3- dione; 6-Methoxy-4-[(4-piperidin-1-ylmethyl-phenylamino)-methylene]-4H-isoquinoline-1,3- dione; (4Z)-6-(3-Furyl)-4-{[(3-hydroxy-4-methoxybenzyl)amino)methylene}isc)qu(noline- 1,3(2H,4H-dione; (4Z)-6-(3-Furyl)-4-{[4-piperidin-1-ylmethyl)phenynarr«no}methylene)}isoquinolR11e- 1,3(2H,4H)-dione; (4Z)-6-Bromo-4-(3,5-dibromo-4-hydroxybenzylidene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Phenyl-4-({[4-piperidin-1-ylmethyl)phenyl]amino}methylene)}isoquinoline- 1,3(2H,4H)-dione; (4 Z)-6-(3-Hyd roxypheny) )-4- ({[4-piperid in-1 - ylmethyl)phenyl]amino}methylene)}isoquinoline-1,3(2H,4H)-dione; -[(4Z)-1,3-Dtoxo-4-({[4-piperidin-1 -ylmethyl)phenyl]amino}methytene)-1,2,3,4- tetrahydroisoquinoline-6-yI]thiophene-2-carbaldehyde; (4Z)-4-{[(3-Hydroxy-4-methoxybenzyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (3d); 5-({[{Z)-(6-lc«Jo-1,3-dioxo-2l34-({4-[2*(dimelhylaR11ino)ethyr|piperaz)n-1-yl}methylene)isoquinoline- 1,3(2H,4H)-dionQ; (4Z)^-({I4-(4-Methylpiperazin-1-yl)phenyl]aR11ino}methylene)-6-thien-3-ylisoquinoline- 1,3(2H,4H)-dione; (4Z>-4-({I4-(4-Methylpiperazin-1-yl)phenyllamino}methylene)-6-thien-3-ylisoquinoline- 1,3(2H,4H)-dione; (4Z)-4-{[(1,3-Benzodioxol-5-ylmethyl)amino]methylene}-6-bromoisoquinoline-1,3(2H,4H)- dione; (4Z)-1, 3-Dioxo-4-({[4-(piperidin-1-yimethyl)phenyl]amino}methylene)1, 2, 3, 4- tetrahydroisoquinoline-6-carbonitrile; (4Z)-6-(4-Chlorophenyl)-4-({[4-(piperidin-1- ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-t(1E)-5-Chloropent-1-enyl]-4-({[4-(piperidin-1- ylmethyl)pheny1]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-6-(4-Chlorophenyl)-4-{[(3-hydroxy-4,5- dimethoxybenzyl)amino]methylene}isoquinolirie-1,3(2H,4H)-dione; (4Z)-6-(4-methoxyphenyl)~4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)- "tsoquinoline-1,3(2H,4H)-dione 4-[(4Z)-4-({[4-(4-MethylpiperaER11-1-yl)phenyl]amino}methylene)-1,3-dioxo-1,2,3,4-tetra- hydroisoquinolin-6-yl]benzatdehyde; (4Z)-6-(4-Methoxyphenyi)-4-({[4-(piperidin-1-ylmethyl)phenyI]amino}methylene)- isoquinoline-1 ,3{2H,4H)-dlone; (4Z)-6-(3-Methoxypheny))-4-({[4-(piperidin-1-ylmethyl)pbenyt]amino}methy)ene)- isoquinoline-1,3(2H,4H)-dione; (4Z)-6-Piperidin-1-yl-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-Piperidin-1-yl-4-({{4-(methylPiperzin-1-yl)phenylJamino}methyIene)isoquinoline- 1,3(2H,4H)-dione; (4Z)-6-Morpholin~4-yl-4-({[4-(piperidin-1-ylmethyl)phenyl]amino}methylene)isoquinoline- 1,3(2H.4H)-dione; (4Z)-6-[(2R)-2-(Methoxymelhyl)pyrrolidin-1-yn-4-({t4-(piperidin-1- ylmethyl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione; (4Z)-4-{[(4-Amino-3-hydroxybenzy))amino]methylene}-6-iodoisoquinoline- 1,3(2H,4H)- dione; (4Z)-6-[(4-Methyl-piperizin-1-yl]-4-({[4-(piperidin-1- ylmethy))phenyI]amino}methylene)isoquinol)ne-1,3(2H,4H)-d)one; 5-[(4Z)^({[4-(4-Methylpiperazin-1-yl)pbenyflamino}R11ethyIene)-1,3-dioxo-1,2,3,4- tetradydroisoquinonlin-6-yl]-2-furaldehyde; 4Z)-6-lodo-4-({[4-(pyrTolidin-1 -ylmethyl) phenyl}amino)methy)ene] isoquinolin- 1,3(2H,4H)-dione; (4Z)-6-(4-Fluorophenyl)-4-({[4-