THE PATENTS ACT, 1970 COMPLETE SPECIFICATION Section 10 "Fused Compounds that Inhibit Vanilloid Receptor Subtype 1(VR 1) Receptor." Abbott Laboratories, a corporation organized and existing under the laws of USA, ofDept. 377/AP6A-1, 100 Abbott Park Road, Abbott Park, Illinois 60064-6008 USA. The following specification particularly describes the nature of this invention and the manner in which it is to be performed: WO 2004/111009 PCT/US2004/018590 FUSED COMPOUNDS THAT INHIBIT VANILLOID RECEPTOR SUBTYPE 1 (VR1) RECEPTOR This application claims priority to U.S. Provisional Application Serial No. 60/477894 filed on June 12,2003. FIELD OF THE INVENTION The present invention relates to compounds of formula (J), which are useful for treating disorders caused by or exacerbated by vanilloid receptor activity and pharmaceutical compositions containing compounds of formula (I). The compounds of the present invention are useful in treating pain, bladder overactivity, or urinary incontinence. BACKGROUND OF INVENTION Nociceptors are primary sensory afferent (C and A8 fibers) neurons that are activated by a wide variety of noxious stimuli including chemical, mechanical, thermal, and proton (pH < 6) modalities. The lipophilic vanilloid, capsaicin, activates primary sensory fibers via a specific cell surface capsaicin receptor, cloned as VR1. The intradermal administration of capsaicin is characterized by an initial burning or hot sensation followed by a prolonged period of analgesia. The analgesic component of VR1 receptor activation is thought to be mediated by a capsaicin-induced desensitization of the primary sensory afferent terminal. Thus, the long lasting antinociceptive effect of capsaicin has prompted the clinical use of capsaicin analogs as analgesic agents. Further, capsazepine, a capsaicin receptor antagonist can reduce inflammation-induced hyperalgesia in animal models. VR1 receptors are also localized on sensory afferents, which innervate the bladder. Capsaicin or resiniferatoxin has been shown to ameliorate incontinence symptoms upon injection into the bladder. The VR1 receptor has been called a "polymodal detector" of noxious stimuli since it can be activated in several ways. The receptor channel is activated by capsaicin and other vanilloids and thus is classified as a ligand-gated ion channel. VR1 receptor activation by capsaicin can be blocked by the competitive VR1 receptor antagonist, capsazepine. The channel can also be activated by protons. Under mildly acidic conditions (pH 6-7), the affinity of capsaicin for the receptor is increased, whereas at pH <6, direct activation of the channel occurs. In addition, when membrane temperature reaches 43°C, the channel is opened. Thus heat can directly gate the channel in the absence of ligand. The capsaicin WO 2004/111009 PCT/US2004/018590 analog, capsazepine, which is a competitive antagonist of capsaicin, blocks activation of the channel in response to capsaicin, acid, or heat The channel is a nonspecific cation conductor. Both extracellular sodium and calcium enter through the channel pore, resulting in cell membrane depolarization. This depolarization increases neuronal excitability, leading to action potential firing and transmission of a noxious nerve impulse to the spinal cord. In addition, depolarization of the peripheral terminal can lead to release of inflammatory peptides such as, but not limited to, substance P and CORP, leading to enhanced peripheral sensitization of tissue. Recently, two groups have reported the generation of a "knock-out" mouse lacking the VR1 receptor (VR1(-/-)). Electrophysiological studies of sensory neurons (dorsal root ganglia) from these animals revealed a marked absence of responses evoked by noxious stimuli including capsaicin, heat, and reduced pH. These animals did not display any overt signs of behavioral impairment and showed no differences in responses to acute non-noxious thermal and mechanical stimulation relative to wild-type mice. The VR1 (-/-) mice also did not show reduced sensitivity to nerve injury-induced mechanical or thermal nociception. However, the VR1 knock-out mice were insensitive to the noxious effects of intradermal capsaicin, exposure to intense heat (50-55°C), and failed to develop thermal hyperalgesia following the intradermal administration of carrageenan. The compounds of the present invention are novel VR1 antagonists and have utility in treating pain, bladder overactivity, or urinary incontinence. SUMMARY OF THE INVENTION The present invention discloses novel compounds, a method for inhibiting the VR1 receptor in mammals using these compounds, a method for controlling pain in mammals, and pharmaceutical compositions including those compounds and a process for making those compounds. More particularly, the present invention is directed to compounds of formula (I) or a pharmaceutically acceptable salt or prodrug thereof, wherein — is absent or a single bond; X1 is N or CR1; X2 is N or CR2; X3 is N, NR3, or CR3; X4 is a bond, N, or CR4; X5 is N or C; provided that at least one of Xi, X2, X3, and X4 is N; Z1 is O, NH, or S; Z2 is a bond, NH, or 0; Ari is selected from the group consisting of c> fa _ fa R9 R0 .'YVRI° /-te^yJ*.. RANtJvR10 WU KJULRii \XXR QCL vJCOC I 11 • -JT \ 11 • TT>1 .and \AA^R11 • R« R12 ™ R12 R12 (II) (HI) (IV) (V) R1, R3, R5, R6, and R7 are each independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, (CF3)2(HO)C-, RB(SO)2RAN-, RAO(SO)2-, RB0(SO)2-, ZAZBN-, (ZAZBN)alkyl, (ZAZBN)carbonyl, (ZAZBN)carbonylalkyl, and (ZAZBN)sulfonyl; R2 and R4 are each independently selected from the group consisiting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, WO 2004/111009 PCT/US2004/018590 alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, (CF3)2(HO)C-, RB(SO)2RAN-, RAO(SO)2-, RBO(SO)2-, ZAZBN-, (ZAZBN)alkyl, (ZAZBN)alkylcarbonyl, (ZAZBN)carbonyl, (ZAZBN)carbonylalkyl, (ZAZBN)sulfonyl, (ZAZBN)C(=NH>, (ZAZBN)C(-NCN)NH- and (ZAZBN)C(«NH)NH-; Rsa is hydrogen or alkyl; Rsb is absent, hydrogen, alkoxy, alkoxycarbonylalkyl, alkyl, alkylcarbonyloxy, alkylsulfonyloxy, halogen, or hydroxy; R9, R10, R11, and R12 are each individually selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkynyl, aryl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, heteroaryl, heterocycle, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, (CF3)2(HO)C-, RB(SO)2RAN-, RAO(SO)2-, RBO(SO)T, ZAZBN-, (ZAZBN)alkyl, (ZAZBN)carbonyl, (ZAZBN)carbonylalkyl, and (ZAZBN)sulfonyl, herein ZA and ZB are each independently hydrogen, alkyl, alkylcarbonyl, formyl, aryl, or arylalkyl, provided that at least one of R9, R10, R11, or R12 is other than hydrogen, or R10 and R11 taken together with the atoms to which they are attached form a cycloalkyl, cycloalkenyl or heterocycle ring; R13 is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl and halogen; RA is hydrogen or alkyl; and RB is alkyl, aryl, or arylalkyl; provided that Rgb is absent when X5 is N. BRIEF DESCRIPTION OF FIGURES The present invention will be further described with respect to the figures wherein: Figure 1 shows the results from the Differential Scanning Calorimetry (DSC) for the compound of Example 13 A. Figure 2 shows the results from X-ray diffraction (XRD) for the compound of Example 13 A. Figure 3 shows the results from DSC for the compound of Example 13B. WO 2004/111009 PCT/US2004/018590 Figure 4 shows the results from XRD for the compound of Example 13B. Figure 5 shows the results from DSC for the compound of Example 13C. Figure 6 shows the results from XRD for the compound of Example 13C. Figure 7 shows the results from DSC for the compound of Example 13D. Figure 8 shows the results from XRD for the compound of Example 13D. DETAILED DESCRIPTION OF THE INVENTION (1) Embodiments. In the principal embodiment, compounds of formula (I) are disclosed 0), or a pharmaceutically acceptable salt or prodrug thereof, wherein — is absent or a single bond; X1 is N or CR1; X2 is N or CR2; X3 is N, NR3, or CR3; X4 is a bond, N, or CR4; X5 is N or C; provided that at least one of X1, X2, X3, and X4 is N; Z1 is O, NH, or S; Z2 is a bond, NH, or O; Ari is selected from the group consisting of R F9 D "?9 R» fa .I^VRIO /-feVRio RAVVR10 ^N-'V*10 R12 Rl2 R« Rl2 (n) (m) (iv) 00 WO 2004/111009 PCT/US2004/018590 R1, R3, R5, R6, and R7 are each independently selected from the group consisiting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, (CF3)2(HO)C-, RB(SO)2RAN-, RAO(SO)2-, RBO(SO)2-, ZAZBN-, (ZAZBN)alkyl, (ZAZBN)carbonyl, (ZAZBN)carbonylalkyl, and (ZAZBN)sulfonyl; R2 and R4 are each independently selected from the group consisiting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, (CF3)2(HO)C-, RB(SO)2RAN-, RAO(SO)2-, RBO(SO)2-, ZAZBN-, (ZAZBN)alkyl, (ZAZBN)alkylcarbonyl, (ZAZBN)carbonyl, (ZAZBN)carbonylalkyl, (ZAZBN)sulfonyl, (ZAZBN)C(=NH)-, (ZAZBN)C(=NCN)NH- and (ZAZBN)C(=NH)NH-; RSa is hydrogen or alkyl; Rgb is absent, hydrogen, alkoxy, alkoxycarbonylalkyl, alkyl, alkylcarbonyloxy, alkylsulfonyloxy, halogen, or hydroxy; R9, R10, R11, and R12 are each individually selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkynyl, aryl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, heteroaryl, heterocycle, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, (CF3)2(HO)C-, RB(SO)2RAN-, RAO(SO)2-, RBO(SO)2-, ZAZBN-, (ZAZBN)alkyl, (ZAZBN)carbonyl, (ZAZBN)carbonylalkyl, and (ZAZBN)sulfonyl, wherein ZA and ZB are each independently hydrogen, alkyl, alkylcarbonyl, formyl, aryl, or arylalkyl, provided that at least one of R9, Rio, Ru, or R12 is other than hydrogen, or Rio and Ru taken together with the atoms to which they are attached form a cycloalkyl, cycloalkenyl, or heterocycle ring; R13 is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, and halogen; RA is hydrogen or alkyl; and RB is alkyl, aryl, or arylalkyl; WO 2004/111009 PCT/US2004/018590 provided that R8b is absent when Xs is N. In another embodiment of the present invention, compounds of formula (I) are disclosed wherein — is a single bond; Xi is CRi; X2 is CR2; X4 is CR4; X3 and Xs are N; Z\ is 0; Z2 is NH; Ari is selected from the group consisting of D "?8 R» Ro RB R« R12 Rl2 R12 (II) (HI) (IV) (V) formula (I). In another embodiment of the present invention, compounds of formula (I) are disclosed wherein — is a single bond; X1 is CR1; X2 is CR2; X4 is CR4; X3 and X5 are N; Z1 is 0;Z2 is NH; Ar1 is K35CRM (VIb) (Vic) 0^0 (c) treating a compound of formula (Vic) with an atmosphere of hydrogen in the presence of palladium on carbon in a solvent such as but not limited to methanol to provide a compound of formula (VId) N02 R1 NH2 R1 fi^ —- fT^ \ .alkyl \ ,alkyl (Vlc)0<^0 (Vld)0^0 (d) treating a compound of formula (VId) with a compound of formula (Vie) in a solvent such as but not limited to acetonitrile to provide a compound of formula (VI) Cfl (Vld)0^0' ° (vie) ° (VI) 0^0 Another embodiment of the present invention is related to a process for preparing a compound having structural formula (VI) using methyl chloroformate and a base such as but WO 2004/111009 PCT/US2004/U1839U not limited to l,8-diazabicyclo[5.4.0]undec-7-ene in step (b), followed by step (c) and (d) to provide the compound of formula (VT). Another embodiment of the present invention there is disclosed a process for preparing a compound having structural formula (VII), H2N fc12 (VII) wherein, as R9, Rio, Rn and R12 are as defined in formula (I), comprising, in toto, the steps of: (a) treating 3-chloropropionyl chloride with aluminum trichloride in dichloromethane followed by addition of a substituted benzene (Vila), wherein R9, Rio, Ri 1 and Rn are as defined in formula (I) to provide a compound of formula (VIIb) ccRl° 0 Hk ^ JLR10 if + MCI3 —IL*. \ \\ T O R12 (vnb) (b) treating a compound of formula (VIIb) with concentrated sulfuric acid to provide a compound of formula (VIIc) O R12 ° R12 (vnb) (vnc) (c) heating a compound of formula (VIIc) and a compound of formula (VIId) in the presence of or absence of an acid such as but not limited to trifluoroacetic acid or p-toluene sulfonic acid in toluene or a similar solvent in a flask fitted with a Dean-Stark trap until an WO 2004/111009 PCT/US2004/018590 approximately equimolar quantity of water based on the starting material has been collected, followed by adding the mixture to a solution of sodium borohydride in ethanol at a temperature less than or about 0 °C, followed by stirring for about 3 hours or more until mere is a consumption of compound of formula (VIIc), followed by the slow addition of water, followed by extraction with ethyl acetate to provide the compound of formula (Vile) which is optionally purified before use in step (d) /YVRI° i^ii ^^s^Rio yuLRii * U^H, —-n gtx (VIIc) (VBd) h (Vfle) (d) treating a compound of formula (VIIe) with an atmosphere of hydrogen at about 40 psi in the presence of about 5- 20 % palladium on carbon in a solvent with an acid to provide a compound of formula (VII) which is optionally purified CMX- — j-SS (Vile) (VU) In another embodiment of the present invention, the substitution of an atmosphere of hydrogen in the presence of palladium or platinum on carbon in a solvent such as but not limited to methanol for sodium borohydride in ethanol in step (c), followed by step (d), will provide the compound of formula (VII). In another embodiment of the present invention, the process for preparing a compound having structural formula (VII) contemplates the use of methanol as a solvent in step (d) to provide the compound of formula (VII). In another embodiment of the present invention, the process for preparing a compound having structural formula (VII) contemplates the use of solvents including aqueous methanol containing 1% acetic acid in step (d) to provide the compound of formula (VII). WO 2004/111009 PCT/US2004/018590 In another embodiment of the present invention, the process for preparing a compound having structural formula (VII) contemplates the use of methanol containing 6 % acetic acid in step (d) to provide the compound of formula (VII). In another embodiment of the present invention, there is disclosed a process of preparing compounds of formula (VII), wherein the compound of formula (VIIe) is further purified by preparing the salt with an acid and recrystallized prior to step (d). In another embodiment of the present invention, there is disclosed a process of preparing compounds of formula (VII), wherein the compound of formula (VIIe) is further purified by preparing the tosylate salt and recrystallized prior to step (d). In another embodiment of the present invention, there is disclosed a process of preparing compounds of formula (VII), wherein the compound of formula (VII) is further purified by preparing the salt with an acid and recrystallized. In another embodiment of the present invention, there is disclosed a process of preparing compounds of formula (VII), wherein the compound of formula (VII) is further purified by preparing the tosylate salt and recrystallized. In another embodiment of the present invention there is disclosed a process for preparing a compound having structural formula (VIII), O II R, HN'^^NH 1*12 /Yj) (XX H K* (vm) wherein, Ri is hydrogen or alkyl and R9, R10, R11 and R12 are as defined in formula (I), comprising, in toto, the steps of: (a) treating a compound of formula (VI) with a compound of formula (VII) to provide a compound of formula (VIla) WO 2004/111009 PCT/US2004/018S90 vO + WR" -—-N>X) ocx11 ° ° (VI) (VII) ?A> (Villa) R» alkyl ^ treating a compound of formula (Villa) with sodium hydroxide or potassium hydroxide in methanol to provide the compound of formula (Vm) Kl} (XX ► (Vina) RQ (vm) R° alkyl In another embodiment of the present invention there is disclosed the use of a compound of formula (VI) in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I). In another embodiment of the present invention there is disclosed the use of a compound of formula (VI) in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I), which is useful for the treatment of a disorder by inhibiting vanilloid receptor subtype 1 in a mammal comprising administering a therapeutically effective amount of a compound of formula (T) or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment of the present invention there is disclosed the use of a compound of formula (VI) in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I), which is useful for the treatment of pain in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment of the present invention there is disclosed the use of a compound of formula (VII) in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I). WO 2004/111009 PCT/US2004/018590 In another embodiment of the present invention there is disclosed the use of a compound of formula (VII) in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I), which is useful for the treatment of a disorder by inhibiting vanilloid receptor subtype 1 in a mammal comprising administering a therapeutically effective amount of a compound of formula CO or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment of the present invention mere is disclosed the use of a compound of formula (VII) in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I), which is useful for the treatment of pain in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. Another embodiment of the present invention relates to a process for preparing a compound having structural formula (DC), (DC) comprising, in toto, the steps of: (a) treating 2-methyl 3-nitro-analine (IXa) of in acetic acid with sodium nitrite to provide a compound of formula (IXb) N02 N02 (DCa) (DCb) . (b) treating a compound of formula (IXb) with methyl chloroformate and a base such as but not limited to l,8-diazabicyclo[5.4.0]undec-7-ene to provide a compound of formula (IXc) WO 2004/111009 PCT/US2004/01859U (Kb) (IXc)0<^0/ (c) treating a compound of formula (IXc) with an atmosphere of hydrogen in the presence of palladium on carbon in a solvent such as methanol to provide a compound of formula (IXd) N02 NH2 (j> (j[> (IXcJo^O7 CKdJo^O7 (d) treating a compound of formula (IXd) with a compound of formula (IXe) in a solvent such as but no limited to acetonitrile to provide a compound of formula (IX) NH2 O o O VNVSjlH Ct> * ty^ —° Co (KcOo^ ° (Ke) ° (K) O^ Another embodiment of the present invention related to a process for preparing a compound having structural formula (X), H2N" (X) comprising, in toto, the steps of: (a) treating 3-chloropropionyl chloride with aluminum trichloride in dichloromethane followed by addition of a tert-butyl benzene (Xa), to provide a compound of formula (Xb) WO 2004/111009 PCT/US2004/018590 o <*» ja ^y clX_~a ♦ «* CJU^ o (Xb) (b) treating a compound of formula (Xb) with concentrated sulfuric acid to provide a compound of formula (Xc) CO*— 90^ o o (Xb) (Xc) (c) heating a compound of formula (Xc) and a compound of formula (Xd) in the presence of or absence of an acid such as but not limited to trifluoroacetic acid or p-toluenesulfonic acid in toluene in a flask fitted with a Dean-Stark trap followed by adding the mixture to a solution of sodium borohydride in ethanol at a temperature of about 0 °C, followed by stirring, followed by the slow addition of water, followed by extraction with ethyl acetate to provide the compound of formula (Xe) which is optionally purified before use in step (d) O = kJU^HN (Xc) (Xd) £ (Xe) (d) treating a compound of formula (Xe) with an atmosphere of hydrogen at 40 psi in the presence of about 5-20 % palladium on carbon in a solvent with or without an acid to provide a compound of formula (X) which is optionally purified WO 2004/111009 PCT/US2004/018590 5 CXe) (X) In another embodiment of the present invention the substitution an atmosphere of hydrogen in the presence of palladium or platinum on carbon in a solvent such as but not limited to methanol for sodium borohydride in ethanol in step (c), followed by step (d) to provide the compound of formula (X). In another embodiment the process for preparing a compound having structural formula (X) contemplates the use of methanol as a solvent in step (d) to provide the compound of formula (X). In a further embodiment the process for preparing a compound having structural formula (X) contemplates the use of solvents including aqueous methanol containing 1% acetic acid in step (d) to provide the compound of formula (X). In another embodiment the process for preparing a compound having structural formula (X) contemplates the use of methanol containing 6 % acetic acid in step (d) to provide the compound of formula (X). In another embodiment of the present invention, there is disclosed a process of preparing compounds of formula (X), wherein the compound of formula (Xe) is further purified by preparing the salt with an acid and recrystallized prior to step (d). In another embodiment of the present invention, there is disclosed a process of preparing compounds of formula (X), wherein the compound of formula (Xe) is further purified by preparing the tosylate salt and recrystallized prior to step (d). In another embodiment of the present invention, there is disclosed a process of preparing compounds of formula (X), wherein the compound of formula (X) is further purified by preparing the salt with an acid and recrystallized. In another embodiment of the present invention, there is disclosed a process of preparing compounds of formula (X), wherein the compound of formula (X) is further purified by preparing the tosylate salt and recrystallized. Another embodiment of the present invention is related to a process for making a compound having structural formula (XI), WO 2004/111009 PCT/US2004/018590 O II (XI) comprising, in toto, the steps of: (a) treating a compound of formula (IX) with a compound of formula (X) to provide a compound of formula (XIa) ° (K) (X) 0-% (XIa) (b) treating a compound of formula (XIa) with sodium hydroxide in methanol to provide the compound of formula (XI) O O 0"S> (XI) (XD Another embodiment of the present invention relates to the use of a compound of formula (IX) in the process of preparing a compound of formula (I). Another embodiment of the present invention relates to the use of a compound of formula (IX) in the process of preparing a compound of formula (XI) which is representative of compound of formula (I) which is useful for the treatment of a disorder by inhibiting vanilloid receptor subtype 1 in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. WO 2004/111009 PCT/US2004/018590 Another embodiment of the present invention relates to the use of a compound of of formula (EX) in the process of preparing a compound of formula (XI) which is representative of compound of formula (I) which is useful for the treatment of pain in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. Another embodiment of the present invention relates to the use of a compound of formula (X) in the process of preparing a compound of formula (I). Another embodiment of the present invention relates to the use of a compound of of formula (X) in the process of preparing a compound of formula (XI) which is representative of compound of formula (T) which is useful for the treatment of a disorder by inhibiting vanilloid receptor subtype 1 in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. Another embodiment of the present invention relates to the use of a compound of of formula (X) in the process of preparing a compound of formula (XI) which is representative of compound of formula (I) which is useful for the treatment of pain in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. The present invention also provides pharmaceutical compositions that comprise compounds of the present invention. The pharmaceutical compositions comprise compounds of the present invention that may be formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions of this invention can be administered to humans and other mammals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments or drops), bucally or as an oral or nasal spray. Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as, but not limited to, lactose, glucose and sucrose; starches such as, but not limited to, corn starch and potato starch; cellulose and its derivatives such as, but not limited to, sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as, but not limited to, cocoa butter and suppository waxes; oils such as, but not limited to, peanut oil, cottonseed oil, safflower oil, WO 2004/111009 PCT/US2004/018590 sesame oil, olive oil, com oil and soybean oil; glycols; such a propylene glycol; esters such as, but not limited to, ethyl oleate and ethyl laurate; agar, buffering agents such as, but not limited to, magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate butler solutions, as well as other non-toxic compatible lubricants such as, but not limited to, sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. Pharmaceutical compositions of this invention for parenteral injection comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), vegetable oils (such as olive oil), injectable organic esters (such as ethyl oleate) and suitable mixtures thereof. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents that delay absorption such as aluminum monostearate and gelatin. In some cases, in order to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution, which in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. WO 2004/111009 PCT/US2004/018590 Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound may be mixed with at least one inert, pharmaceutically acceptable excipient or carrier, such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarding agents such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such carriers as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared with coatings and shells such as enteric coatings and other coatings well-known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of a composition such that they release the active ingredients) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. WO 2004/111009 PCT/US2004/018590 The active compounds can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned carriers. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofurruryl alcohol, polyethylene glycols and fatty acid esters of sorbitan and mixtures thereof. Besides inert diluents, the oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents. Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, tragacanth and mixtures thereof. Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating carriers or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals, which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like. The preferred lipids are natural and synthetic phospholipids and phosphatidyl cholines (lecithins) used separately or together. Methods to form liposomes are known in the art. See, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq. WO 2004/111009 PCT/US2004/018590 Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffers or propellants that may be required. Ophthalmic formulations, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. Actual dosage levels of active ingredients in the pharmaceutical compositions of this invention can be varied so as to obtain an amount of the active compound(s) that is effective to achieve the desired therapeutic response for a particular patient, compositions and mode of administration. The selected dosage level will depend upon the activity of the particular compound, the route of administration, the severity of the condition being treated and the condition and prior medical history of the patient being treated. When used in the above or other treatments, a therapeutically effective amount of one of the compounds of the present invention can be employed in pure form or, where such forms exist, in pharmaceutically acceptable salt, ester or prodrug form. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. The compounds of the present invention can be used in the form of pharmaceutically acceptable salts derived from inorganic or organic acids. Pharmaceutically acceptable salts are well-known in the art. For example, S. M. Berge et al. describe pharmaceutically acceptable salts in detail in (J. Pharmaceutical Sciences, Vol. 66 pages 1 et seq., 1977). The salts can be prepared in situ during the final isolation and purification of the compounds of the invention or separately by reacting a free base function with a suitable organic acid. Representative acid addition salts include, but are not limited to benzenesulfonate, bisulfate, chlorobenzene sulfonic acid, 1,5-napthalene disulfonic acid, thiocyanate, dodecyl sulfuric acid, ethanesulfonate, camphorsulfonate, WO 2004/111009 PCT/US2004/018590 hydrochloride, hydrobromide, 2-hydroxyethansulfonate (isethionate), methanesulfonate, 2-naphthalenesulfonate, sulfate, and p-toluenesulfonate. Examples of acids which can be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, hydrobromic acid, and sulphuric acid. Basic addition salts can be prepared in situ during the final isolation and purification of compounds of this invention by reacting a carboxylic acid-containing moiety with a suitable base such as, but not limited to, the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation or with ammonia or an organic primary, secondary or tertiary amine. Pharmaceutically acceptable salts include, but are not limited to, cations based on alkali metals or alkaline earth metals such as, but not limited to, lithium, sodium, potassium, calcium, magnesium and aluminum salts and the like and nontoxic quaternary ammonia and amine cations including ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine and the like. Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine and the like. The present invention contemplates compounds of formula I formed by synthetic means or formed by in vivo biotransformation of a prodrug. Prodrugs of the present invention may be rapidly transformed in vivo to compounds of formula (I), for example, by hydrolysis in blood. The compounds of the invention can exist in unsolvated as well as solvated forms, including hydrated forms, such as hemi-hydrates. In general, the solvated forms, with pharmaceutically acceptable solvents such as water and ethanol among others are equivalent to the unsolvated forms for the purposes of the invention. The total daily dose of the compounds of this invention administered to a human or lower animal may range from about 0.01 to about 100 mg/kg/day. For purposes of oral administration, more preferable doses can be in the range of from about 0.1 to about 25 mg/kg/day. If desired, the effective daily dose can be divided into multiple doses for purposes of administration; consequently, single dose compositions may contain such amounts or submultiples thereof to make up the daily dose. (2) Definition of Terms. WO 2004/111009 PCT/US2004/018S90 As used throughout this specification and the appended claims, the following terms have the following meanings: The term "alkenyl" as used herein, means a straight or branched chain hydrocarbon containing from 2 to 10 carbons and containing at least one carbon-carbon double bond formed by the removal of two hydrogens. Representative examples of alkenyl include, but are not limited to, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2-heptenyl, 2-methyl-l-heptenyl, and 3-decenyl. The term "alkoxy" as used herein, means an alkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy, and hexyloxy. The term "alkoxyalkoxy" as used herein, means an alkoxy group, as defined herein, appended to the parent molecular moiety through an alkoxy group, as defined herein. Representative examples of alkoxyalkoxy include, but are not limited to, methoxymethoxy, ethoxymethoxy and 2-ethoxyethoxy. The term "alkoxyalkyl" as used herein, means an alkoxy group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of alkoxyalkyl include, but are not limited to, tert-butoxymethyl, 2-ethoxyethyl, 2-methoxyethyl, and methoxymethyl. The term "alkoxycarbonyl" as used herein, means an alkoxy group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representative examples of alkoxycarbonyl include, but are not limited to, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl. The term "alkoxycarbonylalky’’ as used herein, means an alkoxycarbonyl group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of alkoxycarbonylalkyl include, but are not limited to, 3-methoxycarbonylpropyl, 4-ethoxycarbonylbutyl, and 2-tert-butoxycarbonylethyl. The term "alkyl" as used herein, means a straight or branched chain hydrocarbon containing from 1 to 10 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, and n-decyl. WO 2004/111009 PCT/US2004/018590 The term "alkylcarbonyl" as used herein, means an alkyl group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representative examples of alkylcarbonyl include, but are not limited to, acetyl, 1-oxopropyl, 2,2-dimethyl-l-oxopropyl, 1-oxobutyl, and 1-oxopentyl. The term "alkylcarbonylalky” as used herein, means an alkylcarbonyl group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of alkylcarbonylalkyl include, but are not limited to, 2-oxopropyl, 3,3-dimethyl-2-oxopropyl, 3-oxobutyl, and 3-oxopentyl. The term "alkylcarbonyloxy" as used herein, means an alkylcarbonyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representative examples of alkylcarbonyloxy include, but are not limited to, acetyloxy, ethylcarbonyloxy, and tert-butylcarbonyloxy. The term "alkylsulfonyl" as used herein, means an alkyl group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representative examples of alkylsulfonyl include, but are not limited to, methylsulfonyl and ethylsulfonyl. The term "alkylthio" as used herein, means an alkyl group, as defined herein, appended to the parent molecular moiety through a sulfur atom. Representative examples of alkylthio include, but are not limited, methylsulfanyl, ethylsulfanyl, tert-butylsulfanyl, and hexylsulfanyl. The term "alkynyl" as used herein, means a straight or branched chain hydrocarbon group containing from 2 to 10 carbon atoms and containing at least one carbon-carbon triple bond. Representative examples of alkynyl include, but are not limited, to acetylenyl, 1-propynyl, 2-propynyl, 3-butynyl, 2-pentynyl, and 1-butynyl. The term "Ari" as used herein, means an aryl group selected from dihydro-lH-indenyl, lH-indenyl, tetrahydronaphthalenyl, or dihydronaphthalenyl. The Ari group is attached to the parent molecular moiety via any position. Representative examples include, but are not limited to, 2,3-dihydro-lH-inden-l-yl, 2,3-dihydro-lH-inden-2-yl, 2,3-dihydro-lH-inden-4-yl, 2,3-dihydro-lH-inden-5-yl, lH-inden-1-yl, lH-inden-2-yl, lH-inden-3-yl, lH-inden-4-yl, lH-inden-5-yl, 1,2,3,4-tetrahydro-l-naphthalenyl, l,2,3,4-tetrahydro-2-naphthalenyl, l,2,3,4-tetrahydro-5-naphthalenyl, 1 A3,4-tetrahydro-6-naphthalenyl, 1,2-dihydro-1-naphthalenyl, l^-dihydro-2-naphmalenyl, l,2-dihydro-3-naphthalenyl, 1,2- WO 2004/111009 PCT/US2004/018590 dihydro-4-naphthalenyl, l,2-dihydro-5-naphthalenyl, l,2-dihydro-6-naphthalenyl, 1,2-dihydro-7-naphthalenyl, l,2-dihydro-8-naphthalenyl, 3,4-dihydronaphthalen-l-yl, and 3,4-dihydronaphthalen-2-yl. The Ari groups of this invention can be substituted with 1,2,3,4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, (CF3)2(HO)C-, -NRAS(O)2RB, -S(O)2ORA, -S(O)2RB, -NZAZB, (NZAZB)alkyl, (NZAZB)carbonyl, (NZAZs)carbonylalkyl or (NZAZB)sulfonyl, wherein ZA and ZB are each independently hydrogen, alkyl, alkylcarbonyl, formyl, aryl, or arylalkyl. Representative examples of substituted Ar1 groups include, but are not limited to, 5-tert-butyl-2,3-dihydro-lH-inden-1-yl, 5-tert-butyl-2,3-dihydro-lH-inden-2-yl, 5-bromo-2,3-dihydro-lH-inden-l-yl, (3R)-5-tert-butyl-3-methyl-23-dihydro-lH-inden-l-yl, and (3S)-5-tert-butyl-3-methyl-2,3-dihydro-lH-inden-1-yl. The term "aryl" as used herein, means a phenyl group, or a bicyclic or a tricyclic fused ring system wherein one or more of the fused rings is a phenyl group. Bicyclic fused ring systems are exemplified by a phenyl group fused to a cycloalkyl group, as defined herein, or another phenyl group. Tricyclic fused ring systems are exemplified by a bicyclic fused ring system fused to a cycloalkyl group, as defined herein, or another phenyl group. Representative examples of aryl include, but are not limited to, anthracenyl, azulenyl, fluorenyl, indenyl, naphthyl, phenyl and tetrahydronaphthyl. The aryl groups of this invention can be substituted with 1,2,3,4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylsulfonyl, alkylthio, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkyl, ethylenedioxy, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, hydroxy, hydroxyalkyl, methylenedioxy, mercapto, mercaptoalkyl, nitro, -NZCZD, (NZcZD)alkyi, (NZcZD)carbonyl, (NZcZD)carbonylalkyl, (NZcZD)sulfonyl, -NRAS(O)2RB, -S(O)2ORA and -S(O)2RA wherein RA and RB are as defined herein. The term "arylalkyl" as used herein, means an aryl group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples WO 2004/111009 PCT/US2004/018590 of arylalkyl include, but are not limited to, benzyl, 2-phenylethyl, 3-phenylpropyl, and 2-naphth-2-ylethyl. The term "aryloxy" as used herein, means an aryl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representative examples of aryloxy include, but are not limited to, phenoxy, naphthyloxy, 3-bromophenoxy, 4-chlorophenoxy, 4-methylphenoxy, and 3,5-dimethoxyphenoxy. The term "arylthio" as used herein, means an aryl group, as defined herein, appended to the parent molecular moiety through a sulfur atom. Representative examples of arylthio include, but are not limited to, phenylsulfanyl, naphth-2-ylsulfanyl, and 5-phenylhexylsulfanyl. The term "carbonyl" as used herein, means a -C(O)- group. The term "carboxy" as used herein, means a -CO2H group. The term "carboxyalkyl" as used herein, means a carboxy group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of carboxy alkyl include, but are not limited to, carboxymethyl, 2-carboxyethyl, and 3-carboxypropyl. The term "cyano" as used herein, means a -CN group. The term "cyanoalkyl" as used herein, means a cyano group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of cyanoalkyl include, but are not limited to, cyanomethyl, 2-cyanoyethyl, and 3-cyanopropyl. The term "cycloalkyl" as used herein, means a saturated monocyclic ring system containing from 3 to 8 carbon atoms. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. The term "ethylenedioxy" as used herein, means a –O(CH2)2O- group wherein the oxygen atoms of the ethylenedioxy group are attached to the parent molecular moiety through one carbon atom forming a 5 membered ring or the oxygen atoms of the ethylenedioxy group are attached to the parent molecular moiety through two adjacent carbon atoms forming a six membered ring. The term "formyl” as used herein, means a -C(0)H group. The term "halo" or "halogen" as used herein, means -CI, -Br, -I or -F. WO 2004/111009 PCT/US2004/018590 The term "haloalkoxy" as used herein, means at least one halogen, as defined herein, appended to the parent molecular moiety through an alkoxy group, as defined herein. Representative examples of haloalkoxy include, but are not limited to, chloromethoxy, 2-fluoroethoxy, trifiuoromethoxy, 2-chloro-3-fluoropentyloxy, and pentafluoroethoxy. The term "haloalkyl" as used herein, means at least one halogen, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of haloalkyl include, but are not limited to, chloromethyl, 2-fluoroethyl trifluoromethyl, pentafluoroethyl, and 2-chloro-3-fluoropentyl. The term "haloalkylthio" as used herein, means at least one halogen, as defined herein, appended to the parent molecular moiety through an alkylthio group, as defined herein. Representative examples of haloalkylthio include, but are not limited to, trifluoromethylthio. The term "heterocycle," as used herein, refers to a three, four, five, six, seven, or eight membered ring containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The three membered ring has zero double bonds. The four and five membered ring has zero or one double bond. The six membered ring has zero, one, or two double bonds. The seven and eight membered rings have zero, one, two, or three double bonds. The heterocycle groups of the present invention can be attached to the parent molecular moiety through a carbon atom or a nitrogen atom. . Representative examples of heterocycle include, but are not limited to, azabicyclo[2.2.1]heptanyl, azabicyclo[2.2.1.]octanyl, azetidinyl, hexahydro-lH-azepinyl, hexahydroazocin-(2H)-yl, indazolyl, morpholinyl, octahydroisoquinoline, piperazinyl, piperidinyl, pyridinyl, pyrrolidinyl, and thiomorpholinyl. The heterocycles of the present invention are substituted with 0,1,2,3, or 4 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfonyl, alkynyl,aryl, arylalkyl, arylalkoxycarbonyl, carboxy, cyano, formyl, haloalkoxy, haloalkyl, halo, hydroxy, hydroxyalkyl, mercapto, nitro, piperidinyl, and oxo. The term "hydroxy" as used herein, means an -OH group. The term "hydroxyalkyl" as used herein, means at least one hydroxy group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. WO 2004/111009 PCT/US2004/018590 Representative examples of hydroxyalkyl include, but are not limited to, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypentyl, and 2-ethyl-4-hydroxyheptyl. The term "mercapto" as used herein, means a -SH group. The term "mercaptoalkyl” as used herein, means a mercapto group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of mercaptoalkyl include, but are not limited to, 2-mercaptoethyl and 3-mercaptopropyl. The term "methylenedioxy" as used herein, means a -OCH2O- group 'wherein the oxygen atoms of the methylenedioxy are attached to the parent molecular moiety through two adjacent carbon atoms. The term "nitro" as used herein, means a -NO2 group. The term "-NZAZB" as used herein, means two groups, ZA and ZB, which are appended to the parent molecular moiety through a nitrogen atom. ZA and Z& are each independently selected from hydrogen, alkyl, alkylcarbonyl, formyl, aryl and arylalkyl. Representative examples of- NZAZB include, but are not limited to, amino, methylamino, acetylamino, benzylamino, phenylamino, and acetylmethylamino. The term "(NZAZB)alkyl" as used herein, means a -NZAZB group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of (NZAZB)alkyl include, but are not limited to, aminomethyl, 2-(methylamino)ethyl, 2-(dimethylamino)ethyl and (emylmethylamino)methyl. The term "(NZAZB)carbonyl" as used herein, means a -NZAZB group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representative examples of (NZAZs)carbonyl include, but are not limited to, aminocarbonyl, (methylamino)carbonyl, (dimethylamino)carbonyl and (ethylmethylamino)carbonyl. The term "(NZAZB)carbonylalkyl" as used herein, means a (NZAZs)carbonyl group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of (NZAZa)carbonylalkyl include, but are not limited to, (aminocarbonyl)methyl, 2-((methylamino)carbonyl)ethyl and ((dimemylamino)carbonyl)methyl. The term "(NZAZB)sulfonyr as used herein, means a -NZAZB group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. WO 2004/111009 PCT/US2004/018590 Representative examples of (NZAZB)sulfonyl include, but are not limited to, aminosulfonyl, (methylamino)sulfonyl, (dimethylamino)sulfonyl and (ethylmethylamino)sulfonyl. The term "-NZCZD" as used herein, means two groups, Zc and ZD, which are appended to the parent molecular moiety through a nitrogen atom. Zc and ZD are each independently selected from hydrogen, alkyl, alkylcarbonyl, formyl, aryl and arylalkyl. Representative examples of-NZCZD include, but are not limited to, amino, methylamino, acetylamino, benzylamino, phenylamino, and acetylmethylamino. The term "(NZcZD)alkyl” as used herein, means a -NZCZD group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of (NZcZD)alkyl include, but are not limited to, aminomethyl, 2-(methylamino)ethyl, 2-(dimethylamino)ethyl and (ethylmethylamino)methyl. The term "(NZcZD)carbonyl" as used herein, means a -NZCZD group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representative examples of (NZcZD)carbonyl include, but are not limited to, aminocarbonyl, (methylamino)carbonyl, (dimethylamino)carbonyl and (ethylmethylamino)carbonyl. The term "(NZcZD)carbonylalkyl" as used herein, means a (NZcZo)carbonyl group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of (NZcZD)carbonylalkyl include, but are not limited to, (aminocarbonyl)methyl, 2-((methylamino)carbonyl)ethyl and ((dimethylamino)carbonyl)methyl. The term "(NZcZD)sulfonyl" as used herein, means a -NZCZD group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representative examples of (NZcZD)sulfonyl include, but are not limited to, aminosulfonyl, (methylamino)sulfonyl, (dimethylamino)sulfonyl and (ethylmethylamino)sulfonyl. The term "oxo" as used herein, means =0. The term "sulfonyl" as used herein, means a -S(0)2- group. The term "parenterally," as used herein, refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion. The terms "pharmaceutically acceptable carrier," as used herein, mean a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. WO 2004/111009 PCT/US2004/018S90 The terms "therapeutically effective amount" of the compound of the invention mean a sufficient amount of the compound to treat disorders, at a reasonable benefit/risk ratio applicable to any medical treatment. The terms "pharmaceutically acceptable salt" mean those salts which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit/risk ratio. The terms "pharmaceutically acceptable prodrug" or nprodrug,"as used herein, represent those prodrugs of the compounds of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use. The term “amorphous" as used herein, means a solid essentially without cristallinity. The terms "essentially without," in reference to absence of crystallinity, mean at least about 95% amorphous, preferably about 97% amorphous, more preferably about 99% amorphous, and most preferably about 100% amorphous. Compounds of the present invention can exist as stereoisomers, wherein asymmetric or chiral centers are present Stereoisomers are designated (R) or (S), depending on the configuration of substituents around the chiral carbon atom. The terms (R) and (S) used herein are configurations as defined in IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. Vol. 45, pages 13-30 (1976). The present invention contemplates various stereoisomers and mixtures thereof and are specifically included within the scope of this invention. Stereoisomers include enantiomers, diastereomers, and mixtures of enantiomers or diastereomers. Individual stereoisomers of compounds of the present invention may be prepared synthetically from commercially available starting materials, which contain asymmetric or chiral centers, or by preparation of racemic mixtures followed by resolution, a technique well-known to those of ordinary skill in the art These methods of resolution are exemplified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting mixture of diastereomers by recrystallization or chromatography and liberation of the optically pure product from the auxiliary, (2) direct separation of the mixture of optical enantiomers on chiral WO 2004/111009 PCT/US2004/018590 chromatographic columns, or (3) formation of a diastereomeric salt followed by selective recrystallization of one of the diastereomeric salts. Compounds of the present invention were named by ACD/ChemSketch version 5.0 (developed by Advanced Chemistry Development, Inc., Toronto, ON, Canada) or were given names that appeared to be consistent with ACD nomenclature. Abbreviations Abbreviations which have been used in the descriptions of the Schemes and the Examples that follow are: atm for atmosphere(s); DBU for l,8-diazabicyclo[5.4.0]undec-7-ene; IXC for l,3-dicyclohexylcarbodiimide; DMAP for 4-dimemylaminopyridine; DMF for N,N-dimethylformamide; DMSO for dimethylsulfoxide; EDCI or EDC for l-ethyl-3-[3-(dmiemylammo)propyl]-carbodiimide hydrochloride; Et for CH3CH2; HPLC high pressure liquid chromatography; Me for CH3; Ph for phenyl; psi for pounds per square inch; and THF for tetrahydrofuran. (3) Preparation of Compounds of the Present Invention The compounds and processes of the present invention will be better understood in connection with the following synthetic Schemes and Examples that illustrate a means by which the compounds of the present invention can be prepared. WO 2004/111009 PCT/US2004/018590 Scheme 1 O JJ Rl NH2 R! HN'XCfe R2NY^ir!!V'R7 ° R2V^*r!:V'R7 WR. + C,^CCl3 -^ ^^fV^Re R4 R5 R4 R5 (1) (2) J? H . (2) + H2N.AT, DBU ^vyy^ (3) r i * R4 Rs (4) O Ri HN^O'^1 (2)+ HO'*1 DBU R2YTYR7 (5) T I "• R4 Rs (6) Ureas of general formula (4), wherein R1, R2, R4, R5, R6 R7, and Ar1 are as defined in formula (I), may be prepared as described in Scheme 1. 5-Aminoisoquinolines of general formula (1), purchased commercially or prepared using standard chemistry known to those in the art, can be treated with trichloroacetyl chloride and a base such as, but not limited to, triethylamine in a solvent such as dichloromethane to provide trichloroacetamides of general formula (2). Trichloroacetamides of general formula (2) can be treated with amines of general formula (3) and a non-nucleophilic base such as, but not limited to, DBU in a solvent such as, but not limited to, acetonitrile to provide ureas of general formula (4). Carbamates of general formula (6), wherein Ri, R2, R4, R5, R& R7, and Ari are as defined in formula (I), may also be prepared as described in Scheme 1. Trichloroacetamides of general formula (2) can be treated with alcohols of general formula (5) and a non-nucleophilic base such as, but not limited to, DBU in a solvent such as, but not limited to, acetonitrile to provide carbamates of general formula (6). WO 2004/111009 PCT/US2004/018590 Scheme 2 HaN'*1 CIC(Q)CI OCN'^1 (3) - (8) 1 H A Ri NH2 & HN^N' 1 R2N^V^5iV'R7 R2N^^v^V^R7 A JU-p + OCN'*1 S J[IB I J "e ■" | | Re R» Re (8) R» R8 (D (4) Ureas of general formula (4), wherein R1, R2, R4, R5, R6, R7, and Ari are as defined in formula (I), may be prepared as described in Scheme 2. Amines of general formula (3) can be treated with phosgene or triphosgene and DMAP in a solvent such as, but not limited to, dichloromethane to provide isocyanates of general formula (8). 5-Aminoisoquinolines of general formula (1) can be treated with isocyanates of general formula (8) in a solvent such as, but not limited to, toluene or THF or a combination thereof to provide ureas of general formula (4). Scheme 3 R, NH2 Ri NCO R2YVYRT C,C<°>CI R2YTYR7 y y Ke f y Ke R4 R5 R4 Re (D (10) ff H A do) + HN^An ^ TTT (3) Yl^Re R4 Re (4) Ureas of general formula (4), wherein R1, R2, R4, R5, R6, R7, and Ar1 are as defined in formula (I), may be prepared as described in Scheme 3. 5-Aminoisoquinolines of general formula (1) can be treated with phosgene or triphosgene and DMAP in a solvent such as, but not limited to, dichloromethane to provide isocyanates of general formula (10). Isocyanates of general formula (10) can be treated with amines of general formula (3) in a solvent such WO 2004/111009 PCT/US2004/018590 as, but not limited to, toluene or THF or a combination thereof to provide ureas of general formula (4). Scheme 4 D --/ I T Schemes 1-3 V^/ks/R7 >~^.xL ^R? R3 R6 JN T^Re ry% (19) Ra R5 R3 R6 ' (20) (21) N/ I T Schemes 1-3 Jk^W^R7 L^^W^RT XN-V^R * NM I |/TT R3 A, JN T^R« ,N^^Re (22) *3 R8 R3 R8 (23) (24) Ureas of general formula (20), wherein R1, R2, R4, R5, R6, R7, and Ari are as defined in formula (I), and carbamates of general formula (21), wherein Ri, R2, R3, R5, R«, R7, and Ari are as defined in formula (I), may be prepared as described in Scheme 4. 4-Aminoindoles of general formula (19), purchased commercially or prepared using standard chemistry known to those in the art, may be processed as described in Schemes 1-3 to provide ureas of general formula (20) and carbamates of general formula (21). Ureas of general formula (23), wherein R1, R3, R5, R6, R7, and Ari are as defined in formula (I), and carbamates of general formula (24), wherein R1, R3, R5, R6, R7, and Ari are as defined in formula (I), may be prepared as described in Scheme 4. 4-Aminoindazoles of general formula (22), purchased commercially or prepared using standard chemistry known to those in the art, may be processed as described in Schemes 1-3 to provide ureas of general formula (23) and carbamates of general formula (24). WO 2004/111009 PCT/US2004/018590 Scheme 5 O ft NH2 R, Br Ri°Y^OEt R2v^5%s^V^R7 ^^y^^/W^^7 ^2NV^5S^W/^7 ITT NBS ITT (C(0)OEt)2 II T T y y Re IX L 1 ^ R4 R« ft» Re R4 Re (D (27) (28) o Y°° fjf^Y^oEt R1 y^0Et Reducing R2v^%^A%v<'R7 R2v^sr/W^R7 Agent ITT CIC(0)CHa ITT (28) - - H^K^0 K ' > N_A^B T T ^ T T ^ R4 Rs R4 Rs (29) (30) 1 °H Ri i 0Et AT, R1 r^'*1 10%PD/C R2^^\^R7 W R2\X^L/R7 TEA, H2 iU JL JL (3) Til (30) . H^y^R9 ^ "^T^a R< R» R< R, (31) (32) O R1 Ao-^1 HO'*1 R2YVYR7 (5) NN^?^R . (31) ——>. T T ^ R4 Rs (33) Amides of general formula (32), wherein R1, R2, R4, R5, R6, R7, and Ari are as defined in formula (I), can be prepared as described in Scheme 5. Amines of general formula (1) can be treated with an acid such as, but not limited to, concentrated sulfuric acid and N-bromosuccinimide (NBS) to provide bromides of general formula (27). Bromides of general formula (27) can be treated with an organolithium reagent such as, but not limited to, n-butyllithium and diethyl oxalate in a solvent such as, but not limited to, THF to provide keto esters of general formula (28). Keto esters of general formula (28) can be treated with a reducing agent such as, but not limited to, 10% Pd/C under a hydrogen atmosphere (50 psi) in a solvent such as, but not limited to, ethanol to provide hydroxy esters of general formula WO 2004/111009 PCT/US2004/018590 (29). Hydroxy esters of general formula (29) can be treated with an acid chloride such as, but not limited to, acetyl chloride in a solvent such as, but not limited to, pyridine to provide diesters of general formula (30). Diesters of general formula (30) can be treated with 10% Pd/C and a base such as, but not limited to, triethylamine under a hydrogen atmosphere (60 psi) in a solvent such as, but not limited to, ethanol to provide esters of general formula (31). Esters of general formula (31) can be treated with amines of general formula (3) to provide amides of general formula (32). Alternatively, esters of general formula (31) can be treated with aqueous base such as, but not limited to, aqueous sodium hydroxide or aqueous potassium hydroxide to provide the acids which can then be converted into amides of general formula (32) by treatment with amines of general formula (3) under standard IXC or EDCI coupling procedures that are well known in the art. Esters of general formula (33), wherein R1, R2, R4, R5, R6, R7, and Ari are as defined in formula (I), can be prepared as described in Scheme 5. Esters of general formula (31) can be treated with alcohols of general formula (5) under standard transesterification conditions well known to those of skill in the art to provide esters of general formula (33). Scheme 6 N02 N02 N02 \A/R7 /-^^W^-R7 /-^"k^R7 1 J NaN02 N' If T ROC(0)CI N" j| T I Hi R=alkyl L I R« R5 o^O Re (35) (36) ' 1 ; R (37) O NH2 HN^N'^1 (37) lY^ 2) H.NAT, ' YY^ 0^0 R5 (3) QA0 R8 R 08) R (39) O HhT N MeOH/NaOH .fVV 7 (39) ^ Nv,J^L H R5 (40) WO 2004/111009 PCT/US2004/018590 Ureas of general formula (39) and ureas of general formula (40), wherein R5, R& R7, and Ari are as defined in formula (I) and R is alkyl as defined herein, can be prepared as described in Scheme 6. Nitro anilines of general formula (35) can be treated with sodium nitrite and an acid including, but not limited to, acetic acid in water to provide indazoles of general formula (36). Indazoles of general formula (36) can be treated with chloroformates to provide indazoles of general formula (37). Indazoles of general formula (37) can be treated with a transition metal catalyst including, but not limited to, palladium on carbon under a hydrogen atmosphere (about 1 atm to about 60 atm) to provide indazoles of general formula (38). Indazoles of general formula (38) can be processed as described in Scheme 1-3 to provide indazoles of general formula (39). Indazoles of general formula (39) can be treated with a base including, but not limited to, sodium hydroxide or potassium hydroxide to provide indazoles of general formula (40). Scheme 7 Pd/C pr> ^^ N'-5-isoquinolinylurea was resolved by chiral HPLC using a Chiralcel OD, 20 micron, 5 cm ID x 25 cm column with a mobile phase of hexanes (with 0.1% DEA)/ethanol at a 90/10 to 92/8 ratio, the flow rate was 50 ml/minutes. [ct]D +33.3° (c 0.84; MeOH); NMR (DMSO-ds) 1.06 (t, 0.6H (EtOH)), 1.29 (s, 9H), 1.78-1.90 (m, 1H), 2.43-2.54 (m, 1H, buried under DMSO), 2.76-3.05 (m, 2H), 3.44 (q, 0.4H (EtOH)), 5.19 (m, 1H), 7.27 (m, 2H), 7.31 (m, 1H), 7.43 (d, 1H), 7.89 (t, 1H), 8.05 (d, 1H), 8.63 (d, 1H), 8.69 (d, 1H), 9.33 (s, 1H), 9.73 (s, 1H); MS (ESI+) 360 (M+H)+; Elemental: Calculated for C23H25N3O»HCl»0.2H2O«0.2EtOH: C68.76, H6.81.N10.28; Found: C68.69,H6.83,N10.27. Example 7 N-(5-bromo-23-dihydro-1H-inden-l-yl)-N'-5-isoquinolinylurea Example 7A 5-bromo-l-indanone O-methyloxime 5-Bromo-l-indanone and 0-methy1Hydroxylamine hydrochloride were combined in pyridine and stirred at ambient temperature for 16 hours. The mixture was concentrated under reduced pressure and the residue was suspended in diethyl ether. The suspension was filtered and the filter cake was washed with diethyl ether. The filtrate was washed with water, IN HC1, water, and concentrated to provide the title compound. *H NMR (300 MHz, WO 2004/111009 PCT/US2004/018590 D6-DMSO) 7.63 (m, 2H), 7.48 (m, 2H), 3.90 (s, 3H), 3.00 (m, 2H), 2.80 (m, 2H); MS (DCI/NH3) m/e 240 (M+H)+. Example 7B 5-bromo-l-indanamine The title compound was prepared using 5-bromo-l-indanone O-methyloxime and the procedure described in Synthesis, 995-996 (1988). Example 7C N-(5-bromo-2.3-dihydro-1H-inden-l-yl)-N,-S-isoquinolinylurea The title compound was prepared using the procedure described in Example IF using 5-bromo-l-indanamine instead of 5-tert-butyl-2,3-dihydro-1H-inden-l-ylamine. !H NMR (300 MHz, d6-DMSO) 9.80 (s, 1H), 9.52 (s, 1H), 8.72 (m, 3H), 8.08 (d, 1H), 7.90 (t, 1H), 7.67 (d, 1H), 7.49 (m, 1H), 7.40 (m, 1H), 7.31 (d, 1H), 5.20 (m, 1H), 3.02-2.80 (m, 3H), 1.83 (m, 1H); MS (DCI/NH3) m/e 382 (M+H)+; Anal. Calcd. For Ci9Hi6N3OBr. 1.0 HC1.1.5 H20: C 51.20; H 4.52; N 9.43. Found: C 51.21; H 4.18; N 8.90. Example 8 Methyl 4-({[(5-tert-butyl-2,3-dihydro-1H-inden-l-yl)ammo]carbonyl)amino)-1H-indazole-1- carboxylate Example 8A 4-nitro-1H-indazole 2-Methyl-3-nitroaniline (20 g) in acetic acid (-200 mL) was treated with NaN02 (20 g) in water (50 mL) at 4 °C (mechanical stirring). The reaction mixture was allowed to warm to room temperature and stir overnight. The solvent was removed under reduced pressure. The residue was treated with water (700 mL) and the mixture was filtered. The solid was dried at 45 °C in a vacuum oven overnight to provide the title compound. 'H NMR (DMSO) 5 8.56 (s, 1H), 8.2-8.05 (dd, 2H), 7.6 (t, 1H). Alternatively, to a 4-necked 5-L jacketed round bottom flask fitted with a mechanical stirrer and a thermocouple was charged the nitroaniline (100 g, 1.0 equiv.) and acetic acid (2000 mL). The solution was cooled to 14 °C. A chilled to ~1 °C (ice-water bath) solution of sodium nitrite (100 g, 2.2 equiv.) in water (250 mL) was added quickly in one portion. WO 2004/111009 PCT/US2004/018590 The internal temperature rose from 14 °C to 27.6 °C over 5 min., stayed at this temperature for 5 min. before gradually cooling to IS °C. The mixture was stirred for 24 h after which it was concentrated in vacuo to an approximate volume of 500 mL. The residue was reslurried in water (1800 mL) at ambient temperature for 21 hours. The orange solid was filtered, washed with water (3X250 mL), and dried in a vacuum oven at 70 °C to afford 97.0 g of 4-nitroindazole as a bright orange solid. Example 8B methyl 4-nitro-1H-indazole-l-carboxylate NaH (0.3 g, 12.5 mmol) in DMF (5 mL) was treated with 4-nitro-1H-indazole (1.33 g, 10 mmol) at 0 °C. The reaction mixture was allowed to warm to room temperature and stir for 1 hour. The mixture was treated with methyl chloroformate (0.9 mL) and stirred at room temperature for 3 hours. The mixture was treated with water and filtered to provide the title, compound as a solid. 'HNMR (300 MHz, DMS6-d0.15toluene: C68.50, H6.93, N12.56; Found: C68.42, H6.66, N12.42. Example 9 N-(5-tert-butyl-2,3-dihydro-1H-inden-l-yl)-N-1H-indazol-4-ylurea WO 2004/111009 PCT/US2004/018S90 Methyl 4-({[(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)amino]carbonyl}amino)-1H-indazole-1-carboxylate (5.67 g, 14 mmol) in tetrahydrofuran (20 ml) was treated with A 5M solution of sodium hydroxide in methanol (8 ml, 40 mmol). After stirring for 30 minutes, the reaction mixture was diluted with water and filtered. The solid was air-dried and then treated with ethanolic HC1 to provide the title compound as the hydrochloride salt ]H NMR (DMSO-dc) 8 1.06 (t, 1.8H, EtOH), 1.27 (s, 9H), 1.75-1.88 (m, 1H), 2.40-2.48 (m, 1H), 2.76-2.88 (m, 1H), 2.90-3.01 (m, 1H), 3.44 (q, 1.2H, EtOH), 5.12 (m, 1H), 6.84 (br d, 1H), 7.05 (d, 1H), 7.20, (m, 1H), 7.26 (s, 2H), 7.31 (s, 1H), 7.69 (d, 1H), 8.10 (s, 1H), 8.70 (s, 1H); MS (ESI+): 349 (M+H)+; Elemental: Calculated for C2iH24N4O»HCl»0.6EtOH»0.6H2O: C62.98, H7.09, N13.23; Found: C63.09, H6.97, N13.18. Example 10 Methyl 4-[({[(1S)-5-tert-butyl-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)amino]-1H-indazole-1-carboxylate Example 10A (1S)-5-tert-buryl-2,3-dihydro-1H-inden-l-ylamine 5-tert-Butyl-2,3-dihydro-1H-inden-l-ylamine (25.51g, 93% potency), N-acetyl-(L) leucine (23.34g), and methanol (315 mL) were combined and heated at 65 °C for 1 hour. The solution was allowed to cool to ambient temperature. The solids were filtered and washed with toluene. The solid was then resuspended in methanol (125 mL) and brought to reflux. The solution was allowed to cool to ambient temperature and the solids were filtered. The solid was dried at 40°C under reduced pressure to provide the title compound (98.7% ee). Example 10B Methyl 4-[({[(1S)-5-tert-butyl-2}3-dihydro-1H-inden-l-yllammo)carbonyl)amino]-1H- indazole-l -carboxylate The title compound was prepared using the procedure in Example 8D, except using (lS)-5-tert-butyl-2,3-dmyd^1H-inden-l-ylamine (free base prepared from the N-acetyl-(L)-Leucine salt), instead of 5-tert-butyl-2,3-dihydro-1H-inden-l-ylamine. 1H NMR (DMSO-d6)  1.28 (s, 9H), 1.78-1.91 (m, 1H), 2.39-2.48 (m, 1H), 2.75-2.88 (m, 1H), 2.91-3.02 (m, 1H), WO 2004/111009 PCT/US2004/018590 4.04 (s, 3H), 5.17 (m, 1H), 6.73 (d, 1H), 7.27 (s, 2H), 7.30 (m, 1H), 7.50 (m, 1H), 7.69 (d, 1H), 7.88 (d, 1H), 8.39 (s, 1H), 8.84 (s, 1H); MS (ESI+): 407 (M+H)+. Example 11 methyl 4-[({[(1R)-5-tert-butyl-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)amino]-1H-indazole-1-carboxylate Example 11A (1R)-5-tert-butyl-2t3-dihydro-1H-inden-1-ylamine 5-tert-Butyl-2,3-dihydro-1H-inden-l-ylamine (11.70g, 44.4% ee), N-acetyl-(D> leucine (11.78g), and methanol (120 mL) were combined and heated at 65 °C for 1 hour. The solution was allowed to cool to ambient temperature. The solids were filtered and washed with toluene. The solid was then resuspended in methanol (125 mL) and brought to reflux. The solution was allowed to cool to ambient temperature and the solids were filtered. The solid was dried at 40°C under reduced pressure to provide the title compound (98.7% ee). Alternative preparation of (1R)-5-tert-butyl-2,3-dihydro-1H-inden-l-ylamine (1R)-(5-tert-butyl-indan-1-ylidene)-(1-phenyl-ethyl)-amine To a 5 L round bottom flask was added 5-tert-butyl-indan-l-one (370 g, ~95% pure), toluene (3.2 L, 9 vol), (R)-methylbenzylamine (266 mL, 1.05 equiv), and TFA (0.5 mL). The solution was heated to reflux via a Dean-Stark apparatus. The heating mantle was removed after -9.5 hrs at reflux (~5% unreacted ketone by HPLC assay). The brown imine solution was further cooled in an ice bath in preparation for the reduction step. (1R)-(5-tert-butyl-indan-1-yl)-(1-phenyl-ethyl)amine A suspension of NaBH4 (148.7 g, 2.0 equiv) in EtOH (3.0 L) inside a 12 L round bottom flask was cooled to <0 °C. The imine solution was added via an addition funnel over -100 minutes. The addition rate was controlled so the internal temperature did not exceed 0 °C during the addition. Ethanol (200 mL) was applied as a rinse and added to the reaction mixture. The mixture was allowed to stir at 0 ± 5 °C. The reaction was quenched after 2.75 hours by addition of water (470 mL). The bulk of the mixture was concentrated under reduced pressure to ~2.2 L. Some white solids left in the reaction vessel dissolved slowly in water (additional 200 mL). WO 2004/111009 PCT/US2004/018590 The distillation residue was taken up in water (1 L) and EtOAc (2 L) and separated. The aqueous layer was extracted again with EtOAc (0.5 L). Bubbles were observed from the aqueous layer during the extractions. The organic layers were combined, washed with 10% NaCl (1L), and concentrated. The residue was dissolved in toluene (1 L) and EtOAc (1 L). The product was extracted into 1 M H3PO4 (2x2 L). The aqueous layers were combined and washed with MTBE (1L). To isolate the secondary amine, the aqueous fraction was combined with MTBE (2 L) and the pH adjusted to 10 by addition of 10% K2C03 (3.5 L) and 50% NaOH (225 mL). The organic layer (green) obtained was concentrated to yield 405 g of oil. The crude oil was subjected to the next step without further purification. 1H-NMR (CDCI3,400 MHz): 7.43-7.38 ppm (m, 2H), 7.35 - 7.28 (m, 3H), 7.25 - 7.19 (m, 3H), 4.14 - 4.06 (m, 2H), 2.92 (m, 1H), 2.69 (m, 1H), 2.21 (m, 1H), 1.70 (m, 1H), 1.37 (d, J= 6.5 Hz, 3H), 1.31 (s, 9H). 13C-NMR_(CDC13,100 MHz): 150.0 ppm, 146.0,143.1,143.0,128.1,126.5,123.3,123.0,121.4, 60.8,56.7,35.5,34.8,31.8,30.7,25.0. Alternatively, the tosylate salt of the secondary amine may be isolated from imine reduction. 4.3 Kg of secondary amine was concentrated to produce an oil. It was redissolved in EtOAc (7.2 Kg) and added to a solution of TsOH-H20 (1.25 equiv) in EtOAc (26.2 Kg). A lot of solids precipitated. The mixture was heated to ~65 C then cooled back to room temp. The salt was collected by filtration. The wetcake was washed with EtOAc (2 x 6.5 Kg), then dried overnight in a 40 °C vacuum oven. Yield = 6.0 Kg, white solid, 88% w/w yield. 54ert-butyl-indan-ylamine To the reaction vessel was charged the secondary amine (380 g, 75242-165), MeOH (1900 mL), HOAc (10.5 g), water (190 mL), and 20% Pd(OH)2/C (190 g). The mixture was pressured with H2 (40 psi) and shaken at ambient temperature. The mixture was filtered after 6.5 hours to obtain the product in MeOH. The product solution was concentrated to furnish the acetate salt (clear oil that gradually solidified). Crude assay yield was 212.0 g amine, 86.5% yield. The corresponding indane was observed by GC as a minor component of the product mixture, >30 to 1 aminoindane to indane. Mosher's amides were prepared from the acetate salt to determine the amine mixture as having 80.2% ee (9.1 to 1 favoring the R-amine). WO 2004/111009 PCT/US2004/018590 The crude product was extracted into the aqueous layer by partitioning between aqueous HC1 solution (~1200 mL) and organic solvents (675 mL, 2:1 EPAc/MTBE). The pH of the aqueous layer was adjusted to >11 with 6N NaOH, and the product amine was recovered with multiple CH2CI2 extractions. The organic layers were combined, washed once with saturated NaCl solution (400 mL), and dried over Na2S04. After removing the solvent, the oil was assayed to be 230.5 g amine by HPLC. This material was carried forward without additional purification. 1H-NMR (CD3OD, 400 MHz): 7.42 - 7.32 ppm (m, 3H), 4.87 (bs, 3H), 4.72 (dd, J= 4.8 Hz, 7.8 Hz, 1H), 4.32 (dd, J - 4.2 Hz, 9.9 Hz, 1H), 3.05 (dddd, J= 8.6 Hz, 9.6 Hz, 15.3 Hz, 72.5 Hz, 2H), 2.58 (m, 1H), 2.08 (m, 1H), 1.95 (s, 3H), 1.75-1.45 (m,3H), 1.31 (s,9H),0.93(dd,J=3.6Hz,6.2Hz,6H). 13C-NMR(CD3OD, 100 MHz): 179.2 ppm, 171.8,153.7,144.8,136.7,125.0,124.6,122.7,56.6,54.7,43.2, 35.7,32.1,31.9,31.2,26.4,23.9,22.9,22.3. Alternatively, the tosylate salt of the amine may be isolated as follows: The product solution from debenzylation (38.33 g 5-/-Butyl-aminoindan) was distilled under reduced pressure to -390 mL. Toluene (460 mL) was added, then the mixture was distilled again under reduced pressure ~390 mL. The chase distillation with toluene was repeated three more times (460 mL each) to effectively reduce the levels of methanol and acetic acid. Product precipitated during these chase distillations. The product was obtained by filtration. The wetcake was washed with toluene and dried in a vacuum oven. Yield = 96.4% (w/w), 99.2% pure, 99.6% ee. Resolution of 5-tert-butyl-indan-ylamine via N-Ac-D-leucine salt formation To a 5 L jacketed round bottom flask was charged JV-Ac-D-leucine (232.0 g, 1.1 equiv), amine (230.5 g by assay), and MeOH (3 L). After heating the mixture to reflux, more MeOH was added in portions to dissolve all the solids. A total of 4025 mL MeOH (17.5 vol) was needed to obtain a clear solution. The solution was cooled to ambient over 13 hours via the jacket temperature control. After stirring at room temp for at least 4 hrs, the slurry was filtered. The wetcake was washed with toluene (460 mL), then dried in a 40 °C vacuum oven for ~20 hours. The white solid obtained was 243.9 g, 55.3% yield, 100 % potent (127.4 g amine). By Mosher's amides, the material was 98.8% ee (170 to 1 favoring the R-amine). The WO 2004/111009 PCT/US2004/018590 filtrates were combined, concentrated and set aside. This material was 76.5% potent (contained 92.0 g amine), 61.5% ee (4.2 to 1 favoring the R-amine). The white solid was dissolved in 0.5 M NaOH (1.5 L), and the amine extracted with CH2CI2 (2 L, 2 x 250 mL). The organic layers were combined, dried over Na2S04, and concentrated. The crude amine weighed 132.56 g, 93.7% pure. This yellow oil was subjected to coupling without further purification. A'-Acetyl-D-leucine can be recovered from the aqueous layer from above (free-basing with 0.5 M NaOH). To the solution was added cone HC1 until the pH reached ~1. The white solids were filtered and dried overnight in a 40 °C vacuum oven. Approximately 75 mL of cone HC1 was needed to accomplish the pH adjustment The recovered white solid was 107.97 g (93.0% w/w recovery), 95.7% PA (0.7%PA of amine). The remaining aqueous solution still contained some #-Ac-D-leucine. Second alternative preparation of (1R)-5-tert-butyl-23-dihydro-1H-inden-l-ylamine To a 2 L 3-neck round bottom flask was charged 5-tert-butyl-indan-l-one (120.84 g), toluene (906 mL, 7.5 vol), and (R)-memylben2ylamine (165.5 mL, 2.0 equiv). The solution was heated to 110 ± 10 °C under a slight nitrogen sweep to achieve a slow atmospheric distillation for ~22 hours. The total volume was further reduced by vacuum distillation to -420 mL. To a 1 L reactor was charged 5% Pd/C (14.0 g), imine solution (148 g of solution made above), and methanol (350 mL). The mixture was adjusted to ~0 °C, then hydrogenated under 40 psi H2 pressure overnight To the reaction mixture was then charged glacial acetic acid (34.4 mL, 2.5 equiv). The debenzylation reaction occurred under 40 psi of H2 pressure at ~40 °C. When the reaction was complete, the catalyst was filtered and washed with methanol. A solution of the product and TsOH-H2O (43.31 g, 1.0 equiv relative to product by solution assay) in a 1L 3-necked round bottom flask was concentrated under reduced pressure to ~245 mL. The thick oil was heated to >60 °C, then water (410 mL) was added slowly while maintaining the internal temperature at NLT 60 °C. After mixing at ~65 °C for ~30 min, the mixture was cooled to room temperature. The crude crystals were collected by filtration, and the wetcake was washed with water (2 x 205 mL). The wetcake was returned WO 2004/111009 PCT/US2004/018590 to the flask along with toluene (300 mL) and methanol (3.0 mL). The mixture was heated to -65 °C for ~30 min, then cooled back to room temperature. The desired product was isolated by filtration, and the wetcake was washed with toluene (2 x 100 mL). The material was dried in a 65 °C vacuum oven. Yield = 77.9% (w/w), 100% ee. Example 11B methyl 4-[({[(1R)-5-tert-butyl-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)amino]-1H-indazole-1-carboxylate The title compound was prepared using the procedure in Example 8D, except using (1R)-5-tert-butyl-2,3-dihydro-1H-inden-l-ylamine (free base prepared from the N-acetyl-(D)-Leucine salt) instead of 5-tert-butyl-2,3-dihydro-1H-inden-l-ylamine. 1H NMR (DMSO-4) 8 1.28 (s, 9H), 1.78-1.91 (m, 1H), 2.39-2.48 (m, 1H), 2.75-2.88 (m, 1H), 2.91-3.02 (m, 1H), 4.04 (s, 3H), 5.17 (m, 1H), 6.73 (d, 1H), 7.27 (s, 2H), 7.30 (m, 1H), 7.50 (m, 1H), 7.69 (d, . 1H), 7.88 (d, 1H), 8.39 (s, 1H), 8.84 (s, 1H); MS (ESI+) 407 (M+H)+; Elemental: Calculated for C23H26N4O3: C67.96, H6.45.N13.78; Found: C67.85, H6.51,N13.56. Example 12 N-[(1S)-5-tert-butyl-2,3-dihydro-1H-inden-1-yl]-N,-1H-indazol-4-ylurea The title compound was prepared using the procedure in Example 9, except using methyl 4-[({[(l S>5-tert-butyl-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)amino]-1H- indazole-1-carboxylate instead of methyl 4-[({[5-tert-butyl-2,3-dihydro-1H-inden-l-yl]amino}carbonyl)amino]-1H-indazole-l-carboxylate(Ex. 10B). 1H NMR(DMSO-d6)5 1.27 (s, 9H), 1.75-1.88 (m, 1H), 2.40-2.48 (m, 1H), 2.76-2.88 (m, 1H), 2.90-3.01 (m, 1H), 5.15 (m, 1H), 6.84 (br d, 1H), 7.05 (d, 1H), 7.20, (m, 1H), 7.26 (s, 2H), 7.31 (s, 1H), 7.69 (d, 1H), 8.11 (s, 1H), 8.72 (s, 1H); MS (ESI+): 349 (M+H)+; Elemental: Calculated for C2iH24N4O«HCl»0.17hexane: C66.19, H6.91,N14.02; Found: C66.ll, H6.94, N13.96 Example 13 N-[(1R)-5-tert-butyl-2,3-dihydro-1H-inden-1-yl]-N,-1H-indazol-4-ylurea The title compound was prepared using the procedure in Example 9, except using methyl 4-[({[(1R)-5-tert-butyl-2,3-dihydro-1H-inden-l-yl]amino}carbonyl)amino]-1H-indazole-1-carboxylate instead of methyl 4-[({[5-tert-butyl-2,3-dihydro-1H-inden-l-yl]amino}carbonyl)amino]-1H-indazole-l-carboxylate(Ex. 11B). 1H NMR (DMSO-d6)  1.27 (s, 9H), 1.75-1.88 (m, 1H), 2.40-2.48 (m, 1H), 2.76-2.88 (m, 1H), 2.90-3.01 (m, 1H), WO 2004/111009 PCT/US2004/018590 5.15 (m, 1H), 6.84 (br, 1H), 7.05 (d, 1H), 7.20, (m, 1H), 7.26 (s, 2H), 7.31 (s, 1H), 7.69 (d, 1H), 8.17 (s, 1H), 8.83 (s, 1H); MS (ESI+): 349 (M+H)+; Elemental: Calculated for C21H2MOHCI: C65.53, H6.55, N14.56; Found: C65.29, H6.63.N14.23. Alternative method of preparing N-[(1R)-5-tert-butyl-2,3-dihydro-1H-inden-l-yl]-N'-1H- Indazol-4-ylurea. Step A 4-2,5-dioxo-pyrrolidin-l-yloxycarbonylamino)-indazole-l-carboxylic acid methyl ester To a 3-necked 2-L flask fitted with a mechanical stirrer and a nitrogen inlet were charged the aminoindazole carbamate (94.5 g, 1.0 equiv.), N,N'-disuccinimidy carbonate (113.8 g, 1.07 eq), and dry acetonitrile (950 mL, KF - 0.06%). Pyridine (32.8 g, 1.0 eq) was added to the mixture and it was heated to 40 °C and stirred for 15 h during which time a solid precipitated. The solid was filtered, washed with fresh dry acetonitrile (3X100 mL), and dried in a vacuum oven at 40 °C to afford 130.1 g (92.9 % potency adjusted) of the activated succinimidyl carbamate as a light brown solid. StepB (1R)4-[3-(5-tert-butyl-indan-l-yl)-ureido]-indazole-l-carboxylic acid methyl ester Indazole succinimidylcarbamate (33 g, 0.1 mol) was added in 2 portions (over 5 min) to a solution of indanylamine (20.4 g, 0.105 mol, 1.05 eq) and diisopropylethylamine (13.4 g, 0.104 mol) in DMF (165 mL), which was cooled to 20 °C in a water bath under nitrogen atmosphere. An exotherm to 24 °C was observed. After ~ 1 hour, a clear dark brown solution was formed and the reaction was found complete by HPLC. StepC 4-[3-(5-tert-butyl-indan--l-yl)-ureido]-indazole-l-carboxylic acid methyl ester Sodium hydroxide solution in methanol [prepared by dissolving sodium hydroxide (4.8 g 1.2 eq) in methanol (100 mL)] was added to the solution of the penultimate urea, which was precooled to 20°C on a water bath. After stirring for 0.5 hour, the reaction was found complete by HPLC, and the mixture was poured into water (825 mL). An exotherm to 30 °C was observed. After cooling to ambient temperature, the precipitate was filtered off and washed with (1:1) methanol/water (200 mL). The washes were slow, as the wet cake tended to absorb the solvent The wet cake was dried under vacuum overnight at 65 °C to give 34.1 g of the material, which was assayed for 30.7 g of the product by HPLC method. The crude was dissolved in 600 mL of methanol at reflux. The solution was filtered hot and distilled to WO 2004/111009 PCT/US2004/018590 -180 mL volume. The resulting slurry was cooled to ambient temperature, mixed for 2 hours, filtered, washed with methanol (50 mL) and dried under vacuum at 65 °C for 15 hours to provide 27.8 of the title compound (80 % yield). Example 13A N-[(1R)-5-tert-butyl-2,3-dihydro-1H-inden-1-yl]-N,-1H-indazol-4-ylurea The amorphous form of Example 13 was prepared by evaporating a solution of Example 13 in THF (lg/30mL) at ambient temperature under vacuum. Differential scanning calorimetry and X-ray diffraction results are shown in Figure 1 and 2, respectively. Example 13B N-[(1S)-5-tert-butyl-2,3-dihydro-1H-inden-1-yl]-N,-1H-indazol-4-ylurea, hydrochloride Hydrochloric acid (37 % aq, 17mg) was added to a solution of compound of Example 13 (60 mg, 0.17 mmol) in THF 4 mL. After mixing for additional 15 h the precipitate was filtered off and dried to provide 27 mg (40 %) of the salt Differential scanning calorimetry and X-ray diffraction results are shown in Figure 3 and 4, respectively. Example 13C N-[(1R)-5-tert-butyl-23-dihydro-1H-inden-l-yl1-N-1H-mda2ol-4-ylurea,tosylate Tosylic acid monohydrate (33 mg, 0.17 mmol) was added to a solution of compound of Example 13 (60 mg, 0.17 mmol) in THF 4 mL. After mixing for additional 15 h the precipitate was filtered off and dried to provide 65 mg (73%) of the salt._Differential scanning calorimetry and X-ray diffraction results are shown in Figure 5 and 6, respectively. Example 13D N-[(1S)-5-tert-butyl-2,3-dihydro-1H-inden-1-yl]-N,-1H-indazol-4-ylurea, benzenesulfonate Benzenesulfonic acid (26 mg) was added to a solution of compound of Example 13 (60 mg, 0.17 mmol) in THF 4 mL. After mixing for additional 15 h the precipitate was filtered off and dried to provide 45 mg (52 %) of the salt Differential scanning calorimetry and X-ray diffraction results are shown in Figure 7 and 8, respectively. Example 14 WO 2004/111009 PCT/US2004/018590 Methyl 4-[({[5-(trifluoromethyl)-2.3-dihydro-1H-inden-1-yl]amino}carbonyl)amino]-1H- indazole-1-carboxylate The title compound was prepared using the procedure in Example 8D, except using 5-(trifluoromethyl)-23-dihydro-1H-inden-l-ylamine instead of 5-tert-butyl-2,3-dihydro-1H-inden-1-ylamine. 1H NMR (DMSO-d6) 8 1.85-1.98 (m, 1H), 2.50-2.61 (m, 1H), 2.86-2.97 (m, 1H), 3.00-3.12 (m, 1H), 4.04 (s, 3H), 5.29 (m, 1H), 6.85 (d, 1H), 7.51 (m, 1H), 7.57 (m, 2H), 7.64 (s, 1H), 7.70 (d, 1H), 7.85 (d, 1H),8.42 (s, 1H), 8.96 (s, 1H); MS (ESI+): 419 (M+H)+; Elemental: Calculated for C20H17N4O3F3: C57.42, H4.10, N13.39; Found: C57.44, H4.21,N13.03. Example 15 N-1H-indazol-4-yl-N'-r5-(trifluoromemylV2J-dihydro-1H-inden-l-yl]urea The title compound was prepared using the procedure in Example 9, except using methyl 4-[({ [5-(trifluoromethyl)-2,3-dihydro-1 H-inden-1 -yl]ammo}carbonyl)amino]-l H-indazole-1-carboxylate instead of methyl 4-[({[5-tert-butyl-2,3-dihydro-1H-inden-l-yl]ammo}carbonyl)amino]-1H-indazole-l-carboxylate. 'HNMR (DMSO-de) 6 1.06 (t, 2.4H EtOH), 1.82-1.94 (m, 1H), 2.52-2.60 (m, 1H), 2.85-2.97 (m, 1H), 2.98-3.10 (m, 1H), 3.44 (q, 1.6H, EtOH), 5.28 (m, 1H), 7.08 (m, 2H), 7.21 (m, 1H), 7.56 (m, 2H), 7.63 (s, 1H), 7.69 (d, 1H), 8.17 (s, 1H), 8.91 (s, 1H); MS (ESI+) 361 (M+H)+; Elemental: Calculated for Ci8Hi5N4OF3«HCl»0.8EtOH«0.1H2O: C54.06, H4.86, N12.87; Found: C54.02, H4.58, N12.62. Example 16 Methyl 4-({[(5-piperidm-l-yl-2,3-dihydro-1H-inden-l-yl)ammo]carbonyl)amino)-1H- indazole-1-carboxylate Example 16A 5-piperidin-1 -y lindan-1 -one 5-Fluoroindan-l-one (5 g, 33.3 mmol) and piperidine (8.52g, 100 mmol, 10 ml) were dissolved in pyridine (20 ml) and heated to reflux for 3 hours. The reaction mixture was cooled, the solvent removed under vacuum, and the residue taken in diethyl ether. The ether solution was washed with IN aqueous sodium hydroxide and with water, dried with WO 2004/111009 PCT/US2004/018590 magnesium sulfate, filtered, and the filtrate was removed under vacuum to provide the title compound which was used without further purification. *H NMR (CDCI3) 51.67 (m, 6H), 2.63 (m, 2H), 3.02 (m, 2H), 3.40 (m, 4H), 6.78 (d, 1H), 6.86 (dd, 1H), 7.62 (d, 1H); MS (DCI)216(M+H)+. Example 16B 5-piperidin-l-ylindan-l-one O-methyloxime 5-Piperidin-l-ylindan-l-one (4.31 g, 20 mmol) in pyridine (20 ml) was treated with methoxyamine hydrochloride (1.84 g, 22 mmol). After stirring at ambient temperature for 40 hours, the solvent was removed under vacuum and the residue taken in water and extracted with diethyl ether. The combined organic layers were washed with water, dried with magnesium sulfate, filtered, and the filtrate was removed under vacuum to provide the title compound which was used without further purification. *H NMR (CDCI3) 81.56-1.73 (m, 6H), 2.78-2.89 (m, 1H), 2.91-3.02 (m, 1H), 3.20-3.30 (m, 2H), 3.95 (s, 3H), 6.78 (m, 1H), 6.84 (m, 1H), 7.54 (d, 1H); MS (DCI): 245 (M+H)+. Example 16C 5-piperidm-l-yl-2J-dihydro-1H-inden-l-ylamine 5-Piperidin-l-ylindan-l-one O-methyloxime (2.95g, 12 mmol), 10% palladium on carbon (1.45g), and 20% ammonia in methanol (80 ml), were placed in a Parr apparatus, which was charged with hydrogen to 60 psi. The mixture was shaken for 1 hour at ambient temperature and filtered. The filtrate was removed under vacuum to provide the title compound which was used without further purification. 'H NMR (CDCI3) 81.53-1.60 (m, 2H), 1.65-1.79 (m, 4H), 2.42-2.53 (m, 1H), 2.69-2.81 (m, 1H), 2.86-2.96 (m, 1H), 3.12 (t, 4H), 4.31 (t, 1H), 6.82 (m, 2H), 7.20 (d, 1H); MS (DCI) 217 (M+H)+. Example 16D methyl4-({[(5-piperidm-l-yl-2,3-dihydro-1H-inden-l-yl)ammo]carbonyl}amino)-1H- indazole-1-carboxylate The title compound was prepared using the procedure in Example 8D, except using 5-piperidm-l-yl-2,3-dihydro-1H-inden-l-ylamine instead of 5-tert-butyl-2,3-dihydro-1H-inden-1-ylamine. 1HNMR (DMSO-de) 6 1.48-1.66 (m, 6H), 1.75-1.89 (m, 1H), 2.39-2.47 (m, 1H), WO 2004/111009 PCT/US2004/018590 2.70-2.82 (m, 1H), 2.85-2.95 (m, 1H), 3.10 (m, 4H), 4.04 (s, 3H), 6.61 (d, 1H), 6.81 (m, 2H), 7.12 (d, 1H), 7.49 (m, 1H), 7.68 (d, 1H), 7.88 (d, 1H), 8.38 (s, 1H), 8.82 (s, 1H); MS (ESI+) 434 (M+H)+; Elemental: Calculated for C24H27N5O3.0.3CH2Cl2: C63.59, H6.06,N15.26; Found: C63.68, H6.02, N15.14. Example 17 N-1H-indazol-4-yl-N-(5-piperidin-l-yl-23-dihydro-1H-inden-l-yl)urea The title compound was prepared using the procedure in Example 9, except using memyl4-({[(5-piperidm-l-yl-23-dihydro-1H-inden-l-yl)ammo]carbonyl}amino)-1H- indazole-1-carboxylate instead of methyl 4-[({[5-tert-butyl-2,3-dihydro-1H-inden-l-yl]ammo}carbonyl)amino]-1H-indazole-l-carboxylate. 'H NMR (DMSO-de) 8 1.09 (t, 1.2H, Et20), 1.40-2.20 (br m, 7H), 2.52-2.59 (m, 1H), 2.84-2.96 (m, 1H), 2.96-3.07 (m, 1H), 3.38 (q, 0.8H, Et20), 3.52 (m, 4H), 5.24 (m, 1H), 5.76 (s, 0.2H, CH2CI2), 7.05 (d, 1H), 7.21 (m, 1H), 7.33 (m, 1H), 7.50 (d, 1H), 7.65-7.77 (m, 3H), 8.29 (s, 1H), 9.15 (s, 1H); MS (ESI+) 376 (M+H)+; Elemental: Calculated for C22H25N5O«2HCl«0.1CH2Cl2«0.2Et2O: C58.31, H624, N14.85; Found: C58.22, H6.54, N15.00. Example 18 methyl 4-({[(5-hexahvdro-1H-azepm-l-yl-2,3-dihydro-1H-inden-l- yl)ammo1carbonyl)amino)-1H-indazole-l-carboxylate Example 18A 5-hexahydro-1H-azepm-l-ylindan-l-one 5-Fluoroindan-l-one (5 g, 33.3 mmol) and azepane (9.92g, 100mmol) Were dissolved in pyridine (20 ml) and heated at reflux for 3 hours, stirred at ambient temperature for 16 hours, and then heated at reflux for an additional 6 hours. The solvent was removed under vacuum and the residue partitioned between methylene chloride and water. The organic layer was washed with IN aqueous sodium hydroxide, dried with magnesium sulfate, filtered, and the filtrate was concentrated under vacuum. The residue was filtered through a pad of silica gel with 1:1 ethyl acetate:hexanes, and the solvent evaporated under vacuum to provide the title compound which was used without further purification. !H NMR (CDCI3) 8 1.56 (m, WO 2004/111009 PCT/US2004/018590 4H), 1.81 (m, 4H), 2.62 (m, 2H), 3.02 (m, 2H), 3.55 (t, 4H), 6.59 (d, 1H), 6.68 (dd, 1H), 7.61 (d, 1H); MS (DCI) 230(M+H)+. Example 18B 5-hexahvdro-1H-azepin-l-ilindan-l-oneO-methyloxime The title compound was prepared using the procedure in Example 16B, except using 5-hexahydro-1H-azepin-l-ylindan-l-one instead of 5-piperidin-l-ylindan-l-one. 1H NMR (CDC13) 5 1.55 (m, 4H), 1.79 (m, 4H), 2.77-2.88 (m, 1H), 2.92-3.00 (m, 1H), 3.48 (m, 2H), 3.94 (s, 3H), 6.55 (m, 1H), 6.61 (m, 1H), 7.51 (d, 1H) MS (DCI): 259 (M+H)+. Example 18C 5-hexahvdro-1H-azepm-l-yl-2J-dihydro-1H-mdea-l-Ylamine The title compound was prepared using the procedure in Example 16C, except using 5-hexahydro-1H-azepin-l-ylindan-l-one O-methyloxime instead of 5-piperidin-l-ylindan-l-one O-methyloxime. !H NMR (CDCI3) 8 1.55 (m, 4H), 1.60-1.74 (m, 1H), 1.77 (m, 4H), 2.41-2.52 (m, 1H), 2.69-2.69 (m, 1H), 2.86-2.97 (m, 1H), 3.43 (t, 4H), 4.31 (t, 1H), 6.57 (m, 2H), 7.16 (d, 1H); MS (DCI) 231 (M+H)+. Example 18D memyl4-({[(5-hexahydro-1H-azepm-l-yl-23-dihydro-1H-inden-l-yl)amino]carbonyl)amino)-1H-indazole-l-carboxylate The title compound was prepared using the procedure in Example 16D, except using 5-hexahydro-1H-azepm-l-yl-2,3-dihydro-1H-inden-l-ylarnine instead of 5-piperidin-l-yl-23-dihydro-1H-inden-l-ylamine. !H NMR (DMSO-d«) 8 1.17 (t, 0.21H, EtOAc), 1.45 (m, 4H), 1.71 (m, 4H), 1.76-1.86 (m, 1H), 1.99 (s, 0.21H, EtOAc), 2.35-2.48 (m, 1H), 2.69-2.80 (m, 1H), 2.84-2.95 (m, 1H), 3.45 (t, 4H), 4.03 (q, 0.14H, EtOAc), 4.04 (s, 3H), 5.06 (m, 1H), 6.56 (m, 3H), 7.12 (d, 2H), 7.50 (m, 1H), 7.67 (d, 1H), 7.89 (d, 1H), 8.38 (s, 1H). 8.79 (s, 1H); MS (ESI+) 448 (M+H)+; Elemental: Calculated for C25H29N5O3»0.07EtOAc: C66.92, H6.57, N15.44; Found: C66.62, H6.85, N15.70. Example 19 N-(5-hexahydro-1H-azepm-l-yl-23-dihydro-1H-inden-l-yl)-N'-1H-indazol-4-ylurea WO 2004/111009 PCT/US2004/018590 The title compound was prepared using the procedure in Example 9, except using memyl4-({[(5-hexahydro-1H-azepm-l-yl-23-dihydro-1H-inden-l- yl)amino]carbonyl} amino)- 1H-indazole-1-carboxylate instead of methyl 4-[({[5-tert-butyl- 2,3-dihydro-1H-inden-l-yl]amino}carbonyl)amino]-1H-indazole-1-carboxylate. 1H NMR (DMSO-de) 5 1.45 (m, 4H), 1.71 (m, 4H), 1.75-1.81 (m, 1H), 2.38-2.45 (m, 1H), 2.86-2.93 (m, IK), 3.45 (t, 4H), 5.07 (m, 1H), 6.58 (m, 3H), 7.05 (d, 1H), 7.12 (d, IK), 7.21 (m, 1H), 7.68 (d, IK), 8.03 (s, IK), 8.51 (s, IK), 12.97 (s, IK); MS (ESI+) 390 (M+H)+. Example 20 N-1H-indazol-4-yl-N,-[(1R)-5-piperidin-l-yl-2,3-dihydro-1H-inden-l-yl]urea The title compound was obtained from the preparative chiral separation (ChiralPak AD, Hex(0.2% dlemylamine):EtOH:MeOH =8:1:1) of N-1H-indazol-4-yl-N'-(5-piperidin-l-yl-2,3-dihydro-1H-inden-l-yl)urea. *H NMR (300 MHz, d6-DMSO) 13.00 (broad s, IK), 8.60 (s, IK), 8.04 (s, 1H), 7.67 (d, IK), 7.18 (m, 2H), 7.03 (d, IK), 6.80 (m, 2H), 6.66 (d, IK), 5.05 (m, 1H), 3.10 (m, 4H), 2.78 (m, IK), 2.41 (m, IK), 1.80 (m, IK), 1.68-1.45 (m, 7H); MS (DCI/NH3) m/e 376 (M+H)+. Example 21 N-1H-indazol-4-yl-N'-[(1S)-5-piperidin-l-yl-2,3-dihydro-1H-inden-l-yl]urea The title compound was obtained from the preparative chiral separation (ChiralPak AD, Hex(0.2% diethylamine):EtOH:MeOH -8:1:1) of N-1H-indazol-4-yl-N'-(5-piperidin-l-yl-2,3-dihydro-1H-inden-l-yl)urea. 'H NMR (300 MHz, d6-DMSO) 513.00 (broad s, IK), 8.61 (s, IK), 8.04 (s, IK), 7.67 (d, IK), 7.18 (m, 2H), 7.03 (d, IK), 6.80 (m, 2H), 6.66 (d, IK), 5.05 (m, IK), 3.10 (m, 4H), 2.78 (m, IK), 2.41 (m, 1H), 1.80 (m, IK), 1.68-1.45 (m, 7H); MS (DCI/NH3) m/e 376 (M+H)+. Example 22 isopropyl4-({[(5-tert-butyl-23-dihydro-1H-inden-l-yl)amino]carbonyl}amino)1H-indazole- 1-carboxylate Example 22A isopropyl 4-nitro-1H-indazole-l-carboxylate WO 2004/111009 PCT/US2004/018590 The title compound was prepared using the procedure in Example 8B, except using isopropyl chloroformate instead of methyl chloroformate. Example 22B isopropyl 4-amino-1H-indazole-l-carboxylate The title compound was prepared using the procedure in Example 8C, except using isopropyl 4-nitro-1H-indazole-l-carboxylate instead of methyl 4-nitro-1H-indazole-l-carboxylate. Example 22C isopropyl 4^({f(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)amino]carbonyl}amino)-1H-indazole 1-carboxylate The title compound was prepared using the 4 step procedure described in Ex. 8 except using isopropyl chloroformate instead of methyl chloroformate in Ex. 8B. 1H NMR (300 MHz, d6-DMSO) 8.82 (s, 1H), 8.40 (s, 1H), 7.90 (d, 1H), 7.68 (d, 1H), 7.50 (m, 1H), 7.29 (d, 2H), 6.67 (d, 1H), 5.20 (m, 2H), 2.92 (m, 1H), 2.83 (m, 1H), 2.41 (m, 1H), 1.84 (m, 1H), 1.40 (d, 6H), 1.30 (s, 9H); MS (DCI/NH3) m/e 435 (M+H)+; Anal. Calcd. For C25H30N4O3: C 69.10; H 6.96; N 12.89. Found: C 68.89; H 6.90; N 12.83. Example 23 isobutyl4-({r(5-tert-butyl-23-dihydro-1H-inden-1-yl)amino]carbonyl}amino)-1H-indazole- 1-carboxylate Example 23 A isobutyl 4-nitro-1H-indazole-l-carboxylate The title compound was prepared using the procedure in Example 8B, except using isobutyl chloroformate instead of methyl chloroformate. Example 23B isobutyl 4-amino-1H-indazole-l-carboxylate WO 2004/111009 PCT/CS2004/018590 The title compound was prepared using the procedure in Example 8C, except using isobutyl 4-nitro-1H-indazole-l-carboxylate instead of methyl 4-nitro-1H-indazole-l-carboxylate. Example 23C isobittyl4({[(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)amino]carbonyl}-1H-indazole- 1-carboxylate The title compound was prepared using the 4 step procedure described in Ex. 8 except using isobutyl chloroformate instead of methyl chloroformate in Ex. 8B 1H NMR (300 MHz, d6DMSO) 8.82 (s, 1H), 8.40 (s, 1H), 7.90 (d, 1H), 7.68 (d, 1H), 7.50 (m, 1H), 7.29 (d, 2H), 6.70 (d, 1H), 5.19 (m, 1H), 4.23 (d, 2H), 2.88 (m, 1H), 2.80 (m, 1H), 2.41 (m, 1H), 2.10 (m, 1H), 1.84 (m, 1H), 1.40 (d, 6H), 1.27 (s, 9H), 1.00 (d, 6H); MS (DCI/NH3) m/e 435 (M+H)+; Anal. Calcd. For C26H32N4O3 0.2 Et20: C 69.47; H 7.40; N 12.09. Found: C 69.49; H 7.72; N 12.21. Example 24 N-(5-choro-2,3-dihydro-1H-inden-1yl)-N’-1H-indazol-4-ylurea Example 24A 5-chloro-2,3-dihydro-1Hinden-1-ylamine The title compound was made according to the conditions described in Example 57D, except using 5-chloro-l-indanone instead of 2-methyl-2-(l-oxoindan-5-yl)-propionitrile Example 24B N-(5-chloro-2,3-dihydro-1-inden-1-yl-N’-1Hindazol-4-ylurea The title compound was made first according to the conditions described in Ex. 8D except using 5-chloro-2,3-dihydro-1H-inden-1-ylamine instead of 5-tert-butyl-2,3-dihydro-1H-inden-1-ylamine (MS 385 (M+1)). Deprotection of the product obtained by using 5M NaOH in methanol according to Ex. 9 afforded the title compound. NMR (DMSO-d6): 8.92 (s, 1H), 8.20 (s, 1H), 7.68 (d, J 7.5 Hz, 1H), 7.40 - 7.18 (m, 6H), 7.06 (d, J 8 Hz, 2H), 5.20 (m, 1E), WO 2004/111009 PCT/US2004/018590 3.00 - 2.78 (m, 3H), 1.83 (m, 1H). MS (DCI): 327 (M+l). Elemental: Calculated for C17H15N4C1O1.0 HC1«0.6 H20: C 54.59, H 4.63, N 14.98; Found: C54.22, H4.42.N15.18. Example 25 N-(5-fluoro-2,3-dihydro-1H-inden-1-yl)-N’-1H-indazol-4-ylurea Example 25 A 5-fluoro-2,3-dihydro-1H-inden-1-ylamine The title compound was made according to the conditions described in Example 1C and 1D, except using 5-fluoro-1-indanone instead of 5-tert-butyl-1-indanone. Example 25B N-(5-fluoro-2,3-dihydro-1H-inden-1-yl)-N’1H-indazol-4-ylurea The title compound was made first according to the conditions described in Ex. 8D except using 5-fluoro-2,3-dihydro-1H-inden-1-ylamine instead of 5-tert-butyl-2,3-dihydro-1H-inden-1-ylamine (MS 369 (M+1)). Deprotection of the product obtained by using 5M NaOH in methanol according to Ex. 9 afforded the title compound. NMR (DMSO-d6): 8.9 (s, 1H), 8.20 (s, 1H), 7.70 (d, J 7.5 Hz, 1H), 7.38 (m, 1H), 7.23 - 7.00 (m 5H), 5.20 (m, 1H), 3.00 - 2.78 (m, 3H), 1.83 (m, 1H). MS (DCI): 311 (M+1). Elemental: Calculated for C17H15N4FO•1.0 HC1•0.6 H20: C 57.10, H 4.85, N 15.67; Found: C 56.90, H 4.78, N 15.94. Example 26 N-(4,5-dimethoxy-2,3-dihydro-1H-inden-1-yl)-N’-1H-indazol-4-ylurea Example 26A 4.5-Dimethoxy-2,3-dihydro-1H-inden-l-ylamine WO 2004/111009 PCT/US2004/018590 The title compound was made according to the conditions described in Example 1C and ID, except using 4,5-dimeihoxy-l-indanone instead of 5-tert-butyl-l-indanone. Example 26B 4-[3-(4,5-dimethoxy-indan-l-ylVureido]-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4,5-Dimethoxy-2,3-dihydro-1H-inden-l-ylamine instead of 5-(2-methoxy-l,l-dimemyl-ethyl-indan-1-ylamine. MS (DCI) 411 (M+l). Example 26C N-(4,5-dimethoxy-2,3-dihydro-1H-inden-l-yl)-N'-1H-indazol-4-ylurea The title compound was made from 4-[3-(4,5-dimethoxy-indan-l-yl)-ureido]-indazole-1-carboxylic acid methyl ester according to the deprotection procedure by using 5M NaOH in methanol (example 9). NMR (DMSO-d3-(1H-indazol-4-yl>urea (0.34 g, 0.98 mmol) in pyridine (3 mL) was added acetyl chloride (1.0 mL) and mixture stirred for 15 hours at ambient temperature., The reaction mixture was concentrated and chromatographed (EtOAc-hexane, 1:4) to obtain 54 mg (14 %) of desired product. NMR (DMSO-d«): 8.92 (s, 1H), 8.40 (s, 1H), 7.85 (m, 2H), 7.50 (m, 1H), 7.28 (m, 3H), 6.71 (d, J 8 Hz, 1H), 5.18 (m, 1H), 3.00-2.78 (m, 2H), 2.70 (s, 3H), 2.43 (m, 1H), 1.83 (m, 1H). MS (DCI): 391 (M+l). Elemental: Calculated for C18H18N402: C 70.75, H 6.71, N 14.35; Found: C 70.72, H 7.11, N 14.44. WO 2004/111009 PCT/US2004/018590 Example 32 N-[(1S)-4,5-dimetfaoxy-2,3-dihydro-1H-inden-l-yl]-N-1H-indazol-4-ylurea The title compound was prepared by chiral separation of the corresponding racemic compound N-(4,5-«miietooxy-2,3-dihydro4H-inden-1-yl)-N-1H-idazol-4-ylurea (ex. 26) using a chiral column ChiralCel OD. NMR (DMSO-de): 13.0 (broad s, 1H), 8.60 (s, 1H), 8.07 (s, 1H), 7.67 (d, J 7.5 Hz, 1H), 7.20 (m, 1H), 7.04 (m, 2H), 6.92 (d, J 8 Hz, 1H), 6.65 (d, J 8 Hz, 1H), 5.15 (m, 1H), 3.78 (s, 3H), 3.76 (s, 3H), 2.92 (m, 1H), 2.80 (m, 1H), 2.43 (m, 1H), 1.82 (m, 1H). MS (DO): 353 (M+1). Example 33 N-[(1R)-4,5-dimethoxy-2,3-dihydro-1H-inden-l-yl]-N-1H-indazol-4-ylurea The title compound was prepared by chiral separation of the corresponding racemic compound N-(4,5-Klimethoxy-2,3-dihydro-1H-inden-l-yl)-N,-1H-indazol^ylurea (ex. 26) using a chiral column ChiralCel OD. NMR (DMSO-d6): 13.0 (broad s, 1H), 8.60 (s, 1H), 8.07 (s, 1H), 7.67 (d, J 7.5 Hz, 1H), 7.20 (m, 1H), 7.04 (m, 2H), 6.92 (d, J 8 Hz, 1H), 6.65 (d, J 8 Hz, 1H), 5.15 (m, 1H), 3.78 (s, 3H), 3.76 (s, 3H), 2.92 (m, 1H), 2.80 (m, 1H), 2.43 (m, 1H), 1.82 (m, 1H). MS (DCI): 353 (M+1). Example 34 N-1H-indazol-4-yl-N'-[(1S)-5-methoxv-2,3-dihydro-1H-inden-l –yl]urea The title compound was prepared by chiral separation of the corresponding racemic compound N-1H-indazol-4-yl-N'-(5-methoxy-2,3-dihydro-1H-inden-l-yl)urea (ex. 27) using a chiral column ChiralCel OD. NMR (DMSO-d6): 13.0 (broad s, 1H), 8.60 (s, 1H), 8.07 (s, 1H), 7.67 (d, J 7.5 Hz, 1H), 7.22 (m, 2H), 7.06 (d, J 8 Hz, 1H), 6.88 (d, J 1.5 Hz, 1H), 6.80 ' (dd, J 1.5 and 8 Hz, 1H), 6.63 (d, J 8 Hz, 1H), 5.13 (m, 1H), 3.72 (s, 3H), 3.00 - 2.70 (m, WO 2004/111009 PCT/US2004/018590 2H), 2.42 (m, 1H), 1.80 (m, 1H). MS (DCI): 323 (M+l). Example 35 N-1H-indazol-4-yl-N,-[(1R)-5-methoxy-2,3-dihydro-1H-inden-1-yl]urea The title compound was prepared by chiral separation of the corresponding racemic compound N-1H-indazol-4-yl-N'-(5-methoxy-2,3-dihydro-1H-inden-l-yl)urea (ex. 27) using a chiral column ChiralCel OD. NMR (DMSO-de): 13.0 (broad s, 1H), 8.60 (s, 1H), 8.07 (s, 1H), 7.67 (d, J 7.5 Hz, 1H), 7.22 (m, 2H), 7.06 (d, J 8 Hz, 1H), 6.88 (d, J 1.5 Hz, 1H), 6.80 (dd, J 1.5 and 8 Hz, 1H), 6.63 (d, J 8 Hz, 1H), 5.13 (m, 1H), 3.72 (s, 3H), 3.00-2.70 (m, 2H), 2.42 (m, 1H), 1.80 (m, 1H). MS (DCI): 323 (M+l). Example 36 N-1H-indazol-4-yl-N'-[5-(2-methoxy-1,1-dimeyhylethyl)-2,3dihydro-1H-inden-1-yl]urea Example 36A (3-bromo-phenyl)-acetic acid methyl ester To a solution of 3-brophenylacetic acid (5.0 g, 23.3 mmol) in MeOH (50 mL) was added acetyl chloride (5.0 mL) and resulting solution refluxed for 2.5 h. The mixture was cooled to ambient temperature, diluted with ether and washed with water twice. Organic layer was separated and concentrated to obtain 5.4 g of the crude material as an oil. NMR (DMSO-de): 7.50 (m, 2H), 7.28 (m, 2H), 3.72 (s, 2H), 3.61 (s, 3H). MS (DCI): 246 (M+NH4). Example 36B 2-(3-bromo-phenyl)-2-methyl-propionic acid methyl ester To the suspension of NaH (1.65 g, 68.8 mmol, 95%) in THF (100 mL) was added dropwise crude (3-bromo-phenyl)-acetic acid methyl ester (~23.3 mmol) and after 20 min Mel (7.8 g, 55.0 mmol) was added. The milky solution was stirred for 15 h at ambient WO 2004/111009 PCT/US2004/018590 temperature and quenched with i-PrOH and H20. Resulting mixture was exctracted with ether. Organic layer was washed with aq. NH4CI and water, separated and evaporated to obtain desired product (5.0 g, 85%) as an oil. NMR (DMSO-d«): 7.48 (m, 2H), 7.30 (m, 2H), 3.60 (s,3H), 1.50 (s,6H). MS(DCI):274(M+NH4). Example 36C 2-(3-bromo-phenyl)-2-mefliyl-propan-l -ol To a stirred suspension of UAIH4 (0.71 g, 18.7 mmol) in THF (100 mL) was added dropwise 2-(3-bromo-phenyl)-2-methyl-propionic acid methyl ester (4.0 g, 15.6 mmol). After 2 h the mixture was quenched with i-PrOH and H2O and extracted with ether. Organic layer was washed twice with water, separated and concentrated to obtain desired alcohol (3.5 g, 98%). NMR (DMSO-de): 7.52 (m, 1H), 7.38 (m, 2H), 7.24 (m, 1H), 4.72 (t, J 3.5 Hz, 1H), 3.40 (d, J 3.5 Hz, 2H), 1.10 (s, 6H). MS (DCI): 246 (M+NH4). Example 36D l-bromo-3-(2-methoxy-1,1-dimethyl-ethyl)-benzene To a suspension of NaH (0.22 g, 9.00 mmol, 95%) in THF (30 mL) was added dropwise at ambient temperature the solution of 2-(3-bromo-phenyl)-2-methyl-propan-l-ol (1.7 g, 7.46 mmol) in THF (10 mL). After 10 min Mel (0.8 mL, 15 mmol) was added and the mixture stirred for 3 h at ambient temperature. The mixture was diluted with ether and washed twice with water. Organic layer was separated and concentrated to obtain the desired product (1.64 g, 91%) as a clear oil. NMR (DMSO-d6): 7.52 (m, 1H), 7.40 (m, 2H), 7.26 (m, 1H), 3.38 (s, 2H), 3.20 (s, 3H), 1.12 (s, 6H). MS (DCI): 260 (M+NH4). Example 36E [3-(2-methoxy-lJ-Q^emyl-emyl>phenylemynyl1-trimethyl-silane To a solution of l-bromo-3^2-methoxy-l,l-phenylemynyl]-trimethyl-silane instead of 2-memyl-2-(3-trimemylsUanylemynylphenyl>propionitrile NMR (DMSO-dg): 7.58 (m, 2H), 7.43 (m, 1H), 3.42 (s, 2H), 3.20 (s, 3H), 3.09 (m, 2H), 2.60 (m, 2H), 1.24 (s, 6H). MS (DCI): 219 (M+l). Example 36G 5-(2-methoxy-lJ-dimemyl-emyl)-indan-l-ylamine The title compound was made according to the conditions described in Example 1C and JD, except using 5-(2-methoxy-l,l-dimemyl-emyl)-indan-l-one instead of 5-tert-butyl-1-indanone. NMR (DMSO-ds): 7.26 - 7.11 (m, 3H), 4.18 (t, J 7.5 Hz, 1H), 3.31 (s; 2H), 3.20 (s, 3H), 2.80 (m, 1H), 2.66 (m, 1H), 2.30 (m, 1H), 1.55 (m, 1H), 1.11 (s, 6H). MS (DCI): 220 (M+l). Example 36H 4-(2<5-dioxo-pyrroUdm-l-yloxy«irbonylaminoVindazole-l-carboxylic acid methyl ester 4-Amino-indazole-l-carboxylic acid methyl ester (1.9 g, 10 mmol) and disuccmimidylcarbonate (2.8 g, 11 mmol) were mixed in MeCN (100 mL) for 48 hours under nitrogen atmosphere. The solid was filtered off, washed with MeCN (10 mL) and dried under vacuum at ambient temperature to give desired product (2.56 g, 77%) as off-white solid. Example 361 83 WO 2004/111009 PCTAJS2004/018590 4if3-f5^2-me&(«y-lJ-dimemyl^yl>m^ methyl ester 4-(2)5^oxo-pynx)Udin-l-yloxycarbonylamino)-indazole-l-carboxylic acid methyl ester (0.66 g, 2.00 mmol) was added to a solution of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-1-ylamine (0.46 g, 2.1 mmol) and diisopropylethylamine (0.26 g, 2.00 mmol) in DMF (6 mL) under nitrogen atmosphere at ambient temperature. After 30 minutes the mixture was diluted with water (6 mL). The resulting precipitate was filtered off, washed with aqueous MeCN twice and dried to obtain desired product (0.48 g, 55%). NMR (DMSO-de): 8.82 (s, 1H), 8.40 (s, 1H), 7.95 (s, 1H), 7.88 (d, J 7.5 Hz, 1H), 7.69 (d, J 8 Hz, 1H), 7.52 (t, J 8Hz, 1H), 7.24 (m, 2H), 6.70 (d, J 7.5 Hz, 1H), 5.18 (m, 1H), 4.02 (m, 3H), 3.38 (s, 2H), 3.20 (s, 3H), 3.10 - 2.72 (m, 2H), 2.42 (m, 1H), 1.83 (m, 1H), 1.14 (s, 6H). MS (DCI): 437 (M+l). Example 36 N4H-indazol^yl-lsr-r5-(2-methoxy4a-dimemylemylV2.3-dihydro-1H-m^ The title compound was made according to the conditions described in Example 9, substitutmg4-{3-[5^2-methoxy-l,l-Kimera^ carboxylic acid methyl ester forN-(5-tert-butyl-2,3-dihydro-1H-inden-l-yl)-N'-1H-indazol-4-ylurea. NMR (DMSO-d6): 13.0 (broad s, 1H), 8.58 (s, 1H), 8.02 (s, 1H), 7.68 (d, J 7.5 Hz, 1H), 7.23 (m, 4H), 7.08 (d, J 8 Hz, 1H), 6.70 (d, J 8Hz, 1H), 5.19 (m, 1H), 3.38 (s, 2H), 3.20 (s, 3H), 3.01 - 2.70 (m, 2H), 2.42 (m, 1H), 1.82 (m, 1H), 1.23 (s, 6H). MS (DCI): 379 (M+l). Example 37 N45-(2-hydroxy-U-dimefoylefoyiy2^ The title compound was prepared by procedure described in Example 36, substituting l-bromo-3K2-tert-butyl-d^emylsUyl-l,l-dimemyl-emyl)-benzeneforl-bromo-3-(2-methoxy-l,l-dimethyl-ethyl)-benzene. Deprotection by using 5M NaOH in methanol (example 9) afforded title compound. NMR (DMSO-de): 8.80 (broad s, 1H), 8.08 (s, 1H), 7.70 (d, J 7.5 Hz, 1H), 7.23 (m, 4H), 7.06 (d, J 8 Hz, 1H), 6.86 (d, J 8 Hz, 1H), 5.18 (m, 1H), 3.40 (s, 2H), 3.00-2.73 (m, 2H), 2.41 (m, 1H), 1.80 (m, 1H), 1.10 (s, 6H). MS (DCI): 365 (M+l). 84 WO 2004/111009 PCT/US2004/018590 Example 38 N-6J-DMSO) 13.01 (broad s, 1H), 8.87 (s, 1H), 8.08 (s, 1H), 7.71 (d, 1H), 7.33 (s, 1H), 7.30 (d, 1H), 7.21 (m, 2H), 7.09 (d, 1H), 6.87 (d, 1H), 5.33-5.46 (m, 2H), 3.05-3.27 (m, 2H), 1.27 (s, 9H). MS (DCI/NH3) m/e 367 (M+H)+. [a]D -32.75° (c=0.800,1:1 MeOH:CH2Cl2). Structure is cis by ROESY NMR, absolute stereochemistry assigned arbitrarily. Example 41 N-r(i.S:2,SV5-tert-butyl-2-fluoi^23-d^^ The title compound was prepared by chiral separation of the corresponding racemic compound N-(5-tert-butyl-2-fluoro-2,3-dihydro-1H-inden-l-yl)-N'-1H-indazol-4-ylurea (Ex. 39) using a chiral column ChiralCel OD. *H NMR (300 MHz, a>DMSO) 13.01 (broad s, 1H), 8.87 (s, 1H), 8.08 (s, 1H), 7.71 (d, 1H), 7.33 (s, 1H), 7.30 (d, 1H), 7.21 (m, 2H), 7.09 (d, 1H), 6.87 (d, 1H), 5.33-5.46 (m, 2H), 3.05-3.27 (m, 2H), 1.27 (s, 9H). MS (DCI/NH3) m/e 367 (M+H)+. [a]D +19.69° (c=0.975,1:1 MeOH:CH2Cl2). Structure is trans by ROESY NMR, absolute stereochemistry assigned arbitrarily. Example 42 N-r(iS2fly5-tert-butyl-2-fluor(^ The title compound was prepared by chiral separation of the corresponding racemic 87 WO 2004/111009 PCT/US2004/018590 compound N-(5-tert-butyl-2-fluoro-2,3-dihydro-1H^^ (Ex. 39) using a chiral column ChiralCel OD. JH NMR (300 MHz, dVDMSO) 13.01 (broad s, 1H), 8.87 (s, 1H), 8.08 (s, 1H), 7.71 (d, 1H), 7.33 (s, 1H), 7.30 (d, 1H), 7.21 (m, 2H), 7.09 (d, 1H), 6.87 (d, 1H), 5.33-5.46 (m, 2H), 3.05-3.27 (m, 2H), 1.27 (s, 9H). MS (DCI/NH3) m/e 367 (M+H)+. [indan-l-ylamine. MS (DCI) 452 (M+l) Example 48C N-(6-fluoro-5-piperidm-l-yl-23-dihydro-1H-inden-l-ylVN'-1H-indazol-4-ylurea The title compound was made from 4-[3-(6-fluoro-5-piperidino-indan-l-yl)-ureido]-indazole-1-carboxylic acid methyl ester (Ex. 48D) according to the deprotection procedure by using 5M NaOH in methanol (example 9). 'HNMR (300 MHz, dVDMSO) 8.88 (s, 1H), 8.18 (s, 1H), 7.68 (d, 1H), 7.00-7.25 (m, 5H), 5.08 (m, 1H), 3.09 (br, 4H), 2.87-3.00 (m, 1H), 2.72-2.85 (m, 1H), 2.43-2.55 (m, 1H, buried under DMSO), 1.81-1.92 (m, 1H), 1.73 (br, 4H), 1.55 (m, 2H). MS (DCI/NH3) m/e 394 (M+H)+. Anal. Calcd. For C22H24FN5O2HCI: C 56.66; H 5.62; N 15.02. Found: C 57.02; H 5.74; N 15.39. Example 50 N-(5-tert-butyl-2^-difluoro-23-dihydro~1H-m^^ Example 50A 5-tert-Butyl-2.2-difluoro-indan-l -one 5-tert-Butyl-2-fluoro-indan-l-one (0.21g, 1 mmol) andtriethyl amine (0.84ml, 0.61g, 6 mmol) were dissolved in 4ml of methylene chloride. The solution was cooled to 0C, and tert-butyl-dimethylsilyl trifluorosulfonate was added. The reaction was allowed to warm to ambient temperature, stirred 16 hours, and diluted with ethyl ether. The organic solution was 91 WO 2004/111009 PCT/US2004/018590 washed sequentially with saturated sodium bicarbonate solution, IN hydrochloric acid, saturated sodium bicarbonate, and brine, and dried with magnesium sulfate. The solvent was removed under vacuum to give the silyl enol ether which was used at once. The silyl enol ether was dissolved in 10ml acetonitrile, and Accuflor (0.64g, lmmol) was added. The reaction was stirred at ambient temperature for three hours. The solvent was then evaporated under vacuum, and the residue taken in methylene chloride and filtered. The filtrate was washed with water, dried with magnesium sulfate, and the solvent evapporated under reduced pressure to give 0.35g of 5-tert-Butyl-2,2-difluoro-indan-l-one. !H NMR (300 MHz, CDC13) 7.80 (d, 1H), 7.52 (d, 1H), 7.46, (s, 1H), 3.54 (t, 2H), 1.37 (s, 9H). MS (CSI) m/e 242 (M+NH4)+ Example 50B 5-tert-Butyl-2^-difluoro-indan-l-ylamine The title compound was made according to the conditions described in Example 57D, except using 5-tert-butyl-2,2-difluoro-l-indanone instead of 2-methyl-2-(l-oxoindan-5-yl)-propionitrile. *H NMR (300 MHz, CDCI3) 7.35 (s, 2H), 7.23 (s, 1H), 4.41 (t, 1H), 3.30-3.40 (m, 2H), 1.31 (s, 9H). MS (CSI) m/e 226 (M+H)+ Example 50C 4-r3-(54ert-Butyl-22-difluoro-indan-l-ylVureidol-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 5-tert-Butyl-2,2-difluoro-indan-l-ylamine instead of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-1-ylamine. MS (DCI) 443 (M+l). Example 50D N-(5-tert-butyl-2.2indan-l-ylamine. MS (DCI) 407 (M+l). Example 51D l-CS-tert-butyl-indan^-vD-S-dH-indazol-^ylVurea The title compound was made from the compound in Ex. SIC according to the deprotection procedure by using 5M NaOH in methanol (example 9)._*H NMR (300 MHz, dV DMSO) 8.66 (s, 1H), 8.07 (s, 1H), 7.67 (d, 1H), 7.32 (s, 1H), 7.19 (m, 2H), 7.03 (d, 1H), 6.81 (br, 1H), 4.46 (br, 1H), 3.44 (q, EtOH) 3.14-3.26 (m, 2H), 2.71-2.82 (m, 2H), 1.27 (s, 9H), 1.06 (t, EtOH). MS (DCI/NH3) m/e 349 (M+H)+. Anal. Calcd. For C2iH24N4O-HCl-0.33H2O-0.5EtOH: C 63.84; H 6.98; N 13.54. Found: C 63.89; H 7.30; N 13.75. Example 52 N4H-indazol-4-yl-N,-(7-memyl-2J-dihydro-1H-inden-l-vnurea Example 52A 7-Methyl-indan-1 -one Polyphosphoric acid (15g) was heated in a water bath to 85C. 3-m-tolyl-propionic acid (2.0g, 12.2 mmol) was added, and the reaction stirred at 75-85C for 1 hour. The reaction was cooled, and quenched with ice and water. The quenched mixture was extracted with ethyl ether and the organics washed with saturated sodium bicarbonate. The solution was dried with magnesium sulfate and the solvent evaporated under vacuum. The residue was chromatographed using 1:10 ethyl acetate&exane as the eleuent, to give 0.66g of 7-methyl-indan-1-one and 0.76g of 5-methyl-indan-l-one. 7-methyl-indan-l-one: *H NMR (300 MHz, CDCI3) 7.42 (t, 1H), 7.23 (d, 1H), 7.10 (d, 1H), 3.09 (m, 2H), 2.66 (m, 2H), 2.64 (s, 3H). MS (CSI) m/e 147 (M+H)+. 94 WO 2004/111009 PCT/US2004/018590 Example 52B 7-Methyl-indan-l-ylamine The title compound was made according to the conditions described in Example 1C and ID, except using 7-methyl-indan-l-one instead of 5-tert-butyl-l-indanone. *H NMR (300 MHz, CDCh) 7.05-7.15 (m, 3H), 6.97 (d, 1H), 4.48 (dd, 1H), 3.07-3.18 (m, 1H), 2.80 (ddd, 1H), 2.41 (s, 3H), 2.26-2.40 (m, 1H), 1.81-1.91 (m, 1H). MS (CSI) m/e 148 (M+H)+. Example 52C 4-r3-(-7-Methyl-indan-l-yl)-ureido]-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 7-memyl-indan-l-ylamine (Ex. 52B) instead of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DO) 365 (M+l). Example 52D N-1H-indazol-4-yl-N,-(7-methyl-2.3-dihydro-1H-inden-l-ynurea The title compound was made from the compound in Ex. 52C according to the deprotection procedure by using 5M NaOH in methanol (example 9). *H NMR (300 MHz, d$-DMSO) 12.97 (br s, 1H), 8.50 (s, 1H), 8.01 (s, 1H), 7.70 (d, 1H), 7.12-7.24 (m, 3H), 7.05 (m, 2H), 6.67 (d, 1H), 5.26 (m, 1H), 2.99-3.10 (m, 1H), 2.81 (ddd, 1H), 2.24-2.37 (m, 1H), 2.31 (s, 3H), 1.92-2.02 (m, 1H). MS (DCI/NH3) m/e 307 (M+H)+. Anal. Calcd. For C2iH24N4O-HC10.4 THF: C 70.23; H 6.37; N 16.71. Found: C 70.03; H 6.30; N 16.52. Example 53 N-1H-indazol^yl-N'-fS-memyl^J-dihydro-1H-inden-l-ynurea Example 53A 5-Methyl-indan-l-one 95 WO 2004/111009 PCT/US2004/018S90 Polyphosphoric acid (lSg) was heated in a water bath to 85C. 3-m-tolyl-propionic acid (2.0g, 12.2 mmol) was added, and the reaction stirred at 7S-85C for 1 hour. The reaction was cooled, and quenched with ice and water. The quenched mixture was extracted with ethyl ether and the organics washed with saturated sodium bicarbonate. The solution was dried with magnesium sulfate and the solvent evaporated under vacuum. The residue was chromatographed using 1:10 ethyl acetateihexane as the eleuent, to give 0.66g of 7-methyl-indan-l-oneand0.76gof5-methyl-indan-l-one. 5-methyl-indan-l-one: 'H NMR (300 MHz, CDC13) 7.65 (d, 1H), 7.28 (s, 1H), 7.18 (d, 1H), 3.09 (m, 2H), 2.67 (m, 2H), 2.44 (s, 3H). MS (CSI) m/e 147(M+H)+. Example 53B S-Methyl-indan-1-ylamine The title compound was made according to the conditions described in Example 1C and ID, except using 5-methyl-indan-l-one instead of 5-tert-butyl-l-indanone. *H NMR (300 MHz, CDCI3) 7.22 (d, 1H), 7.04 (s, 1H), 7.03 (d, 1H), 4.34 (t, 1H), 2.93 (ddd, 1H), 2.71-2.83 (m, 1H), 2.44-2.55 (m, 1H), 2.33 (s, 3H), 1.64-1.75 (m, 1H). MS (CSI) m/e 148 (M+H)+. Example 53C 4-r3-(-5-Memyl-indan-l-yl)-ureido]-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 5-memyl-indan-l-ylainine (Ex. 53B) instead of S-p-methoxy-l^-dimethyl-erayO-indan-l-ylamine. MS (DCI) 365 (M+l). Example 53D N-1H-indazol^yl-N'-fS-memyl^J-dihydro-1H-inden-l-vnurea The title compound was made from the compound in Ex. 53C according to the deprotection procedure by using 5M NaOH in methanol (example 9). !H NMR (300 MHz, dV DMSO) 8.65 (s, 1H), 8.06 (s, 1H), 7.68 (d, 1H), 7.22 (m, 2H), 7.06 (m, 2H), 6.75 (d, 1H), 5.15 (m, 1H), 2.87-2.97 (m, 1H), 2.73-2.84 (m, 1H), 2.41-2.51 (m, 1H, buried under DMSO), 2.30 (s, 3H), 1.74-1.87 (m, 1H). MS (DCI/NH3) m/e 307 (M+H)+, 329 (M+Na)+. Anal. 96 WO 2004/111009 PCT/US2004/018590 Calcd. For C2iH24N4OHCl-0.25 THF: C 71.57; H 6.86; N 15.90. Found: C 71.82; H 6.90; N 15.73. Example 54 N-1H-mda2ol4-yl-1^^5-isopropyl-2J-Klihvdro-1H-inden-l-yl>urea Example 54 A 3-Chloro-l-(4-isopropyl-phenyl)-propan-l-one The title compound was prepared according to the procedure described in Ex. 1 A, except using isopropylbenzene instead of t-butyl benzene. *H NMR (300 MHz, CDCI3) 7.90 (d, 2H), 7.33 (d, 2H), 3.92 (t, 2H), 3.43 (t, 2H), 2.97 (septet, 1H), 1.27 (d, 6H). MS (CSI) m/e 211 (M+H)+, CI isotope pattern seen. Example 54B 5-Isopropyl-indan-l -one The title compound was prepared according to the procedure described in Ex. IB, except using compound from Ex. 54A instead of l-(4-tert-butylphenyl>3-chloro-l-propanone. !H NMR (300 MHz, CDCI3) 7.69 (d, 1H), 7.32 (s, 1H), 7.23 (d, 1H), 3.11 (m, 2H), 2.99 (septet, 1H), 2.68 (m, 2H), 1.27 (d, 6H). MS (CSI) m/e 175 (M+H)+. Example 54C 5-Isopropyl-indan-l -ylamine The title compound was made according to the conditions described in Example 1C and ID, except using 5-isopropyl-indan-l-one (Ex. 54B) instead of 5-tert-butyl-l-indanone. *H NMR (300 MHz, CDCI3) 7.69 (d, 1H), 7.32 (s, 1H), 7.23 (d, 1H), 3.11 (m, 2H), 2.99 (septet, 1H), 2.68 (m, 2H), 1.27 (d, 6H). MS (CSI) m/e 175 (M+H)+ Example 54D 4"r3-(-5-Isopropyl-indan-l-yl)-ureido]-indazole-l-carboxylic acid methyl ester 97 WO 2004/111009 PCT/US2004/018590 The title compound was made according to the conditions described in Example 361 except using 5-isopropyl-indan-l-ylamine (Ex. 54C) instead of 5-(2-methoxy-l,l-dimethyl-ethyl>indan-l-ylamine. MS (DCI) 393 (M+l). Example 54E N-1H-indazol^yl-N'^5-isopropyl-2,3-dihydro-1H-inden-l-yl')urea The title compound was made from the compound in Ex. 54D according to the deprotection procedure by using 5M NaOH in methanol (example 9). !H NMR (300 MHz, d«-DMSO) 12.97 (br s, 1H), 8.56 (s, 1H), 8.03 (s, 1H), 7.67 (d, 1H), 7.05-7.27 (m, 5H), 6.68 (d, 1H), 5.15 (m, 1H), 2.73-3.00 (m, 2H), 2.40-2.50 (m, 1H, buried under DMSO), 1.77-1.88 (m, 1H), 1.20(d,6H). MS(DCI/NH3)m/e335(M+H)+- Anal.Calcd.ForC21H24N4OHCIO.2 THF0.2 NaOH: C 68.68; H 6.07; N 17.04. Found: C 68.61; H 5.75; N 16.95. Example 56 N-1H-indazol-4-yl-N'-(4-piperidm-l-yI-23-dihydro-1H-inden-l-yl)urea Example 56A 4-Bromo-indan-l-one O-methyl-oxime 4-Bromoindan-l-one (5.08g, 24.1mmol) was added to a mixture of methoxyamine hydrochloride (2.2 lg, 26.5mmol) in pyridine (40mL) under nitrogen atmosphere and stirred overnight at ambient temperature. The reaction mixture was concentrated, added ethyl acetate (200mL), washed with 3N hydrochloric acid (200mL), dried with brine and anhydrous sodium sulfate, and concentrated. Obtained 4-bromoindan-l-one O-methyloxime (5.66g, 98%) as an orange liquid. MS (DCI/NH3) m/z: 239.94 [M+H]+- 1H NMR (DMSO-rf6) D: 2.83 (m, 2H), 2.96 (m, 2H), 3.91 (s, 3H), 7.25 (t, 1H), 7.56 (d, 1H), 7.60 (d, 1H). Example 56B 4-Piperidin-l-yl-indan-l-one O-methyl-oxime 4-Bromoindan-l-one O-methyloxime (6.40g, 26.7mmol) was added to a mixture of piperidine (2.72g, 31.9mmol), sodium tert-butoxide (3.84g, 40.0mmol), Pd2(dba>3 (0.74g, 0.81mmol) and BINAP (1.49g, 2.39mmol) in dioxane (50mL) under nitrogen atmosphere. 98 WO 2004/111009 PCT/US2004/018590 The stirred mixture was heated at 170°C for 5 minutes on the microwave. After cooling to ambient temperature, the reaction mixture was filtered through celite, then silica gel with 25% ethyl acetate in hexane. The filtrate was concentrated to a brown oil and chromatographed on silica gel with 4% ethyl acetate in hexane. Obtained 4-piperidin-l-ylindan-1-one O-methyloxime (4.33g, 66%) as an orange oil. MS (ESI) m/z: 245.00 [M+H]+. 'HNMR (DMSO-^) D: 1.55 (m, 2H), 1.64 (m, 4H), 2.79 (m, 2H), 2.91 (m, 6H), 3.87 (s, 3H), 6.94 (dd, 1H), 7.19 (m, 2H). Example 56C 4-Piperidm-l-yl-indan-l-ylamine 4-Piperidin-l-ylindan-l-one O-methyloxime (4.33g, 17.7mmol) was added to a mixture of 20% ammonia in methanol (200mL) and Raney 2800 nickel (43g) in a stainless steel autoclave. The reactor was sealed and flushed with nitrogen, and then it was pressurized with hydrogen (60psi). The mixture was stirred at ambient temperature for 90 minutes. The Raney nickel was filtered off, washed with methanol and the filtrate was concentrated. Obtained 4-piperidin-l-ylindan-l-yl-amine (3.81g, 99%) as a yellow oil. MS (DCI/NH3) m/z: 217.13 [M+H]+- 'HNMR(DMSO-rf6) 8:1.51 (m, 3H), 1.62 (m, 4H), 1.77 (s, 2H), 2.28 (m, 1H), 2.62 (m, 1H), 2:80 (m, 3H), 2.94 (m, 2H), 4.14 (t, 1H), 6.71 (d, 1H), 6.95 (d,1H),7.09(t,1H). Example 56D 4-r3-(4-Pirwridm-l-yl-indan-l-yl)-urddo1indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-piperidm4-yl-indan-l-ylamine (Ex. 56C) instead of 5-(2-methoxy-l,l-dimemyl-e%l>indan-l-ylamine. MS (DCI) 434 (M+l). Example 56E 1 -(i/f-Indazol-4-yl)-3-(4-piperidin-l -yl-indan-1 -yl)-urea 4^2,5-IMoxopyiTolidm-l-yl-oxycarbonylammo)-indazole-l-carboxylic acid methyl ester (5.57g, 16.8mmol) was added to a solution of 4~piperidm-l-ylindan-l-ylamine (3.81g, 99 WO 2004/111009 PCTYUS2004/018590 17.6mmol) and DIPEA (3.0mL, 17.2mmol) in DMF (80mL) under nitrogen atmosphere at ambient temperature. After 30 minutes the reaction solution was diluted with water (350mL), the resulting beige precipitate was filtered off, washed with water and air-dried. The wet cake was added to a solution of methanol (200mL), water (3mL) and TEA. (7.0mL, 50.2mmol). The mixture was refluxed for 90 minutes, cooled to room temperature, diluted with water (200mL), collected the beige precipitate by filtration, rinsed with water and air-dried. The wet cake was vacuum dried to constant weight, yielding l-(/i/-indazol-4-yl>3-(4-piperidin-l-ylindan-l-yl)-urea (5.89g, 93%) as a beige solid. MS (ESI) m/z: 376.00 [M+H]+. ^NMR (DMSO-rf6) 8:1.56 (m, 2H), 1.65 (m, 4H), 1.78 (m, 1H), 2.44 (m, 1H), 2.77 (m, 1H), 2.85 (m, 3H), 2.95 (m, 2H), 5.16 (q, 1H), 6.66 (d, 1H), 6.81 (d, 1H), 6.95 (d, 1H), 7.07 (d, 1H), 7.22 (m, 2H), 7.68 (d, 1H), 8.05 (s, 1H), 8.62 (s, 1H), 13.00 (s, 1H). Anal Calcd for C22H25N5O: C, 70.38; H, 6.71; N, 18.65. Found: C, 70.24; H, 6.72; N, 18.47. Example 57 l-f5-(Cyano-isopropylVindan-l-yl1-3-(iif-indazol-4-yl)-urea Example 57A 2-(3-Bromo-phenyl)-2-methyl-propionitrile The title compound was made according to the procedure described in Ex. 36B except using 3-bromophenyl- acetonitrile instead of 3-bromophenyl-acetic acid methyl ester. Example 57B 2-Memyl-2-(3-trimemylsaanylethypyl-phenyl')-propionitrile Ethynyltrimethylsilane (4.0mL, 28.9mmol) was added to a mixture of ACN (lOOmL), TEA (25mL), 2-(3-bromophenyl)-2-methylpropionitrile (5.0g, 22.3mmol), (PhgP^PdCk (780mg, 1.1 lmmol) and copper® iodide (130mg, 0.68mmol) under nitrogen atmosphere. The reaction mixture was refluxed for 3 hours, cooled to ambient temperature, concentrated to a black residue and filtered through silica gel with 20% ethyl acetate in hexane. The filtrate was concentrated to a red oil and chromatographed on silica gel with 2% ethyl acetate in hexane. Obtained 2-memyl-2-(3-trimemyManylemynylphenyl)-r«ropionitrile (4.00g, 74%) as an orange oil. !H NMR (DMSO-d6) 8: 0.24 (s, 9H), 1.69 (s, 6H), 7.43 (m, 2H), 7.56 (m,2H). 100 WO 2004/111009 PCT/US2004/018590 Example 57C 2-Methyl-2-(l -oxo-indan-5-ylVpropionitrile 2-Methyl-2^3-trimethylsilanylethynylphenyl>propioiutrile (4.00g, 16.6mmol) was added to a mixture of THF (35mL), TEA (4.82mL, 34.6mmol), water (3.12mL, 173mmol), [Rh(COD)Cl]2 (83mg, 168umol) and triphenylphosphine (1.81g, 6.90mmol) in a stainless steel autoclave. The reactor was sealed and flushed with carbon monoxide, and then it was pressurized with carbon monoxide (SOOpsi). The stirred mixture was heated at 160°C for 4 hours. After cooling to ambient temperature, the reaction mixture was concentrated to a black residue and chromatographed on silica gel with 20-40% ethyl acetate in hexane. Obtained 2-methyl-2-(l-oxo-indan-5-yl)-propionitrile (2.71g, 82%) as a brown solid. MS (DCI/NH3) m/z: 200.0 [M+Hf. 'H NMR (DMSO-40 6:1.73 (s, 6H), 2.65 (m, 2H), 3.14 (m, 2H), 7.60 (dd, 1H), 7.68 (d, 1H), 7.74 (d, 1H). Example 57D 2-(l-Ammo-indan-5-ylV2-methyl-propionitrile 2-Methyl-2-(l-oxoindan-5-yl)-propionitrile (6.00g, 30.1mmol) was added to a mixture of ammonium acetate (69.6g, 903mmol) in IP A (600mL) under nitrogen atmosphere at ambient temperature. After stirring 1 hour, sodium cyanoborohydride (6.62g, 105mmol) was added to the mixture and refluxed for 2 hours. The reaction solution was cooled to room temperature, added 3N sodium hydroxide (300mL), extracted with TBME (2 x SOOmL) and concentrated the organic extracts to an oil. Dissolved in ethyl acetate (SOOmL), extracted with IN hydrochloric acid (3 x 300mL), combined the aqueous layers, added 3N sodium hydroxide (400mL), extracted with ethyl acetate (2 x 1L), dried with brine and anhydrous sodium sulfate, and concentrated. Obtained 2-(l-aminoindan-5-yl)-2-methylpropionitrile (4.26g, 71%) as a yellow oil. MS (DCI/NH3) m/r. 201.10 [M+H]+. lR NMR (DMSO-4.) 8: 1.60 (m, 1H), 1.66 (s, 6H), 1.93 (br, 2H), 2.35 (m, 1H), 2.74 (m, 1H), 2.86 (m, 1H), 4.17 (t, lH),7.32(m,3H). Example 57E l-rS-fCyano-isopropylVindan-l-yll-S-fiff-indazoM-ylVurea 4-(2,5-Dioxopyrrolidin-l-yl-oxycarbonylamino)-indazole-l-carboxylic acid methyl ester (3.31g, 9.96mmol) was added to a solution of 2-(l-aminoindan-5-yl>2- 101 WO 2004/111009 PCT/US2004/018590 methylpropionitrile (2.09g, 10.5mmol) and DEPEA (1.8mL, 10.3mmol) in DMF (40mL) under nitrogen atmosphere at ambient temperature. After 1 hour the reaction solution was diluted with water (200mL), the resulting white precipitate was filtered off, washed with water and air-dried. The wet cake was added to a solution of methanol (lOOmL), water (3mL) and TEA (2.8mL, 20.1mmol). The mixture was refluxed for 30 minutes, cooled the solution to room temperature, diluted with water (SOOmL), collected the white precipitate by filtration, rinsed with water and air-dried. The wet cake was vacuum dried to constant weight, yielding l-[5-(c7ano-isopropyl)-indan-l-yl]-3-(7if-indazol-4-yl)-urea (3.32g, 93%) as a white solid. MS (ESI) m/r. 360.07 [M+Hf !H NMR (DMSO*fe) 8:1.69 (s, 6H), 1.87 (m, 1H), 2.47 (m, 1H), 2.89 (m, 1H), 2.98 (m, 1H), 5.19 (q, 1H), 6.73 (d, 1H), 7.08 (d, 1H), 7.22 (t, 1H), 7.39 (s, 2H), 7.44 (s, 1H), 7.66 (d, 1H), 8.04 (s, 1H), 8.59 (s, 1H), 13.00 (s, 1H). Anal Calcd for C21H21N5O «0.4H2O: C, 68.80; H, 5.99; N, 19.10. Found: C, 68.94; H, 5.72; N, 18.95. Example 58 N-lH-todazol-4-yl-N'-{5-r4-(triflTO Example 58A 5-(4-Trifluoromemyl-piperidm-l-ylVmdan-l-ylamine The title compound was made according to the conditions described in Examples 16A-16C, except using 4-trifluoromethylpiperidine instead of piperidine in ex. 16A. Example 58B 4-{3-r5-(4-trifluoromemyl-piperidm-l-ylVmdan-l-yl1-ureidol-mdazol-l-<^boxyUcacid methyl ester The title compound was made according to the conditions described in Example 361 except using 5-(4-trifluoromemyl-piperidln-l-yl)-mdan-l-ylamine (Ex. 58A) instead of 5-(2-memoxy-l,l-dimemyl-e%l>mdan-l-ylamine. MS (DCI) 502 (M+l). Example 58C N-lH-todazol-4-yl-N'-f5-r4-(trifluorom 102 WO 2004/111009 PCT/US2004/018590 The title compound was made from the compound in Ex. 58B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z\ 444.1 [M+H]+. 'HNMR(DMSO-4D D: 1.56 (m, 2H), 1.79 (m, 1H), 1.83 (m, 2H), 2.46 (m, 1H), 2.71 (t, 2H), 2.80 (m, 1H), 2.91 (m, 1H), 3.73 (d, 2H), 5.09 (q, 1H), 6.61 (d, 1H), 6.87 (m, 2H), 7.07 (d, 1H), 7.21 (m, 2H), 7.67 (d, 1H), 8.04 (s, 1H), 8.55 (s, 1H), 12.99 (s, 1H). Example 59 N4H-mdazoM-yl-N'-(5^isK)(^ydroisoqufa^ Example 59A 5^cis^rtahvdro-isoqumolm-2-ylVmd^-l-ylamine The title compound was made according to the conditions described in Examples 16A-16C, except using octahydroisoquinoline instead of piperidine in ex. 16A. Example 59B 4-{3-f5-(cis-OctahydrO'isoqumolm-2-yl)-mdan-l-vl1-ureido)-mda2ol-l-carboxyU^ methyl ester The title compound was made according to the conditions described in Example 361 except using 5^0ctahydro4sc>qumolm-2-yl)-md^-l-ylamine (Ex. 59A) instead of 5-(2-memoxy4,l-dimemyUthyl)-indan-l-ylamine. MS (DCI) 488 (M+l). Example 59C N-lH-mdarol^yl-N,-(5-cis^ctahydroiso<^ The title compound was made from the compound in Ex. 59B according to the deprotection procedure by using 5M NaOH in methanol (example 9). 1H NMR (DMSO-^6) D: 1.33 (m, 1H), 1.47 (m, 4H), 1.57 (m, 3H), 1.78 (m, 4H), 2.44 (m, 1H), 2.78 (m, 1H), 2.88 (m, 3H), 5.09 (q, 1H), 6.60 (d, 1H), 6.81 (m, 2H), 7.07 (d, 1H), 7.14 (d, 1H), 7.21 (t, 1H), 7.67 (d, 1H), 8.04 (s, 1H), 8.56 (s, 1H), 12.98 (s, 1H). 103 WO 2004/111009 PCT/US2004/018590 Example 60 N-r5^1.4'-bipiperidfa4Wiy23-dm^^ Example 60A 5-fl.41Bipiperidmvl-lWl-indan-l-vlamine The title compound was made according to the conditions described in Examples 16A-16C, except using [l,4']bipiperidinyl instead of piperidine in ex. 16A. Example 60B 4-r3-(5-ri,41Bipiperidmyl-r-Ylrmdan-l-vlVureido1-mdazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 5-[l,4']Bipiperidmyl-r-yl-mdan-l-ylamine (Ex. 60A) instead of 5-(2-methoxy-14-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 517 (M+l). Example 60C N4S-a.4'-bipiperidm4,-vlV23-dmydro-m-mden4-vl1-N,-lH-mdazol^-vlurea The title compound was made from the compound in Ex. 60B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 459.20 [M+Hf. 'H NMR (DMSO-indan-l-ylamine. MS (DCI) 510 (M+l). Example 61C N-lH-mdazol4-yl-N'-r5-(4-phenylpiperid^-l-ylV23Kimydro-lH-inden-l-yl1urea The title compound was made from the compound in Ex. 61B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/r. 452.20 [M+H]+. 'H NMR (DMSO-40 8:1.8 (m, 5H), 2.44 (m, 1H), 2.75 (m, 3H), 2.92 (m, 1H), 3.76 (d, 2H), 5.12 (q, 1H), 6.64 (d, 1H), 6.89 (m, 2H), 7.07 (d, 1H), 7.21 (m, 3H), 7.29 (m, 4H), 7.67 (d, 1H), 8.04 (s, 1H), 8.56 (s, 1H), 12.99 (s, 1H). Anal Calcd for C28H29N5O •O.IH2O: C, 74.18; H, 6.49; N, 15.45. Found: C, 74.09; H, 6.35; N, 15.58. Example 62 N-lH-mda2X)M-vl-N'-r5-(4-phenylpiperazm-l-ylV23-dmydrc)-lH-mden-l"yl1urea Example 62A 5^4-Phenyl-piperazm-l-ylVmdan-l-ylamine The title compound was made according to the conditions described in Examples 16A-16C, except using 4-phenyl-piperazine instead of piperidine in ex. 16A. Example 62B 4-{3-f5-(4-Phenyl-pipera2in>l-ylVmdan-l-yl1-ureido)-indazole-l-carboxylic acid methyl ester 105 WO 2004/111009 PCT/US2004/01839U The title compound was made according to the conditions described in Example 361 except using S-(4-phenyl-piperazm-l-yl)-mdan-l-ylamine (Ex. 62A) instead of 5-(2-methoxy-1 J-dimerayl^yl)-indan-l-ylamine. MS (DCI) 511 (M+l). Example 62C N-lH-fadazol^yl-N'-f5-(4-phenylpip^ The title compound was made from the compound in Ex. 62B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z\ 453.16 [M+Hf. 'HNMR (DMSO-40 8:1.82 (m, 1H), 2.44 (m, 1H), 2.82 (m, 1H), 2.93 (m, 1H), 3.27 (s, 8H), 5.10 (q, 1H), 6.62 (d, 1H), 6.81 (t, 1H), 6.92 (m, 2H), 7.01 (d, 2H), 7.07 (d, 1H), 7.21 (q, 4H), 7.67 (d, 1H), 8.04 (s, 1H), 8.56 (s, 1H), 12.99 (s, 1H). Anal Calcd for C27H28N6O: C, 71.66; H, 6.24; N, 18.57. Found: C, 71.40; H, 6.10; N, 18.62. Example 63 N-lH-mdazol^yl-N'-r5-(4-memylpiperidm-l-ylV2,3-4mYdro-lH-mden-l-yl1urea Example 63A 5^4-Memyl-piperidm-l-ylVmdan-l-ylamine The title compound was made according to the conditions described in Examples 16A-16C, except using 4-methyl-piperidine instead of piperidine in ex. 16A. Example 63B 4-{3-f5-(4-Mefoyl-piperidm-l-yl)-mdan-l-yl> acid methyl ester The title compound was made according to the conditions described in Example 361 except using 5^4-memyl-piperidm-l-yl)-mdan-l-ylamine (Ex. 63A) instead of 5-(2-memoxy-14-4imemyl-emyl)-indan-l-ylamine. MS (DCI) 448 (M+l). Example 63C 106 WO 2004/111009 PCT/US2004/018590 N-lH-mdazol^vl->r-r5-(4-meftyto^^ The title compound was made from the compound in Ex. 62B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 390.12 [M+H]+. lH NMR QMSO-ck) 8:0.94 (d, 3H), 1.23 (m, 2H), 1.48 (m, 1H), 1.65 (d, 2H), 1.80 (m, 1H), 2.45 (m, 1H), 2.63 (t, 2H), 2.78 (m, 1H), 2.90 (m, 1H), 3.60 (d, 2H), 5.10 (q, 1H), 6.59 (d, 1H), 6.83 (m, 2H), 7.07 (d, 1H), 7.15 (d, 1H), 7.21 (t, 1H), 7.67 (d, 1H), 8.03 (s, 1H), 8.54 (s, 1H), 12.98 (s, 1H). Anal Calcd for C23H27N5O: C, 70.92; H, 6.99; N, 17.98. Found: C, 70.75; H, 6.63; N, 17.74. Example 64 N-lH-mdazol4-vl-N'-r5-(3-memvlpiperidm-l-vlV23-dmvdro-lH-inden^ Example 64A 5-(3-Methyl-piperidin-l -yfl-indan-1 -ylamine The title compound was made according to the conditions described in Examples 16A-16C, except using 3-methyl-piperidine instead of piperidine in ex. 16A. Example 64B 4-{3-r5-(3-Memyl-piperidm-l-ylVmdan-l-yl1-ureido)-mdazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 5-(3-Memyl-piperidm-l-yl)-mdan-l-ylamine (Ex. 64A) instead of 5-(2-memoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 448 (M+l). Example 64C N4H-mdazol^vl-N-r5-(3-meftylpiperid^ The title compound was made from the compound in Ex. 64B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 390.10 [M+H]+. 'H NMR (DMSO-4D 5: 0.92 (d, 3H), 1.02 (m, 1H), 1.58 (m, 1H), 1.72 (m, 4H), 107 WO 2004/111009 PCT/US2004/018590 2.28 (t, 1H), 2.45 (m, 1H), 2.57 (m, 1H), 2.78 (m, 1H), 2.90 (m, 1H), 3.56 (m, 2H), 5.10 (q, 1H), 6.61 (d, 1H), 6.83 (m, 2H), 7.07 (d, 1H), 7.18 (q, 2H), 7.67 (d, 1H), 8.03 (s, 1H), 8.55 (s, 1H), 12.97 (s, 1H). Anal Calcd for C23H27N6O •0.2H2O: C, 70.27; H, 7.03; N, 17.82. Found: C, 70.15; H, 6.63; N, 17.74. Example 65 N-lH-mdazol4-yl-W-f5-(2-oxo^ Example 65A Hl-Amino-indan-5-yl)-piperidin-2-one The title compound was made according to the conditions described in Examples 16A-16C, except using piperidin-2-one instead of piperidine in ex. 16A. Example 65B 4-(3-r5-(2-Oxo-piperidm-l-ylVmclan-l-yl1-ureido|-mda2Ple-l-(?arboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using l-(l-ammo-mdan-5-yl)-piperidin-2-one (Ex. 65A) instead of 5-(2-methoxy-l,l-dmethyl-ethyl>indan-l-ylamine. MS (DCI) 448 (M+l). Example 65C N-lH-mdazol4-yl-N'-r5-(2-oxopiperidm-l-yl)-2,3-Kimydro-lH-mden-l-yl1urea The title compound was made from the compound in Ex. 65B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 390.07 [M+H]+. lH NMR (DMSO-40 8:1.85 (m, 5H), 2.37 (t, 2H), 2.47 (m, 1H), 2.85 (m, 1H), 2.94 (m, 1H), 3.57 (t, 2H), 5.17 (q, 1H), 6.73 (d, 1H), 7.08 (t, 2H), 7.16 (s, 1H), 7.22 (t, 1H), 7.32 (d, 1H), 7.67 (d, 1H), 8.05 (s, 1H), 8.60 (s, 1H), 13.00 (s, 1H). Anal Calcd for C22H23N6O2 «0.8H2O: C, 65.43; H, 6.14; N, 17.34. Found: C, 65.40; H, 6.45; N, 17.41. Example 66 108 WO 2004/111009 PCT/US2004/018590 N-lH-todazol^yl-N'-r5-(2-meth^ Example 66A 5-(2-Metfayl-piperidin-l-ylVindan-l-Ylamine The title compound was made according to the conditions described in Examples 16A-16C, except using 2-methyl-piperidine instead of piperidine in ex. 16A. Example 66B 4^(3-f5-(2-Memyl-piperidm-l-ylVindan-l-yl1-ureido>-inda2ole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 5^2-Memyl-piperidm-l-yl)-indan-l-ylamine (Ex. 66A) instead of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 448 (M+l). Example 66C N-lH-mdazol^yl-N'-f5-(2-memylpiperidm-l-ylV2t3-dmydro-lH-mden-l-yl1urea The title compound was made from the compound in Ex. 66B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/r. 390.17 [M+H]+. !HNMR (DMSO-da) 8: 0.93 (d, 3H), 1.54 (m, 4H), 1.77 (m, 3H), 2.43 (m, 1H), 2.79 (m, 1H), 2.87 (m, 2H), 3.13 (m, 1H), 3.91 (m, 1H), 5.08 (q, 1H), 6.61 (d, 1H), 6.82 (m, 2H), 7.07 (d, 1H), 7.18 (q, 2H), 7.67 (d, 1H), 8.03 (s, 1H),.8.55 (s, 1H), 12.99 (s, 1H). Anal Calcd for C23H27N5O •O.6H2O: C, 69.01; H, 7.10; N, 17.49. Found: C, 68.78; H, 6.71; N, 17.48. Example 68 N-(4-azepan-l-yl-23-dmydro-lH-mden-l-yl)-N'-lH-indazol-4-ylurea Example 68A 4-Azepan-l-yl-indan-l-ylamine 109 WO 2004/111009 PCT/USZUU4/U1BS9U The title compound was made according to the conditions described in Examples 56B-56C, except using azepane instead of piperidine in ex. 56B. Example 68B 4-f3-(4-Azepan-l-yl-indan-l-vlVureido1-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-azepan-l-yl-indan-l-ylamine (Ex. 68A) instead of 5-(2-methoxy-l,l- dimemyl-emyl)-mdan4-ylamine. MS (DO) 434 (M+l). Example 68C N^4-azepan-l-yl-2,3Klmydro-lH-mden-l-ylVN,-lH-mdazol-4-ylurea The title compound was made from the compound in Ex. 68B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 390.14 [M+H]+. !H NMR (pMSO-dt) 8:1.59 (s, 4H), 1.75 (s, 5H), 2.44 (m, 1H), 2.85 (m, 1H), 2.94 (m, 1H), 5.11 (q, 1H), 6.66 (d, 1H), 6.74 (d, 1H), 6.79 (d, 1H), 7.07 (m, 2H), 7.21 (t, 1H), 7.67 (d, 1H), 8.05 (s, 1H), 8.61 (s, 1H), 12.99 (s, 1H). Anal Calcd for C23H27N60 '0.6H2O: C, 69.01; H, 7.10; N, 17.49. Found: C, 69.26; H, 6.95; N, 16.89. Example 69 N-lH-mdarol-4-yl-N'-r4-(4-memylpipCT Example 69A 4-(4-Memyl-piperidm-l-ylVmdan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using 4-methyl-piperidine instead of piperidine in ex. 56B. Example 69B 4-(3-r4-(4-Memyl-piperidm-l-ylVindan-l-yl1-ureido)-indazole-l-carboxylic acid methyl ester 110 WO 2004/111009 PCT/US2004/018590 The title compound was made according to the conditions described in Example 361 except using 4-(4-memyl-piperidin-l-yl>indan-lylamine (Ex. 69A) instead of 5-(2-methoxy-l,l-dimemyl-^^yl)-mdan4-ylamine. MS (DCI) 448 (M+l). Example 69C N-lH-indazol4-vl-N'-f4-(4-mefayfo^ The title compound was made from the compound in Ex. 69B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/r. 390.15 [M+H]+. 'HNMRODMSO-^) 5:0.98 (d, 3H), 1.28 (m, 2H), 1.49 (m, 1H), 1.74 (m, 3H), 2.43 (m, 1H), 2.55 (m, 1H), 2.67 (m, 1H), 2.77 (m, 1H), 2.84 (m, 1H), 3.20 (d, 1H), 5.18 (q, 1H), 6.66 (d, 1H), 6.81 (d, 1H), 6.95 (d, 1H), 7.07 (d, 1H), 7.15 (t, 1H), 7.21 (t, 1H), 7.67 (d, 1H), 8.05 (s, 1H), 8.61 (s, 1H), 12.99 (s, 1H). Anal Calcd for C23H27N80 -0.2H2O: C, 70.27; H, 7.03; N, 17.82. Found: C, 70.36; H, 7.20; N, 17.69. Example 70 N-lH-indazol-4-yl-N'-f4-(3-methylpiperidin-l -yl)-2,3-dihydro- lH-inden-1 -yllurea Example 70A 4-(3-Memyl-piperidm-l-ylVmd^-l-ylamine The title compound was made according to the conditions described in Examples 566-56C, except using 3-methyl-piperidine instead of piperidine in ex. 56B. Example 70B 4-{3-r4-(3-Memyl-piperidm-l-ylVmdan-l-yl1-ureido>-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-(3-memyl-piperidm-l-yl)-mdfin-l-ylamine (Ex. 70A) instead of 5-(2-memoxy4,l-dimemyl-e%l)-mdan-l-ylamine. MS (DCI) 448 (M+l). Ill WO 2004/111009 PCT/US2004/018590 Example 70C N-lH-fadarol^vl-N'-r4-(4-methrt^^ The title compound was made from the compound in Ex. 70B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/r. 390.15 [M+Hf. 'HNMR (DMSO-dfe) 8:0.93 (t, 3H), 1.05 (m, 1H), 1.62 (m, 1H), 1.75 (m, 4H), 2.27 (m, 1H), 2.46 (m, 1H), 2.62 (m, 1H), 2.82 (m, 2H), 3.18 (m, 2H), 5.18 (q, 1H), 6.70 (d, 1H), 6.81 (d, 1H), 6.95 (d, 1H), 7.07 (d, 1H), 7.21 (m, 2H), 7.67 (d, 1H), 8.05 (s, 1H), 8.62 (s, 1H), 12.99 (s, 1H). Anal Calcd for C23H27N6O «0.5H2O: C, 69.32; H, 7.08; N, 17.57. Found: C, 69.24; H, 7.06; N, 17.36. Example 71 N-lH-mdazol^yl->W(2-meftvfo^^ Example 71A 4^2-Memvl-piperidm-l-ylVmdan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using 2-methyl-piperidine instead of piperidine in ex. 56B. Example 71B 4-(3-r4-(2-Methyl-piperidm-l-yl)-mdan-l-yl1-ureido)-mdazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4^2-memyl-piperidm-l-yl)-mdan-l-ylaniine (Ex. 71A) instead of 5-(2-memoxy44-dimemyl-^myl>mdan-l-ylamine. MS (DCI)<448 (M+l). Example 71C N4H-mdaroM-yl-N'-r4-(2-me&yto^ The title compound was made from the compound in Ex. 70B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 390.10 [M+H]+. 'HNMR(DMSO-*)8:0.87 (t, 3H), 1.44(m,2H), 1.62 (m,5H),2.39(m, 1H), 2.65 (m, 1H), 2.74 (m, 1H), 2.87 (m, 1H), 3.06 (m, 1H), 5.20 (m, 1H), 6.69 (m, 1H), 6.95 (m, 112 WO 2004/111009 PCT/US2004/018590 3H), 7.19 (m, 2H), 7.67 (d, IK), 8.05 (d, IK), 8.62 (d, IK), 13.00 (s, 1H). Anal Calcd for C23H27N5O «0.9H2O: C, 68.09; H, 7.15; N, 17.26. Found: C, 67.98; H, 6.81; N, 17.12. Example 72 N-lH-fadazol^vlWMM-pfo^^ The title compound was prepared by chiral separation of the corresponding racemic compound l-(7/f-mdazol-4-yl)-3-(4-piperidin-l-yl-indan-l-yl>urea (Ex. 56E) using a chiral column ChiralCel OD. [ct]D: +89.5° (HC1 salt, c: 1.02, MeOH). MS (ESI) m/z: 376.00 [M+H]+ .'HNMR (DMSO-4J) 8:1.56 (m, 2H), 1.65 (m, 4H), 1.78 (m, 1H), 2.44 (m, 1H), 2.77 (m, 1H), 2.85 (m, 3H), 2.95 (m, 2H), 5.16 (q, IK), 6.66 (d, IK), 6.81 (d, IK), 6.95 (d, IK), 7.07 (d, IK), 7.22 (m, 2H), 7.68 (d, IK), 8.05 (s, 1H), 8.62 (s, IK), 13.00 (s, IK). Anal Calcd for C22H25N5O: C, 70.38; H, 6.71; N, 18.65. Found: C, 70.45; H, 6.91; N, 18.00. Example 73 N4H-mdazol^vl-N'-r(i^4-piperidm-l-vl-2.3^mY(iro-lH-mden4-vl1urea The title compound was prepared by chiral separation of the corresponding racemic compound l-(i/f-mdazol^yl)-3-(4-piperidin-l-yl-indan-l-yl)-urea (Ex. 56E) using a chiral column ChiralCel OD. [a]D: -98.5° (HC1 salt, c: 1.02, MeOH). MS (ESI) m/z: 376.00 [M+Hf .'H NMR (DMSO-ck) 5:1.56 (m, 2H), 1.65 (m, 4H), 1.78 (m, 1H), 2.44 (m, IK), 2.77 (m, IK), 2.85 (m, 3H), 2.95 (m, 2H), 5.16 (q, IK), 6.66 (d, IK), 6.81 (d, 1H), 6.95 (d, IK), 7.07 (d, 1H), 7.22 (m, 2H), 7.68 (d, IK), 8.05 (s, 1H), 8.62 (s, IK), 13.00 (s, 1H). Anal Calcd for C22H25N5O: C, 70.38; H, 6.71; N, 18.65. Found: C, 70.18; H, 6.93; N, 18.42. Example 74 N-lH-mdazol^yl-N'^4-Pvrrolidm-l-vl-2jHimYdro-lH-inden-l--yl')urea Example 74A 4-PvrroUdm-l-yl-indan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using pyrrolidine instead of piperidine in ex. 56B. 113 WO 2004/111009 PCT/US2004/018590 Example 74B 4-r3-(4-PvrroUdm-l-yl-mdan-l-yl)-ureido1-indazole-l-^^rboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-PyrroUdm-l-yl-indan-l-ylamine (Ex. 74A) instead of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 420 (M+l). Example 74C N-lH-todazol^yl->T-(4-pyrroHdto^^ The title compound was made from the compound in Ex. 74B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/r. 362.11 [M+Hf. 'HNMR(DMSO--l-memylemyn-23-dm^^ The title compound was prepared by chiral separation of the corresponding racemic compound l-fS^cyano^sopropyl^indan-l-yy-S^i/f-indazoM-yO-urea (Ex. 57E) using a chiral column ChiralCel OD. [a]D: +35.4° (c: 1.04, MeOH). MS (ESI) m/z: 360.07 [M+Hf .'HNMR(DMSO-rf6) D: 1.69 (s, 6H), 1.87 (m, 1H), 2.47 (m, 1H), 2.89 (m, 1H), 2.98 (m, 1H), 5.19 (q, 1H), 6.73 (d, 1H), 7.08 (d, 1H), 7.22 (t, 1H), 7.39 (s, 2H), 7.44 (s, 1H), 7.66 (d, 1H), 8.04 (s, 1H), 8.59 (s, 1H), 13.00 (s, lH).Anal Calcd for C2iH21N50 '0.3H2O: C, 69.14; H, 5.97; N, 19.20. Found: C, 69.08; H, 5.95; N, 19.31. Example 76 N4(i.SV5^1^ano-l-mefoylemyl)-23-dmyd The title compound was prepared by chiral separation of the corresponding racemic compound l-[5-(cyano-isopropyl)-indan-l-yl]-3-(i/f-indazol-4-yl)-urea (Ex. 57E) using a 114 WO 2004/111009 PCT/US2004/018590 chiral column ChiralCel OD. MS (ESI) m/r. 360.07 [M+Hf 'H NMR (DMSO-cfe) 8:1.69 (s, 6H), 1.87 (m, 1H), 2.47 (m, 1H), 2.89 (m, 1H), 2.98 (m, 1H), 5.19 (q, 1H), 6.73 (d, 1H), 7.08(d, 1H), 7.22 (t, 1H), 7.39 (s, 2H), 7.44 (s, 1H), 7.66 (d, 1H), 8.04 (s, 1H), 8.59 (s, 1H), 13.00 (s, 1H). Anal Calcd for C2iH2iN80 '0.45H2O: C, 68.63; H, 6.01; N, 19.05. Found: C, 68.82; H, 5.89; N, 18.36. Example 77 N4H-hda2x>l^ylW4-(2-memvlpyrro^^ Example 77A 4^2-Memvl-pvrroHdm-l-vlVmdan-l-vlamine The title compound was made according to the conditions described in Examples 56B-56C, except using 2-methyl-pyrrolidine instead of piperidine in ex. 56B. Example 77B 4-l3-r4-(2-Memyl-pyn^ohdm-l-ylVindan-l-yl1-ureido>-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4^2-memyl-pyrrohdin-l-yl)-indan-l-ylamine (Ex. 77A) instead of 5-(2-memoxy-l,lKlimemyUmyl>indan-l-ylamine. MS (DCI) 420 (M+l). Example 77C N-lH-mdazol^yl-N'44^2-memylpyrroUdm4-ylV23-dmydro-lH-mden4-yl1urea The title compound was made from the compound in Ex. 77B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/r. 376.12 [M+Hf. 'H NMR (DMSCMs) 8:1.00 (t, 3H), 1.57 (m, 1H), 1.79 (m, 1H), 1.91 (m, 1H), 2.14 (m, 1H), 2.30 (m, 1H), 2.88 (m, 2H), 3.12 (m, 2H), 3.55 (m, 1H), 3.89 (m, 1H), 5.18 (m, 1H), 6.59 (t, 1H), 6.66 (d, 1H), 6.73 (dd, 1H), 7.08 (m, 2H), 7.22 (t, 1H), 7.67 (d, 1H), 8.06 (d, 1H), 8.64 (m, 1H), 12.99 (s, 1H). Anal Calcd for C22H25N5O: C, 70.38; H, 6.71; N, 18.65. Found: C, 65.16; H, 5.42; N, 16.53. 115 WO 2004/111009 PCT/US2004/018590 Example 78 N-r4^2-azabicyclor22.1Thept^^ Example 78A 4^2-Aza-bicvclor2>2.1Thept-2-vl')-indan-l-vlamine The title compound was made according to the conditions described in Examples 56B-56C, except using 2-aza-bicyclo[2.2.1]heptane instead of piperidine in ex. 56B. Example 78B 4-(3-r4-(2-Memyl-pyrroKdm-l-ylVmdan-l-yl1-ureido)-m6!azole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4^2-aza-bicyclo[2.2.1]hept-2-yl)-indan-l-ylamine (Ex. 78A) instead of 5-(2-methoxy-l,l-dimethyl-ethyl>indan-l-ylamine. MS (DCI) 446 (M+l). ■ Example 78C N-r4-(2-azabicvclor2.2.nhert-2-vl>2J-^^ The title compound was made from the compound in Ex. 78B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 388.13 [M+H]+. *H NMR (DMSO-de) 8:1.30 (m, 1H), 1.46 (d, 1H), 1.64 (m, 4H), 1.79 (m, 1H), 2.27 (m, 1H), 2.87 (m, 3H), 3.15 (m, 1H), 3.62 (m, 1H), 4.10 (d, 1H), 5.09 (m, 1H), 6.42 (dd, 1H), 6.61 (m, 2H), 7.05 (m, 2H), 7.21 (t, 1H), 7.67 (d, 1H), 8.05 (d, 1H), 8.63 (d, 1H), 12.99 (s, 1H). Anal Calcd for C23H25N5O '1.7H20: C, 66.07; H, 6.85; N, 16.75. Found: C, 66.18; H, 6.77; N, 16.24. Example 79 N-r4^8-a2abicyclor3.2.11oct-8-ylV2.3-dmydro-lH-inden-l-vl1-N,-lH-indazol-4-ylurea Example 79A 4-f8-Aza-bicvclor3.2.noct-8-yl')-indan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using 8-aza-bicylo[3.2.1]octane instead of piperidine in ex. 56B. 116 WO 2004/111009 PCT/US2004/01859O Example 79B 4-l3-f4-(8-A2»-bicyclor32.11od-8-yl>hd^ methyl ester The title compound was made according to the conditions described in Example 361 except using 4-(8-Aza-bicyclo[3.2.1]oct-8-yl)-indan-l-ylamine (Ex. 79A) instead of 5-(2-memoxy4,l-a^emyl-emyl>indan-l-ylamine. MS (DCI) 460 (M+l). Example 79C N-r4-f8-azabicvclor32.11oct-8-vl>2^ The title compound was made from the compound in Ex. 79B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 401.98 [M+H]+. 'H NMR (DMSO-40 8:1.42 (d, 2H), 1.48 (m, 1H), 1.67-1.90 (m, 7H), 1.96 (m, 1H), 2.45 (m, 1H), 2.83 (m, 1H), 2.91 (m, 1H), 3.98 (d, 1H), 4.07 (d, 1H), 5.12 (q, 1H), 6.64 (d, 1H), 6.72 (d, 1H), 6.79 (d, 1H), 7.07 (m, 2H), 7.21 (t, 1H), 7.68 (d, 1H), 8.05 (s, 1H), 8.61 (s, 1H), 13.00 (s, 1H). Anal Calcd for C24H27N5O »0.5H2O •0.2TEA: C, 70.27; H, 7.25; N, 16.91. Found: C, 70.08; H, 7.50; N, 17.36. Example 80 N-lH-mdazol-4-yl-N'-r4-(trmuoromemylV2,3-dmydro-lH-inden-l-yl1urea Example 80A 4-Trifluoromethyl-indan-l-one The title compound was made according to the procedure described in Ex.57B-57C except using 2-trifluoromemyl-bromobenzene instead of 2-(3-bromophenyl)-2-methylpropionitrile in Ex. 57B. Example 80B 4-Trifluoromethyl-indan-1 -y lamine 117 WO 2004/111009 PCT/US2004/018590 The title compound was made according to the conditions described in Example 1C and ID, except using 4-trifluoromethyl-indan-l-one (Ex. 80A) instead of 5-tert-butyl-l-indanone. Example 80C 4-f3^4-Trifluoromemyl-mdm-l-vlVurddo1-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-trifluoromemyl-mdan4-ylamine (Ex. 80B) instead of 5-(2-methoxy-l,l-dimemyUthyl)-indan-l-ylamine. MS (DCI) 419 (M+l). Example 80D N-lH-indazol-4-yl->F-r4-(tifflw The title compound was made from the compound in Ex. 80C according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 360.92 [M+H]+. *H NMR (DMSO-ck) 6:1.93 (m, 1H), 2.54 (m, 1H), 3.02 (m, 1H), 3.13 (m, 1H), 5.27 (q, 1H), 6.81 (d, 1H), 7.09 (d, 1H), 7.22 (t, 1H), 7.46 (t, 1H), 7.65 (m, 3H), 8.06 (s, 1H), 8.65 (s, 1H), 13.00 (s, 1H). Anal Calcd for C1BH15N4OF3: C, 60.00; H, 4.20; N, 15.55. Found: C, 59.73; H, 3.98; N, 15.24. Example 81 N4'4^Moro-2.3-4ihydro-lH-inden-l-yl)-N'-lH-indazol-4-ylurea Example 81A 4-Chloro-indan-l-ylamine The title compound was made according to the conditions described in Ex. 57D, except using 4-chloro-indan-l-one instead of 2-methyl-2-(l-oxoindan-5-yl)-propionitrile. Example 81B 4-r3-(4-CMoro-indan-l-yl')-ureido1-indazole-l-carboxylic acid methyl ester 118 WO 2004/111009 PCT/US2004/018590 The title compound was made according to the conditions described in Example 361 except using 4-chloro-indan-l-ylamine (Ex. 81A) instead of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 385 (M+l). Example 81C N^4^Moro-2jKimvo^-lH-mden-l-vlVN'-lH-inda2ol-4-vlurea The title compound was made from the compound in Ex. 81B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 326.92 [M+H]+. lH NMR (DMSO-40 6:1.88 (m, 1H), 2.54 (m, 1H), 2.88 (m, 1H), 2.99 (m, 1H), 5.31 (q, 1H), 6.79 (d, 1H), 7.09 (d, 1H), 7.22 (t, 1H), 7.31 (m, 3H), 7.65 (d, 1H), 8.05 (s, 1H) 8.64 (s, 1H), 13.00 (s, 1H). Anal Calcdfor C17H15N4OCI: C, 62.48; H, 4.63; N, 17.14. Found: C, 62.29; H, 4.41; N, 16.85. Example 83 N-lH-iralazol^yl-N'-r4-(trifluoro^ Example 83A 4-trifluoromethoxy-indan-l -one The title compound was made according to the procedure described in Ex.57B-57C except using 2-trifluoromethoxy-bromobenzene instead of 2-(3-bromophenyl)-2-methylpropionitrile in Ex. 57B. Example 83B 4-Trifluoromemoxy-indan-l-ylamine The title compound was made according to the conditions described in Example 1C and ID, except using 4-trifluoromethoxy-indan-l-one_(Ex. 83A) instead of 5-tert-butyl-l-indanone. Example 83C 4-r3^4-Trifluoromemoxy-indan-l-vlVureidol-indazole-l-carboxvlic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-trifluoromemoxy-mdan-l-ylamine (Ex. 83B) instead of 5-(2-methoxy-l,l-d^emyl-ethyl)-indan-l-ylamine. MS (DCI) 435 (M+l). 119 WO 2004/111009 PCT/US2004/018590 Example 83D N-lH-indazol^vl-N'-r4-(trifluorometfaoxyV23-dihvdro-lH-inden-l-vl1i^ The title compound was made from the compound in Ex. 83C according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 376.88 [M+H]+. *H NMR (DMSCMs) 5:1.91 (m, 1H), 2.54 (m, 1H), 2.90 (m, 1H), 3.02 (m, 1H), 5.30 (q, 1H), 6.81 (d, 1H), 7.09 (d, 1H), 7.22 (m, 2H), 7.40 (m, 2H), 7.65 (d, 1H), 8.05 (s, 1H), 8.63 (s, 1H), 13.00 (s, 1H). Anal Calcd for CieH^OaFa: C, 57.45; H, 4.02; N, 14.89. Found: C, 57.25; H, 3.96; N, 14.68. Example 84 N-(4-bromo-2,3Khliydro-lH-mden-l-vl)-N'-lH-indazol-4-ylurea Example 84A 4-Bromo-indan-l -ylamine The title compound was made according to the conditions described in Ex. 57D, except using 4-bromo-indan-l-one instead of 2-methyl-2-(l-oxoindan-5-yl)-propionitrile. Example 84B 4-f3-(4-Bromo-indan-l-yl)-ureido1-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-bromo-indan-l-ylamine (Ex. 84A) instead of 5-(2-metooxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 431 (M+l). Example 84C N-(4-bromo-23-dihydro-lH-inden-l-yl)-Nl-lH-indazol-4-ylurea The title compound was made from the compound in Ex. 84B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 372.78 [M+H]+ JH NMR (DMSO-de) 8:1.88 (m, 1H), 2.53 (m, 1H), 2.86 (m, 1H), 2.94 (m, 1H), 5.30 (q, 1H), 6.80 (d, 1H), 7.09 (d, 1H), 7.22 (m, 2H), 7.34 (d, 1H), 7.46 (d, 1H), 7.65 (d, 120 WO 2004/111009 PCT/US2004/018590 1H), 8.06 (s, 1H), 8.64 (s, 1H), 13.00 (s, 1H). Anal Calcd for Ci7Hi5N4OBr: C, 55.00; H, 4.07; N, 15.09. Found: C, 54.89; H, 3.81; N, 14.93. Example 85 N-lH-mdarol^yl-N'^4-octahydroi Example 85A 4^0ctahydro-isoquinolin-2-yl')-indan-l -vlamine The title compound was made according to the conditions described in Examples 56B-56C, except using octahydro-isoquinoline instead of piperidine in ex. 56B. Example 85B 4-(3-r4-(Octahydjx)-isoqumolm-2-ylVmdan-l-yll-ureido)-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-(octahydro-isoquinolin-2-yl)-indan-l -ylamine (Ex. 85A) instead of 5-(2-memoxy-14-dimemyl^myl>indan-l-ylamine. MS (DCI) 488 (M+l). Example 85C N-lH-fadazol-4-yl->T-(4-o(^ydroisoqufaolm^ The title compound was made from the compound in Ex. 85B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 430.13 [M+H]+. 'HNMR (DMSO-40 6:1.20-2.04 (m, 13H), 2.38-3.22 (m, 7H), 5.16 (m, 1H), 6.68 (d, 1H), 6.81 (d, 1H), 6.93 (t, 1H), 7.07 (d, 1H), 7.15 (t, 1H), 7.22 (t, 1H), 7.67 (d, 1H), 8.04 (s, 1H), 8.62 (d, 1H), 13.00 (s, 1H). Anal Calcd for C26H31N5O •0.5H2O: C, 71.21; H, 7.35; N, 15.97. Found: C, 71.10; H, 7.67; N, 15.95. Example 86 N44-(cvanomemylV2,3-dmydro-lH-inden-l-yll-N'-lH-inda2ol-4-ylurea Example 86A 121 WO 2004/111009 PCT/US2004/018590 4-cyanomethvl-indan-l-one The title compound was made according to the procedure described in Ex.57B-57C except using 2-cyanomethyl-bromobenzene instead of 2-(3-bromophenyl>2-methylpropionitrile in Ex. 57B. Example 86B n-Amino-indan-4-vlVacetonitrile The title compound was made according to the conditions described in Example 1C and ID, except using 4-cyanomethyl-indan-l-one_(Ex. 86A) instead of 5-tert-butyl-l-indanone. Example 86C 4-r3-(4-Cvanomethyl-indan-l-vlVureido1-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using (l-amino-indan-4-yl)-acetonitrile (Ex. 86B) instead of 5-(2-methoxy-l,l- . dimethyl-ethyl>indan-l-ylamine. MS (DCI) 390 (M+l). Example 86D N-r4-(cyanomemylV2J-dmydro-lH-mden-l-yll-N'-lH-indazol--4-ylurea The title compound was made from the compound in Ex. 86C according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 331.96 [M+H]+. 'HNMR (DMSO-rf6) 5:1.85 (m, 1H), 2.54 (m, 1H), 2.85 (m, 1H), 2.98 (m, 1H), 4.01 (s, 2H), 5.22 (q, 1H), 6.74 (d, 1H), 7.08 (d, 1H), 7.22 (d, 1H), 7.27 (m, 2H), 7.33 (m, 1H), 7.66 (d, 1H), 8.05 (s, 1H), 8.61 (s, 1H), 13.00 (s, 1H). Anal Calcd for C19H17N5O: C, 68.87; H, 5.17; N, 21.13. Found: C, 68.49; H, 4.91; N, 20.92. Example 87 N-lH-mdazol^yl-N'^4-memyl-23Himydro-lH-inden-l-yl')urea Example 87A 4-Methyl-indan-l-vlamine 122 WO 2004/111009 PCT/US2004/018590- The title compound was made according to the conditions described in Ex. 57D, except using 4-methyl-indan-l-one instead of 2-methyl-2-(l-oxoindan-5-yl)-propionitrile. Example 87B 4-r3-(4-Memyl-indan-l-ylVureido1-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-methyl-indan-l-ylamine (Ex. 87A) instead of 5-(2-methoxy-l,l-dimethyl-ethyl>indan-l-ylamine. MS (DCI) 365 (M+l). Example 87C N4H-mdazoM-yl-hr^4-memvl-2.3Kiaydro-lH-inden-l-ynurea The title compound was made from the compound in Ex. 87B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 306.96 [M+H]+. 'HNMR (DMSO-^6) 6:1.81 (m, 1H), 2.25 (s, 3H), 2.48 (m, 1H), 2.76 (m, 1H), 2.89 (m, 1H), 5.21 (q, 1H), 6.68 (d, 1H), 7.05-7.24 (m, 5H), 7.67 (d, 1H), 8.04 (s, 1H), 8.59 (s, 1H), 12.99 (s, 1H). Anal Calcd for Ci8H18N40: C, 70.57; H, 5.92; N, 18.29. Found:.C, 70.35; H, 5.80; N, 18.00. Example 88 l-rfRVS-chloro-indan-l-ylVS-dH-indazoM-yD-urea Example 88A 5-(RMM>ro-mdan-l-ylamine 5-cUoro-2,3-dmydro-lH-mden-l-ylamine (3.13g, 18.7mmol),N-acetyl-(D>leucine (3.24g, 18.7 mmol) were dissolved in refluxing ethanol (125 mL).The solution was allowed to cool to ambient temperature. The solids were filtered and rinsed with cold EtOH. The solid was then resuspended in ethanol (45 mL) and brought to reflux. The solution was allowed to cool to ambient temperature and the solids were filtered. The solid was dried at 40°C under reduced pressure to provide the title compound (0.9g) as a salt Example 88B 443-(R)5-CMoro-indan-l-ylVureidol-inda2X)le-l-carboxylic acid methyl ester 123 WO 2004/111009 PCT/US2004/018590 The title compound was made according to the conditions described in Example 361 except using 5CUoro-indan-l-ylamine (Ex. 88A) as a free base instead of 5-(2-methoxy-l,lsiimemyl*myl>mdan4-ylamine. MS (DCI) 385 (M+l). Example 88C l-rOlVS^Moro-indan-l-vlV3-(lH-indazol-4-vlVurea The title compound was made from the compound in Ex. 88B according to the deprotection procedure by using 5MNaOH in methanol (example 9). [CJ]D: +33.2° (c: 1.0,1:1 MeOH:DMSO) MS (ESI) m/r. 327.02 [M+H]+ .'HNMRpMSCwfc) 8:1.85 (m, 1H), 2.53 (m, 1H), 2.87 (m, 1H), 2.96 (m, 1H), 5.17 (q, 1H), 6.78 (d, 1H), 7.08 (d, 1H), 7.22 (t, 1H), 7.29 (d, 1H), 7.34 (m, 2H), 7.66 (d, 1H), 8.07 & 1H), 8.66 (s, 1H), 13.00 (s, 1H). Anal Calcd for C17H15N4OCI: C, 62.48; H, 4.63; N, 17.14. Found: C, 62.57; H, 4.52; N, 17.17. Example 90 l-r5^1J-Dioxo-l-tMomorpholm4-vlVmdan-l-yn-3^7iy-indazol-4-vl)-urea Example 90A 5-(lJ-IMoxo-l-thiomorpholm^-yl>mdan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using thiomorpholine 1,1-dioxane instead of piperidine in ex. 56B. Example 90B 4.(3.f5-(lj-I^oxo-l-tMomoroholm^yl>todan-l^ methyl ester The title compound was made according to the conditions described in Example 361 except using 5-(l,l-Dioxo-l-thiomorpholm^yl)-mdan-l-ylamine (Ex. 90A) instead of 5-(2-memoxy-l,l-dimemyl-^^yl>mdan4-ylainine. MS (DCI) 484 (M+l). Example 90C l-rS^lJ-Dioxo-l-thiomoroholm^ylVmdan-l-yll-S-riJy-mdazoM-ylVurea 124 WO 2004/111009 PCT/US2004/01859U The title compound was made from the compound in Ex. 90B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 425.91 [M+H]+. *H NMR (DMSCwfc) 8:1.82 (m, 1H), 2.46 (m, 1H), 2.81 (m, 1H), 2.92 (m, 1H), 3.11 (s, 4H), 3.75 (s, 4H), 5.10 (q, 1H), 6.63 (d, 1H), 6.90 (d, 1H), 6.95 (s, 1H), 7.07 (d, 1H), 7.22 (m, 2H), 7.66 (d, 1H), 8.04 (s, 1H), 8.55 (s, 1H), 12.97 (s, 1H). Anal Calcd for C21H23N6O3S •O.oTfeO •0.4Ni: C, 54.87; H, 5.31; N, 15.23. Found: C, 54.85; H, 5.32; N, 15.48. Example 91 l-ClH-mdazoM-ylVS^-morpholin^yl-indan-l-ylVurea Example 91A 4-Morpholm-4-yl-indan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using morpholine instead of piperidine in ex. 56B. Example 91B 4-r3-(4-Morpholm^yl-indan-l-ylVureido1-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-morpholme^-yl-mdan-l-ylamine (Ex. 91A) instead of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 436 (M+l). Example 91C l-(lH-mdazoM-yl)0^4-morpholin-4-yl-indan-l-yl)-urea The title compound was made from the compound in Ex. 91B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 377.91 [M+H]+. !H NMR (DMSO-di) 8:1.79 (m, 1H), 2.44 (m, 1H), 2.79 (m, 1H), 2.90 (m, 3H), 2.99 (m, 2H), 3.74 (m, 4H), 5.16 (q, 1H), 6.67 (d, 1H), 6.83 (d, 1H), 7.00 (d, 1H), 7.07 (d, 1H), 7.19 (q, 2H), 7.67 (d, 1H), 8.05 (s, 1H), 8.62 (s, 1H), 12.99 (s, 1H). Anal Calcd for C21H23N5O2: C, 66.83; H, 6.14; N, 18.55. Found: C, 66.63; H, 5.99; N, 18.29. Example 92 l-(!H-Indazol-4-vl)-3-(4-ri.41oxazepan-4-yl-indan-l-yl')-urea 125 WO 2004/111009 PCT/US2004/018S90 Example 92 A 4-H .410xazepan-4-yl-todan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using [l,4]oxazepan instead of piperidine in ex. 56B. Example 92B 4-r3-(4-ri.410xazepan^vl-mdan-l-vlVureido1-indazole-l-carboxvlic acidmethvl ester The title compound was made according to the conditions described in Example 361 except using 3-[l,4]oxazapan^-yl-indan-l-ylamine (Ex. 92A) instead of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 450 (M+l). Example 92C HlH-Indazol-4-vn-3-(4-ri.41oxazepan-4-yl-indan-l-yl')-urea The title compound was made from the compound in Ex. 92B according to the deprotection procedure by using 5MNaOH in methanol (example 9). MS (ESI) m/z: 392.12 [M+H]+ 'H NMR (DMSO-^S) 5:1.76 (m, 1H), 1.93 (m, 2H), 2.43 (m, 1H), 2.82 (m, 1H), 2.89 (m, 1H), 3.33 (m, 4H), 3.75 (m, 4H), 5.13 (q, 1H), 6.65 (d, 1H), 6.80 (d, 1H), 6.87 (d, 1H), 7.07 (d, 1H), 7.12 (t, 1H), 7.21 (t, 1H), 7.67 (d, 1H), 8.05 (s, 1H), 8.61 (s, 1H), 12.99 (s, 1H). Anal Calcd for C22H25N5O2 «0.26MeOH: C, 66.87; H, 6.56; N, 17.52. Found: C, 67.06; H, 6.32; N, 17.11. Example 93 l-r4-(2t6-Dimemyl-morphoto^ylVmdan-l-yl1-3^1H-indazol-4-yl)-urea Example 93A 4-(2,6-Dimefcyl-morpholm^-ylVmdan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using 2,6-dimethyl-morpholine instead of piperidine in ex. 56B. Example 93B 126 WO 2004/111009 PCT/US2004/018590 4-(3-r4-(2.6-Dimethvl-moroholfo^^^ methyl ester The title compound was made according to the conditions described in Example 361 except using 4^2,6-dime%l-morpholm^yl)-ma^-l-ylamine (Ex. 93A) instead of 5-(2-memoxy-l,lslimettyl^thyl>mdan-l-ylamine. MS (DCI) 463 (M+l). Example 93C l-r4^2.6-13imemvl-mon)holm^vlVmdan-l-vl1-3^1H-mdazol^vlVurea The title compound was made from the compound in Ex. 93B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 406.18 [M+H]+. 'HNMR(DMSCwfc) 8:1.13 (t,5H), 1.26(dd, 1H), 1.79 (m, 1H),224(t, 1H),2.39 (t, 1H), 2.46 (m, 1H), 2.80 (m, 1H), 2.85 (m, 1H), 3.12 (d, 1H), 3.19 (d, 1H), 3.72 & 4.05 (pair of m, 2H), 5.16 (q, 1H), 6.67 (d, 1H), 6.81 (d, 1H), 6.99 (d, 1H), 7.08 (d, 1H), 7.18 (t, 1H), 7.22 (t, 1H), 7.67 (d, 1H), 8.05 (s, 1H), 8.61 (s, 1H), 13.00 (s, 1H). Anal Calcd for C23H27N5O2: C, 68.13; H, 6.71; N, 17.27. Found: C, 68.28; H, 6.71; N, 16.98. Example 94 HlH-mdazol^ylV3-r4-(4-memyl-pipera2m-l-yl>indan-l-yl1-urea Example 94A 4^4-Mettyl-pir)erazm-l-ylVmdan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using 1-methyl-piperazine instead of piperidine in ex. 56B. Example 94B 4.(3.f4-(4-Methyl-piperazm-l-yl)-mdan-l-yl1-ureido)-mdazole-l-carb^ acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-(4-metoyl-piperazm-l-yl)-mdan-l-ylamine (Ex. 94A) instead of 5-(2-metooxy-14-dimemyl-ethyl)-mdan4-ylamine. MS (DCI) 449 (M+l). Example 94 l-nH-mdazol-4-ylV3-r4-(4-methyl-pipeiazin-l-ylV-indan-l-yn-urea 127 WO 2004/111009 PCT/US2004/018590 The title compound was made from the compound in Ex. 94B according to the deprotecuon procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 391.13 [M+H]+. !H NMR (DMSO-4D 6:1.78 (m, 1H), 2.24 (s, 3H), 2.44 (m, 1H), 2.48 (m, 4H), 2.77 (m, 1H), 2.89 (m, 3H), 3.00 (m, 2H), 5.16 (q, 1H), 6.67 (d, 1H), 6.82 (d, 1H), 6.97 (d, 1H), 7.08 (d, 1H), 7.17 (t, 1H), 7.22 (t, 1H), 7.68 (d, 1H), 8.05 (s, 1H), 8.62 (s, 1H), 13.00 (s, 1H). Anal Calcd for C22H28N60 •0.8H2O »1.2MeOH: C, 62.85; H, 7.37; N, 18.96. Found: C, 62.73; H, 7.48; N, 18.91. Example 95 l-nH-mdazoM-vlVS^-pyridin-S-yl-indan-l-yn-urea Example 95A 4-Pyridin-3-yl-indan-l-one O-methvl-oxime 4-Bromoindan-l-one O-methyloxime (720mg, 3.0mmol) was added to a mixture of pyridine-3-boronic acid (406mg, 3.3mmol), sodium carbonate (477mg, 4.5mmol) and Pd(dppf)Cl2»CH2Cl2 (122mg, 0.15mmol) in 7:2:3 DME:EtOH:H20 (15mL). The stirred mixture was heated at 160°C for 3 minutes on the microwave. After cooling to ambient temperature, the reaction mixture was filtered through celite, then silica gel with ethyl acetate. The filtrate was concentrated to a brown oil and chromatographed on silica gel with 70% ethyl acetate in hexane. Obtained 4-pyridin-3-yl-indan-l-one O-methyloxime (667mg, 93%) as a yellow oil. MS (ESI) m/z: 239.1 [M+H]+ .'H NMR (DMSO-4D 8:2.81 (m, 2H), 3.08 (m, 2H), 3.92 (s, 3H), 7.45 (m, 2H), 7.48 & 7.51 (pair of dd, 1H), 7.63 (dd, 1H), 7.94 & 7.97 (pair of dd, 1H), 8.60 (dd, 1H), 8.72 (dd, 1H). Example 95B 4-Pyridin-3-yl-indan-l-ylamine The title compound was made according to the conditions described in Example ID, except using 4-pyridin-3-yl-indan-l-one O-methyl-oxime instead of 5-tert-Butyl-l-indanone O-methyloxime. 128 WO 2004/111009 PCT/US2004/018590 Example 95C 4-r3-f4-Pvridin-3-yl-mdan-l-vlVureido1-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-Pyridm-3-yl-indan-l-ylamine (Ex. 95B) instead of 5-(2-methoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 428 (M+l). Example 95 l-(lH-mdazoM-ylV3-(4-pyridin-3-yl-indan-l-vn-urea The title compound was made from thufompound in Ex. 9SC according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 370.07 [M+Hf. *H NMR QM&O-ck) 8:1.84 (m, 1H), 2.47 (m, 1H), 3.00 (m, 2H), 5.30 (q, 1H), 6.77 (d, 1H), 7.09 (d, 1H), 7.23 (t, 1H), 7.39 (m, 3H), 7.50 & 7.53 (pair of dd, 1H), 7.68 (d, 1H), 7.92 (dt, 1H), 8.07 (t, 1H), 8.59 (dd, 1H), 8.66 (s, 1H), 8.72 (dd, 1H), 13.00 (s, 1H). Anal Calcd for C22H19N5O: C, 71.53; H, 5.18; N, 18.96. Found: C, 71.27; H, 5.21; N, 18.90. Example 96 l-(lH-Indazol-4-yl>3-(4-pyridin-4-yl-indan-l-ylVurea Example 96A 4-Pyridin-4-yl-indan-l-one O-methyl-oxime The title compound was made according to the procedure described in Example 95A except using pyridine-3-boronic acid instead of pyridine-3-boronic acid. Example 96B 4-Pyridin-4-yl-indan-l-ylamine The title compound was made according to the conditions described in Example ID, except using 4-pyridin-4-yl-indan-l-one O-methyloxime instead of 5-tert-Butyl-l-indanone O-methyloxime. Example 96C 129 WO 2004/111009 PCT/US2004/018S90 4-r3^4-Pvridin-4-vl-indan-l-vlVureido1-indazole-l-carboxvlic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-pyridm-4-yl-indan-l-ylainine(Ex. 96B) instead of 5-(2-memoxy-l,l-dimethyl-ethyl)-indan-l-ylamine. MS (DCI) 428 (M+l). Example 96 HlH-mdazoM-vlVS^-pyridin^-vl-indan-l-ylVurea The title compound was made from the compound in Ex. 96C according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 370.00 [M+H]+. 'H NMR (DMSO-<&) 5:1.84 (m, 1H), 2.47 (m, 1H), 3.03 (m, 2H), 5.28 (q, 1H), 6.78 (d, 1H), 7.09 (d, 1H), 7.23 (t, 1H), 7.41 (m, 3H), 7.52 (dd, 2H), 7.68 (d, 1H), 8.06 (s, 1H), 8.66 (m, 3H), 13.01 (s, 1H). Anal Calcd for C22HUM5O: C, 71.53; H, 5.18; N, 18.96. Found: C, 71.22; H, 5.07; N, 18.79. Example 97 l-(lH-mdazol-4-yl)-3-(4-pyridin-2-yl-indan-l-yl)-urea Example 97A 4-Pyridin-2-yl-indan-l-one O-methyl-oxime 2-Pyridylzinc bromide (lOmL, 5mmol, 0.5M in THF) was added to 4-bromoindan-l-one O-methyl-oxime (600mg, 2.5mmol) and Pd(PPh3)4 (58mg, 0.05mmol) under nitrogen atmosphere. The stirred solution was heated at 120°C for 10 minutes on the microwave. After cooling to ambient temperature, the reaction mixture was filtered through celite, then silica gel with ethyl acetate. The filtrate was concentrated to a brown oil and chromatographed on silica gel with 20-40% ethyl acetate in hexane. Obtained 4-pyridin-2-ylindan-1-one Omethyloxime (326mg, 55%) as a yellow oil. MS (DCI/NH3) m/z: 239.09 [M+H]+. *HNMR (DMSO-cfe) 8:2.82 (m, 2H), 3.29 (m, 2H), 3.92 (s, 3H), 7.36 & 7.38 (pair of dd, 1H), 7.43 (t, 1H), 7.64 (dd, 1H), 7.74 (dd, 1H), 7.75 (dt, 1H), 7.91 (td, 1H), 8.68 & 8.69 (pair of dd, 1H). Example 97B 4-Pyridm-2-yl-mdan-l-ylamine 130 WO 2004/111009 PCT/US2004/018S90 The title compound was made according to the conditions described in Example ID, except using 4-Pyridin-2-yl-indan-l-one 0-methyl-oxime_instead of 5-tert-Butyl-l-indanone O-methyloxime. Example 97C 4«r3^4-Pyridm-2-vl-mdan-l-vlVureido1-mdazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-pyridin-2-yl-indan-l-ylamine (Ex. 97B) instead of 5-(2-methoxy-l,l- dimemyl-ethyl>indan-l-ylamine. MS (DO) 428 (M+l). Example 97 l-(lH-mdazol^ylV3-(4-pyridin-2-yl-indan-l-yl)-urea The title compound was made from the compound in Ex. 97C according to the deprotection procedure by using SM NaOH in methanol (example 9). MS (ESI) m/r. 370.0 [M+H]+. *H NMR (DMSO-<&) 8:1.83 (m, 1H), 2.47 (m, 1H), 3.12 (m, 2H), 5.29 (q, 1H), 6.78 (d, 1H), 7.09 (d, 1H), 7.23 (t, 1H), 7.38 (m, 3H), 7.63 (dd, 1H), 7.69 (d, 1H), 7.70 (dt, 1H), 7.91 (td, 1H), 8.06 (s, 1H), 8.64 (s, 1H), 8.69 & 8.70 (pair of dd, 1H), 13.01 (s, 1H). Anal Calcd for C22H19N5O «0.16H2O: C, 70.97; H, 5.23; N, 18.81. Found: C, 70.93; H, 5.21; N, 18.91. Example 98 1 -f4-(4-Fluoro-piperidin-1 -yl)-indan-l-yl1-3-(l H-indazol-4-yl)-urea Example 98A 4-(4-Fluoro-piperidm-l-ylVmdan-l-ylamine The title compound was made according to the conditions described in Examples 56B-56C, except using 4-fluoro-piperidine instead of piperidine in ex. 56B. Example 98B 4-(3-r4-(4-Fluoro-piperidm-l-ylVmdan-l-yl1-ureido)-mda2Ple-l-carboxylicacidmemyl ester 131 WO 2004/111009 PCT/U8Z0U4/U1855W The title compound was made according to the conditions described in Example 361 except using 4-(4-fluoro-piperidm-l-yl)-indan-l-ylamine (Ex. 98A) instead of 5-(2-methoxy-U-dimemyl-emyl)-mdan-l-ylamine. MS (DCI) 452 (M+l). Example 98C The title compound was made from the compound in Ex. 98B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 394.08 [M+H]+. JH NMR (DMSO-40 8:1.75-2.08 (m, 5H), 2.45 (m, 1H), 2.74-3.14 (m, 6H), 4.76 & 4.92 (pair of 7,1H), 5.19 (q, 1H), 6.67 (d, 1H), 6.85 (d, 1H), 6.98 (d, 1H), 7.07 (d, 1H), 7.17 (t, 1H), 7.22 (t, IH), 7.67 (d, 1H), 8.05 (s, 1H), 8.62 (s, 1H), 13.00 (s, 1H). Anal Calcd for C22H24N5OF •0.38H2O: C, 66.01; H, 6.23; N, 17.49. Found: C, 66.10; H, 6.54; N, 17.22. Example 99 l-r4-(3-Fluoro-piperio!fa-l-yl)-md^-l-yl1-3-(lH-indazol-4-Yl')-urea Example 99A 4-(3-Fluoro-piperidin-1 -ylV-indan-1 -y lamine The title compound was made according to the conditions described in Examples 56B-56C, except using 3-fluoro-piperidine instead of piperidine in ex. 56B. Example 99B 4-(3-r4-(3-Fluoro-pir)eridm-l-yn-indan-l-yn-ureido)-indazole-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-(3-fluoro-piperid^-l-yl)-mdan-l-ylamine (Ex. 99A) instead of 5-(2-memoxy-l^-dimemyl-emyl)-mdan-l-ylamine. MS (DCI) 452 (M+l). Example 99C l-r4-(3-Fluoro-piperidin-l-yl)-indan-l-yl1-3-(lH-indazol-4-yl)-urea 132 WO 2004/111009 PCT/US2004/018590 The title compound was made from the compound in Ex. 99B according to the deprotection procedure by using SM NaOH in methanol (example 9). MS (ESI) m/z: 394.11 [M+H]+. *H NMR (DMSO-40 8:1.62-1.98 (m, 5H), 2.44 (m, 1H), 2.73-3.03 (m, 5H), 3.11 (m, 1H), 4.72 & 4.88 (pair of m, 1H), 5.19 (q, 1H), 6.69 (d, 1H), 6.84 (d, 1H), 6.98 (d, 1H), 7.08 (d, 1H), 7.18 (t, 1H), 7.22 (t, 1H), 7.67 (d, 1H), 8.05 (s, 1H), 8.62 (d, 1H), 12.99 (s, 1H). Anal Calcd for C22H24N5OF -0.18H2O: C, 66.61; H, 6.19; N, 17.65. Found: C, 66.66; H, 6.61; N, 17.51. Example 100 l-r4-(3,3-Difluoro-piperidm-l-ylVmdan-l-yl1-3-(lH-indazol-4-yl)-urea Example 100A 4-(3,3-difluoro-piperidin-l-yl')-indan-l -ylamine 1 The title compound was made according to the conditions described in Examples 56B-56C, except using 3,3-difluoro-piperidine instead of piperidine in ex. 56B. Example 100B 4-(3-r4-(3,3-difluoro-piperidm-l-yl>mdan-l-yll-ureido>-inda2X)le-l-carboxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4-(3^-difluoro-piperidm-l-yl)-indan-l-ylamine (Ex. 100A) instead of 5-(2-memoxy-l,l-dime%l-emyl>mdan-l-ylamine. MS (DO) 470 (M+l). Example 100C l-r4-(33-difluoro-piperidm-l-ylVmdan-l-yl1-3-(lH-indazol-4-ylVurea The title compound was made from the compound in Ex. 100B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 412.04 [M+H]+. 'HNMR(DMSO-4,)5: 1.82 (m, 3H),2.04 (7,2H),2.46(m, 1H), 2.81 (m,2H), 2.93 (m, 1H), 3.05 (m, 1H), 3.19 (t, 1H), 3.29 (t, 1H), 5.20 (q, 1H), 6.67 (d, 1H), 6.86 (d, 1H), 7.01 (d, 1H), 7.08 (d, 1H), 7.19 (q, 2H), 7.67 (d, 1H), 8.05 (s, 1H), 8.63 (s, 1H), 13.00 (s, 1H). 133 WO 2004/111009 PCT/US2004/018590 Anal Calcd for C22H23N5OF2 »0.98H2O: C, 61.58; H,.5.86;N, 16.32. Found: C, 61.63; H, 5.32; N, 15.95. Example 101 l-r4^4t4-Difluoro-piperidin-l-ylVmdan-l-yll-3-(lH-kdazol-4-vlVurea Example 101A 4-(4,4-Difluoro-piperidin»l -ylVindan-1 -vlamine The title compound was made according to the conditions described in Examples 56B-56C, except using 4,4-difluoro-piperidine instead of piperidine in ex. 56B. Example 101B 4-(3-r4^4.4-DMuoro-piperidm-l-ylVmdan-l-yl1-ureido>-mo,azole-lK^boxylic acid methyl ester The title compound was made according to the conditions described in Example 361 except using 4^4,4-difluoro-piperidm-l-yl)-indan-l-ylamine (Ex. 101 A) instead of 5-(2-memoxy-l,l-dimemylmdan-l-yl10-(lH-indazol-4-yl>-urea The title compound was made from the compound in Ex. 101B according to the deprotection procedure by using 5M NaOH in methanol (example 9). MS (ESI) m/z: 412.04 [M+H]+. 'H NMR (DMSO-rf6) 6:1.80 (m, 1H), 2.12 (m, 4H), 2.46 (m, 1H), 2.81 (m, 1H), 2.88 (m, 1H), 3.05 (m, 2H), 3.11 (m, 2H), 5.20 (q, 1H), 6.68 (d, 1H), 6.89 (d, 1H), 7.01 (d, 1H), 7.08 (d, 1H), 7.22 (q, 2H), 7.67 (d, 1H), 8.05 (s, 1H), 8.62 (s, 1H), 13.00 (s, 1H). Anal Calcd for C22H23N5OF2: C, 64.22; H, 5.63; N, 17.02. Found: C, 64.49; H, 5.50; N, 16.72. (5) Determination of Biological Activity (a) In Vitro Data - Determination of Inhibition Potencies Dulbecco's modified Eagle medium (D-MEM) (with 4.5 mg/mL glucose) and fetal bovine serum were obtained from Hyclone Laboratories, Inc. (Logan, Utah). Dulbecco's phosphate-buffered saline (D-PBS) (with 1 mg/mL glucose and 3.6 mg/1 Na pyruvate, without phenol red), L-glutamine, hygromycin B, and Lipofectamine™ were obtained from 134 WO 2004/111009 PCT/US2004/018590 Life Technologies (Grand Island, NY). G418 sulfate was obtained from Calbiochem-Novabiochem Corp. (San Diego, CA). Capsaicin (8-methyl-N-vanillyl-6-nonenainide) was obtained from Sigma-Aldrich, Co. (St. Louis, MO). Fluo-4 AM (N-[4-[6-[(acetyloxy)memoxy]-2,7-dffluoi^3-oxo-3H-xM [(acetyloxy)meraoxy]-2-oxyemyl]amino]-5-memy^ [(acetyloxy)methoxy]-2-oxyethyl]-glycine, (acetyloxy)methyl ester) was purchased from Molecular Probes (Eugene, OR). The cDNAs for the human VR1 receptor were isolated by reverse transcriptase-polymerase chain reaction (RT-PCR) from human small intestine poly A+RNA supplied by Clontech (Palo Alto, CA) using primers designed surrounding the initiation and termination codons identical to the published sequences (Hayes et ah Pain Vol. 88 pages 205-215, 2000). The resulting cDNA PCR products were subcloned into pCIneo mammalian expression vector (Promega) and fully sequenced using fluorescent dye-terminator reagents (Prism, Perkin-Elmer Applied Biosystems Division) and a Perkin-Elmer Applied Biosystems Model 373 DNA sequencer or Model 310 genetic analyzer. Expression plasmids encoding the hVRl cDNA were transfected individually into 1321N1 human astrocytoma cells using Lipofectamine™. Forty-eight hours after transfection, the neomycin-resistant cells were selected with growth medium containing 800 u.g/mL Geneticin (Gibco BRL). Surviving individual colonies were isolated and screened for VR1 receptor activity. Cells expressing recombinant homomeric VR1 receptors were maintained at 37 °C in D-MEM containing 4 mM L-glutamine, 300 ng/mL G418 (Cal-biochem) and 10% fetal bovine serum under a humidified 5% C02 atmosphere. The functional activity of compounds at the VR1 receptor was determined with a Ca2+ influx assay and measurement of intracellular Ca2+ levels ([Ca2+]i). All compounds were tested over an 11-point half-log concentration range. Compound solutions were prepared in D-PBS (4x final concentration), and diluted serially across 96-well v-bottom tissue culture plates using a Biomek 2000 robotic automation workstation (Beckman-Coulter, Inc., Fullerton, CA). A 0.2 uM solution of the VR1 agonist capsaicin was also prepared in D-PBS. The fluorescent Ca2+ chelating dye fluo-4 was used as an indicator of the relative levels of [Ca2+]i in a 96-well format using a Fluorescence Imaging Plate Reader (FLIPR)(Molecular Devices, Sunnyvale, CA). Cells were grown to confluency in 96-well black-walled tissue culture plates. Then, prior to the assay, the cells were loaded with 100 uL per well of fluo-4 135 WO 2004/111009 PCT/US2004/018590 AM (2 uM, in D-PBS) for 1-2 hours at 23 °C. Washing of the cells was performed to remove extracellular fluo-4 AM (2 x 1 mL D-PBS per well), and afterward, the cells were placed in the reading chamber of the FLIPR instrument 50 ]xL of the compound solutions were added to the cells at the 10 second time mark of the experimental run. Then, after a 3 minute time delay, 50 \iL of the capsaicin solution was added at the 190 second time mark (0.05 uM final concentration)(final volume - 200 uL) to challenge the VR1 receptor. Time length of the experimental run was 240 seconds. Fluorescence readings were made at 1 to 5 second intervals over the course of the experimental run. The peak increase in relative fluorescence units (minus baseline) was calculated from the 190 second time mark to the end of the experimental run, and expressed as a percentage of the 0.05 uM capsaicin (control) response. Curve-fits of the data were solved using a four-parameter logistic Hill equation in GraphPad Prism® (GraphPad Software, Inc., San Diego, CA), and ICJO values were calculated. The compounds of the present invention were found to be antagonists of the vanilloid receptor subtype 1 (VR1) receptor with ICso» from about 2200 nM to about 1.0 nM. In a preferred range, compounds tested had ICsos from about 200 nM to about 1.0 nM. (b) In Vfvo Data - Determination of Antinociceptive Effect Experiments were performed on 400 adult male 129J mice (Jackson Laboratories, Bar Harbor, ME), weighing 20-25 g and male Sprague-Dawley rats (Charles River, Wilmington, MA) weighing 200-300 grams were utilized. Animals were kept in a vivarium, maintained at 22 °C, with a 12 hour alternating light-dark cycle with food and water available ad libitum. All experiments were performed during the light cycle. Animals were randomly divided into separate groups of 6 animals each. Each animal was used in one experiment only and was sacrificed immediately following the completion of the experiment. All animal handling and experimental procedures were approved by an IACUC Committee. The antinociceptive test used was a modification of the abdominal constriction assay described in Collier, et al, Br. J. Pharmacol. Chemother. Vol. 32 pages 295-310, (1968). Each animal received an intraperitoneal (i.p.) injection of 0.3 mL of 0.6% acetic acid in normal saline to evoke writhing. Animals were placed separately under clear cylinders for the observation and quantification of abdominal constriction. Abdominal constriction was defined as a mild constriction and elongation passing caudally along the abdominal wall, accompanied by a slight twisting of the trunk and followed by bilateral extension of the hind 136 WO 2004/111009 PCMJS2004/018590 limbs. The total number of abdominal constrictions was recorded from 5 to 20 minutes after acetic acid injection. The EDso* were determined based on the i.p. injection. The other antinociceptive test used was Complete Freund's Adjuvant-induced Thermal Hyperalgesia (CFA) assay described in Pircio et al. Eur J Pharmacol. Vol. 31(21 pages 207-215 (1975). Chronic inflammatory hyperalgesia was induced in one group of rats following the injection of complete Freund's adjuvant (CFA, 50%, 150 ul) into the plantar surface of the right hindpaw 48 hours prior to testing. Thermal nociceptive thresholds were measured in three different groups of rats. The EDsos were determined based on the oral administration. The compounds of the present invention tested were found to have antinociceptive effects with ED50s from about 1 mg/kg to about 500 mg/kg. The in vitro and in vivo data demonstrates that compounds of the present invention antagonize the VR1 receptor and are useful for treating pain. Compounds of the present invention are also useful for ameliorating or preventing additional disorders such as, but not limited to, infammatory thermal hyperalgesia, bladder overactivity, and urinary incontinence as described by Nolano, M. et al., Pain Vol. 81 page 135 (1999); Caterina, M.J. and Julius, D., Annu. Rev. Neurosci. Vol. 24, pages 487-517 (2001); Caterina, M.J. et al, Science Vol. 288 pages 306-313 (2000); Caterina, MJ. et al., Nature Vol. 389 pages 816-824 (1997); Fowler, C. Urology Vol. 55 page 60 (2000); and Davis, J. et al., Nature Vol. 405 pages 183-187 (2000). 137 1. A process for preparing a compound having structural formula (VI), \ *•* 0' Nil R. <■> ••■-■..... <■'' "' N alky I „ -o {VI) wherein, Ri is hydrogen or alkyl, comprising, in toto, the steps of: (a) treating a 2-alkyl substituted 3-nitro-aniline (Via) in acetic acid with sodium nitrite to provide a compound of formula (VIb) MO; H, NO- ,. Y - NH;, iVI.M - -. ** 1" "T * . .... .^. -; .Vlhi (b) treating a compound of formula (VIb) with an alkyl chloroformate and a base to provide a compound of formula (Vic) NO, ri| >K>, ,,. H . .0 *V ■Vlfcl •.Vk;n'-:-"-(V (c) treating a compound of formula (Vic) with an atmosphere of hydrogen in the presence of palladium on carbon in a solvent to provide a compound of formula (VId) MO; .""' N"2 RI N ► | M ■:■■■■ N •■■■-- '"-N .»....a 4' .>.,/,Ky' (d) treating a compound of formula (VId) with a compound of formula (Vie) in a solvent to provide a compound of formula (VI) < M J NHj R o C * ;r-"-0' NM K, .■-.:,.-< .-< -I >-. ° -••:. •' ll "■ VN •• [ N O' 'O N | - | '.N 1-..J.'—-N' ■-■•' •>■-" -. "A tvm>o ° W -VU-! iVij o' '• 2. A process for preparing a compound having structural formula (VII), ,- -.- :-----KrJ V'"' r''"'■ Rn (VII) wherein, R9, Rio, Rn, and Ri2 are each individually selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkyicarbonylaikyl, alkylcarbonyloxy, alkylthio, alkynyl, aryl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, formylalkyl, haloalkoxy, haloalkyl, haloalkylthio, halogen, heteroaryl, heterocycle, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, (CF3)2 (HO) C-, RB (SO)2 RAN-, RAO (SO)2-, RBO (SO)2-, ZAZBN-, (ZAZBN) alkyl, (ZAZBN) carbonyl, (ZAZBN) carbonylalkyl, and (ZAZBN) sulfonyl, wherein ZA and ZB are each independently hydrogen, alkyl, alkylcarbonyl, formyl, aryl, or arylalkyi, provided that at least one of Rg, Rio, Rn, or R12 is other than hydrogen, or R10 and Rn taken together with the atoms to which they are attached form a cycloalkyl, cycloalkenyl, or heterocycle ring; comprising, in toto, the steps of: (a) treating 3-chloropropionyl chloride with aluminum trichloride in dichloromethane followed by addition of a substituted benzene (Vila), wherein R9, R™, Rn, and Ri2 are as defined in claim 1 to provide a compound of formula (Vllb) •J, R; it n ii R, ..C. X 0 R|, 0 K.2 .VD-: (b) treating a compound of formula (VIlb) with concentrated sulfuric acid to provide a compound of formula (Vile) p. ?» CI ,■■'.:;.. ...R„-. ,1. i^ i ;i ' - w Of" Ti 'if T -R'» Y'T '* H () R1;, " !(■; ivcibi iv:ic,. (c) heating a compound of formula (Vile) and a compound of formula (Vlld) in the presence of or absence of an acid in toluene in a flask fitted with a Dean-Stark trap followed by adding the mixture to a solution of sodium borohydride in ethanol at a temperature less than or about 0 °C, followed by stirring, followed by the slow addition of water, followed by extraction with ethyl acetate to provide the compound of formula (Vile) which is optionally purified before use in step (d) *' f if' "■■.;■*' ■RD '•'" ") 1 "R.. '■"•'-:_--'-- -.-Nil O H, Ms ,-- if '"'\ .■*•.:, HN •'. -J-M., R.. ivik. ;V!i:i: :virf. (d) treating a compound of formula (Vile) with an atmosphere of hydrogen at about 40 psi in the presence of about 5-20 % palladium on carbon in a solvent with or without an acid to provide a compound of formula (VII) which is optionally purified Ro '^III ■'■ P ^N K, (VKul ,vu, 3. The process as claimed in claim 2, wherein the compound of formula (Vile) is further purified by preparing the salt with an acid and recrystallized prior to step (d). 4. The process as claimed in claim 2, wherein the compound of formula (Vile) is further purified by preparing the tosylate salt and recrystallized prior to step (d). 5. The process as claimed in claim 2, wherein the compound of formula (Vll) is further purified by preparing the salt with an acid and recrystallized. 6. The process as claimed in claim 2, wherein the compound of formula (Vll) is further purified by preparing the tosylate salt and recrystallized. 7. A process for preparing a compound having structural formula (VIII), Ri HU NH ™\i M' H Ha R II. {YIH'i wherein, Ri is hydrogen or alkyl and R9, R10l Rn, and R-i2 are as defined in claim 2, comprising, in toto, the steps of: (a) treating a compound of formula (VI) with a compound of formula (Vll) to provide a compound of formula (Villa) Ri alkyi HN '0 "'■-■ V I ■o-t.Vl: ? IS tVlh akyl I hN'' "NH ■'% -:vi R, (b) treating a compound of formula (Villa) with sodium hydroxide in methanol to provide the compound of formula (VIII) R, 0" '-Q ,>L.b) »- N'' H {K "Nil Ri: IV III I a-yyi 8. The compound of Formula (VI) of claim 1, useful in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I). 9. The compound of Formula (VI) of claim 1, useful in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I), which is useful for the treatment of a disorder by inhibiting vanilloid receptor subtype 1 in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. 10. The compound of Formula (VI) of claim 1, useful in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I), which is useful for the treatment of pain in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. 11. The compound of Formula (VII) of claim 2, useful in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I). 12. The compound of Formula (VII) of claim 2, useful in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I), which is useful for the treatment of a disorder by inhibiting vanilloid receptor subtype 1 in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. 13. The compound of Formula (VII) of claim 2, useful in the process of preparing a compound of formula (VIII) which is representative of compound of formula (I), which is useful for the treatment of pain in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. 14. A process for preparing a compound having structural formula (IX), ■ -^ o i '••••■ N O " NH a ■■'■■■■■...... ■ I N ■•■■■"•■ H UN' comprising, in toto, the steps of: (a) treating 2-methyl 3-nitro-analine (IXa) of in acetic acid with sodium nitrite to provide a compound of formula (IXb) NO; N^i ■X -■-■* Q-> Nil, H lX.il ll\t>i (b) treating a compound of formula (IXb) with methyl chloroformate and a base to provide a compound of formula (IXc) 0, NO- •V..- "N - to- '' '1 VN •:"-N H ilV.ii A. .'' (c) treating a compound of formula (IXc) with an atmosphere of hydrogen in the presence of palladium on carbon in a solvent to provide a compound of formula (IXd) NO, Nri;! .J-. ..-.. ..-. T N — " '. > ..,;;'-N ■■-.-■■■■■■» '.Xc:,-/ 0 .IX, o;" 0' (d) treating a compound of formula (IXd) with a compound of formula (IXe) in a solvent to provide a compound of formula (IX) /-f ° -0/ ° aNO 6' ,.x. o;>» . 15. A process for preparing a compound having structural formula (X), H5N ...>(' (b) treating a compound of formula (Xb) with concentrated sulfuric acid to provide a compound of formula (Xc) AlCj 'CI iXol ,c ..-• L) D IXI" (c) heating a compound of formula (Xc) and a compound of formula (Xd) in the presence of or absence of an acid in toluene in a flask fitted with a Dean-Stark trap followed by adding the mixture to a solution of sodium borohydride in ethanol at a temperature of about 0 °C, followed by stirring, followed by the slow addition of water, followed by extraction with ethyl acetate to provide the compound of formula (Xe) which is optionally purified before use in step (d) NH? ■:\ui ;.v-i (d) treating a compound of formula (Xe) with an atmosphere of hydrogen at 40 psi in the presence of about 5-20 % palladium on carbon in a solvent with or without an acid to provide a compound of formula (X) which is optionally purified :Xe.i <-.X> 16. The process as claimed in claim 15, wherein the compound of formula (Xe) is further purified by preparing the salt with an acid and recrystallized prior to step (d). 17. The process as claimed in claim 15, wherein the compound of formula (Xe) is further purified by preparing the tosylate salt and recrystallized prior to step (d). 18. The process as claimed in claim 15, wherein the compound of formula (X) is further purified by preparing the salt with an acid and recrystallized. 19. The process as claimed in claim 15, wherein the compound of formula (X) is further purified by preparing the tosylate salt and recrystallized. 20. A process for preparing a compound having structural formula (XI), o UN' NH i XI i comprising, in toto, the steps of: (a) treating a compound of formula (IX) with a compound of formula (X) to provide a compound of formula (Xla) o o c. X N > ,.. J-, 0 / '" ' | •-.. N' '""'■'" H,N N""":::-.--'' "0'"'v,. ~X (b) treating a compound of formula (Xla) with sodium hydroxide in methanol to provide the compound of formula (XI) o IIN' 'NH N'-'"""'''"' l: '■.. N '■'■■-■ I O c (XI.!, HN " H-i IXI: 21. The compound of Formula (IX) of claim 14, useful in the process of preparing a compound of formula (XI) which is representative of compound of formula (I). 22. The compound of Formula (IX) of claim 14, useful in the process of preparing a compound of formula (XI) which is representative of compound of formula (I) which is useful for the treatment of a disorder by inhibiting vanilloid receptor subtype 1 in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. 23. The compound of Formula (IX) of claim 14, useful in the process of preparing a compound of formula (XI) which is representative of compound of formula (I) which is useful for the treatment of pain in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. 2.4. The intermediate of Formula (X) of claim 15, useful in the process of preparing a compound of formula (XI) which is representative of compound of formula (I). 25. The compound of Formula (X) of claim 15, useful in the process of preparing a compound of formula (XI) which is representative of compound of formula (I) which is useful for the treatment of a disorder by inhibiting vanilloid receptor subtype 1 in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. 26. The compound of Formula (X) of claim 15, useful in the process of preparing a compound of formula (XI) which is representative of compound of formula (I) which is useful for the treatment of pain in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof. Dated this 05tn day of December 2007 / /j f Of Anand Ana Anand Advocates Attorney for the Applicants Abstract: FUSED COMPOUNDS THAT INHIBIT VANILLOID RECEPTOR SUBTYPE 1(VR1) RECEPTOR The present invention discloses novel compounds of general formula (I), or a pharmaceutically acceptable salt or prodrug thereof (in which X, - X5, R5 - R8b, Z\ - Z2 and An are defined herein), a method for inhibiting the VR1 receptor in mammals using these compounds, a method for controlling pain in mammals, and pharmaceutical compositions including those compounds and a process for making those compounds.