FORM 2 The Patents Act, 1970 (39 of 1970) & The Patent Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) 'SUBSTITUTED DIAZABICYCLOALKANE DERIVATIVES AS LIGANDS AT ALPHA 7 NICOTINIC ACETY LCHOLINE RECEPTORS" ABBOTT LABORATORIES, a corporation organized and existing under the laws of United States of America, having its Registered Office at Dept.377 Bldg AP6A-1, 100 Abbott Park Road, Abbott Park, Illinois 60064-6008 (US) The following specification particularly describes the invention and the manner in which it is to be performed FORM 5 The Patents Act, 1970 (39 of 1970) & The Patents Rules, 2003 DECLARATION AS TO INVENTORSHIP [See section 10(6) rule 13(6)] We, Abbott Laboratories, hereby declare that the true and the first inventors of the invention disclosed in the complete specification filed in pursuance of our Application numbered ,dated are: (1) (a) BASHA, Anwer (b) Nationality - U.S.A. (c) 41 Heron Road, Lake Forest, Illinois 60045 (US) (2) (a) BUNNELLE, William (b) Nationality - U.S.A. (c) 1826 Victoria Road, Mundelein, Illinois 60060 (US) (3) (a) DART, Michael (b) Nationality - U.S.A. (c) 844 Yale Lane, Highland Park, Illinois 60035 (US) (4) (a) GALLAGHER, Megan (b) Nationality - U.S.A. c) 2772 N. Lincoln Avenue, #205, Chicago, Illinois 60614 (US) (5) (a) JI, Jianguo (b) Nationality - CA / U.S.A. (c) 1973 Sparrow Court, Libertyville, Illinois 60048 (US) (6) (a) PACE, Jennifer (b) Nationality-U.S.A. (c) 343 Stevens Court, Grayslake, Illinois 60030 (US) (7) (a) RYTHER, Keith (b) Nationality - U.S.A. (c) 862 Waterview Drive, Round Lake Park, Illinois 60073 (US) (8) (a) TIETJE, Karin (b) Nationality - U.S.A. (c) 485 Killarney Pass Circle, Mundelein, Illinois 60060 (US) (9) (a) MORTELL, Kathleen (b) Nationality - U.S.A. (c) 2018 N. Oakley Avenue, Chicago, Illinois 60647 (US) (10) (a) NERSESIAN, Diana (b) Nationality -U.S.A. (c) 4207 Coral Berry Path # 103, Gurnee, Illinois 60031 (US) (11) (a) SCHRIMPF, Michael. (b) Nationality - U.S.A. (c) 327 Cambridge Drive, Grayslake, Illinois 60030 (US) (12) (a) LI, Tao (b) Nationality - CN (c) 33524 N. Gagewood Court, Grayslake, Illinois 60030 (US) Dated this 31st day of March, 2006. ■4/V ,M. Maniar) To, The Controller of Patents, The Patent Office at Mumbai. Form 18 The Patents Act, 1970 (FOR OFFICE USE ONLY) (39 of 1970) & RQ.No.: The Patent Rules, 2003 Filing Date: Amount of Fee Paid: Request for examination of Application for CBRNo.: patent Signature: (See Section 1 IB, Rules 20(4)(ii), 24B(l)(i)) APPLICANT (S) (a) NAME: Abbott Laboratories (b) NATIONALITY: U.S.A. (c) ADDRESS: Dept. 377 Bldg. AP6A-1,100 Abbott Park Road, Abbott Park, IL 60064 (US). Statement in case of request for examination made by the applicant(s) We hereby request that our application for patent no. filed on for the invention titled "SUBSTITUTED DIAZABICYCLOALKANE DERIVATIVES AS LIGANDS AT ALPHA 7 NICOTINIC ACETY LCHOLINE RECEPTORS" shall be examined under Sections 12 and 13 of the Act. ADDRESS FOR SERVICE Telephone No. 2266 3713 Crawford Bayley & Co., Fax No. 2266 0355 State Bank Buildings, E-mail: N.G.N. Vaidya Marg, maniar(2),crawfordbayley.com Mumbai-400 023. Dated this 31st day of March, 2006. A v--. To, The Controller of Patents, The Patent Office at Mumbai. (CM. Maniar) Pkd-PCTUS04/030735 WO 2005/028477 PCT/US2004/030735 SUBSTITUTED DIAZABICYCL.OALKANE DERIVATIVES AS LIGANDS AT ALPHA 7 NICOTINIC ACETY LCHOLINE RECEPTORS BACKGROUND OF THE INVENTION Technical Field The invention relates to diazabicycloalkane derivatives, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. Description of Related Technology Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central (CNS) and peripheral (PNS) nervous systems. Such receptors play an important role in regulating CNS function, particularly by modulating release of a wide range of neurotransmitters, including, but not necessarily limited to acetylcholine, norepinephrine, dopamine, serotonin and GABA. Consequently, nicotinic receptors mediate a very wide range of physiological effects, and have been targeted for therapeutic treatment of disorders relating to cognitive function, learning and memory, neurodegeneration, pain and inflammation, psychosis and sensory . gating, mood and emotion, among others. Many subtypes of the nAChR exist in the CNS and periphery. Each subtype has a different effect on regulating the overall physiological function. Typically, nAChRs are ion channels that are constructed from a pentameric assembly of subunit proteins. At least 12 subunit proteins, oc2-al0 and p2-p4, have been identified in neuronal tissue. These subunits provide for a great variety of homomeric and heteromeric combinations that account for the diverse receptor subtypes. For example, the predominant receptor that is responsible for high affinity binding of nicotine in brain tissue has composition (a4)2(B2)3 (the a4(52 subtype), while another major population of receptors is comprised of the homomeric (0:7)5 (the a.7 subtype). Certain compounds, like the plant alkaloid nicotine, interact with all subtypes of the nAChRs, accounting for the profound physiological effects of this compound. While nicotine has been demonstrated to have many beneficial properties, not all of WO 2005/028477 PCT/US2004/030735 the effects mediated by nicotine are desirable. For example, nicotine exerts gastrointestinal and cardiovascular side effects that interfere at therapeutic doses, and its addictive nature and acute toxicity are well-known. Ligands that are selective for interaction with only certain subtypes of the nAChR offer potential for achieving beneficial therapeutic effects with an improved margin for safety. The a 7 nAChRs have been shown to play a significant role in enhancing cognitive function, including aspects of learning, memory and attention (Levin, E.D., J. Neurobiol. 53: 633-640, 2002). For example, a7 nAChRs have been linked to conditions and disorders related to attention deficit disorder, attention deficit hyperactivity disorder (ADHD), Alzheimer's disease (AD), mild cognitive impairment, senile dementia, dementia associated with Lewy bodies, dementia associated with Down's syndrome, AIDS dementia, Pick's Disease, as well as cognitive deficits associated with schizophrenia, among other systemic activities. The activity at the a7 nAChRs can be modified or regulated by the administration of cc7 nAChR ligands. The ligands can exhibit antagonist, agonist, partial agonist, or inverse agonist properties. Thus, a7 ligands have potential in treatment of various cognitive disorders. Although various classes of compounds demonstrating ct7 nAChR-modulating activity exist, it would be beneficial to provide additional compounds demonstrating activity at the (NRARB)alkyl, (NRARB)carbonyl, (NRARB)sulfonyl, and phenyl; provided that when Yi is O or S, Y2 is N, Y3 is -CR3 and R3 is hydrogen, and Y4 is C, then Ar2 is not 5-tetrazolyI; X1, X2, X3, and X4 are each independently selected from the group consisting of N and -CR3, provided that R3 is not hydrogen at least in one occurrence when X1, X2, X3, and X4 are all -CR3; Yi, Y2, and Y3 are each independently selected from the group consisting of N, O, S, and -CR3; Y4 is selected from the group consisting of C and N, provided that when Y4 is C at least one of Y1f Y2, and Y3, is other than -CR3-, -3- c WO 2005/028477 PCT/US2004/030735 I, m, n, o, and p are each independently selected from the group consisting of 0, 1, or 2, provided that the sum total of I, m, n, o, and p is 3, 4, or 5, and further provided that the sum of I and o is at least 1 and the sum of m and p is at least 1; Fit is selected from the group consisting of hydrogen, alkenyl, alkyl alkoxycarbonyl, arylalkyl, and heteroarylalkyl; R2 at each occurrence is independently selected from the group consisting of hydrogen, alkoxycarbonyl, and alkyl; R3 at each occurrence is independently selected from the group consisting of hydrogen and alkyl; RA and RB are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, formyl and (NRcRD)sulfonyl; and Rc and RD are each independently selected from the group consisting of hydrogen and alkyl. Another aspect of the invention relates to pharmaceutical compositions comprising compounds,of the invention. Such compositions can be administered in accordance with a method of the invention, typically as part of a therapeutic regimen for treatment or prevention of conditions and disorders related to nAChR activity, and more particularly oc7 nAChR activity. i Yet another aspect of the invention relates to a method of selectively modulating to nAChR activity, for example a7 nAChR activity. The method is useful for treating and/or preventing conditions and disorders related to oc7 nAChR activity • modulation in mammals. More particularly, the method is useful for conditions and disorders related to attention deficit disorder, attention deficit hyperactivity disorder (ADHD), Alzheimer's disease (AD), mild cognitive impairment, senile dementia, AIDS dementia, Parkinson's disease, Pick's Disease, dementia associated with Lewy bodies, dementia associated with Down's syndrome, amyotrophic lateral sclerosis, Huntington's disease, diminished CNS function associated with traumatic brain injury, acute pain, post-surgical pain, chronic pain, inflammatory pain, neuropathic pain, infertility, need for new blood vessel growth associated with wound healing, need for new blood vessel growth associated with vascularization of skin .grafts, and -4- WO 2005/028477 PCT/US2004/030735 lack of circulation, more particularly circulation around a vascular occlusion, among other systemic activities. The compounds, compositions comprising the compounds, and methods for treating or preventing conditions and disorders by administering the compounds are further described herein. DETAILED DESCRIPTION OF THE INVENTION Definition of Terms Certain terms as used in the specification are intended to refer to the following definitions, as detailed below. 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-1-heptenyl, and 3-decenyl. The term "alkoxy" 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 another alkoxy group, as defined herein. Representative examples of alkoxyalkoxy include, but are not limited to, 'tert-butoxymethoxy, 2-ethoxyethoxy, 2-methoxyethoxy, and methoxymethoxy. 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" means an alkoxy group, as defined herein, appended to the parent molecular moiety through a carbonyl group, represented by - -5- ;., wit*5-.AiAdlwtW - WO 2005/028477 PCT/US2004/030735 C(O)-, as defined herein. Representative examples of alkoxycarbonyl include, but are not limited to, methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl. The term "alkoxysulfonyl" as used herein, means an alkoxy group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representative examples of alkoxysulfonyl include, but are not limited to, methoxysulfonyl, ethoxysulfonyl and propoxysulfonyl. The term "alkyl" means a straight or branched chain hydrocarbon containing from 1 to 6 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, and n-hexyl. 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-dimethy!-1-oxopropyl, 1-oxobutyl, and 1-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, methylthio, ethylthio, tert-butylthio, and hexylthio. 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-pentynyI, and 1-butynyl. The term "aromatic" refers to a planar or polycyclic structure characterized by a cyclically conjugated molecular moiety containing 4n+2 electrons, wherein n is the -6- WO 2005/028477 PCT/US2004/030735 absolute value of an integer. Aromatic molecules containing fused, or joined, rings also are referred to as bicylic aromatic rings. For example, bicyclic aromatic rings containing heteroatoms in a hydrocarbon ring structure are referred to as bicyclic heteroaryl rings. The term "aryl," as used herein, means a phenyl group or a naphthyl group. The aryl groups of the present invention can be optionally substituted with one, two, three, four, or five substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, aryicarbonyl, alkylcarbonyloxy, alkylthio, alkynyl, carboxy, cyano, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, and nitro. 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 of arylalkyl include, but are not limited to, benzyl, 2-phenylethyl, 3-phenylpropyl, and 2-naphth-2-ylethyl. The term "aryicarbonyl" as used herein, means an aryl group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representative examples of aryicarbonyl include, but are not limited to, benzoyl and naphthoyl. The term "carbonyl" as used herein, means a -C(O)- group. The term "carboxy" as used herein, means a -C02H group. The term "cyano" as used herein, means a -CN group. The term "fomnyl" as used herein, means a -C(0)H group. The term "halo" or "halogen" means -CI, -Br, -I or -F. 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, trifluoromethoxy, and pentafluoroethoxy. The term "haloalkyl" 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, chloromethyi, 2-fluoroethyl, trifluoromethyl, pentafluoroethyl, and 2-chloro-3-fluoropentyl. -7- WO 2005/028477 PCT/US2004/030735 The term "heteroaryl" means an aromatic five- or six-membered ring containing 1, 2, 3, or 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. The heteroaryl groups are connected to the parent molecular moiety through a carbon or nitrogen atom. Representative examples of heteroaryl include, but are not limited to, furyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazinyl, and triazolyl. The heteroaryl groups of the invention are substituted with 0,1, 2, or 3 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfonyl, alkylthio, alkynyl, carboxy, cyano, formyl, haloalkoxy, haloalkyl, halo, hydroxy, hydroxyalkyl, mercapto, nitro, -NRARB, (NRARB)carbonyl, and (NRARB) sulfonyl. The term "bicyclic heteroaryl" refers to fused aromatic nine- and ten-membered bicyclic rings containing 1, 2, 3, or 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. The bicyclic heteroaryl groups are connected to the parent molecular moiety through a carbon or nitrogen atom. Representative examples of. bicycle heteroaryl rings include, but are not limited to, indolyl, benzothiazolyl, benzofuranyl, isoquinolinyl, and quinolinyl. Bicycle heteroaryl groups of the invention are substituted with 0, 1, 2, or 3 substituents independently selected from alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfonyl, alkylthio, alkynyl, carboxy, cyano, formyl, haloalkoxy, haloalkyl, halo, hydroxy, hydroxyalkyl, mercapto, nitro, -NRARB, (NRARB)carbonyl, and (NRARB)sulfonyl. The term "heteroarylalkyl" as used herein, means a heteroaryl, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of heteroarylalkyl include, but are not limited to, pyridin-3-ylmethyl and 2-(thien-2-yl)ethyl. 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, is appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of hydroxyalkyl include, but are not -8- WO 2005/028477 PCT/US2004/030735 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 "nitro" as used herein, means a -N02 group. The term "-NRARB" as used herein, means two groups, RA and RB, which are appended to the parent molecular moiety through a nitrogen atom. RA and RB are each independently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, formyl or (NRcRD)sulfonyl. Representative examples of -NRARB include, but are not limited to, amino, methylamino, acetylamino, and acetylmethylamino. The term "(NRARB)alkyl" as used herein, means a -NRARB group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of (NRARB)alkyl include, but are not limited to, (amino)methyl, (dimethylamino)methyl, and (ethylamino)methyl. The term "(NRARB)alkoxy" as used herein, means a -NRARB group, as defined herein, appended to the parent molecular moiety through an alkoxy group, as defined herein. Representative examples of (NRARBJalkoxy include, but are not limited to, (amino)methoxy, (dimethylamino)methoxy, and (diethylamino)ethoxy. The term "(NRARB)carbonyl" as used herein, means a -NRARB group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representative examples of (NRARB)carbonyl include, but are not limited to, aminocarbonyl, (methylamino)carbonyl, (dimethylamino)carbonyl, and (ethylmethylamino)carbonyl. The term "(NRARB)sulfonyr as used herein, means a -NRARB group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representative examples of (NRARB)sulfonyl include, but are not limited to, aminosulfonyl, (methylamino)sulfonyl, (dimethylamino)sulfonyl, and (ethylmethylamino)sulfonyl. The term "-NRCRD" as used herein, means two groups, Rc and RD, which are appended to the parent molecular moiety through a nitrogen atom. RC and RD are each independently hydrogen or alkyl. Representative examples of-NRCRD include, but are not limited to, amino, methylamino and dimethylamino. -9- *> WO 2005/028477 PCT/US2004/030735 The term "(NRcRD)sulfonyl" as used herein, means a -NRCRD group, as defined herein, appended to the parent molecular moiety through a sulfonyl group, as defined herein. Representative examples of (NRcRo)sulfonyl include, but are not limited to, aminosulfonyl, (methylamin5)sulfonyl, (dimethylamino)sulfonyl, and (ethylmethylamino)sulfonyl. Although typically it may be recognized that an asterisk is used to indicate that the exact subunit composition of a receptor is uncertain, for example a 3b4* indicates a receptor that contains the - N-S- R1—N, N N, .N. * ' and X Ri The substituent represented by Ri can be selected from hydrogen, alkoxycarbonyl, alkyl, arylalkyi, and heteroarylalkyl, particularly methyl, benzyl and pyridin-3-ylmethyl. R2 can be selected from hydrogen, alkenyl, alkyl, and alkoxycarbonyl, particularly methyl. The AP| moiety can be selected independently of the moiety selected for Z. Suitable moieties for An are those represented by a 5- or 6-membered aromatic ring of the formula: -11- ililHiiTOTMirtMh WO 2005/028477 PCT/US2004/030735 (a) or In such moieties, X1, X2, X3, and X4 are each independently selected from the group consisting of N and -CR3, provided that R3 is not hydrogen at least in one occurrence when X1, X2, X3, and X4 all are -CR3, such that a phenyl group contains at least one substituent The moiety represented by formula (a) is attached to the diazabicyclic amine and the Ar2 moiety by 1,4-substitution or para-attachment. Preferably, the moiety represented by formula (a) contains at least one heteroatom, particularly when Ar2 is a phenyl group. Formula (b) represents a five-membered ring wherein Y1, Y2, and Y3 are each independently selected from the group consisting of N, O, S, and -CR3. Y4 is selected from C or N. When Y4 is C at least one of the substituents represented by Yi, Y2, and Y3, is other than -CR3, such that the moiety represented by formula (b) contains at least one heteroatom. The moiety generally is attached to the diazabicyclic amine and the Ar2 moiety by 1,3-substitution. Examples of specific rings suitable for An include, but are not limited to, isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, thiadiazolyl, isothiazolyl, thiazolyl, thienyl, and phenyl, wherein the pyridazinyl, pyridyl, and phenyl, are substituted with 0 or 1 substitutent selected from the group consisting of alkoxy, alkyl, cyano, and hydroxy. More particularly, the rings represented by An are, for example, / r -N jr- N H- N (iii) (i) R3 (ii) R3 N—N 'I S' (iv) .N. S—N (v) N—N 9 * O (vi) (vii) -12- WO 2005/028477 PCT/US2004/030735 Z can have substituents represented by R-i and R2. Examples of moieties suitable for Z can include, but are not limited to: N R N—p— Ri—N N-S- .N- .N. * '■ and X N- .N. 'Ri The substituent represented by R1 can be selected from hydrogen, alkoxycarbonyl, alkyl, arylalkyl, and heteroarylalkyl, particularly methyl, benzyl and pyridin-3-ylmethyl. R2 can be selected from hydrogen, alkenyl, alkyl, and alkoxycarbonyl, particularly methyl. The An moiety can be selected independently of the moiety selected for Z. Suitable moieties for An are those represented by a 5- or 6-membered aromatic ring of the formula: WO 2005/028477 PCT/US2004/030735 The preferred ring for Art is pyridazinyl, exemplified by (i), wherein R3 is hydrogen, alkoxy, alkyl, cyano, or hydroxy, wherein hydrogen or methyl are preferred. Another preferred ring for An is pyridyl, exemplified by (ii), wherein R3 is hydrogen, alkoxy, alkyl, cyano, or hydroxy, wherein hydrogen or cyano are preferred. Another preferred ring for An is pyrimidinyl, exemplified by (iii). Another preferred ring for An is thiadiazolyl, exemplified by (iv) and (v). Another preferred ring for An is oxadiazolyl, exemplified by (vi). Another preferred ring for An is pyrazolyl, exemplified by (vii) and (viii). Another preferred ring for An is isoxazolyl, exemplified by (ix). Another preferred ring for An is thiazolyl, exemplified by (x) and (xi). Another preferred ring for An is thienyl, exemplified by (xii). Another preferred ring for An is oxazolyl, exemplified by (xiii). Another preferred ring for An is phenyl, exemplified by (xiv), wherein R3 is hydrogen, alkoxy, alkyl, cyano, or hydroxy. It is to be understood that either end of the rings (i), (ii), (iii), (v), (vii), (ix), (x), (xi), (xii), and (xiii) can be attached to Z. Ar2 can be independently selected regardless of the moiety selected for Z or An. When Ar2 is phenyl or substituted phenyl, An preferably contains at least one heteroatom. Moieties suitable for Ar2 can be an unsubstituted or substituted 5- or 6-membered heteroaryl ring; an unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; or phenyl. The carbazolyl, tetrahydrocarbazolyl, naphthyl, and phenyl moieties can be substituted with 0, 1, 2, or 3 substituents preferably in the meta- or para-position. Examples of heteroaryl or bicyclic heteroaryl rings are, for example, furyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazinyl, triazolyl, indolyl, benzothiazolyl, benzofuranyl, isoquinolinyl, and quinolinyl. WO 2005/028477 PCT/US2004/030735 Suitable substituents for the heteroaryl and bicyclic heteroaryl ring include, but are not limited to, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfonyl, alkylthio, alkynyl, carboxy, cyano, formyl, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, nitro, -NRARB, wherein RA and RB are each independently selected from hydrogen, alkyl, alkylcarbonyl, or formyl, (NRARB)carbonyl, and (NRARB)sulfonyl. More particularly, Ar2 are preferably selected from benzofuranyl; benzothienyl; furyl; imidazolyl; 3-methylindazolyl; 3-indolyl; 5-indolyl; 1-methyl-3-indolyl; 1-methyl-5-indolyl; 3-methyl-5-indolyl; 3-[(dimethylamino)methyl]indolyl; 1-[(4-methylphenyl)sulfonyl]indolyl; 3,5-dimethylisoxazolyl; naphthyl; pyrazolyl; 3,5-dimethylpyrazolyl; 1-methylpyrazolyl; 6-oxopyridazinyl; pyridyl; 6-aminopyridyl; 2-cyanopyridyl; pyrimidinyl; 2-methoxypyrimidinyl; 2-pyrrolyl; 3-pyrrolyl; quinolinyl; or thienyl. Phenyl and substituted phenyl groups, for example benzodioxolyl and 3,4-(methylenedioxy)phenyl, also are suitable for Ar2. Additional suitable substituents for the phenyl ring can include, but are not limited to, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfonyl, alkylthio, alkynyl, carboxy, cyano, formyl, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, nitro, -NRARB, (NRARB)alkyl, (NRARB)carbonyl, (NRAREi)sulfonyl, and phenyl. RA and RB are each independently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, formyl or (NRcRo)sulfonyl. Re and RD are each independently hydrogen or alkyl. For example, Ar2 can be phenyl substituted with 0, 1, or 2 substituents, such as alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. More specific examples of moieties suitable for Ar2 include, but are not limited to: -14- WO 2005/028477 PCT/US2004/030735 R4 R4 R( R4 R4 • R4 R4 R4 , R4 R4 . R4 . R4 , R4 R? R.4 R.4 FU R4 R4 1 R4 1 R4 > R4 1 R4 1 R4 . R4 • and R4 > wherein R4 at each occurrence is independently selected and represents a subsistent selected from the group consisting of hydrogen, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. Preferably, the subsistent represented by R4 is selected from the group consisting of hydrogen, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, -NRARB, and haloalkyl. Preferred moieties for Ar2, particularly when Ar-i is heteroaryl, are phenyl, para-acetylaminophenyl, meta-aminophenyl, para-aminophenyl, para(2-(diethylamino)ethoxy)phenyl, meta(2-(diethylamino)ethoxy)phenyl, para-(dimethylamino)phenyl, para-bromophenyl, meta-cyanophenyl, para-cyanophenyl, meta-hydroxyphenyl, para-hydroxyphenyl, para-iodophenyl, meta-methylphenyl, para-methylphenyl, 3,5-dimethylphenyl, meta- -15- WO 2005/028477 PCT/OS2004/030735 methoxyphenyl, para-methoxyphenyl, meta-trifluoromethoxyphenyl, meta-nitrophenyl, para-nitrophenyl, meta-trifluoromethylphenyl, and the like. When ring of formula (b) is defined by Yi is 0 or S, Y2 is N, Y3 is -CR3 and R3 is hydrogen, and Y4 is C, then Ar2 is not 5-tetrazolyl. One example of a particular embodiment of the compounds for the invention is wherein Z is a seven-membered fused bicyclic ring, for example Ar1 is selected from the group consisting of isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, 4-methylpyridazinyl, 5-methylpyridazinyl, pyridyl, 5-cyanopyridyl, pyrimidinyl, thiadiazolyl, thiazolyl, thienyl, and phenyl substituted with 0 or 1 substituent selected from the group consisting alkoxy, alkyl, cyano, and hydroxy; Ar2 is selected from the group consisting of benzofuranyf, benzothienyl, carbazolyl, tetrahydrocarbazolyl, furyl; imidazolyl, 3-methylindazolyl, 3-indolyl, 5-indolyl, 1-methyl-3-indolyl, 1-methyl-5-indolyl, 3-methyl-5-indolyl, 3-[(dimethylamino)methyl]indolyl, 1-[(4-methylphenyl)sulfonyl]indolyl, 3,5-dimethylisoxazoIyl, naphthyl, pyrazolyl, 3,5-dimethylpyrazolyl, 1-methylpyrazolyl, 6-oxopyridazinyl, pyridyl, 6-aminopyridyl, 2-cyanopyridyl, pyrimidinyl, 2-methoxypyrimidinyl, 2-pyrrolyl, 3-pyrrolyl, quinolinyl, thienyl, 3,4-(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. An is pyridazinyl or pyridyl, and Ar2 is as described, either generally or particularly, and more particularly Ar2 is selected from the group consisting of 3-indolyl, 5-indolyl, Another example of a particular embodiment of the compounds for the invention is wherein Z is a seven-membered fused bicyclic ring, for example WO 2005/028477 . PCT/US2004/030735 1-methyl-3-indolyl, 1-methyl-5-indoIyl, 3-methyl-5-indolyl, 3,4-(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. One example of a particular embodiment of the compounds for the invention is wherein Z is an eight-membered bridged bicyclic ring, for example -k' R'i ^ or V Ar1 is selected from the group consisting of isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, 4-methylpyridazinyl, 5-methylpyridazinyl, pyridyl, 5-cyanopyridyl, pyrimidinyl, thiadiazolyl, thiazolyl, thienyl, and phenyl substituted with 0 or 1 substituent selected from the group consisting alkoxy, alkyl, cyano, and hydroxy; Ar2 is selected from the group consisting of benzofuranyl, benzothienyl, carbazolyl, tetrahydrocarbazolyl, furyl; imidazolyl, 3-methylindazolyl, 3-indolyl, 5-indolyl, 1-methyl-3-indolyl, 1-methyl-5-indolyl, 3-methyl-5-indolyl, 3-[(dimethylamino)methyl]indolyl, 1-[(4-methylphenyI)sulfonyl]indolyl, 3,5-dimethylisoxazolyl, naphthyl, pyrazolyl, 3,5-dimethylpyrazolyl, 1-methylpyrazolyl, 6-oxopyridazinyl, pyridyl, 6-aminopyridyl, 2-cyanopyridyl, pyrimidinyl, 2-methoxypyrimidinyl, 2-pyrrolyl, 3-pyrrolyl, quinolinyl, thienyl, 3,4-(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. Another example of a particular embodiment of the compounds for the invention is wherein Z is an eight-membered bridged bicyclic ring, for example WO 2005/028477 PCT/US2004/030735 or Ar1 is pyridazinyl, and Ar2 is as described, either generally or particularly, and more particularly Ar2 is phenyl substituted with 0, 1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyi, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. One example of a particular embodiment of the compounds for the invention is wherein Z is a eight-membered fused bicyclic ring, for example R<—N N-S- Ar1 is selected from the group consisting of isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, 4-methylpyridazinyl, 5-methylpyridazinyl, pyridyl, 5-cyanopyridyl, pyrimidinyl, thiadiazolyl, thiazolyl, thienyl, and phenyl substituted with 0 or 1 substituent selected from the group consisting alkoxy, alkyl, cyano, and hydroxy; Ar2 is selected from the group consisting of benzofuranyl, benzothienyl, carbazolyl, tetrahydrocarbazolyl, furyl; imidazolyl, 3-methyIindazolyl, 3-indolyl, 5-indolyl, 1-methyl-3-indolyl, 1-methyl-5-indolyl, 3-methyl-5-indolyl, 3-[(dimethylamino)methyl]indolyl, 1-[(4-methylphenyl)sulfonyl]indolyl, 3,5-dimethylisoxazolyl, naphthyl, pyrazolyl, 3,5-dimethylpyrazolyl, 1-methylpyrazolyl, 6-oxopyridazinyl, pyridyl, 6-aminopyridyl, 2-cyanopyridyl, pyrimidinyl, 2-methoxypyrimidinyl, 2-pyrrolyl, 3-pyrrolyl, quinolinyl, thienyl, 3,4-(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyi, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. A Q WO 2005/028477 PCT/US2004/030735 Yet another example of a particular embodiment of the compounds for the invention is wherein Z is an eight-membered fused bicyclic ring, for example, N-S- ; Ar1 is pyridazinyl; and Ar2 is as described, or more particularly, phenyl substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. Still yet another example of a particular embodiment of the compounds for the invention is wherein Z is an eight-membered fused bicyclic ring, for example, R— N. N-S- Ar1 is pyridyl; and Ar2 is as described, or more particularly, furyl, benzothienyl, or phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. Particularly in this embodiment, Ar2 preferably is heteroaryl or bicyclic heteroaryl when Ar1 is pyridyl, provided that Ar2 is not 1-pyrrolyl or 1-indolyl. Yet another example of a particular embodiment of the compounds for the invention is wherein Z is an eight-membered fused bicyclic ring, for example, Ri—N Ar1 is either isoxazolyl, oxadiazolyl, pyrazolyl, pyrimidinyl, thiadiazolyl, or thiazolyl; and Ar2 is as described, or more particularly, furyl or phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. One example of a particular embodiment of the compounds for the invention is wherein Z is a eight-membered fused bicyclic ring, for example WO 2005/028477 PCT/US2004/030735 Ar1 is selected from the group consisting of isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, 4-methylpyridazinyl, 5-methylpyridazinyl, pyridyl, 5-cyanopyridyl, pyrimidinyl, thiadiazolyl, thiazolyl, thienyl, and phenyl substituted with 0 or 1 substituent selected from the group consisting alkoxy, alkyl, cyano, and hydroxy; Ar2 is selected from the group consisting of benzofuranyl, benzothienyl, carbazolyl, tetrahydrocarbazolyl, furyl; imidazolyl, 3-methylindazolyI, 3-indolyl, 5-indolyl, 1-methyl-3-indolyl, 1-methyl-5-indolyl, 3-methyl-5-indolyl, 3-[(dimethylamino)methyl]indolyl, 1-[(4-methylphehyl)sulfonyl]indolyl, 3,5-dimethylisoxazolyl, naphthyl, pyrazolyl, 3,5-dimethylpyrazolyl, 1-methylpyrazolyl, 6-oxopyridazinyl, pyridyl, 6-aminopyridyl, 2-cyanopyridyl, pyrimidinyl, 2-methoxypyrimidinyl, 2-pyrrolyl, 3-pyrrolyl, quinolinyl, thienyl, 3,4-(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0, 1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. Another example of a particular embodiment of the compounds for the invention is an eight-membered fused bicyclic ring, for example wherein Z is Ar1 is pyridazinyl, pyrimidinyl, or thiazolyl; and Ar2 is as described, or more particularly, selected from the group consisting of 3,4-(methylenedioxy)phenyl and phenyl wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. Another example of a particular embodiment of the compounds for the invention is an eight-membered fused bicyclic ring, for example wherein Z is WO 2005/028477 PCT/US2004/030735 N R1 or >■— —-v • A^ is selected from the group consisting of isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, 4-methylpyridazinyl, 5-methylpyridazinyl, pyridyl, 5-cyanopyridyl, pyrimidinyl, thiadiazolyl, thiazolyl, thienyl, and phenyl substituted with 0 or 1 substituent selected from the group consisting alkoxy, alkyl, cyano, and hydroxy; Ar2 is selected from the group consisting of benzofuranyl, benzothienyl, carbazolyl, tetrahydrocarbazolyl, furyl; imidazolyl, 3-methylindazolyl, 3-indolyl, 5-indolyl, 1-methyI-3-indolyl, 1-methyl-5-indolyl, 3-methyl-5-indolyl, 3-[(dimethylamino)methyl]indolyl, 1-[(4-methylphenyl)sulfonyl]indolyl, 3,5-dimethylisoxazolyl, naphthyl, pyrazolyl, 3,5-dimethylpyrazolyl, 1-methylpyrazolyl, 6-oxopyridazinyl, pyridyl, 6-aminopyridyl, 2-cyanopyridyl, pyrimidinyl, 2-methoxypyrimidinyl, 2-pyrrolyl, 3-pyrrolyl, quinolinyl, thienyl, 3,4-(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0, 1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. Another example of a particular embodiment of the compounds for the invention is a seven-membered bridged bicyclic ring, for example wherein Z is Ri' "" ; Ar1 is selected from the group consisting of isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, 4-methylpyridazinyl, 5-methylpyridazinyl, pyridyl, 5-cyanopyridyl, pyrimidinyl, thiadiazolyl, thiazolyl, thienyl, and phenyl substituted with 0 or 1 substituent selected from the group consisting alkoxy, alkyl, cyano, and hydroxy; Ar2 is selected from the group consisting of benzofuranyl, benzothienyl, carbazolyl, tetrahydrocarbazolyl, furyl; imidazolyl, 3-methylindazolyl, 3-indolyl, 5-indolyl, 1-methyl-3-indolyl, 1-methyl-5Tindolyl, 3-methyl-5-indolyl, 3-[(dimethylamino)methyl]indolyl, 1-[(4-methylphenyl)sulfonyl]indolyl, -91- WO 2005/028477 PCT/US2004/030735 3,5-dimethylisoxazolyl, naphthyl, pyrazolyl, 3,5-dimethylpyrazolyl, 1-methylpyrazolyl, 6-oxopyridazinyl, pyridyl, 6-aminopyridyl, 2-cyanopyridyl, pyrimidinyl, 2-methoxypyrimidinyI, 2-pyrrolyl, 3-pyr-roJyl, quinoliny], thienyl, 3,4-(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0, 1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)a!koxy, and phenyl. Another example of a particular embodiment of the compounds for the invention is a nine-membered fused bicyclic ring, for example wherein Z is 1 ^^ ; Ar1 is selected from the group consisting of isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, 4-methylpyridazinyl, 5- methylpyridazinyl, pyridyl, 5-cyanopyridyl, pyrimidinyl, thiadiazolyl, thiazolyl, thienyl, and phenyl substituted with 0 or 1 substituent selected from the group consisting alkoxy, alkyl, cyano, and hydroxy; Ar2 is selected from the group consisting of benzofuranyl, benzothienyl, carbazolyl, tetrahydrocarbazolyl, furyl; imidazolyl, 3- methylindazolyl, 3-indolyl, 5-indolyl, 1-methyl-3-indolyl, 1-methyl-5-indolyl, 3-methyl- 5-indolyl, 3-[(dimethylamino)methyl]indolyl, 1-[(4-methylphenyl)sulfonyl]indolyl, 3,5-dimethylisoxazolyl, naphthyl, pyrazolyl, 3,5-dimethylpyrazolyl, 1-methylpyrazolyl, 6-oxopyridazinyl, pyridyl, 6-aminopyridyl, 2-cyanopyridyl, pyrimidinyl, 2-methoxypyrimidinyl, 2-pyrrolyl, 3-pyrrolyl, quinolinyl, thienyl, i 3,4~(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0, 1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. Specific embodiments contemplated include, but are not limited to, compounds of formula (I), as defined, wherein: 3-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[3.2.1]octane; 8-methyl-3-(6-phenyI-pyridazin-3-yl)-3,8-diaza-bicyclo[3.2.1]octane; 6-methyl-3-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicycio[3.2.1]octane; WO 2005/028477 PCT/US2004/030735 3-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 8-methyl-3-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 2-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrro!e; 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-m-tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-methyl-5-(6-m-tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(4-methoxy-phenyl)-pyridazin-3-yl]-octahydro-pyrro(o[3,4-c]pyrrole; 2-(6-biphenyl-3-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-biphenyl-3-yl-pyridin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(3-trifiuoromethyl-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-methyl-5-[6-(3-trifIuoromethyl-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 3-[5-(hexahydro-pyrrolo[3,4-c]pyrro!-2-yl)-pyridin-2-yl]-phenylamine; 5-(6-furan-3-yl-pyridin-3-yl)-hexahydro~pyrrolo[3,4-c]pyrrole; 2-(6-furan-3-yl-pyridin-3-yl)-5-methyi-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-benzo[b]thiophen-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-benzo[b]thiophen-2-yl-pyridin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-(5-phenyl-pyridin-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-me'thyl-5-(5-phenyl-pyridin-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(2-phenyl-pyrimidin-5-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-methy!-5-(2-phenyl-pyrimidin-5-yl)-octahydro-pyrrolo[3,4-c]pyrrole; diethyl-(2-{3-[6-(hexahydro-pyrroIo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenoxy}-ethyl)- amine; diethyl-(2-{3-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]- phenoxy}-ethyl)-amine; 2-(5-phenyl-[1,3,4]thiadiazol-2-yl)-octahydro-pyrrolo[3,4-c3pyrrole; 2-(3-phenyl-[1,2,4]thiadiazol-5-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-methyl-5-(3-phenyl-[1,2,4]thiadiazol-5-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(1 -phenyl-1 h-pyrazol-4-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(2-methoxy-biphenyl-4-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(2-methoxy-biphenyl-4-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-methyl-5-(3-phenyi-isoxazol-5-yl)-octahydro-pyrrolo[3,4-c]pyrrole; (1S, 5S) 3-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; WO 2005/028477 PCT/US2004/030735 (1S, 5S)- 6-methyl-3-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5S)-6-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5S)-3-methyl-6-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicycIo[3.2.0]heptane; (1R, 5R) 3-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-6-methyl-3-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-3-(6-benzo[1,3]dioxol-5-yl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane;. (1R, 5R)-3-(6-benzo[1,3]dioxol-5-yl-pyridazin-3-yl)-6-methyl-3,6-diaza- bicyclo[3.2.0]heptane; (1R, 5R)-1 -{4-[5-(3,6-diaza-bicyc!o[3.2.0]hept-3-yl)-pyridin-2-yl]-phenyl}-ethanone; (1R, 5R)-1-{4-[5-(6-methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]- phenyl}ethanone; 6a-methyl-5-(6-m-tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-b]pyrrole; 2-(5-phenyl-thiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-methyl-5-(5-pheny!-thiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 3-(6-Phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 8-(6-Phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyc!o[3.2.1]octane; 6a-Methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-b]pyrrole; 2-(6-Phenyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrrole-3a-carboxylicacid ethyl ester; 2,5-Bis-(6-phenyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrrole-3a-carboxylicacid ethyl ester; (1R, 5R)-6-(6-Phenyl-pyridazin-3-yl)-2,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-2-(6-Phenyl-pyridazin-3-yl)-2,6-diaza-bicyclo[3.2.0]heptane; Ethyl 2-Methyl-5-(6-phenyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrrole-3a- carboxylate; 5-Methyl-2-(6-phenyl-pyridazin-3-yl)-octahydro-pyrro!o[3,4-c]pyridine; 1-Benzyl-6a-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-b]pyrrole; 3-Methyl-6-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.1]octane; 8-(6-Phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; WO 2005/028477 PCT/US2004/030735 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[3.2.1]octane; 1,6a-Dimethyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-b]pyrrole; 2-[6-(4-Bromo-phenyl)-pyridazin-3-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; (1S, 5S)- 3-[6-(4-Bromo-phenyl)-pyridazin-3-yl]-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)- 3-[6-(4-Bromo-phenyl)-pyridazin-3-yl]-6-methyl-3,6-diaza- bicyclo[3.2.0]heptane; 3-[6-(Hexahydro-pyrrolo[3,4-c]pyrro!-2-yl)-pyridazin-3-yl]-1 H-indole; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1 H-indole; (1R, 5R)-3-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; (1S, 5S)-3-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; (1R, 5R)-3-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; 2-[6-(4-Nitro-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(2-Nitro-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(3-Nitro-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[6-(4-nitro-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[6-(3-nitro-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-lmidazol-1-yl-pyridazin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-lmidazol-1-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; (1R, 5S)-6-[6-(4-lodo-phenyl)-pyridazin-3-yI]-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)-3-[6-(4-lodo-phenyl)-pyridazin-3-yl]-3,6-diaza-bicyclo[3.2.01heptane; (1S, 5S)-3-[6-(4-lodo-phenyl)-pyridazin-3-yl]-6-methyl-3,6-diaza- bicyclo[3.2.0]heptane; 2-(5-Methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(4-Methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(4-methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-o-Tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-p-Tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; ' 2-[6-(3,5-Dimethyl-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Furan-3-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Thiophen-3-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-MethyI-5-(6-thiophen-3-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; -25- WO 2005/028477 PCT/US2004/030735 5-[6-(Hexahydro-pyrro!o[3,4-c]pyrrol-2-yl)-pyridazin-3-yi]-1H-indole; 5-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1-methyl-1H-indo!e; 2-Methyl-5-(6-o-tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-p-tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(3,5-Dimethyl-phenyl)-pyridazin-3-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Furan-3-yl-pyridazin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 3-Methy!-8-{6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 5-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-y!)-pyridazin-3-yl]-1H-indole; 3-Methyl-5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H- indole; 2-Methyl-5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]- phenylamine; 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenylamine; 4-[6-(5-Methyl-hexahydro-pyrrolot3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H-indole; 2-(6-Benzofuran-2-yl-pyridazin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 5-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-pyridin-2-ylamine; 2-Methyl-5-[6-(1H-pyrrol-3-yl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-thibphen-2-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[6-(1H-pyrazol-4-yl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-9H-carbazole; 2-(6-Furan-2-yl-pyridazin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-pyrimidin-5-yl-pyridin-2-yl)-octahydro-pyrroIo[3)4-c]pyrrole; 2-Methyl-5-[5-(1H-pyrazol-4-yl)-pyridin-2-yi]-iDctahydro-pyrrolo[3,4-c]pyrrole; 3-[6-(5-Methyl-hexahydro-pyrroio[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-benzonitrile; 2-[5-(2-Methoxy-pyrimidin-5-yl)-pyridin-2-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-[5-(3,5-Dimethyl-1H-pyrazol-4-yl)-pyridin-2-yl]-5-methyl-octahydro-pyrrolo[3,4- c]pyrrole; 2-Methyl-5-[5-(1-methyl-1H-pyrazol-4-yl)-pyridin-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-[5-(3,5-Dimethyl-isoxazol-4-yl)-pyridin-2-yl]-5-methyl-octahydro-pyrrolo[3,4- c]pyrrole; 6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-[3,3']bipyridinyl; 6-(5-Methyl-hexahydro-pyrro!o[3,4-c]pyrrol-2-ylH3,4']bipyridinyl; *-. WO 2005/028477 , PCT/US2004/030735 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrro!-2-yl)-pyridin-3-yl]-benzonitrile; 6'^S-Methyl-hexahydro-pyrrolofS^-cjpyrrol^-yO-tS.S'Jbipyridinyl-e-ylamine; 2-Methyl-5-[5-(1H-pyrrol-3-yl)-pyridin-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[5-(1H-pyrrol-2-yl)-pyridin-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 6'^S-Methyl-hexahydro-pyrrolot[3,4-c]pyrrol-2-yl]-[3-,3]bipyridinyl-2-carbonitrile; 2-(5-Furan-3-yl-pyridin-2-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-thiophen-2-yl-pyridin-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-thiophen-3-yl-pyridin-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(5-Benzofuran-5-yl-pyridin-2-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-(5-Furan-2-yl-pyridin-2-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-9H-carbazole; 5-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-1H-indole; 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-1H-indole; 2-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-2H-pyridazin-3-one; 2-(6-Phenyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-o-Tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-m-Tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(3-Methoxy-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole 2-[6-(3-Trifluoromethoxy-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Thiophen-3-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 8-[5-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-quinoline; 2-(6-Naphthalen-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Benzofuran-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-o-tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-m-tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-phenyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(3-Methoxy-phenyl)-pyridin-3-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[6-(3-trifluoromethoxy-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4- c]pyrrole; 2-MethyI-5-[6-(3-nitro-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-thiophen-3-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 8-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yI)-pyridin-2-yI]-quinoline; 07 WO 2005/028477 PCT/US2004/030733 2-Methyl-5-(6-naphthalen-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 5-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-1H-indole; 4-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-1H-indole; 5-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-quinoline; (1R, 5R)-3-(6-p-Tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)- 3-(6-o-Tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)- 3-(6-m-Tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)~ 6-Methyl-3-(6-p-tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)- 6-Methyl-3-(6-o-tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)-5-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; (1S, 5S)-5-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; (1S, 5S)-4-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-y!)-pyridazin-3-yl]-1 H-indole; (1S, 5S)-3-(6-Benzofuran-5-yl-pyridazin-3-yl)-6-methyl-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)- 4-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridaziri-3-yl]-phenylamine; (1R, 5S)- 3-[6-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-pyridazin-3-yl]-thiophene; (1R, 5S)- 5-[6-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-pyridazin-3-yl]-1 H-indole ; (1R, 5S)- 4-[6-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-pyridazin-3-yl]-1 H-indole ; 3-Methyl-5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H-indazole; (1S, 5S)- 5-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-3-yl]-3-methyl-1 H-indazole; (1R,5R)-{4-[5-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-phenyl}-dimethyl-amine; (1R,5R)-6-Methyl-3-(6-m-tolyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (iR,5R)-6-Methyl-3-(6-p-tolyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-3-[5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-benzonitrile; (1R, 5R)-3-[6-(4-Ethyl-phenyl)-pyridin-3-yl]-6-methyl-3,6-diaza-bicyclo[3.2.0]heptane; (1R,5R)-Dimethyl-{4-[5-(6-methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-phenyl}-amine; (IR.SRJ-S-ie-CS-Methoxy-phenyO-pyridin-S-yll-S-methyl-S.e-diaza-bicyclo[3.2.0]heptane; WO 2005/028477 PCT/US2004/030735 (1R, 5R)-3-(6-Benzo[1,3]dioxol-5-yl-pyridin-3-y!)-6-methyl-3,6-diaza- bicyclo[3.2.0]heptane; (1R, 5R)-3-[6-(4-Methoxy-phenyl)-pyridin-3-yl]-6-methyl-3,6-diaza- bicyclo[3.2.0]heptane; (1R, 5R)-3-[6-(3,4-Dimethoxy-phenyl)-pyridin-3-y!]-6-methyl-3,6-diaza- bicyclo[3.2.0]heptane; (1R, 5R)-6-Methyl-3-(6-phenyl-pyridin-3-y!)-3,6-diaza-bicyclo[3.2.03heptane; (1R, 5R)-5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-[2,3']bipyridinyI; (1R, 5R)- 5-[5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-1 H-indole; (1S, 5S)- 5-[5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-1 H-indole; (1R, 5S)-6-(6-Phenyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5S)- 6-(6-m-Tolyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5S)- 3-Methyl-6-(6-phenyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5S)- 5-[5-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-pyridin-2-yl]-1 H-indole; (1S, 5S)- 5-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-3-yl]-1 H-indole; (1S, 5S)- 3-(5-Phenyl-pyridin-2-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)- 6-Methyl-3-(5-phenyl-pyridin-2-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)-5-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-3-yl]-1 H-indole; 2-(4-Phenyl-thiophen-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-phenyl-[1,3,4]thiadiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(2-Phenyl-thiazol-5-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(2-phenyl-thiazol-5-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(4-Phenyl-thiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Benzyl-5-(6-phenylpyridazin-3-yl)-octahydropyrrolo[3,4-c]pyrrole; 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-4-ylmethyl)-octahydropyrrolo[3,4-c]pyrrole; 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-2-ylmethyl)-octahydropyrrolo[3,4-c]pyrrole; 2-(6-Chloropyridin-3-ylmethyl)-5-(6-phenylpyridazin-3-yl)-octahydropyrrolo[3,4- c]pyrrole; 2-(6-Phenylpyridazin-3-yl)-5-(2-pyridin-3-ylethyl)-octahydropyrrolo[3,4-c]pyrrole; 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl)-octahydropyrrolo[3,4-c]pyrrole; 2-Allyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-But-2-enyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; WO 2005/028477 PCT7US2004/030735 2-Ethyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Phenyl-pyridazin-3-yl)-5-propyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-lsopropyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; (SaR.GaRVS^S-Phenyl-tl.S^loxadiazol^-yO-octahydro-pyrrolop^-blpyrrole; 2-(5-Phenyl-[1,3,4]oxadiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[5-(4-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-[5-(4-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-5-methyl-octahydro-pyrrolo[3,4-cjpyrrole; 2-[5-(4-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 6-Methyl-3-(5-phenyl-[1,3,4]oxadiazol-2-yl)-3,6-diaza-bicyclo[3.2.1]octane; 4-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-biphenyl-2-ol; 4-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-biphenyl-2-ol; Diethyl-(2-{3-[6-(hexahydro-pyrrolo[3,4-c]pyrro!-2-yl)-pyridazin-3-yl]-phenoxy}-ethyl)-amine; 4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenol; Diethyl-(2-{4-[6-(hexahydro-pyrroIo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenoxy}-ethyl)-amine; (2-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenoxy}-ethyl)-dimethyl-amine; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenol; 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenol; Diethyl-(2-{4-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenoxy}-ethyl)-amine; N-{4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-methanesulfonamide; N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-benzamide; N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-methanesulfonamide; N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-dimethylaminosulfonamide; N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-acetamide; WO 2005/028477 PCT/US2004/030735 N-{4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}- acetamide; 2-[5-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-yl]-phenol; 2-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-yl]-phenol; 2-(4-Pyridin-3-yl-phenyl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(4-pyridin-3-yl-phenyl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Biphenyl-4-yl-octahydro-pyrrolo[3,4-c]pyrrole;. 2-Biphenyl-4-yl-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 1-Methyl-5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H- indole; Dimethyl-{5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H- indol-3-ylmethyl}-amine; (1S,5S)-6-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-2,3,4,9- tetrahydro-1 H-carbazole; (1R, 5S)- 5-(3,6-Diaza-bicyclo[3.2.0]hept-6-yl)-2-thiophen-2-yl-nicotinonitrile; (1R, 5S)- 5-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-2-thiophen-2-yl- nicotinonitrile; (1S, 5S)- 3-(4-Pyridin-3-yl-phenyl)-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)- 6-Methyl-3-(4-pyridin-3-yl-phenyl)-3,6-diaza-bicyclo[3.2.0]heptane; and (1S, 5S)- 5-[4-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-phenyl]-3-methyl~1 H-indazole; or pharmaceutical^ acceptable salts, esters, amides, and prodrugs thereof. Compound names are assigned by using AUTONOM naming software, which is provided by MDL Information Systems GmbH (formerly known as Beilstein Informationssysteme) of Frankfurt, Germany, and is part of the CHEMDRAW® ULTRA v. 6.0.2 software suite. Compounds of the invention may exist as stereoisomers wherein, asymmetric or chiral centers are present. These stereoisomers are "R" or "S" depending on the configuration of substituents around the chiral element. The terms "R" and "S" used herein are configurations as defined in IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem., 1976, 45:13-30. The invention contemplates various stereoisomers and mixtures thereof and are specifically included within the scope of this invention. Stereoisomers include enantiomers and WO 2005/028477 PCT/US2004/030735 diastereomers, and mixtures of enantiomers or diastereomers. Individual stereoisomers of compounds of the 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 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 optional liberation of the optically pure product from the auxiliary as described in Furniss, Hannaford, Smith, and Tatchell, "Vogel's Textbook of Practical Organic Chemistry", 5th edition (1989), Longman Scientific & Technical, Essex CM20 2JE, England, or (2) direct separation of the mixture of optical enantiomers on chiral chromatographic columns or (3) fractional recrystallization methods. Methods for Preparing Compounds of the Invention As used in the descriptions of the schemes and the examples, certain abbreviations are intended to have the following meanings: Ac for acetyl; Bu for n-butyl; BINAPfor2,2,-bis(diphenylphosphino)-1,1'-binaphthyl; DBU for 1,8-diazabicyclo[5.4.0]undec-7-ene; DMSO for dimethylsulfoxide; EtOAc for ethyl acetate; EtOH for ethanol; Et3N for triethylamine; Et20 for diethyl ether; HPLC for high pressure liquid chromatography; i-Pr for isopropyl; MeOH for methanol; NBS for N-bromosuccinimide; OAc for acetate; Ph for phenyl; t-Bu for tert-butyl; and THF for tetrahydrofuran. The reactions exemplified in the schemes are performed in a solvent appropriate to the reagents and materials employed and suitable for the transformations being effected. The described transformations may require modifying the order of the synthetic steps or selecting one particular process scheme over another in order to obtain a desired compound of the invention, depending on the functionality present on the molecule. Nitrogen protecting groups can be used for protecting amine groups present in the described compounds. Such methods, and some suitable nitrogen protecting groups, are described in Greene and Wuts (Protective Groups In Organic Synthesis, Wiley and Sons, 1999). For example, suitable nitrogen protecting groups include, WO 2005/028477 PCT/US2004/030735 but are not limited to, tert-butoxycarbonyl (BOC), benzyloxycarbonyl (CBZ), benzyl (Bn), acetyl, and trifluoracetyl. More particularly, the BOC protecting group may be removed by treatment with an acid such as trifluoroacetic acid or hydrochloric acid. The CBZ and Bn protecting groups may be removed by catalytic hydrogenation. The acetyl and trifluoracetyl protecting groups may be removed by a hydroxide ion. R3 Scheme 1 R3 R3 R3 Ar2B(OH)2 CI CI Pd(0), base CI N-N (2) Ar2 N-N R3 Ra P-N T N (3) base heat Ra Ar5 P-N Aro W // N-N (2) W // N-N CI Ar? (3) deprotect H-N J N R3 R3 W // N-N (4) Scheme 1. 3,6-Dichloropyridazines can be. WO 2005/028477 PCT/US2004/030735 Scheme 2 R3 R3 NH CI—^\ ^>—CI + N-N R3 R3 P-N BINAP pVHf\-/>-CI Pd(0), base Ov_7 N-N Ar2B(OH)2 Pd(°)- base V_A^ N-N (8) (3) R3 Rq Rq K3 (3) Scheme ] R-N Y N—^ />—Ar2 *" UJ N-N R=H or alkyl An alternative procedure for preparing pyridazines of general formula (4) and (5), wherein Ar2 and R3 are as defined in formula (I), is exemplified in Scheme 2. 3,6-Dichloropyridazines can be treated with diazabicycles of the present invention, palladium (0), BINAP, and a base to provide pyridazines of general formula (8), wherein P is a nitrogen protecting group. Pyridazines of general formula (8) can be treated with a boronic acid, palladium (0), and a base to provide pyridazines of general formula (3). Pyridazines of general formula (3) can be processed as described in Scheme 1 to provide pyridazines of general formula (4) and (5). Scheme 3 • R3 R3 P-N T U-\ \~C^_ R3 R3 Pd(0) UJ VN P-N Y NH )={ B'NAP (11) R3 Kj^J + Br-/X />-CI _base_ P-N (10) (11) Ar2B(OH)2 ' Pd(0), base R3 R R3 R3 N Vhf~Ar2 Scheme^ R"\j^/~\jf^ (13) R3 (14) R3 R=H or alkyl Pyridines of general formula (14) and (16), wherein Ar2 and R3 are as defined in formula (I), can be prepared as described in Scheme 3. 2,5-Dihalopyridines can be treated with palladium (0), BINAP, a base, and diazabicycles of the present invention wherein P is a nitrogen protecting group to provide 5-diazabicyclo-2-halopyridines of general formula (11) and 2-diazabicyclo-5-halopyridines of general formula (12). 5-Diazabicyclo-2-halopyridines of general formula (11) and 2-diazabicyclo-5-halopyridines of general formula (12) can be processed as described in Scheme 1 to provide pyridines of general formula (14) and (16). Scheme 4 R3 r^o Rl/R3 P-N NH /=0) ^U + Br-irf~H R3 (20) Pd(0), BINAP base Ra KEryt (21) R3 H ■*■ P-N (21) NBS Ar2B(OH)2 Pd- baSe, P-N^N (23) R3 R3 Ar2 (23)Sch£me1^R_NQQN_^V (14) R3 R=H or alkyl An alternative procedure for preparing pyridines of general formula (14), wherein Ar2 and R3 are as defined in formula (I), is exemplified in Scheme 4. Diazabicycles of the present invention, wherein P is a nitrogen protecting group, can be treated with 5-bromopyridine, BINAP, palladium (0), and a base to provide pyridines of general formula (21). Pyridines of general formula (21) can be treated with N-bromosuccinimide to provide bromides of general formula (22). Bromides of WO 2005/028477 PCT/US2004/03073:, general formula (22) can be treated with a boronic acid, palladium (0), and a base to provide biarylcompounds of general formula (23). Biarylcompounds of general formula (23) can be processed as described in Scheme 1 to provide pyridines of general formula (14). Scheme 5 R3 (25) (26) R3 R3 Ar2B(OH)2 R3 NBS rY^ >=Nv Pd(0). base r^T\ /=m , P-NJ^N-^-B . P-NJj^^J-* (27) R3 (28) R R3 <28)scheme1. R_NGCN"C}_Ar2 3 (29) R3 R=H or alkyl Pyrimidines of general formula (29), wherein Ar2 and R3 are as defined in formula (I), can be prepared as described in Scheme 5. Diazabicycies of the present invention, wherein P is a nitrogen protecting group, can be treated with 5-bromopyrimidines of general formula (25), BINAP, palladium (0), and a base to provide pyrimidines of general formula (26). Pyrimidines of general formula (26) can be treated with N-bromosuccinimide to provide bromides of general formula (27). Bromides of general formula (27) can be treated with a boronic acid, palladium (0), and a base to provide biarylcompounds of general formula (28). Biarylcompounds of general formula (28) can be processed as described in Scheme 1 to provide pyrimidines of general formula (29). WO 2005/028477 PCT/US2004/030735 Scheme 6 P-N T NH (D R" Y1-Y2 Y3 (31) Ar, Pd(0), BINAP base ,Yi.x PV T W>- Ar? (32) R'=CI, Br, or I R-N (32) Scheme 1 (33) R=H or alkyl Compounds of general formula (33), wherein Ar2, Y-i, Y2, Y3, and Y4 are as defined in formula (I) can be prepared as described in Scheme 6. Diazabicyclic compounds of general formula (1), can be treated with 5-membered aromatic heteroaryls of general formula (31), purchased commercially or prepared using methodology well-known to those in the art, preferably in the presence of palladium (0), BINAP, and a base to provide compounds of general formula (32). Compounds of general formula (32) can be processed as described in Scheme 1 to provide compounds of general formula (33). Scheme 7 P-N P-N R' Y-|-Y2 Y34 "R" (35) R'=CI, Br, or I R"=CI, Br, or I Pd(0), BINAP base ,Yi Ar2 (36) Ar2B(OH)2 p_N' Y \/^Y2 Pd(0), base Dri(f\\ l-»no<-» ill * \r Y3-T4. (32) Ar2 (32) Scheme 1 K-^CT^"-/*"2 Y.-Y4 (33) R=H or alkyl An alternate method of preparing compounds of general formula (33), wherein Ar2, Y1, Y2l Y3, and Y4 are as defined in formula (I), is described in Scheme 7. WO 2005/028477 PCT/US2004/030735 Diazabicyclic compounds of general formula (1) can be treated with dihalo-5-membered aromatic heteroaryls of general formula (35), purchased commercially or prepared using methodology well-known to those in the art, in the presence of palladium (0), BINAP, and a base to provide monohalo compounds of general formula (36). Monohalo compounds of general formula (36) can be treated with boronic acids, palladium (0), and a base to provide compounds of general formula (32). Compounds of general formula (32) can be processed as described in Scheme 1 to provide compounds of general formula (33). Scheme 8 ^^ -3 R3 Pd{0)- R3 R3 r^o v-/ B|NAP ^^ V_0 + Br-^ ^-H _^ P-\X/^ /rH 0) R3 OCH3 (39) R3 OCH3 (38) P-N NH /=\ base r^r^ R3 ,R3 Ar2B(OH)2 TIOAc ry^\ )=\ Pd(0), base ,,00^, y\_A (39) P-N I N-^V-I —— P-N I N-^>-Ar2 R3 OCH3 (41) R3 OCH3 (40) R3 ,R3 Scheme 1 Ar2 (4i)^cnem^R_N^j^N_y^ R3 OCH3 R=H or alkyl (42) R3 R3 BBr, < j 'N-O-AT, R3 OH ^3 (43) Compounds of general formula (42) and (43), wherein Ar2 and R3 are as defined in formula (I), can be prepared as described in Scheme 8. Diazabicycles of the present invention, wherein P is a nitrogen protecting group, can be treated with bromides of general formula (38), BINAP, palladium (0), and a base to provide compounds of general formula (39). Compounds of general formula (39) can be WO 2005/028477 PCT/US2004/030735 treated with iodine and thallium acetate to provide iodo compounds of general formula (40). lodo compounds of general formula (40) can be treated with a boronic acid, palladium (0), and a base to provide biarylcompounds of general formula (41). Biarylcompounds of general formula (41) can be processed as described in Scheme 1 to provide compounds of general formula (42) and (43). The compounds and intermediates of the invention may be isolated and purified by methods well-known to those skilled in the art of organic synthesis. Examples of conventional methods for isolating and purifying compounds can include, but are not limited to, chromatography on solid supports such as silica gel, alumina, or silica derivatized with alkylsilane groups, by recrystallization at high or low temperature with an optional pretreatment with activated carbon, thin-layer chromatography, distillation at various pressures, sublimation under vacuum, and trituration, as described for instance in "Vogel's Textbook of Practical Organic Chemistry", 5th edition (1989), by Furniss, Hannaford, Smith, and Tatchell, pub. Longman Scientific & Technical, Essex CM20 2JE, England. The compounds of the invention have at least one basic nitrogen whereby the compound can be treated with an acid to form a desired salt. For example, a compound may be reacted with an acid at or above room temperature to provide the desired salt, which is deposited, and collected by filtration after cooling. Examples of acids suitable for the reaction include, but are not limited to tartaric acid, lactic acid, succinic acid, as well as mandelic, atrolactic, methanesulfonic, ethanesulfonic, toluenesulfonic, naphthalenesulfonic, carbonic, fumaric, gluconic, acetic, propionic, salicylic, hydrochloric, hydrobromic, phosphoric, sulfuric, citric, or hydroxybutyric acid, camphorsulfonic, malic, phenylacetic, aspartic, glutamic, and the like. Compositions of the Invention The invention also provides pharmaceutical compositions comprising a therapeutically effective amount of a compound of formula (I) in combination with a pharmaceutically acceptable carrier. The compositions comprise compounds of the invention formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions can be formulated for oral WO 2005/028477 PCT/US2004/030735 administration in solid or liquid form, for parenteral injection or for rectal administration. The term "pharmaceutically acceptable carrier," as used herein, means a nontoxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as 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 one skilled in the art of formulations. 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. The term "parenterally," as used herein, refers to modes of administration, including intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous, intraarticular injection and infusion. Pharmaceutical compositions for parenteral injection comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (propylene glycol, polyethylene glycol, glycerol, and the like, and suitable mixtures thereof), vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate, or suitable mixtures thereof. Suitable fluidity of the composition may be maintained, for WO 2005/028477 PCT/US2004/030735 example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. These compositions can also contain adjuvants such as preservative agents, wetting agents, emulsifying agents, and dispersing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It also can be desirable to include isotonic agents, for example, sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin. In some cases, in order to prolong the effect of a drug, it is often 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 can depend upon its rate of dissolution, which, in turn, may depend upon crystal size and crystalline form. Alternatively, a parenterally administered drug form can be administered by dissolving or suspending the drug in an oil vehicle. Suspensions, in addition to the active compounds, can contain suspending agents, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, tragacanth, and mixtures thereof. If desired, and for more effective distribution, the compounds of the invention can be incorporated into slow-release or targeted-delivery systems such as polymer matrices, liposomes, and microspheres. They may be sterilized, for example, by filtration through a bacteria-retaining filter or by incorporation of sterilizing agents in the form of sterile solid compositions, which may be dissolved in sterile water or some other sterile injectable medium immediately before use. Injectable depot forms are made by forming microencapsulated 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 A -I >-- WO 2005/028477 PCT/US2004/030735 formulations also are prepared by entrapping the drug in liposomes or microemulsions which 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. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation also can be a sterile injectable solution, suspension or emulsion in a nontoxic, parenterally acceptable diluent or solvent such as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, one or more compounds of the invention is mixed with at least one inert pharmaceutically acceptable carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and salicylic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, 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. WO 2005/028477 PCT/US2004/030735 Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using lactose or milk sugar as well as high molecular weight polyethylene glycols. 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 can optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract in a delayed manner. Examples of materials useful for delaying release of the active agent can include polymeric substances and waxes. 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 such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsipns, 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, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. A desired compound of the invention is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, eardrops, eye WO 2005/028477 PCT/US2004/030735 ointments, powders and solutions are also contemplated as being within the scope of this invention. The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to the compounds of this invention, lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as chlorofluorohydrocarbons. Compounds of the invention also can 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 multilamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any nontoxic, physiologically acceptable and metabolizable lipid capable of forming liposomes may be used. The present compositions in liposome form may contain, in addition to the compounds of the invention, stabilizers, preservatives, and the like. The preferred lipids are the natural and synthetic phospholipids and phosphatidylcholines (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. Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffers or propellants. Ophthalmic formulations, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. Aqueous liquid compositions of the invention also are particularly useful. The compounds of the invention can be used in the form of pharmaceutically acceptable salts, esters, or amides derived from inorganic or organic acids. The term "pharmaceutically acceptable salts, esters and amides," as used herein, include salts, zwitterions, esters and amides of compounds of formula (I) which are, within WO 2005/028477 PCT/US2004/030735 the scope of sound medical judgment, suitable for use in contact with the tissues of, humans and lower animals without undue toxicity, irritation, allergic response, and the like, are commensurate with a reasonable benefit/risk ratie, and are effective for their intended use. The term "pharmaceutically acceptable salt" refers to those salts which are, within the scope of sound medical judgment, 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. Pharmaceutically acceptable salts are well-known in the art. 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 acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyeth an sulfonate (isethionate), lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, phosphate, glutamate, bicarbonate, p-toluenesulfonate and undecanoate. Also, the basic nitrogen-containing groups can be quatemized with such agents as lower alkyl halides such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides; dialkyl sulfates such as dimethyl, diethyl, dibutyl and diamyl sulfates; long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides; arylalkyi halides such as benzyl and phenethyl bromides and others. Water or oil-soluble or dispersible products are thereby obtained. Examples of acids which can be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, hydrobromic acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid, and citric 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 the hydroxide, carbonate or bicarbonate of a > WO 2005/028477 PCT/US2004/030735 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 lithium, sodium, potassium, calcium, magnesium, and aluminum salts, and the like, and nontoxic quaternary ammonia and amine cations including ammonium, tetramethyiammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine and the such as. Other representative organic amines useful for the formation of base addition salts include ethylenediamine, ethanolamine, diethanolamine, piperidine, and piperazine. The term "pharmaceutically acceptable ester," as used herein, refers to esters of compounds of the invention which hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Examples of pharmaceutically acceptable, non-toxic esters of the invention include Ci-to-C6 alkyl esters and C5-to-C7 cycloalkyl esters, although Crto-C4 alkyl esters are preferred. Esters of the compounds of formula (I) can be prepared according to conventional methods. Pharmaceutically acceptable esters can be appended onto hydroxy groups by reaction of the compound that contains the hydroxy group with acid and an alkylcarboxylic acid such as acetic acid, or with acid and an arylcarboxylic acid such as benzoic acid. In the case of compounds containing carboxylic acid groups, the pharmaceutically acceptable esters are' prepared from compounds containing the carboxylic acid groups by reaction of the compound with base such as triethylamine and an alkyl halide, alkyl trifilate, for example with methyl iodide, benzyl iodide, cyclopentyl iodide. They also can be prepared by reaction of the compound with an acid such as hydrochloric acid and an alkylcarboxylic acid such as acetic acid, or with acid and an arylcarboxylic acid such as benzoic acid. The term "pharmaceutically acceptable amide," as used herein, refers to nontoxic amides of the invention derived from ammonia, primary C-i-to-C6 alkyl amines and secondary Ci-to-C6 dialkyi amines. In the case of secondary amines, the amine can also be in the form of a 5- or 6-membered heterocycle containing one nitrogen atom. Amides derived from ammonia, Crto-C3 alkyl primary amides and Ci-to-C2 dialkyi secondary amides are preferred. Amides of the compounds of formula (I) can be prepared according to conventional methods. Pharmaceutically acceptable -46- WO 2005/028477 PCT/US2004/030735 amides can be prepared from compounds containing primary or secondary amine groups by reaction of the compound that contains the amino group with an alkyl anhydride, aryl anhydride, acyl halide, or aroyl halide. In the case of compounds containing carboxylic acid groups, the pharmaceutically acceptable esters are prepared from compounds containing the carboxylic acid groups by reaction of the compound with base such as triethylamine, a dehydrating agent such as dicyclohexyl carbodiimide or carbonyl diimidazole, and an alkyl amine, dialkylamine, for example with methylamine, diethylamine, piperidine. They also can be prepared by reaction of the compound with an acid such as sulfuric acid and an alkylcarboxylic acid such as acetic acid, or with acid and an arylcarboxylic acid such as benzoic acid under dehydrating conditions as with molecular sieves added. The composition can contain a compound of the invention in the form of a pharmaceutically acceptable prodrug. The term "pharmaceutically acceptable prodrug" or "prodrug," as used herein, represents those prodrugs of the compounds of the invention which are, within the scope of sound medical judgment,.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. Prodrugs of the invention can be rapidly transformed in vivo to a parent compound of formula (I), for example, by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems„V. 14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press (1987). The invention contemplates pharmaceutically active compounds either chemically synthesized or formed by in vivo biotransformation to compounds of formula (I). Methods of the Invention Compounds and compositions of the invention are useful for modulating the effects of nAChRs, and more particularly ct7 nAChRs. In particular, the compounds and compositions of the invention can be used for treating and preventing disorders WO 2005/028477 PCT/US2004/030735 modulated by a7 nAChRs. Typically, such disorders can be ameliorated by selectively modulating the a7 nAChRs in a mammal, preferably by administering a compound or composition of the invention, either alone or in combination with another active agent, for example, as part of a therapeutic regimen. The compounds of the invention, including but not limited to those specified in the examples, possess an affinity for nAChRs, and more particularly a7 nAChRs. As cc7 nAChRs ligands, the compounds of the invention can be useful for the treatment and prevention of a number of oc7 nAChR-mediated diseases or conditions. For example, ct7 nAChRs have been shown to play a significant role in enhancing cognitive function, including aspects of learning, memory and attention (Levin, E.D., J. Neurobiol. 53: 633-640, 2002). As such, a7 ligands are suitable for the treatment of cognitive disorders including, for example, attention deficit disorder, attention deficit hyperactivity disorder (ADHD), Alzheimer's disease (AD), mild cognitive impairment, senile dementia, AIDS dementia, Pick's Disease, dementia associated with Lewy bodies, and dementia associated with Down's syndrome, as well as cognitive deficits associated with schizophrenia. In addition, a7-containing nAChRs have been shown to be involved in the neuroprotective effects of nicotine both in vitro (Jonnala, R. B. and Buccafusco, J. J., J. Neurosci. Res. 66: 565-572, 2001) and in vivo (Shimohama, S. et al., Brain Res. 779: 359-363, 1998). More particularly, neurodegeneration underlies several progressive CNS disorders, including, but not limited to, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, dementia with Lewy bodies, as well as diminished CNS function resulting from traumatic brain injury. For example, the impaired function of a7 nAChRs by f5-amyloid peptides linked to Alzheimer's disease has been implicated as a key factor in development of the cognitive deficits associated with the disease (Liu, Q.-S., Kawai, H., Berg, D. K., PNAS 98: 4734-4739, 2001). The activation of a7 nAChRs has been shown to block this neurotoxicity (Kihara, T. et al., J. Biol. Chem. 276:13541-13546, 2001). As such, selective ligands that enhance a7 activity can counter the deficits of Alzheimer's and other neu-odegenerative diseases. WO 2005/028477 PCT/US2004/030735 Parkinson's disease is characterized by muscular rigidity, tremor, and bradykinesia. Epidemiologic studies have long demonstrated that cigarette-smoking subjects have lower risk of parkinsonism than nonsmerkers (Baron, J. A. Neurology 36: 1490-1496,1986). Moreover, direct administration of nicotine has been shown to improve tremor in Parkinson's patients. At least part of the beneficial effect of nicotine is thought to involve neuroprotection, a feature that is now understood to be mediated by a7 neuronal nAChRs (Jonnala, R. R., Buccausco, J. J. J. Neurosci. Res. 66: 565-571,2001). Schizophrenia is a complex disease that is characterized by abnormalities in perception, cognition, and emotions. Significant evidence implicates the involvement of oc7 nAChRs in this disease, including a measured deficit of these receptors in post-mortem patients (Leonard, S. Eur. J. Pharmacol. 393: 237-242, 2000). Deficits in sensory processing (gating) are one of the hallmarks of schizophrenia. These deficits can be normalized by nicotinic ligands that operate at the a7 nAChR (Adler L. E. et al., Schizophrenia Bull. 24: 189-202,1998; Stevens, K. E. et al., Psychopharmacology 136: 320-327, 1998). Thus, oc7 ligands demonstrate potential in the treatment schizophrenia. Angiogenesis, a process involved in the growth of new blood vessels, is important in beneficial systemic functions, such as wound healing, vascularization of skin grafts, and enhancement of circulation, for example, increased circulation around a vascular occlusion. Non-selective nAChR agonists like nicotine have been shown to stimulate angiogenesis (Heeschen, C. et al., Nature Medicine 7: 833-839, 2001). Improved angiogenesis has been shown to involve activation of the oc7 nAChR (Heeschen, C. et al, J. Clin. Invest. 110: 527-536, 2002). Therefore, nAChR ligands that are selective for the a7 subtype offer improved potential for stimulating angiogenesis with an improved side effect profile. A population of a7 nAChRs in the spinal cord modulate serotonergic transmission that have been associated with the pain-relieving effects of nicotinic compounds (Cordero-Erausquin, M. and Changeux, J.-P. PNAS 98:2803-2807, 2001). The a7 nAChR ligands demonstrate therapeutic potential for the treatment of pain states, including acute pain, post-surgical pain, as well as chronic pain states including inflammatory pain and neuropathic pain. Moreover, a7 nAChRs are WO 2005/028477 PCT/US2004/030735 expressed on the surface of primary macrophages that are involved in the inflammation response, and that activation of the a.7 receptor inhibits release of TNF and other cytokines that trigger the inflammation response (Wang, H. et al Nature 421: 384-388, 2003). Therefore, selective a.7 ligands demonstrate potential for treating conditions involving inflammation and pain. The mammalian sperm acrosome reaction is an exocytosis process important in fertilization of the ovum by sperm. Activation of an a7 nAChR on the sperm cell has been shown to be essential for the acrosome reaction (Son, J.-H. and Meizel, S. Biol. Reproduct. 68:1348-1353 2003). Consequently, selective a7 agents demonstrate utility for treating fertility disorders. Compounds of the invention are particularly useful for treating and preventing a condition or disorder affecting cognition, neurodegeneration, and schizophrenia. Cognitive impairment associated with schizophrenia often limits the ability of patients to normally function, a symptom not adequately treated by commonly available treatments, for example, treatment with an atypical antipsychotic. (Rowley, M. et al., J. Med. Chem. 44: 477-501, 2001). Such cognitive deficit has been linked to dysfunction of the nicotinic cholinergic system, in particular with decreased activity at a.7 receptors. (Friedman, J. I. et al., Biol Psychiatry, 51: 349-357, 2002). Thus, activators of a.7 receptors can provide useful treatment for enhancing cognitive function in schizophrenic patients who are being treated with atypical antipsychotics. Accordingly, the combination of an al nAChR ligand and an atypical antipsychotic would offer improved therapeutic utility. Specific examples of suitable atypical antipsychotics include, but are not limited to, clozapine, risperidone, olanzapine, quietapine, ziprasidone, zotepine, iloperidone, and the like. 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. However, it is within the skill of the art to start doses of the -50- WO 2005/028477 PCT/US2004/030735 compound at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. When used in the above or other treatments, a therapeutically effective amount of one of the compounds of the invention can be employed in pure form or, where such forms exist, in pharmaceutically acceptable salt, ester, amide or prodrug form. Alternatively, the compound can be administered as a pharmaceutical composition containing the compound of interest in combination with one or more pharmaceutically acceptable carriers. The phrase "therapeutically effective amount" of the compound of the invention means a sufficient amount of the compound to treat disorders, at a reasonable benefit/risk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage of the compounds and compositions of the 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. For example, it is well within the skill of the art to start doses of the compound at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. The total daily dose of the compounds of this invention administered to a human or lower animal range from about 0.10 mg/kg body weight to about 1 g/kg body weight. More preferable doses can be in the range of from'about 0.10 mg/kg body weight to about 100 mg/kg body weight. 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. >~. WO 2005/028477 PCT/US2004/030735 The compounds and processes of the invention will be better understood by reference to the following examples and reference examples, which are intended as an illustration of and not a limitation upon the scope of the invention. EXAMPLES Examples 1-25, entitled "Diamine Cores", describe diamine moieties that can be are used as referenced in the Examples to prepare compounds identified in Examples 31-110, 114-128, 131-188, 191-197, 204-213, 225-240, and 243-320. General procedures for coupling the 3-chloro-6-phenylpyridazine, deprotecting the resulting compound, methylating the amine nitrogen, and preparing a salt of the compound obtained thereof, as described in the Examples, are described in Example 31, and additional methods are further described in later Examples. Diamine Cores Example 1 3,8-Diaza-bicvclor3.2.noctane-8-carboxylic acid tert-butvl ester Example 1A 5-Oxo-pyrrolidine-2-carboxvlic acid methyl ester To a solution of DL-pyroglutamic acid (50 g, 0.387 mol) in 157 mL CH3OH (3.87 mol) and 100 mL toluene was added concentrated H2S04 (2.5 mL). This mixture was warmed to reflux and allowed to stir for 16 h. Since starting material remained, another 4 mL concentrated H2SO4 was added and the mixture stirred at reflux for an additional 24 h then was cooled to ambient temperature and 20% aqueous NaOH was added to bring the solution to pH ~6. The mixture was concentrated under reduced pressure and the residue was dissolved in CH2CI2 filtered through Celite® diatomaceous earth, concentrated and purified via Kugelrohr distillation. The resulting material was carried on directly to the next reaction. Example 1B 1-Benzyl-5-oxo-pyrrolidine-2-carboxvlic acid methyl ester WO 2005/028477 PCT/US2004/030735 To a slurry of NaH (22 g of 60% NaH in mineral oil, 0.55 mol) in 400 mL benzene was added the product of Example 1A (0.387 mol) in 100 mL benzene dropwise via addition funnel. The mixture stirred-for 30 minutes after the addition was complete, then was warmed to reflux and allowed to stir for 1.5 h. The reaction was cooled to 45 °C and stirred for 16 h. A portion of benzyl bromide (45 mL, 0.38 mol) was added, the mixture was warmed to reflux and an additional amount of benzyl bromide was added (45 mL, 0.38 mol). This solution stirred for 24 h at reflux, then was cooled to ambient temperature, filtered through Celite® diatomaceous earth and the residue was washed with CH2CI2. The combined filtrates were concentrated under reduced pressure and excess benzyl bromide was removed via distillation. The distillation residue was purified via column chromatography (Si02, 75% hexanes-EtOAc) to give 46.6 g of the title compound (0.2 mol, 52% yield). MS (DCI/NH3) m/z 234 (M+H)+. Example 1C 1-Benzvl-5-ethoxv-2-methoxvcarbonvl-3,4-dihydro-2H-pvrroliumtetrafluoroborate The product of Example 1B (46.6 g, 0.2 mol) in 200 mL CH2CI2 was added via addition funnel to a solution of Meerwein's reagent (Et30+BF4") (Aldrich, 200 mL of 1 M solution in CH2CI2, 0.2 mol) at ambient temperature. The reaction mixture stirred for 18 h then was concentrated and the residue was determined to be a 1.8:1 mixture of starting material to product. This mixture was carried on to the next step without further purification. Example 1D 1 -Benzyl-5-nitromethvlene-pvrrolidine-2-carboxylic acid methyl ester To the mixture obtained in Example 1C (0.2 mol) in 130 mL CH2CI2 at ambient temperature was added Et3N (33.5 mL, 0.24 mol) followed by CH3N02 (13 mL, 0.24 mol). The mixture stirred at ambient temperature for 8 h then was diluted with CH2CI2, the layers were separated and the organic layer was washed with 20 mL 5% H2SO4 and 20 mL brine. The organic layer was dried over anhydrous Na2S04, concentrated and purified via column chromatography (Si02,50% hexanes-EtOAc) to give 10.2 g of the title compound (36.9 mmol). MS (DCI/NH3) m/z 277 (M+H)+. WO 2005/028477 PCT/US2004/030735 Example 1E 8-Benzyl-3,8-diaza-bicvclor3.2.11octan-2-one The product of Example 1D (10.2 g, 36.9 mmol) and 5% Pt/C (2 g) in 200 mL CH3OH was shaken under a 30 psi atmosphere of H2 at ambient temperature for 24 h. The mixture was then filtered through Celite® diatomaceous earth, and concentrated to give 2.88 g (13.3 mmol, 36%) of the title. MS (DCI/NH3) m/z 217 (M+H)+. Example 1F 8-Benzvl-3,8-diaza-bicvclor3.2.noctane The product of Example 1E (2.88 g, 13.3 mmol) in 40 ml_ THF was added via cannula to a mixture of LiAIH4 (1.52 g, 39.9 mmol) in 40 mL THF at 0 °C. After the addition was complete, the reaction mixture was allowed to warm to ambient temperature and stir for 2 h. The mixture was warmed to reflux and stirred for 1 h. The reaction was cooled to 0 °C then 1.5 mL H20,1.5 mL 15 % NaOH and 4.5 mL H2O were added sequentially to quench the reaction. The material was filtered, the residue was washed with EtOAc, and the filtrate was concentrated under reduced pressure and carried on directly to the next reaction. MS (DCI/NH3) m/z 203 (M+H)+. Example 1G ■; 1-(8-Benzvl-3,8-diaza-bicvclof3.2.11oct-3-yl)-2,2,2-trifluoro-ethanone To the product of Example 1F (2.0 g, 9.8 mmol) in 50 mL CH2CI2 was added Et3N (7.0 mL, 50 mmol). The mixture was cooled to 0 °C and trifluoroacetic anhydride (3.53 mL, 25 mmol) was added. The ice-bath was removed after the addition was complete and the reaction stirred for 16 h at ambient temperature. The mixture was concentrated under reduced pressure and purified by column chromatography (SiC>2,50% hexanes-EtOAc) to give 2.5 g of the title compound (8.4 mmol, 86% yield). MS (DCI/NH3) m/z 299 (M+H)+. Example 1H WO 2005/028477 PCT/US2004/030735 3-(2,2,2-Trifluoro-acetvl)-3,8-diaza-bicvclor3.2.1]octane-8-carboxylicacidtert-butvl ester To the product of Example 1G (2.5 g, 8.4 mmol) in 20 mL EtOAc, was added di-tert-butyl dicarbonate (2.0 g, 9.22 mmol) and Pd/C (10 wt%, 0.25 g). This mixture was placed under 1 atm. of H2 via balloon and was allowed to stir for 48 h. The reaction mixture was filtered, concentrated under reduced pressure and purified via column chromatography (Si02, 50% hexanes-EtOAc) to give 2 g of the title compound (6.5 mmol, 77% yield). MS (DCI/NH3) m/z 253 (M+H)+. Example 11 3,8-Diaza-bicyclof3.2.noctane-8-carboxylic acid tert-butyl ester To the product of Example 1H (2.0 g, 6.5 mmol) in 57 mL CH3OH and 11 mL H20 was added 2.8 g K2C03 (20.3 mmol). The mixture stirred for 16 h at ambient temperature then was filtered, concentrated under reduced pressure and purified via column chromatography (SiO2i50% hexanes-EtOAc) to give 1.2 g of the title compound (5.65 mmol, 87% yield). MS (DCI/NH3) m/z 213 (M+H)+. Example 2 3,6-Diaza-bicyclo[3.2.noctane-6-carboxylic acid tert-butyl ester Example 2A tert-Butyl 2-Azabicyclor2.2.nhept-5-en-2-carboxylate Aqueous formalin (37%, 114 mL, 1.41 mol) was added to a well-stirred solution of NH4CI (85.0 g, 1.59 mol) in water (250 mL). Freshly distilled cyclopentadiene (170 g, 2.58 mol) was added all at once, and the mixture was stirred vigorously at ambient temperature for 17 h. The lower, aqueous phase was separated, and was treated with di-t-butyl dicarbonate (172 g, 0.78 mol). Aqueous 1M NaOH (100 mL) was added to adjust the pH to ~8, and the mixture was stirred for 7 h at ambient temperature with addition of solid NaOH (40 g total) to maintain pH - 8. The mixture was extracted with hexanes (2 x 200 mL), and the combined organic phase was washed with brine (50 mL), dried over MgS04, and concentrated under vacuum. The residue was distilled under vacuum to provide the title WO 2005/028477 PCT7US2004/030735 compound (bp 80-92 °C/10 Torr) as a pale yellow liquid that crystallized on cooling (123 g, 0.63 mol, 45% yield). 1H NMR (CDCI3, 300 MHz) 8 1.44 (s, 9H), 1.57 (m, 2H), 2.63 (m, 1H), 3.16 (br s, 1H), 3.31 (dd, J=9, 3 Hz, 1H), 4)55-4.73 (br m, 1H), 6.25-6.41 (br m, 2H). MS (DCI/NH3) m/z 196 (M+H)+. Example 2B 2,4-Diformvl-pvrrolidine-1-carboxylic acid tert-butyl ester Through a solution of Example 2A (0.57 g, 2.9 mmol) in 1.5 mL acetic acid and 25 mL CH2CI2 at -78 °C was bubbled 03 until the solution turned blue. 02 was then flushed through the system for 10 min after which dimethylsulfide (0.54 mL, 7.30 mmol) was added. The mixture was slowly warmed to 20 °C and allowed to stir for 18 h. The solution was concentrated and the crude product was carried on directly to the next reaction. MS (DCI/NH3) m/z 228 (M+H)+. Example 2C 3-Benzyl-3,6-diaza-bicyclof3.2.noctane-6-carboxylic acid tert-butyl ester To a solution of the crude product of Example 2B (2.92 mmol) in CH3OH at 0 °C was added benzylamine (0.35 mL, 3.21 mmol) and NaCNBH3 (1.83 g, 29.2 mmol). The ice-bath was removed and the mixture stirred at 20 °C for 24 h. The solution was cooled to 0 °C and 10 mL EtOAc and 10 mL H20 were added followed by 5 mL of saturated, aqueous NaHCo3. The layers were separated and the aqueous layer was extracted with 10 mL EtOAc. The combined organic layers were washed with 5 mL H20 followed by 5 mL brine, then were dried over anhydrous Na2S04. The mixture was filtered and the filtrate was concentrated and purified via flash column chromatography to give 0.68 g (2.25 mmol, 77% two-step yield) of the title compound. 1H NMR (CH3OH-d4, 300 MHz) 8 1.37 and 1.51 (s, rotamers, 9H), 1.46 (m, 1H), 1.57 (dd, J=11.2,7.46 Hz, 1H), 1.88 (m, 1H), 1.97 (m, 1H), 2.32 (m, 2H), 2.82 (m, 1H), 3.02 (m, 1H), 3.52 (m, 3H), 3.91 (m, 1H), 7.20 (m, 1H), 7.27 (m, 4H); MS (DCI/NH3) m/z 303 (M+H)+. Example 2D 3,6-Diaza-bicyclor3.2.noctane-6-carboxylic acid tert-butyl ester 56 WO 2005/028477 PCT/US2004/030735 To the product of Example 2C (0.553 g, 1.83 mmol) in 50 mL CH3OH was added 111 mg Pd(OH)2/C (20 wt%). The mixture was put under 60 psi of H2, warmed to 50 °C and allowed to stir for 36 hv The solution was then cooled to 20 °C, filtered through Celite® diatomaceous earth, and concentrated to give the desired product. 1H NMR (CH3OH-d4, 300 MHz) 5 1.46 and 1.48 (s, rotamers, 9H), 1.78 (dd, J=11.2, 5.43 Hz, 1H), 1.91 (m, 1H), 2.28 (m, 1H), 2.61 (d, J=12.9 Hz, 1H), 2.82 (m, 3H), 3.41 (m, 2H), 3.93 (m, 1H); MS (DCI/NH3) m/z 213 (M+H)+. Example 3 3,8-Diaza-bicvclor4.2.01octane-8-carboxvlic acid tert-butyl ester Example 3A 3-Oxo-piperidine-1,4-dicarboxvlic acid 1-tert-butyl ester 4-ethyl ester A mixture of commercially available ethyl-N-benzyl-3-oxo-4~ piperidinecarboxylate hydrochloride (Aldrich, 75.4 g, 0.25 mol), di-t-butyl dicarbonate (58.5 g, 0.27 mol), Et3N (36 mL, 0.26 mol), and Pd(OH)2/C (7.5 g, 50% in H20) in 660 mL EtOH was put under 60 psi of H2 and was shaken for 25 min. The mixture was then filtered and the filtrate was concentrated under reduced pressure to provide the title compound which was used in the next step without further purification. MS (DCI/NH3) m/z 272 (M+H)+. Example 3B 5-((1RV1-Phenyl-ethvlamino)-3,6-dihydro-2H-pyridine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester A mixture of the product of Example 3A (72 g, 0.265 mol) and D-(+)-a-methylbenzylamine (Aldrich, 35.9 mL, 0.279 mol) in 750 mL of toluene was combined in a 1 L, round-bottom flask equipped with a Dean-Stark trap. The mixture was refluxed for 36 h with water being removed via the Dean-Stark trap. After cooling to ambient temperature, the solution was concentrated and redissolved in EtOAc. Filtration through silica gel and Celite® diatomaceous earth gave the crude title compound which was carried on directly to the next reaction. MS (DCI/NH3) m/z 375 (M+H)+. WO 2005/028477 PCT/US2004/030735 Example 3C 3-((1RV1-Phenvl-ethvlamino)-piperidine-1,4-dicarboxylic acid 1-tert-butvl ester 4- ethyl ester To a mixture of the product of Example 3B (0.265 mol), NaBH(OAc)3 (280.8 g, 1.33 mol), and 200 g of 4A powdered molecular sieves in 900 mL toluene in a 3-neck round bottom flask equipped with an internal thermometer, mechanical stirrer and addition funnel at 0 °C was added acetic acid (303 mL, 5.3 mol) dropwise via the addition funnel. After the addition was complete, the mixture was allowed to warm to ambient temperature and stir for 16 h. The reaction was filtered and concentrated under reduced pressure to remove as much of the acetic acid as possible. The residue was dissolved in 750 mL EtOAc and 500 mL saturated aqueous NaHC03 solution was added slowly to neutralize the residual acid. The layers were separated i and the aqueous layer was extracted with 2 X 100 mL EtOAc. The combined organics were dried over Na2S04 and concentrated under reduced pressure to give the title compound which was carried on to the next reaction without further purification. MS (DCI/NH3) m/z 377 (M+H)+. Example 3D 4-Hydroxymethvl-3-((1 R)-1-phenvl-ethvlamino)-piperidine-1-carboxvlic acid tert-butvl ester To a slurry of LiAIH4 (0.292 mol) in 1 L tetrahydrofuran at 0 °C was added the product of Example 3C (0.265 mol) dropwise via addition funnel. The ice-bath was removed after the addition was complete and the mixture stirred at ambient temperature for 1 h. The reaction was quenched by the slow addition of approximately 100 g Na2SO4 . 10H2O (excess). The mixture stirred for 16 h then was filtered, concentrated under reduced pressure and purified via column chromatography (Sio2, 33% hexanes-EtOAc) to give 76.5 g of the mixture of isomers (0.23 mol, 86%). MS (DCI/NH3) m/z 335 (M+H)+. Example 3E WO 2005/028477 PCT/US2004/030735 8-((1 R)-1-Phenvl-ethvl)-3,8-diaza-bicyclor4.2.0loctane-3-carboxvlic acid tert-butyl ester To the mixture of isomers from Example 3D (76.5 g, 0.23 mol) in 1.1 L of tetrahydrofuran at 0 °C was added Et3N (95.8 mL, 0.687 mol) followed by methanesulfonyl chloride (23 mL, 0.30 mol). The ice-bath was removed after the additions were complete and the reaction was allowed to warm to ambient temperature and stiredr for 1 h. CS2CO3 (excess) was added and the mixture was warmed to 60 °C and stirred for 16 h. The reaction was cooled to ambient temperature, filtered, and the filtrate was washed with 2 X 100 mL H20. The layers were separated and the aqueous layer was extracted with 2 X 100 mL EtOAc. The combined organics were dried over Na2So4 and concentrated under reduced pressure. The material was purified and the isomers separated via column chromatography (SiC>2, 50% hexanes-EtOAc) to give 30.65 g of the major isomer ((1S,6R)-3,8-diaza-bicyclo[4.2.0]octane-3-carboxylic acid tert-butyl ester (97 mmol, 42%) and 16.5 g of the minor isomer ((1 R,6S)-3,8-diaza-bicyclo[4.2.0]-octane-3-carboxylic acid tert-butyl ester (52 mmol, 23%). MS (DCI/NH3) m/z 317 (M+H)+. Example 3F (1 R,6S)-8-((1 R)-1 -Phenvl-ethvl)-3,8-diaza-bicvclor4.2:01octane To the minor isomer product of Example 3E (9.3 g, 29.4 mmol) in 40 mL CH2CI2 at 0 °C was added 20 mL trifluoroacetic acid. The ice bath was removed after the addition and the mixture stirred at ambient temperature for 3 h then was concentrated under reduced pressure and the residue was purified via column chromatography (Si02, 1% NH4OH : 9% CH3OH : 90% CH2CI2) to give the title compound. MS (DCI/NH3) m/z 217 (M+H)+. Example 3G 2,2,2-Trifluoro-1-r(1R,6S)-8-(1-phenvl-ethvn-3,8-diaza-bicvclor4.2.01oct-3-vn- ethanone To the product of Example 3F (29.4 mmol) in 210 mL tetrahydrofuran (THF) at -30 °C was added triethylamine (5.15 mL, 36.8 mmol) followed by trifluoroacetic WO 2005/028477 PCT/US2004/030735 anhydride (TFAA, 4.36 mL, 30.9 mmol). The mixture was warmed to -10 °C and stirred for 30 min. The reaction was quenched with 50 mL saturated, aqueous NaHC03 then was diluted with 100 mL H20 and 100 mL EtOAc. The layers were separated and the aqueous layer was extracted 2 X 50 mL EtOAc. The combined organic layers were dried over Na2S04, filtered through silica gel and Celite® diatomaceous earth with EtOAc and the filtrate was concentrated under reduced pressure to give 8.8 g of the title compound (28.2 mmol, 96% two-step yield). MS (DCI/NH3)m/z313(M+H)+. Example 3H (1R,6S)-3-(2,2,2-Trifluoro-acetvl)-3,8-diaza-bicyclof4.2.01octane-8-carboxvlicacid tert-butyl ester A mixture of the product of Example 3G (8.8 g, 28.2 mmol), di-t-butyl dicarbonate (6.15 g, 28.2 mmol), and 2.21 g of 20% Pd(OH)2/C in 100 mL CH3OH was shaken under 60 psi of H2 for 5 h at 50 °C then for 9.5 h at ambient temperature. The reaction was filtered and concentrated under reduced pressure. 1H-NMR indicated the presence of a bis-di-t-butyl dicarbamide-3,8-diaza-bicyc!o[4.2.0]octane side product which carried on to the next step along with the crude product. MS (DCI/NH3) m/z 326 (M+NH4f. Example 31 (1R.6S)-3.8-Diaza-bicyclo[4.2.01octane-8-carboxvlic acid tert-butyl ester To the crude product of Example 3H (-28.2 mmol) in 140 mL CH3OH and 30 mL H2O was added 4.7 g K2CO3 (33.8 mmol). The mixture stirred at ambient temperature for 16 h then was diluted with a 100 mL of a solution of 1 % NH4OH : 9% CH3OH : 90% CH2CI2 and filtered through Celite® diatomaceous earth and silica gel. The filtrate was concentrated under reduced pressure and purified via column chromatography (Si02.1% NH4OH : 9% CH3OH : 90% CH2CI2) to give 3.3 g of the title compound (15.6 mmol, 55% yield). MS (DCI/NH3) m/z 213 (M+H)+. Example 4 (1S,6R)-3,8-Diaza-bicyclol4.2.01octane-8-carboxylic acid tert-butyl ester WO 2005/028477 PCT/US2004/030735 The major isomer from Example 3E was processed according to the procedures of Examples 3F, 3G, 3H, and 31 to provide the title compound: MS (DCI/NH3) m/z 213 (M+H)+ Example 5 t-Butyl 3,6-diazabicyclo[3.2.noctane-3-carboxylate Example 5A 1-(3-Benzyl-3,6-diazabicvclor3.2.noct-6-vn-2,2,2-trifluoro-ethanone To the product of Example 2C (0.68 g, 2.25 mmol) in 7 mL CH2CI2 at 0 °C was added 3.5 mL trifluoroacetic anhydride. The ice-bath was removed and the mixture stirred at 20 °C fr 2 h. The solution was then concentrated and the residue was dissolved in THF (15 mL). Triethylamine (0.41 mL, 2.92 mmol, 1.3 eq) was added, followed by trifluoroacetic anhydride (0.38 mL, 2.70 mmol, 1.2 eq). The mixture was stirred for 15 min at 0 °C then was allowed to warm to 20 °C at which temperature it stirred for 18 h. The solution was concentrated and purified via flash column chromatography to give quantitative yield of the desired trifluoroacetamide (0.67 g, 2.25 mmol, 100% two-step yield). 1H NMR (CH3OH-d4, 300 MHz) 8 1.97 (m, 1H), 2.06 (m, 1H), 2.12 (m, 1H), 2.84 (m, 1H), 3.41 (m, 2H), 3.61 (m, 2H), 3.82 (m, 1H), 4.32 (m, 2H), 4.64 (m, 1H), 7.48 (m, 5H); MS (DCI/NH3) m/z 299 (M+H)+. Example 5B t-Butyl 3,6-Diazabicyclof3.2.1 loctane-6-carboxylate i To the product of Example 5A (0.67 g, 2.25 mmol) and Boc20 (0.55 g, 2.51 mmol, 1.1 eq) in 50 mL CH3OH was added 135 mg Pd(OH)2/C (20 wt%). The mixture was put under 60 psi of H2 and allowed to stir for 18 h. The solution was then filtered through Celite®, and concentrated. The residue was dissolved in CH3OH (10 mL) and H20 (2 mL) and treated with K2C03 (0.5 g, 3.62 mmol, 1.6 eq). The mixture stirred for 20 h and then concentrated. The residue was taken up in a mixture of 90% CH2CI2, 9% CH3OH and 1% NH4OH and filtered through diatomaceous earth and silica gel. The filtrate was concentrated to provide 0.47 g of the title compound (2.21 mmol, 98% yield). 1H NMR (CH3OH-d4l 300 MHz) 5 1.42 WO 2005/028477 PCT/US2004/030735 (m, 1H), 1.46 (s, 9H), 1-89 (m, 2H), 2.58 (m, 1H), 3.00 (m, 2H), 3.12 (m, 2H), 3.78 (m, 1H), 3.84 (dd, J = 12.88, 3.39 Hz, 1H), 3.92 (brd, J = 13.9 Hz, 1H); MS - - (DCI/NH3) m/z 213 (M+H)+. Example 6 Hexahvdro-pvrrolof3,4-c1pyrrole-2-carboxvlic acid tert-butyl ester Example 6A 5-Benzyl-tetrahydro-pvrrolo|"3,4-c1pvrrole-1,3-dione To the maleimide (80.4 g, 0.83 mol) in 1.5 L of CH2CI2 in a 3-neck, 3-L round bottom flask equipped with an addition funnel, internal thermometer, and N2 inlet at 0 °C was added trifluoroacetic acid (TFA) (6.4 mL, 83 mmol). Benzyl(methoxymethyl)trimethylsilylmethylamine (261 g, 1.1 mol) in 500 mL CH2CI2 was added dropwise via addition funnel over 3 hours with the reaction temperature being maintained below 5 °C. After the addition was complete, the mixture was allowed to warm slowly to ambient temperature and then was stirred for 16 h. The mixture was concentrated and the residue was dissolved in 500 mL CH2CI2 and was washed with 2 X 50 mL saturated NaHC03. The layers were separated and the aqueous layer was extracted 2 X 25 mL CH2CI2. The combined organics were washed with 25 mL brine, dried over saturated, aqueous Na2S03, and concentrated under reduced pressure to give the title compound which was carried on to the next step without further purification. MS (DCI/NH3) m/z 231 (M+H)+. Example 6B 1 5-Benzvl-hexahvdro-pyrrolor3,4-c1pvrrole-2-carboxvlic acid tert-butyl ester To a slurry of LiAIH4 (25 g, 0.63 mol) in 1 L THF at 0 °C in a 3-L round bottom flask equipped with an addition funnel and an N2 inlet, was added 48 g (0.19 mmol) of the crude product of Example 6A (0.21 mol) in 500 mL THF dropwise via the addition funnel over 3 h. After the addition was complete, the ice-bath was removed and the mixture stirred at ambient temperature for 30 min before being warmed to reflux and stirred for 4 h. The reaction was cooled to 0 °C and quenched by the slow addition of Na2SO4'10H2O (excess). This mixture stirred for 16 h at ambient temperature then was filtered and the residue was washed with EtOAc. The WO 2005/028477 PCT/US2004/030735 combined filtrates were concentrated and the residue was dissolved in 500 ml_ THF. Di-t-butyl dicarbonate (46 g, 0.21 mol) and 100 mL saturated, aqueous NaHC03 were added and the mixture stirred for 16 h at ambient temperature. The reaction was quenched with 50 mL H20 and 250 mL EtOAc was added. The layers were separated, the aqueous layer was extracted 3 X 50 mL EtOAc, and the combined organic layers were dried over Na2S04 and concentrated under reduced pressure. Purification via column chromatography (SiC>2, 50% hexanes-EtOAc) gave 33.4 g of the title compound (0.11 mol, 53% yield). MS (DCI/NH3) m/z 303 (M+H)+. Example 6C Hexahvdro-pyrrolo[3,4-c]pvrrole-2-carboxvlic acid tert-butyl ester To the product of Example 6B (107.8 g, 0.356 mol) in 250 mL CH3OH was added 10.8 g of 20% Pd(OH)2/C, wet. This mixture was hydrogenated for 2.5 h under 60 psi of H2 at 50 °C. The mixture was filtered and concentrated to give 74 g of the title compound (0.35 mmol, 98% yield). MS (DCI/NH3) m/z 213 (M+H)+. Example 7 Benzyl (1 S,5S>3,6-diazabicyclof3.2.Q1heptane-3-carboxvlate Example 7A (2,2-Dimethoxy-ethyl)-carbamic acid benzyl ester Benzyl chloroformate (Aldrich, 231.3 g, 1.3 mol) was added gradually to a mixture .of aminoacetaldehyde dimethyl acetal (Aldrich, 152.0 g, 1.3 mol) in toluene (750 mL) and aqueous NaOH (72.8 g, 1.82 mol; in 375 mL of water) at 10-20 °C. After the addition was complete, the mixture was stirred at ambient temperature for 4 h. The layers were separated and the organic layer was washed with brine (2 x 100 mL) and concentrated under reduced pressure to provide the title compound as an oil (281.5 g, 90% yield). 1H NMR (CDCI4, 300 MHz) 5 3.33 (t, J=6.0 Hz, 2H), 3.39 (s, 6H), 4.37 (t, J=6.0 Hz, 1H), 5.11 (s, 2H), 7.30 (m, 5H); MS (DCI/NH3) m/z 257 (M+NH4)+, 240 (M+H)+. Example 7B WO 2005/028477 PCT/US2004/030735 Allvl-(2,2-dimethoxv-ethv0-carbamic acid benzyl ester The product of Example 7A (281.0 g, 1.18 mol) in dry toluene (1.0 L) was treated with powdered KOH (291.2 g, 5.20 mol) and triethylbenzylammonium chloride (Aldrich, 4.4 g, 0.02 mol). A solution of allyl bromide (Aldrich, 188.7 g, 1.56 mol) in toluene (300 mL) was then added dropwise over 1 hour at 20-30 °C. The mixture was stirred for -18 h at ambient temperature and then water (300 mL) was added over 20 minutes at 20-30 °C. The layers were separated and the aqueous phase was extracted with toluene (2 x 300 mL). The organic phases were combined, washed with brine (2 x 100 mL), dried (K2C03), filtered and the filtrate concentrated under reduced pressure to provide the title compound as an oil (315.6 g, 1.13 mol, 96%, yield). 1H NMR (MeOH-d4, 300 MHz) 5 3.32 (s, 3H) 3.37 (m, 5H), 3.97 (d, J=5.4 Hz, 2H), 4.50-4.40 (m, 1H), 5.15 (m, 4H), 5.75 (m, 1H), 7.23 (m, 5H); MS (DCI/NH3) m/z 297 (M+NH4)+, 280 (M+H)+. Example 7C Allvl-(2-oxo-ethyl)-carbamic acid benzyl ester The product of Example 7B (314.0 g, 1.125 mol) was treated with formic acid (88%, 350 mL) at room temperature and allowed to stir for 15 hours. Most of the formic acid was removed by concentration under reduced pressure at 40-50 °C. The residue was extracted with ethyl acetate (3 x 500 mL). The extracts were combined and washed with brine until the wash had a pH = 6-7. The organic phase was concentrated under reduced pressure to provide the title compound as a slightly yellow oil (260.0 g, 1.12 mmol 99% yield). 1H NMR (CDCI3, 300 MHz) 5 3.20 (m, 1H), 3.97 (m, 2H), 4.10 (m, 1H), 5.10 (m, 4H), 5.75 (m, 1H), 7.45 (m, 5H), 9.50 (d, J=6.4 Hz, 1H); MS (DCI/NH3) m/z 234 (M+H)+. Example 7D Allyl-(2-hydroxvimino-ethvl)-carbamic acid benzyl ester The product of Example 7C (260 g, 1.12 mol) in acetonitrile (1.5 L) was treated with sodium acetate trihydrate (170.6 g, 4.41 mol, in 0.75L distilled water) and NH2OH.hydrochIoride (98.0 g, 4.41 mol) under N2. The mixture was stirred at ambient temperature over 20 hours. The volatiles were removed under reduced WO 2005/028477 PCT/US2004/030735 pressure and the residue was extracted with ethyl acetate (2 x 750 ml_). The combined organic phases were washed with brine until the wash had a pH = 7. The organic phase was concentrated under reduced pressure to provide the title compound as an oil (271 g, 1.09 mol, 98% yield). 1H NMR (MeOH-d4, 300 MHz) 5 3.94 (m, 2H), 3.98 (d, J=5.5 Hz, 1H), 4.17 (d, J=4.4Hz, 1H), 5.30 (m, 4H), 5.60 (m, 1H), 7.40 (m, 5H); MS (DCI/NH3) m/z 266 (M+NH4)+, 249 (M+H)+. Example 7E benzyl (cis)-3-amino-4-(hvdroxvmethvl)-1-PVrrolidinecarboxvlate A solution of the product of Example 7D (240 g, 0.97 mol) in xylene (1.0 L) was heated at reflux under N2 for 10 hours. The resulting brown solution was cooled to 10-15 °C and acetic acid (1.0 L) was added under N2. Zinc powder (100 g, 1.54 mol) was added gradually, and the gray mixture was stirred at ambient temperature for 3 hours. The mixture was filtered and water (1.0 L) was added to the filtrate. The filtrate was stirred for 10 minutes and the brown organic layer was separated. The aqueous phase was washed well with xylenes (4 x 400 ml_) and then concentrated under reduced pressure to a volume of approximately 200 mL. This residue was adjusted to pH 9-10 by cautious addition of saturated, aqueous Na2C03. The precipitated white solid was removed by filtration and the filtrate was extracted with CHCI3 (3 x 600 mL). The combined organic phases were washed with saturated, aqueous Na2C03 solution (2 x 50 mL) and dried over anhydrous Na2C03. The mixture was filtered through a short column of diatomaceous earth and the filtrate was concentrated under reduced pressure to provide the title compound as a slightly yellow oil (145 g, 0.58 mol, 60% yield). 1H NMR (MeOH-d4, 300 MHz) 5 2.40 (m, 1H), 3.30 (m, 2H), 3.80-3.50 (m, 5H), 5.10 (s, 2H), 7.35 (m, 5H); MS (DCI/NH3) m/z 251 (M+H)+. Example 7F Benzyl (cis)-2,2-dimethvlhexahvdropvrrolo[3,4-dlf1,3loxazine-6(4H)-carboxylate (R)-Mandelate The product of Example 7E (140g, 0.56 mol) in dry acetone (150 mL) was treated with 2-methoxypropene (55 mL, 0.57 mol) at ambient temperature for -18 h. WO 2005/028477 PCT/US2004/030735 The reaction mixture was concentrated under reduced pressure and the residue was dissolved in dry acetone (750 mL). (R)-Mandelic acid (85 g, 0.56 mol) was added and the brown solution was stirred at ambient temperature for 48 hours. The precipitate was isolated by filtration and dried under reduced pressure to a mixture of the title compound as a white solid (57.0 g, 0.13 mol, yield, 23%) and the hydrolyzed compound benzyl (cis)-3-amino-4-(hydroxymethyl)-1-pyrrolidinecarboxylate (R)-mandelate. 1H NMR for title compound (MeOH-D4,300 MHz) 8 1.20-1.40 (m, 3H), 2.09 (s, 3H), 3.30 (m, 1H), 3.48-3.75 (m, 6H), 4.20 (m, 1H), 5.10 (m, 3H), 7.25-7.52 (m, 10H); MS (DCl/NH3) m/z 291 (M+H)+ (for the title compound) 251 (M+H)+ (for the hydrolyzed product). Example 7G Benzyl (3S,4S)-3-Utert-butoxvcarbonv0aminol-4-(hydroxvmethviyi- pyrrolidinecarboxylate The product of Example 7F (56 g, 127 mmol) in ethanol (50 mL) was treated with 5% aqueous H2SO4 (100 mL) at ambient temperature and allowed to stir for 16 hours. The mixture was adjusted to pH -10 with 20% aqueous NaOH (50 mL) and then the mixture was treated with di-t-butyl dicarbonate (41.5 g, 190 mmol) in ethanol (50 mL) at 10-20 °C. After stirring at ambient temperature for 4 hours, the ethanol was removed under reduced pressure and the residue was extracted with ethyl acetate (3 x 500 mL). The combined organic phases were washed with brine (2 x 100 mL) arid concentrated under reduced pressure to provide the title compound (43.7 g, 0.125 mol, 98% yield). 1H NMR (MeOH-d4) 300 MHz) 8 1.46 (s, 9H), 2.50 (m, 1H), 3.25 (m, 1H), 3.40 (m, 1H), 3.50-3.75 (m, 4H), 4.20 (m, 1H), 5.10 (s, 2H), 7.35 (m, 5H); MS (DCl/NH3) m/z 368 (M+NH4)+, 351 (M+H)\ The enantiopurity of the title compound was determined to be >99% ee by HPLC (HPLC conditions: Chiracel AD column; ethanol/hexanes=20/80, flow rate, 1.0 mL/min; uv 220 nm; retention time for the title compound as the more mobile isomer: 10.8 minutes; Retention time for less mobile isomer: 13.9 minutes; reference: JP 2000 026408). Example 7H Ronwi (3S.4S)-3-[(tert-butoxvcarbonyl)aminol-4-{f(methvlsulfonvl)oxvlmethylV-1- WO 2005/028477 PCT/US2004/030735 Pyrrolidinecarboxylate The product of Example 7G (43.7 g, 125 mmol) and triethylamine (25.2 g, 250 mmol) in CH2CI2 (600 mL) were treated with methanesulfonyl chloride (12.6 mL, 163 mmol) over 30 minutes at -10 °C. The solution was allowed to warm to ambient temperature over 1 hour and was monitored by HPLC. When the reaction was completed, it was quenched with water (100 mL). The layers were separated and the aqueous phase was extracted with CH2CI2 (2 x 400 mL). The combined organic phases were washed with brine (2 x 100 mL), dried over Na2SC>4, filtered and the filtrate concentrated under reduced pressure to provide the title compound as a brown oil (52.0 g, 0.12 mol, 97% yield). 1H NMR (CDCI3, 300 MHz) 5 1.46 (s, 9H), 2.80 (m, 1H), 3.08 (s, 3H), 3.40(m, 2H), 3.70 (m, 2H), 4.10 (m, 1H), 4.40 (m, 2H), 4.75 (m, 1H), 5.16 (s, 2H), 7.30 m, 5H); MS (DCI/NH3) m/z 446 (M+NH4)+, 429 (M+H)+. HPLC conditions: HPLC conditions: Zorbax-XDB-C8 column 4.6x250 mm with solvents H20 (0.2v.% HCI04)/MeCN (from v.80:20 to 10:90 within 15 min.) at 1.0 mL/Min., UV detection @220 nm. 20/80, flow rate, 1.0 mL/min; uv 220 nm; t,R=13.1 minutes. Example 71 Benzyl (3S,4S)-3-(amino)-4-{[(methylsulfonyl)oxv1methyl>-1-pyrrolidinecarboxylate trifluroacetate The product of Example 7H (43.7 g, 125 mmol) in CH2CI2 (150 mL) was treated with trifluoroacetic acid (50 mL) at ambient temperature and allowed to stir for 1 h. The reaction was monitored with HPLC. After the reaction went to completion, the mixture was concentrated under reduced pressure to give the title compound in quantitative yield. 1H NMR (CDCI3, 300 MHz) 8 2.80 (m, 1H), 3.15 (s, 3H), 3.40 (m, 1H), 3.70 (m, 3H), 4.10 (m, 1H), 4.05 (m, 1H), 4.44 (m, 2H), 5.16 (s, 2H), 7.30-7.50 (m, 5H); MS (DCI/NH3) m/z 329 (M+H-CF3C02H)\ HPLC conditions: Zorbax-XDB-C8 column 4.6x250 mm with solvents H20 (0.2v.% HCI04)/CH3CN (from v.80:20 to 10:90 within 15 min.) at 1.0 mL/Min., UV detection @220 nm. 20/80, flow rate, 1.0 mL/min; uv 220 nm; tR=8.2 minutes. Example 7J WO 2005/028477 PCT/US2004/030735 Benzyl (1 S,5S)-3,6-diazabicvclor3.2.01heptane-3-carboxylate The product of Example 71 (125 mrriol) was dissolved in ethanol (250 mL) and adjusted to pH -12 with 25% aqueous NaOH. The mixture was warmed to 6(T°C for 1.5 h and monitored via HPLC. After the reaction went to completion, it was allowed to cool down to ambient temperature and used for the next step with the exception of -1 mL which was used for characterization. The -1 mL sample was concentrated under reduced pressure to remove most of the ethanol. The residue was extracted with CHCI3 (2x5 mL). The extracts were combined, washed with brine (3x2 mL) and then passed through a short column of diatomaceous earth. The filtrate was concentrated under reduced pressure to provide the title compound as a yellow oil. 1H NMR (MeOH-d4, 300 MHz) 5 3.30-3.16 (m, 3H), 3.36 (m, 1H), 3.82 (m, 3H), 4.55 (m, 1H), 5.20 (s, 2H), 7.36 (m, 5H); MS (DCI/NH3) m/z 250 (M+NH4)+, 233 (M+H)+. HPLC conditions: Zorbax-XDB-C8 column 4.6x250 mm with solvents H20 (0.2v.% HCI04)/MeCN (from v.80:20 to 10:90 within 15 min.) at 1.0 mL/Min., UV detection @220 nm. 20/80, flow rate, 1.0 mL/min; uv 220 nm; tR=7.2 min. Example 8 tert-Butyl (1 R,5S)-3.6-diazabicyclof3.2.01heptane-6-carboxylate Example 8A 3-Benzyl, 6-tert-butyl-(1R,5S)-3,6-diazabicvclof3.2.0lheptane-3.6-dicarboxvlate To the solution of Example 7J (-125 mmol) was slowly added di-t-butyl dicarbonate (40.9 g, 188 mmol) ethanol (50 mL) solution over 30 min at ambient temperature. The mixture was stirred at ambient temperature for an additional 0.5-1 h with monitoring by HPLC. After the reaction went to completion, it was concentrated under reduced pressure to remove most of the ethanol. The residue was extracted with EtOAc (3 x 500 mL). The extracts were combined, washed with brine (3 x 50 mL) and stirred with KHSO4 (5%, 100 mL) for 10 min. to remove unreacted di-t-butyl dicarbonate. The layers were separated and the organic layer was washed with brine (3 x 50 mL) and passed through a short column of diatomaceous earth. The filtrate was concentrated under reduced pressure to provide the title compound as a yellow oil (40.2 g, 97% three-step yield). 1H NMR WO 2005/028477 PCT/US2004/030735 (MeOH-d4, 300 MHz) 6 1.4(s, 9H), 3.10(m, 2H), 3.30 (m, 1H), 3.45 (m, 1H), 3.90 (d, J=12.2 Hz, 1H), 4.06 (m, 2H), 4.66 (dd, J=6.4, 2.0 Hz, 1H), 5.16 (s, 2H), 7.36 (m, 5H); MS (DCI/NH3) m/z 333 (M+H)+. HPLC conditions: Zorbax-XDB-C8 column 4.6x250 mm with solvents H20 (0.2v.% HCI04)/MeCN (from v.80:20 to 10:90 within 15 min.) at 1.0 mL/Min., UV detection @220 nm. 20/80, flow rate, 1.0 mL/min; uv 220 nm; tR=13.6minutes. Example 8B tert-Butvl(1R,5S)-3,6-diazabicyclor3.2.01heptane-6-carboxvlate The product of Example 8A (40.0 g, 0.120 mol) was dissolved in methanol (400 mL) and treated with Pd/C (10 wt%, 4.0g) under H2 at ambient temperature for 10 h. The reaction was monitored with HPLC. After the reaction was complete, the catalyst was removed by filtration through a short column of diatomaceous earth. The filtrate was concentrated under reduced pressure to provide the title compound as a colorless oil (22.8g, 11.5 mmol, 96% yield). 1H NMR (MeOH-d4, 300 MHz) 5 1.43 (s, 9H), 2.47 (dd, J=12.6, 3.8 Hz, 1H), 2.62 (dd, J=12.2, 5.7 Hz, 1H), 2.96 (m, 1H), 3.05 (d, J=12.2 Hz, 1H), 3.22 (d, J=12.5 Hz, 1H), 3.45 (m, 1H), 3.95 (m, 1H), 4.63 (dd, J=6.1, 3.7 Hz, 1H); MS (DCI/NH3) m/z 199 (M+H)+. HPLC conditions: Zorbax-XDB-C8 column 4.6x250 mm with solvents H20 (0.2v.% HCI04)/MeCN (from v.80:20 to 10:90 within 15 min.) at 1.0 mL/Min., UV detection @ 220 nm. 20/80, flow rate, 1.0 mL/min; uv 220 nm; tR=8.6 minutes. Example 9 Benzyl (1 R,5R)-3,6-diazabicvclof3.2.01heptane-3-carboxvlate The product of Example 7E was processed according to the procedure of Example 7F, substituting (S)-mandelic acid for the (R)-mandelic acid therein. The resulting material was processed according to the procedures of Examples 7G, 7H, 71, and 7J to provide the title compound: 1H NMR (MeOH-d4, 300 MHz) 5 3.30-3.16 (m, 3H), 3.36 (m, 1H), 3.82 (m, 3H), 4.55 (m, 1H), 5.20 (s, 2H), 7.36 (m, 5H); MS (DCI/NH3) m/z 250 (M+NH4)+, 233 (M+H)+. Example 10 WO 2005/028477 PCT/US2004/030735 tert-Butyl (1 S,5R)-3,6-diazabicyclor3.2.Q1heptane-6-carboxylate The product of Example 9 was treated with di-t-butyl dicarbonate, then Pd/C under a hydrogen atmosphere according to the procedures of Example 8A and 8B, to provide the title compound. 1H NMR (MeOH-d4, 300 MHz) 1.43 (s, 9H), 2.47 (dd, J=12.6, 3.8 Hz, 1H), 2.62 (dd, J=12.2, 5.7 Hz, 1H), 2.96 (m, 1H), 3.05 (d, J=12.2 Hz, 1H), 3.22 (d, J=12.5 Hz, 1H), 3.45 (m, 1H), 3.95 (m, 1H), 4.63 (dd, J=6.1, 3.7 Hz, 1H); MS (DCI/NH3) m/z 199 (M+H)+. i Example 11 Benzyl 2,6-diazabicyclof3.2.1"|octane-6-carboxvlate Example 11A Benzyl 3-oxo-2,6-diazabicyclof3.2.1]octane-6-carboxylate Benzyl 5-oxo-2-azabicyclo[2.2.1]heptane-2-carboxylate (2.46 g, 10.0 mmol), prepared according to the procedures described by (Carroll, F. I.; et. al., J. Med. Chem. (1992) 35, 2184), in 50 mL of 95% aqueous ethahol at ambient temperature was treated with sodium acetate (2.47 g, 30.1 mmol) and hydroxylamine hydrochloride (3.48 g, 50.1 mmol). After 45 minutes, the mixture was concentrated under reduced pressure and the residue was diluted with saturated aqueous NaHC03 and extracted with EtOAc. The organic extract was dried (MgS04) and concentrated to afford 2.50 grams (96%) of a mixture of the desired oximes as a white solid. A portion of this material (1.57 g, 6.03 mmol) was stirred in a 5:1 solution of CH2CI2/trimethylsilylpolyphosphate for 12 hours at ambient temperature. The solution was diluted with H2O and extracted twice with EtOAc. The combined organic extracts were dried (MgSCU) and concentrated under reduced pressure. The residue was purified by chromatography (silica gel; 95:5 C^Cb/MeOH) to provide 1.08 grams (68%) of the title compound as a white solid. MS (DCI/NH3) m/z 261 (M+H)\ 278 (M+NH4V Example 11B benzyl 2,6-diazabicyclof3.2.1 foctane-6-carboxylate _70_ WO 2005/028477 PCT/US2004/030735 The product from example 11A (800 mg, 3.07 mmol) in THF (12 ml_) at 0 °C was treated dropwise with a 2.0 M solution of borane-methyl sulfide complex in THF (3.4 mL, 6.8 mmol). The solution was stirred for 14 hours at ambient temperature, then recooled to 0 °C and quenched by the careful addition of MeOH and concentrated under reduced pressure. The residue was dissolved in toluene (12 mL) and treated with n-propylamine (1.7 mL). The mixture was stirred for 3 hours at 60 °C, allowed to cool to ambient temperature, and concentrated under reduced pressure. The residue was diluted with saturated aqueous NaHCC>3 and extracted with CH2CI2 (4X). The organic extracts were combined, dried (K2C03), and concentrated. The residue was purified by chromatography (silica gel; 90:10:1 CH2CI2/MeOH/NH4OH) to provide 453 mg (60%) of the title compound as a colorless oil. MS (DCI/NH3) m/z 247 (M+H)+. Example 12 tert-butvli2,6-diazabicvclof3.2.Hoctane-2-carboxvlate The product from Example 11B (140 mg, 0.568 mmol) in CH2CI2 at ambient temperature was treated with triethylamine followed by di-tert-butyl dicarbonate. The solution was stirred for 2 hours, diluted with saturated aqueous K2CO3, and extraced with CH2CI2 (2X). The organic extracts were combined, dried (Na2SC>4), and concentrated under reduced pressure to provide 190 mg a colorless oil. A suspension of the oil and 10% Pd/C (20 mg) in MeOH (10 mL) were stirred under one atmosphere of hydrogen (balloon) for 6 hours. The catalyst was removed by filtration through a plug of Celite (CH2CI2 wash). The filtrate was concentrated to provide (106 mg, 91%) the title compound as a colorless oil. MS (DCI/NH3) m/z 213 (M+H)+, 230 M+NH4)+. Example 13 9-Methvl-3,9-diazabicvclo[4.2.nnonane The title compound was prepared as described in U.S. Patent 2,999,091. Example 14 tert-butyl (3aR,6aR)-hexahvdropyrrolof3,4-blpvrrole-1(2H)-carboxvlate WO 2005/028477 PCT/US2004/030735 Example 14A ethyl ([1R)-1 –phenvlethvllaminolacetate Ethyl bromoacetate (4.14 g; 24.8 mmol) was treated with (R) oc-methylbenzylamine (3 g, 24.8 mmol) and ethyldiisopropylamme (3.2 g; 24.8 mmol) in toluene (100 mL). After heating at reflux for 18 hours, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by flash chromatography (Si02, 20% ethyl acetate/pentane) to provide the title compound (3.2 g, 63% yield). MS (DCI/NH3) m/z 208 (M+H)+. Example 14B {f(1 R)-1-phenylethyllamino)acetic acid The product from Example 14A (4.5 g; 15.6 mmol) in water (100 mL) was heated to reflux for 18 hours. The mixture was cooled to 30 °C and concentrated under reduced pressure to provide the title compounds as a white solid (2.7 g; 80% yield). MS (DCI/NH3) m/z 180 (M+H)+. Example 14C ethyl cis-l-rdRM-phenvlethynhexahydropyrrolofS^-blpyrrole-SdHVcarboxylate The product from Example 14B (27.5 g, 154 mmol) and ethyl allyl(2-oxoethyl)carbamate (26.3 g, 154 mmol), prepared as described in (US 5071999), in toluene (500 mL) were heated at reflux for 17 hours. The solvent was evaporated under reduced pressure to provide the crude product (45 g) as a nearly 1:1 mixture of diastereomers. These were separated by flash chromatography on silica gel, eluting with 30% ethyl acetate in pentane. The more mobile diastereomer was obtained as a thick syrup (Rf = 0.42, pentane:ethyl acetate (3:7) 17 g, 38% yield). The stereocenters were determined to be (R,R) using X-Ray diffraction as described in Example 14E. MS (DCI/NH3) m/z 289 (M+H)+. The less mobile diastereomer was obtained as a thick syrup (Rf = 0.21, pentane:ethyl acetate (3:7) 17.8 g, 40% yield). The stereocenters were determined to be (S,S) using X-Ray diffraction as described in Example 15B. MS (DCI/NH3) m/z 289 (M+H)+. WO 2005/028477 PCT/US2004/030735 Example 14D (3aR,6aR)-1 -f(1 R)-1 -phenvlethvnoctahvdropvrrolor3,4-b1pyrrole The more mobile diastereomer from Example 14C (17 g, 59.0 mmol) in hydrochloric acid (12N, 200 mL) was heated in an oil bath at 120 °C for 20 hours. The mixture was cooled to 20 °C and concentrated under reduced pressure to remove excess HCI. The residue was taken in 10% Na2C03 (100 mL) and extracted with CH2CI2 (3 x 200 mL). The organic layers were combined, washed with brine, dried (Na2C03), and concentrated. The residue was purified by chromatography (Si02, eluted with CH2CI2:MeOH:NH4OH; 90:10:1) to afford the title compound as a brownish oil (11.4 g, 89% yield). MS (DCI/NH3) m/z 217 (M+H)+. Example 14E (3aR,6aR)-5-r(4-nitrophenvl)sulfonvn-1-f(1R)-1-phenylethvlloctahydropvrrolor3,4- blpyrrole The product from Example 14D was processed as described in Example 15B to provide the title compound. The stereocenters were determined to be (R,R) using X-ray diffraction as described in Example 15B. Example 14F (3aR,6aR)-1-f(1R)-1-phenvlethvn-5-(trifluoroacetvl)octahvdropvrrolof3,4-b1pyrrole The product from Example 14D (11.3 g, 52 mmol) and triethylamine (6.8 g, 68 mmol) in anhydrous THF (200 mL) at 0-5 °C was treated with trifluoroacetic anhydride (25.2 g, 63 mmol) dropwise. The reaction mixture was allowed to warm to room temperature overnight. The THF was removed under reduced pressure and replaced with CH2CI2 (200 mL). The methylene chloride was washed with brine, dried (MgS04), and concentrated. The residue was purified using chromatography (Si02, eluting with 5-15% ethyl acetate/hexanes) to provide the title compound as a light yellow oil (13.7 g, 84% yield). MS (DCI/NH3) m/z 313 (M+Hf. Example 14G WO 2005/028477 PCT/US2004/030735 tert-butvl(3aR,6aR)-5-(trifluoroacetvl)hexahvdropvrrolor3,4-b1pyrrole-1f2H)- cjutoxyjate The product from Example 14F (11.2 g; 35.8 mmol) and di-tert-butyl dicarbonate (8.58 g, 39.4 mmol) in methanol (400 mL) was treated with 10% Pd/C (0.6 g). The mixture was shaken under an atmosphere of hydrogen (4 atm) at 25 °C for 18 hours. After filtration, the solution was concentrated under reduced pressure and the residue was purified by chromatography (Si02, 2:1 ethyl acetate.-hexanes) to provide the title compound as a crystalline solid (9.88 g, 89% yield). MS (DCI/NH3) m/z 326 (M+NH4)+. Example 14H tert-butvl (3aR,6aR)-hexahvdropyrrolof3,4-b1pvrrole-1(2H)-carboxvlate The product from Example 14G (9.88 g, 32 mmol) in methanol (200 mL) and water (40 mL) was treated with solid potassium carbonate (4.86 g; 35 mmol). After stirring at 20 °C for 18 hours, the solvent was removed under reduced pressure. The residue was azeotroped with ethyl acetate (50 mL) twice and finally with toluene (100 mL). The dry powder was stirred with 20% MeOH/CH2CI2 (100 mL), filtered, and the filtercake was rinsed with 20% MeOH/CH2CI2 (100 mL). The filtrate was concentrated to provide the title compound as a white solid. MS (DCI/NH3) m/z 213 (M+H)+. Example 15 (tert-butvl (3aS,6aS)-hexahvdropvrrolor3,4-b1pyrrole-1(2H)-carboxylate Example 15A (3aS,6aS)-1-r(1R)-1-phenvlethvnoctahydropyrrolor3,4-b1pvrrole The less mobile diastereomer from Example 14C was processed as described in Example 14D to provide the title compound as a brownish oil (11.3 g,76% yield). MS (DCI/NH3) m/z 217 (M+H)+. Example 15B WO 2005/028477 PCT/US2004/030735 (3aS,6aS)-5-K4-nitrophenvl)sulfonvn-1-[(1R)-1-phenvlethvnoctahvdropyrrolor3,4- blpyrrole The product from Example 15A (148 mg, 0.68 mmol) and triethyl amine (0.15 mL, 1.08 mmol) in dichloromethane (5 mL) at 0 °C was treated with 4-nitrobenzenesulfonyl chloride (166 mg, 0.75 mmol) in dichloromethane (2 mL) over 1 minute. The reaction mixture was allowed to warm to room temperature. After 1 hour, the mixture was diluted with dichloromethane (20 mL) and washed with 5% NaHC03 (10 mL), brine (10 mL), dried (MgS04) and concentrated under reduced pressure to provide the title compound as a light yellow solid (270 mg, 98%). Single crystals suitable for x-ray diffraction were grown by slow evaporation from ethyl acetate solution. Crystal data: MW=401.48, C20H23N3O4S, crystal dimensions 0.60X0.10X0.10 mm, orthorhombic, P212121 (#19), a=5.4031(5), b=16.168(2), c=22.687(2) A, V=1981.8(3) A3, Z=4, Dcaic=1.345 g/crrf3. Crystallographic data were collected using Mo K D radiation (0=0.71069 A). Refinement of the structure using full matrix least squares refinement of 253 parameters on 2005 reflections with !>3.00D(I) gave R=0.117, Rw=0.123. Example 15C (3aS,6aS)-1-[(1R)-1-Phenvlethvn-5-(trifluoroacetvl)octahvdropvrrolo[3,4-b1pyrrole The product from Example 15A (11.3 g, 52 mmol) was processed as described in Example 14F to provide the title compound (11.2 g, 69% yield). MS (DCI/NH3)m/z313(M+H)+. Example 15P tert-butvl(3aS,6aS)-5-(trifluoroacetvl)hexahvdropvrrolo[3,4-blpyrrole-1(2H)- carboxylate The product from example 15C was processed as described in Example 14G to provide the title compound (97% yield). MS (DCI/NH3) m/z 326 (M+NH4)+. Example 15E tert-butvl (3aS,6aS)-hexahvdropvrrolo[3.4-b1pyrrole-1(2H)-carboxylate -75- WO 2005/028477 PCT/US2004/030735 The product from Example 15D was processed as described in the Example 14H to provide the title compound. Example 16 tert-butvl (3aR,6aRVhexahvdropyrrolof3.4-blpvrrole-5-carboxvlate The product of Example 14D was treated with di-t-butyl dicarbonate, then hydrogenated over palladium according to US 5,071,999 (Example 3) to provide the title compound. Example 17 tert-butvl (3aS,6aS)-hexahvdropvrrolo(3,4-blpvrrole-5-carboxvlate The product of Example 15A was processed as described in Example 16 to provide the title compound. Example 18 (1R.6SV3,8-Diaza-bicyclo[4.2.01octane-3-carboxvlic acid tert-butvl ester To the minor isomer product of Example 3E (2.4 g, 7.5 mmol) in 30 mL CH3OH was added 0.58 g of 20% Pd(OH)2/C (wet). This mixture was shaken under 60 psi of H2 for 16.5 h at 50 °C. The mixture was filtered, concentrated to proved the title compound, suitable for use without further purification. MS (DCI/NH3) m/z 213 (M+H)+. Example 19 (1S,6R)-3,8-Diaza-bicyclo|,4.2.0loctane-3-carboxvlic acid tert-butvl ester The major product from Example 3E was processed according to the procedure of Example 18 to provide the title compound: MS (DCI/NH3) m/z 213 (M+H)+. Example 20 6a-Methvl-octahvdro-pvrrolo[3,4-blpyrrole Example 20A -76- 1 WO 2005/028477 PCT/US2004/030735 N-Allvl-N-(2-hvdroxvpropyl)-carbamic acid benzyl ester The product of Example 7C (13.2 g, 56.6 mmol) in THF (100 ml_) was treated with MeMgBr (3M in THF, 24.5 mL, 73.5 mmol) at -78 DC over 2 hours. The mixture was then warmed to ambient temperature. The reaction was quenched with saturated, aqueous NH4CI solution (50-mL) at 0 °C, the layers were separated and the aqueous layer was extracted with EtOAc (3 x 200 mL). The organic layers were combined and concentrated under reduced pressure. The residues were purified by column chromatography (Si02, 40% hexanes - ethyl acetate) to give the title compound (6.48 g, 26 mmol, 46% yield). 1H NMR (CDCI3, 300 MHz) 5 1.16 (d, J=6.4 Hz, 3H), 3.14-3.41 (m, 2H), 3.83-4.09 (m, 3H), 5.02-5.22 (m, 4H), 5.69-5.90 (m, 1H), 7.20-7.40 (m, 5H); MS (DCI/NH3) m/z 250 (M+H)+', 267 (M+NH4)+. Example 20B N-Allyl-N-(2-oxo-propyl)-carbamic acid benzyl ester Dimethylsulfoxide (DMSO, 4.7g, 60.1 mmol) was added slowly into a solution of oxalyl chloride (3.82 g, 30.1 mmol) in CH2CI2 (150ml) at -78 °C. After the addition was complete, the mixture was stirred for 15 minutes. The product of Example 20A (6.25 g , 25.1 mmol) in CH2CI2 (20 mL) was added to the above mixture at -78 °C. After the mixture was stirred for 30 minutes, triethylamine (12.6 g, 125 mmol) was added. The reaction mixture was then warmed slowly to ambient temperature. After the reaction was complete, it was quenched with water (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3 x 200 ML). The extracts were combined and concentrated under reduced pressure. The residue was purified by column chromatography (Si02,40% hexanes - ethyl acetate) to give the title compound (4.3 g, 17.4 mmol, 70% yield). 1H NMR (CDCI3. 300 MHz) 5 2.05 (s, 1.4 H), 2.14 (s, 1.6H), 3.91-4.08 (m, 4H), 5.06-5.21 (m, 4H), 5.68-5.86 (m, 1H), 7.25-7.40 (m, 5H); MS (DCI/NH3) m/z 248 (M+H)+, 265 (M+NH4)+. Example 20C 1-Benzvl-6a-methvl-hexahydro-pvrrolo[3,4-blpvrrole-5-carboxvlic acid benzyl ester The product of Example 20B (3.0g, 12.1 mmol) was treated with benzylaminoacetic acid (Aldrich, 2.0g, 12.1 mmol) in toluene (50 mL) at 110 °C over WO 2005/028477 PCT/US2004/030735 2 days. The toluene was removed under reduced pressure and the residue was purified by column chromatography (Si02, 40% hexanes - ethyl acetate) to give the title compound (2.8 g, 8.0 mmol, 66% yield). 1H NMR (MeOH-d4, 300 MHz) 5 1.23 (s, 3H), 1.49-1.64 (m, 1H), 1.93-2.10 (m, 1H), 2.36-2.51 (m, 1H), 2.56-2.67 (m, 1H), 2.73-2.87 (m, 1H), 3.10 (d, J=11.5Hz, 1H), 3.32-3.41 (m, 1H), 3.52 (d, J=13.2 Hz, 1H), 3.58-3.78 (m, 3H), 5.03-5.22 (m, 2H), 7.14-7.42 (m, 10H); MS (DCI/NH3) m/z 351 (M+H)+. Example 20D 1-Benzvl-6a-methvl-octahvdro-pyrrolo[3,4-blpvrrole The product of Example 20C (1.7 g, 4.85 mmol) was treated with Pd/C (10 wt%, 300mg) i-PrOH (50 mL) at ambient temperature under 1 atm of H2 for 18 h. After the reaction went completion, the catalyst was filtered off and the filtrate was concentrated under reduced pressure to give the title compound (0.7 g, 3.2 mmol, 66% yield). 1H NMR (MeOH-d4, 300 MHz) 5 1.23 (s, 3H), 1.32-1.46 (m, 1H), 1.94-2.07 (m, 1H), 2.23-2.39 (m, 2H), 2.46-2.56 (m, 1H), 2.66-2.75 (m, 2H), 2.95-3.04 (m, 2H), 3.62 (d, J=12.9 Hz, 1H), 3.73 (d, J=12.9 Hz, 1H), 7.13-7.37 (m, 5H); MS • (DCI/NH3)m/z217(M+H)+. Example 20E 1-Benzyl-6a-methvl-hexahvdro-pvrrolof3,4-blpvrrole-5-carboxylic acid tert-butyl ester The product of Example 20D (700 mg, 3.24 mmol) was treated with di-tert-butyl dicarbonate (706 mg, 3.24 mmol) and Et3N (2 mL) in CH2CI2 (10 mL) for 16 hours. The mixture was then concentrated under reduced pressure and purified by column chromatography (Si02, 40% hexanes - ethyl acetate) to give the title compound (1.02 g, 3.24 mmol, 100% yield). 1H NMR (MeOH-d4, 300 MHz) 5 1.22 (s, 3H), 1.47 (s, 9H), 1.49-1.62 (m, 1H), 1.94-2.11 (m, 1H), 2.34-2.46 (m, 1H), 2.57-2.68 (m, 1H), 2.73-2.87 (m, 1H), 3.02 (d, J=11.5 Hz, 1H), 3.21-3.27 (m, 1H), 3.50-3.74 (m, 4H), 7.15-7.32 (m, 5H); MS (DCI/NH3) m/z 317 (M+H)+. Example 20F WO 2005/028477 PCT/US2004/030735 6a-Methvl-hexahvdro-pvrrolor3,4-blpyrrole-1.5-dicarboxvlic acid 1-benzyl ester 5-tert- butyl ester The product of Example 20E (1.02 g, 3.24 mmol) was treated with Pd/C (10 wt%, 100 mg) in MeOH (50 mL) under 1 atm. H2 at 50 °C for 16 hours. The reaction mixture was cooled to ambient temperature. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. The residue was treated with CbzCI (0.5 mL, 3.5 mmol) and Et3N (3 mL) in CH2CI2 (20 mL) at 0 °C for 2 h. After the reaction was complete, it was quenched with water (5 mL) and extracted with CH2CI2 (3 x 20 mL). The extracts were combined and concentrated under reduced pressure. The residue was purified by column chromatography (Si02,40% hexanes - ethyl acetate) to give the title compound (0.87 g, 2.42 mmol, 75% yield). 1H NMR (MeOH-d4, 300 MHz) 5 1.36-1.50 (m, 13H), 1.67-1.80 (m, 1H), 1.98-2.14 (m, 1H), 2.53-2.68 (m, 1H), 3.14-3.32 (m, 2H), 3.49-3.68 (m, 3H), 5.09 (s, 2H), 7.22-7.42 (m, 5H). Example 20G 6a-Methvl-hexahydro-pyrrolof3.4-blpyrrole-1-carboxylic acid benzyl ester The product of Example 20F (0.8 g, 2.22 mmol) was treated with TFA (5 mL) in CH2CI2 (10 mL) at ambient temperature for 1 h. The mixture was then concentrated under reduced pressure and the residue was purified by column chromatography (Si02, 90 : 9 :1 CH2CI2 : MeOH : NH4OH) to give the title compound (0.32 g, 1.23 mmol, 55% yield). 1H NMR (MeOH-d4, 300 MHz) 5 1.42,1.47 (s, 3H, rotamers), 1.63-1.75 (m, 1H), 1.98-2.13 (m, 1H), 2.37-2.52 (m, 1H), 2.62-2.76 (m, 2H), 3.00-3.12 (m, 1H), 3.26, 3.47 (d, J=12.6 Hz, 1H, rotamers), 3.53-3.62 (m, 2H), 5.08, 5.13 (s, 2H, rotamers), 7.25-7.42 (m, 5H); MS (DCI/NH3) m/z 261 (M+H)+. Example 21 Hexahydro-pvrrolo|"3,4-c1pyrrole-3a-carboxvlic acid ethyl ester Example 21A 2,5-Dibenzvl-hexahvdro-pyrrolof3,4-clpyrrole-3a-carboxylic acid ethyl ester WO 2005/028477 PCT/US2004/030733 To the ethyl propynoate (Aldrich, 3.96 g, 40 mmol) in THF (200 mL) in a 3-neck, 3-L round bottom flask equipped with an addition funnel, internal thermometer, and N2 inlet at 0 °C was added trifluoroacetic acid (TFA) (Aldrich, 0.3 mL, 4 mmol). Benzyl(methoxymethyl)trimethylsilylmethylamine (Aldrich, 23.7 g, 100 mmol) in 50 mL THF was added dropwise via addition funnel over 30 minutes with the reaction temperature being maintained below 5 °C. After the addition was complete, the mixture was allowed to warm slowly to ambient temperature and then was stirred for 10 h. The mixture was concentrated and the residue was dissolved in 500 mL EtOAc. It was washed with 2 X 50 mL saturated NaHC03 and 25 mL brine, dried over Na2S04, and concentrated under reduced pressure. The residue was purified by column chromatography (Si02,50% hexanes-EtOAc) to give 14.5 g of the title compound (36.6 mmol, 91% yield). MS (DCI/NH3) m/z 365 (M+H)+. Example 21B Hexahvdro-pvrrolor3,4-c]pvrrole-3a-carpoxylic acid ethyl ester To the product of Example 21A (1.0 g, 2.75 mmol) in EtOH (10 mL) was added Pd(OH)2/C (Aldrich, 20% wet, 0.20 g). This mixture was hydrogenated for 2.5 h under H2 at 50 °C. The mixture was filtered and concentrated to give the title compound (0.50 g, 2.71 mmol, 99% yield). 1H NMR (CDCI3, 300 MHz) D 1.26 (t, J=7.1 Hz, 3 H), 2.67 (dd, J=11.5, 4.4 Hz, 2 H), 2.79 (d, J=11.9 Hz, 2 H), 2.87 - 3.03 (m, 1 H), 3.10 (dd, J=11.5, 7.8 Hz, 2 H),4.17 (q, J=7.1 Hz, 2 H); MS (DCI/NH3) m/z 185 (M+H)+. Example 22 Cis-3-methvl-3,8-diazabicyclo|4.3.01nonane Example 22A 2-Benzvl-hexahydro-cvclopenta[c1pvrrol-4-one A 3-neck, 1-L round bottom flask equipped with an addition funnel, internal thermometer, and N2 inlet at RT was charged with cyclopentenone (16.48 g, 0.20 mol) in 0.5 L of CH2CI2. Benzyl(methoxymethyl)trimethylsilylmethylamine (5.0 grams, 21 mmol) and trifluoroacetic acid (TFA) (1.07 mL, 13.9 mmol) were added. To this -80- WO 2005/028477 PCT/US2004/030735 mixture was added additional benzyl(methoxymethyl)-trimethylsilylmethylamine (40 g, 0.168mol) dropwise via addition funnel over 1 hour with the reaction temperature being maintained below 25 °C (water bath). After the addition was complete, the mixture was stirred for 4 h. The mixture was washed with 1 X 100 mL 10% Na2C03. The layers were separated and the organic layer was washed with 1 X 100 mL 23% NaCI. The organic extract was concentrated under reduced pressure to give an oil. The oil was redissolved in methyl-t-butyl ether (250 mL) and extracted into 1M H3PO4 (200 mL). The aqueous layer was basified with 50% NaOH to pH 12. The product was extracted with methyl-t-butyl ether (250 mL). The layers were separated and the organic layer was washed with 23% NaCI. The layers were separated. The organic layer was charged with acetonitrile (50 mL) and silica gel (10 gms). The mixture was stirred 5 minutes and filtered through a silica gel pad (10 grams). The filtrate was concentrated to give the title compound (35.0 grams,81.4% of theory), which was carried on to the next step without further purification. MS (ESI/APCI) m/z 216(M+H)+. Example 22B 2-Benzyl-hexahydro-cyclopentafc|pyrrol-4-one oxime To the ketone from Example 22A (32.4 grams, 150 mmol) in a 1-L round bottom flask equipped with an condenser and an N2 inlet was added EtOH (absolute, 375 mL). To this solution was added a solution comprised of hydroxylamine hydrochloride (13.08 g, 190 mmol) and NaOAc in water (40 mL). The reaction mixture was heated at 65 °C for 1 h until TLC showed the reaction was complete (5:1 MTBE/CH3CN w/ 0.1 % Et3N; PMA char; Rf SM 0.75, Rf 0.3 and 0.4 for oxime isomers). The reaction mixture was concentrated in vacuo to dryness. The residue was extracted with MTBE (200 mL) and water (200 mL). The biphasic mixture was treated with 50% NaOH solution until the pH of the solution was >12. The MTBE layer was washed with 23% NaCI solution (1X50 mL). The layers were separated and the organic layer was concentrated in vacuo to afford 34 g of crude material. The residue was dissolved in MTBE (25 mL) and pentane (40 mL) and seeded with ~ 10 mg of authentic seeds. The mixture was stirred and swirled occasionally for 20 minutes and filtered. The cake was washed with 2:1 pentanes-MTBE (3X25 mL). -81- WO 2005/028477 PCT/US2004/030735 The solid was dried in a vacuum oven to a constant weight of 11.4 grams (33%). The solid was primarily one geometrical isomer of the oxime. MS (ESI) m/z 231 (M+H)+. Example 22C 2-Benzvl-octahydro-pvrrolo[3.4-c1pvridin-4-one A 500 mL, 3-neck, round bottom flask was charged with the syn-oxime from Example 22B (12.0 g, 51.9 mmol) and polyphosphoric acid (120 g). The flask was purged with ^/vacuum 3 times. The thick mixture was heated for 1.25 h at 100 °C. The mixture was cooled to rt and poured onto ice (240 g). The mixture was adjusted to pH = 12 with 25 % NaOH and extracted with EtOAc (150mL). The layers were separated and the aqueous layer was washed with 1X100 mL EtOAc. The organic layers were combined and washed with 1X 50mL of 23% aq. NaCI. The residue was concentrated in vacuo to afford 11 g of an oil. The oil was dissolved in MTBE (40mL) and treated with ~ 10 mg of seed crystals, followed by pentane (15 mL). The resulting slurry was stirred for 30 minutes, filtered and washed with 2:1 MTBE-pentanes. The solid was dried to a constant weight of 6.4 grams. MS (CI) m/z 231 (M+H)+. Example 22D 2-Benzyl-octahydro-pyrrolof3,4-c1pyridine To a solution of the lactam from Example 22C (0.46 g) in THF (5 mL) was added 1M LiAIH4 (4.0 mL). The mixture was heated at 50 °C for 2 h, cooled to 15 °C, and quenched by cautious addition of water (0.15 mL), followed by 15% NaOH (0.15 mL), then water (0.456 mL). The mixture was stirred for 5 minutes and filtered and washed with THF (3X5 mL). The filtrate was concentrated in vacuo to afford 442 mg of the title compound as a clear oil (quantitative yield). MS (CI) m/z 217 (M+H)+; 1H NMR: 5 1.8 - 1.5 (m, 3H), 2.33 - 2.10 (m, 2H), 2.8 - 2.4 (m, 8H), 3.75 (s, 2H), 7.25 ppm (m, 5H). Example 23 3,8-Diaza-bicvclof3.2.1loctane-3-carboxylic acid tert-butvl ester -82- WO 2005/028477 PCT/US2004/030735 Example 23A 8-Benzyl-3,8-diaza-bicvclor3.2.1loctane-3-carboxylic acid tert-butyl ester Di-tert-butyl dicarbonate (0.79 g, 3.6 mmol) was added to a mixture of the product of Example 1F (0.70 g, 3.5 mmol) in tetrahydrofuran (30 ml_).and saturated, aqueous NaHCCb (5 mL). This mixture was stirred at ambient temperature for 18 h then diluted with H20 (10 mL) and EtOAc (15 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3x5 mL). The combined extract was dried over anhydrous Na2S04, concentrated and purified by column chromatography (Si02, 50% hexanes in EtOAc) to provide the title compound (0.62 g, 59% yield). MS (DCI/NH3) m/z 303 (M+H)+. Example 23B 3,8-Piaza-bicvclof3.2.1)octane-3-carboxylic acid tert-butyl ester A solution of the product of Example 23A (0.62 g. 0.12 mmol) in EtOH (10 mL) was stirred with Pd/C (Aldrich, 60 mg, 10 wt%) under 1 atmosphere of H2 (balloon) for 18 h. The mixture was filtered, concentrated and purified by column chromatography (Si02,1% NH4OH : 9% CH3OH : 90% CH2CI2) to provide the title compound (0.44 g, 100% yield). MS (DCI/NH3) m/z 213 (M+H)+. Example 24 6-Benzyl-2,6-diaza-bicyclor3.2.01heptane Example 24A (2S, 3S)-3-Hvdroxy-pyrrolidine-1,2-dicarboxylicacid 1-tert-butyl ester 3-Hydroxy-pyrrolidine-2-carboxylic acid (Aldrich, 1.31 g, 10 mmol) was treated with di-tert-butyl dicarbanate (Aldrich, 2.18 g, 10 mmol) and NaOH (5%, 20 mL, 25 mmol) at room temperature for 2 hours. The mixture was acidified with 5% HCI solution at 0-10 °C to bring to pH=4. The mixture was extracted with EtOAc (3 x 50 mL). The extracts were combined and washed with brine (2x10 mL). The organic solution was concentrated under vacuum to give the title compound as white solid (2.0 g, 8.6 mmol, 86% yield). 1H NMR (300 MHz, CH3OH-d4) 5 1.40 -1.49 (m, 9 H), 1.82 -1.93 -83- J— WO 2005/028477 PCT/US2004/030735 (m, 1 H), 1.97 - 2.12 (m, 1 H), 3.46 - 3.60 (m, 2 H), 4.07 - 4.18 (m, 1 H), 4.38 (dd, J=4.2, 1.9 Hz, 1 H); MS (DCI/NH3) m/z 232 (M+H)+. Example 24B (2R, 3S)-3-Hvdroxv-2-hydroxvmethvl-pvrrolidine-1-carboxylic acid tert-butyl ester -The product of Example 24A (2.0 g, 8.6 mmol) was treated with BH3 (Aldrich, 1M, in THF, 17 mL, 17 mmol) in THF (50 mL) at 65 °C for 1 h. The mixture was cooled and quenched with methanol (5 mL) at 0-10 °C, then concentrated under reduced pressure. The residue was treated with saturated NaHC03 solution (15 mL) and stirred for additional 1 h. The slightly yellow mixture was extracted with EtOAc (3 x 50 mL). The extracts were combined, washed with brine (2 x 10 mL), and then concentrated under vacuum to give 1.8 gram title compound as white solid (8.25 mmol, 96% yield). 1H NMR (300 MHz, CH3OH-d4) 5 1.47 (s, 9 H), 1.76 - 1.88 (m, 1 H), 2.03 - 2.19 (m, 1 H), 3.33 - 3.58 (m, 3 H), 3.59 - 3.71 (m, 2 H), 4.30 (dd, J=15.8, 3.6 Hz, 1 H); MS (DCI/NH3) m/z 218 (M+H)+. Example 24C (2R, 3S)-3-Methanesulfonvloxv-2-methanesulfonyloxvmethvl-pvrrolidine-1- carboxylic acid tert-butyl ester The product of Example 24B (1.8 g, 8.25 mmol)was treated with methanesulfonyl chloride (Aldrich, 2.37 g, 20.7 mmol) and triethylamine (3.3 g, 33.1 mmol) in methylene chloride (50 mL) at 0°C for 4 h. The mixture was concentrated and the residue was diluted with ethyl acetate (100 mL), washed with saturated NaHCOa (3 x 10 mL) and brine (2x10 mL). The organic solution was concentrated and the residue was purified by column chromatography (SiC>2, hexanes:EtOAc = 40:60, v.) to provide the title compound (3.0g, 8.0 mol, 97% yield). 1H NMR (300 MHz, CH3OH-d4) 8 1.45 - 1.54 (s, 9 H), 2.14 - 2.28 (m, 1 H), 2.28 - 2.46 (m, 1 H), 3.08 - 3.19 (m, 6 H), 3.51 (dd, J=9.8, 5.8 Hz, 2 H), 4.19 (s, 1 H), 4.25 - 4.46 (m, 2 H), 5.24 (s, 1 H); MS (DCI/NH3) m/z 374 (M+H)+. Example 24D (2R, 5R)-6-Benzyl-2,6-diaza-bicvclof3.2.01heptane-2-carboxylic acid tert-butyl ester -84- WO 2005/028477 PCT/US2004/030735 Example 23A 8-Benzyl-3,8-diaza-bicvclo[3.2.noctane-3-carboxylic acid tert-butvl ester Di-tert-butyl dicarbonate (0.79 g, 3.6 mmol) was added to a mixture of the product of Example 1F (0.70 g, 3.5 mmol) in tetrahydrofuran (30 ml_).and saturated, aqueous NaHC03 (5 mL). This mixture was stirred at ambient temperature for 18 h then diluted with H20 (10 mL) and EtOAc (15 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3x5 mL). The combined extract was dried over anhydrous Na2S04, concentrated and purified by column chromatography (Si02, 50% hexanes in EtOAc) to provide the title compound (0.62 g, 59% yield). MS (DCI/NH3) m/z 303 (M+H)Example 23B 3,8-Diaza-bicyclor3.2.1]octane-3-carboxylic acid tert-butyl ester A solution of the product of Example 23A (0.62 g. 0.12 mmol) in EtOH (10 mL) was stirred with Pd/C (Aldrich, 60 mg, 10 wt%) under 1 atmosphere of H2 (balloon) for 18 h. The mixture was filtered, concentrated and purified by column chromatography (Si02,1 % NH4OH : 9% CH3OH : 90% CH2CI2) to provide the title compound (0.44 g, 100% yield). MS (DCI/NH3) m/z 213 (M+H)+. Example 24 6-Benzyl-2,6-diaza-bicyclo[3.2.01heptane Example 24A (2S, 3S)-3-Hvdroxv-pvrrolidine-1,2-dicarboxvlic acid 1-tert-butvl ester 3-Hydroxy-pyrrolidine-2-carboxylic acid (Aldrich, 1.31 g, 10 mmol) was treated with di-tert-butyl dicarbanate (Aldrich, 2.18 g, 10 mmol) and NaOH (5%, 20 mL, 25 mmol) at room temperature for 2 hours. The mixture was acidified with 5% HCI solution at 0-10 °C to bring to pH=4. The mixture was extracted with EtOAc (3 x 50 mL). The extracts were combined and washed with brine (2x10 mL). The organic solution was concentrated under vacuum to give the title compound as white solid (2.0 g, 8.6 mmol, 86% yield). 1H NMR (300 MHz, CH3OH-d4) 5 1.40 - 1.49 (m, 9 H), 1.82 - 1.93 -83- WO 2005/028477 PCT/US2004/030735 The product of Example 24C (3.0 g, 8 mmol) was treated with benzyl amine (Aldrich, 2.67 g, 25 mmol) in toluene (50 mL) at 110 °C for 16 h. Toluene was removed under vacuum, and the residue was diluted with methylene chloride (50 mL), then washed with 1N NaOH. solution (2x5 mL). The organic solution was concentrated and the residue was purified by column chromatography (Si02, hexanes/EtOAc = 20/80, v.) to provide the title compound (1.8 g, 6.25 mol, 78% yield). 1H NMR (300 MHz, CH3OH-d4) 5 1.44 (d, J=11.2 Hz, 9 H), 1.52 - 1.65 (m, J=8.3, 3.6 Hz, 2 H), 3.15 - 3.21 (m, 2 H), 3.59 - 3.76 (m, 4 H), 3.99 (t, J=5.4 Hz, 1 1.1C7HaS03 Ca. 61.53, H 5.66, N12.68. Found C, 61.53. H.5.50, N, 12.82 42 Example 21B 1)A 2) S3 2-(6-Phenyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrrole-3a-carboxylic acid ethyl ester trihydrochloride'H NMR (MeOH-d4, 300 MHz) 5 1.34 (t, J=7.1 Hz, 3 H), 3.46 - 3.72 (m, 4 H), 3.78 (dd, J=11.7, 7.0 Hz. 1 H), 3.93 (dd, J=11.7, 4.6 Hz, 1 H), 4.02 -4.20 (m, 2 H), 4.24 - 4.45 (m, 3 H), 7.40 - 7.75 (m, 3 H), 7.43 - 7.74 (m, 3 H), 7.86 (d. J=9.8 Hz, 1 H), 7.91 - 8.14 (m, 2 H), 8.47 (d. J=9.8 Hz, 1 H), 8.46 (d, 1 H); MS (DCI/NH3) m/z 339 (M+Hf. Anal. Calculated for C19H22N,' [m. 3 H), 4.09 - 4.31 (m, 3 H), 4.60 (d, J=13.9 Hz, 1 H), 5.03 (dd. J=7.1, 5.1 Hz, 1 H), 7.19 (d, J=7.8 Hz. 2 H), 7.57 (d, J=9.8 Hz, 1 H), 7.61 - 7.T-. [m, 4 H), 7.90 (d, J=8.8 Hz, 2 H), 8.14 (d, J=9.5 Hz, 1 H); MS (DCI/NH,; TI/Z 345 (M+H)*, 347 (M+Hf; Anal. Calculated for Ci6H,7BrlV1.40C7H8SO3>0.50H2O: C. 52.05; H, 4.94; N, 9.41. Found: C. 52.31; H, 4.89; N, 9.09. Examples 70-74 The listed diamine was coupled with 3-(6-chIoropyridazin-3-yl)-1 H-indole lr. place of 3-chloro-6-phenylpyridazine, and further processed according to the listed methods, to provide the title compounds. Example Starting Material Conditions Resulting Compound 70 Example 6C 1) C2) FB3) S2 3-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1 H-indole Bis(trifluoroacetate)'H NMR yrrolo[3,4-c]pyrrole bis hydrochloride -102- WO 2005/028477 PCT/US2004/030735 3) S3 'H NMR (MeOD-d4.300 MHz) 8 3.33 - 3.42 (m. 4 H) 3.61-3.70 (m, 2 H) 3.72-3.77 (m, 2 H) 3.83-3.90 (m. 2 H) 7.35 (d, J=9.8 Hz, 1 H) 7.77 - 7.82 (m, 1 H) 8.01 (d, J=9.8 Hz, 1 H) 8.29 - 8.32 (m, 1 H) 9.68 [t. J=1.5 Hz, 1 H); MS (DCI/NH3) m/z 257 (M+Hf; Anal. C13H,6N6-2.2HCI: C, H, N. Examples 83-85 The title compounds were prepared by coupling the listed diamine with 3-(4-iodophenyl)-6-chloropyridazine (described in Example 83F) and processing according to the specified methods to provide the title salt. Example 83 Example 83A 2-Bromo-1-(4-iodo-phenvl)-ethanone A solution of bromine (79.3 g, 508 mmo) in glacial acetic acid (50 mL) was added at room temperature to a solution of 1-(4-lodo-phenyl)-ethanone (Aldrich, 125 g, 508 mmol) in glacial acetic acid (600 mL). The mixture was stirred for 10 h, then concentrated under reduced pressure and the residue was diluted with ethyl acetate (100 mL), and washed with brine (3 x 50 mL). The organic layer was concentrated, and the residue was crystallized from ethyl ether to provide the title compound as a yellow solid (150 g, 462 mmol, 91% yield). 1H NMR (300 MHz, CDCI3) 5 4.39 (s, 2 H), 7.69 (d, J=8.5 Hz, 2 H), 7.87 ppm (d, J=8.5 Hz, 2 H); MS (DCI/NH3) m/z 246 (M-Br)+ 264 (M-Br+NH4)+. 1 Example 83B 2-f2-(4-lodo-phenyl)-2-oxo-ethvn-malonic acid diethyl ester Diethyl malonate (8 g, 50 mmol) was treated with sodium hydride (1.2 g, 50 mmol) in dry THF (120 mL) under nitrogen at 0 °C for 30 minutes. A solution of the product from Example 83A (15.8 g, 48.6 mmol) in THF (30 mL) was added, and the mixture stirred for 30 minutes. The reaction mixture was diluted with ethyl acetate (200 mL) and washed with brine (3 x 20 mL). The organic layer was concentrated to -103- WO 2005/028477 PCT rS2i)04/030735 give the title compound as oil (15 g, 36 mmol, 74% yield): 1H NMR (30C MHz, CDCI3) 5 1.25 - 1.32 (m, J=7.1, 7.1 Hz, 7 H), 3.57 (d, J=7.1 Hz, 2 H), 4.16 - ±29 (m, 4 H), 7.69 (d, J=8.5 Hz, 2 H), 7.84 ppm (d, J=8.8 Hz, 2 H); MS (DCI/NH3) mt 405 (M+H)+, 422 (M+NH4)+. Example 83C 2-f2-(4-lodo-phenyl)-2-oxo-ethvn-malonicacid ! The product of Example 83B (1 g, 2.5 mmol) was treated with NaOH solution (1 N, 7.5 ml, 7.5 mmol) in ethanol (5 mL) at 60 °C for 1.5 hours, and then filtered through a pad of diatomaceous earth. The filtrate was concentrated under vacuum and the residue was diluted with water (20 mL) and acidified with HCI (6 Nl) to bring to pH=1. The resulting precipitate was collected by filtration and dried to rrovide the title compound as white solid (730 mg, 2.1 mmol, 84% yield): 1H NMR (300 MHz, MeOH-D4) 6 3.58 (d, J=7.1 Hz, 2 H), 3.93 (t, J=7.0 Hz, 1 H), 7.75 (d, >3.5 Hz, 2 H), 7.91 ppm (d, J=8.8 Hz, 2 H); MS (DCI/NH3) m/z 366 (M+NH4f. Example 83D 6-(4-lodo-phenvl)-4.5-dihvdro-2H-pvridazin-3-one The product of Example 83C (25 g, 71.8 mmol) was treated with hydrazine hydrate (55% aq., 16 mL, -275 mmol) in ethanol (300 mL) at 78°C for 60 hours. The mixture was then concentrated under reduced pressure, and the residue was stirred with water (250 mL) for 1h. The solid was filtered and dried under vacuum to provide the title compound (20.5 g, 68.3 mmol, 95.1% yield): 1H NMR (300 MHz, CDCI3) 5 2.62 (t, J=8.3 Hz, 2 H), 2.96 (t, J=8.3 Hz, 2 H), 7.45 (d, J=8.5 Hz, 2 H), 7.75 (d, J=8.8 Hz, 2 H), 8.51 ppm (s, 1 H); MS (DCI/NH3) m/z 301 (M+H)+ 318 (M+NH4)+. Example 83E 6-(4-lodo-phenvl)-2H-pyridazin-3-one The product of Example 83D (20.5 g, 68.3 mmol) in glacial acetic acid (200 mL) was treated with a solution of bromine (12 g, 75 mmol) in glacial acetic acid (50 mL) at 100°C for 1 h. The mixture was then cooled to room temperature and stirred ■ -104- WO 2005/028477 PCT/US2004/030735 for an additional 16 h. Most of the acetic acid solvent was removed under vacuum, and the residue was stirred with water (250 ml_) for 1 h. The solid was filtered and dried under vacuum to provide the title compound (20 g, 66.7 mmol, 98% yield): 1H NMR (300 MHz, MeOH-D4) 5 7.06 (d, J=9.8 Hz, 1 H), 7.65 (d, J=8.8 Hz, 2 H), 7.84 (d, J=8.8 Hz, 2 H), 8.01 ppm (d, J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 299 (M+H)+. Example 83F 3-Chloro-6-(4-iodo-phenvl)-pyridazine The product of Example 83E (20 g, 66.7 mmol) was treated with POCI3 (200 ml_) at 100° for 16 hours. Most of the POCI3 was removed by distillation, and the residue was poured into ice (500 g) slowly while stirring. The precipitated solid was filtered and dried under vacuum to provide the title compound (19.2 g , 60.7 mmol, 91% yield): 1H NMR (300 MHz, CHLOROFORM-D) 5 ppm 7.57 (d, J=8.8 Hz, 1 H), 7.76 - 7.83 (m, 3 H), 7.85 - 7.91 ppm (m, 2 H); MS (DCI/NH3) m/z 317 (M+H)+. Example Starting Material Conditions Resulting Compound 83 Example 7 DC2)TFA 3)S4 (1R, 5S)-6-[6-(4-lodo-phenyl)-pyridazin-3-yl]-3,6-diaza-bicyclo[3.2.0]heptaneTrifIuoroacetate'H NMR (CH3OH-d,, 300 MHz) 5 ppm 3.23 - 3.31 (m, 1 H), 3.39 (dd, J=12.4, 7.3 Hz, 1 H), 3.4,7 - 3.60 (m, 1 H), 3.76 (d, J=12.2 Hz, 1 H), 3.82 - 3.93 (m, 2 H), 4.32 (t, J=8.3 Hz, 1 H), 5.24 (dd, J=6.4, 3.7 Hz, 1 H), 7.04 (d, J=9.5 Hz, 1 H>; 7.69 - 7.76 (m, J=8.8 Hz, 2 H), 7.86 (d, J=8.5 Hz, 2 H), 7.95 (d, J=9.2 Hz, 1 H); MS (DCI/NH3) m/z 379 (M+H)*; Anal. CsH,slN4"1.(l5C2F3H02: C, H, N. 84 Example 8 DC2)FB3)S4 (1S, 5S)-3~[6-(4-lodo-phenyl)-pyridazin-3-yl]-3,6-diaza-bicyclo[3.2.0]heptaneTrifluoroacetate'H NMR (CH30H-d4, 300 MHz) 6 ppm 3.42 (dd, J=11.4. 6.3 Hz, 1 H), 3.50 - 3.67 (m, 2 H), 3.78 (dd, J=11.4, 5.3 Hz, 1 H), 4.20 (d, J=11.5 Hz, 1 H), 4.30 (dd, J=11.2, 8.5 Hz, 1 H), 4.51 (d, J=13.6 Hz, 1 H), 5.12 (dd. J=6.8, 5.8 Hz, 1 H), 7.45 (d, J=9.5 Hz, 1 H), 7.76 (d, J=8.8 Hz, 2 H), 7.89 (d, J=8.8 Hz, 2 H), 8.08 (d, J=9.5 Hz, 1 H); MS [DCI/NH3) m/z 379 (M+H)*; Anal. CisHl5IN4-1.85C2F3H02: C, H, N. 85 Example 8 DC 2) EC 3)S4 (1S, 5S)-3-[6-(4-lodo-phenyl)-pyridazin-3-yl]-6-methyl-3,6-diaza-bicyclo[3.2.0]heptaneTrifluoroacetate'H NMR (CH3OH-d4, 300 MHz) 8 ppm 3.02 (s, 3 H), 3.34 - 3.44 (m, 1 H), 3.49 (dd, J=13.7, 4.9 Hz, 1 H), 3.54 - 3.66 (m, 1 H), 4.04 - 4.22 -105- WO 2005/028477 PCT/US2004/030735 (m, 3 H). 4.55 (d, J=13.9 Hz, 1 H), 4.92 - 5.01 (m, 1 H), 7.35 (d, J=9.5 Hz, 1 H), 7.76 (d, J=8.5 Hz, 2 H), 7.88 (d, J=8.8 Hz, 2 H). 8.01 (d, J=9.5 Hz, 1 H); MS (DCI/NH3) m/z 393 (M+H)*; Anal. C16H17IN4'1.3C2F3H02: C, H, N. Example 86 Examples 86A and 86B The product of Example 6C (0.60 g, 2.8 mmoi), 3,6-dichloro-4-methylpyridazine (Aldrich, 0.60 g, 3.7 mmol), Cs2C03 (1.4 g, 4.2 mmol), 1,3-bis(2,6-di-i-propylphenyl)imidazolium chloride (Strem, 0.12 g, 0.28 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 0.10 g, 0.11 mmol) were combined and the mixture was evacuated, then purged with N2 (three times). This reaction mixture was warmed to 85 °C, stirred for 18 h then cooled to ambient temperature and filtered. Purification via column chromatography (Si02, 50% hexanes in EtOAc) yielded 0.40 g of the major regioisomer (5-(6-Chloro-5-methyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid tert-butyl ester, Example 86A.1.2 mmol, 42% yield) and 0.27 g of the mino regioisomer (5-(6-Chloro-4-methyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylicacid tert-butyl ester, Example 86B, 0.80 mmol, 28% yield). Major and minor regioisomer: MS (DCI/NH3) m/z 339 (M+H)+. Examples 86-89 A chloropyridazinyl diamine (Example 86A or 86B) (0.40 g, 1.2 mmol), phenylboronic acid (0.29 g, 2.4 mmol), aqueous Na2C03 (2 M, 2 ml_), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 43 mg, 0.047 mmol) and 1,3-bis(2,6-di-i-propylphenyl)imidazolium chloride (Strem, 50 mg, 0.12 mmol) were combined and evacuated, then purged with N2 (three times). The mixture was stirred at 85 °C for 20 h then was cooled to ambient temperature, filtered, concentrated under reduced pressure and purified via column chromatography (Si02, 50% hexanes in EtOAc) to provide the phenyl-substituted pyridazine. This product was processed through the deprotection, methylation (if applicable) and salt -106- WO 2005/028477 PCT/US2004/030735 formation steps according to the conditions in the table below to provide the title compounds. Example Starting Material Conditions Resulting Compound 86 Example 86A 1)FB 2)S1 2-(5-Methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole bis-p-toluenesulfonate'H NMR (300 MHz. CD3OD) 8 ppm 2.35 (s, 6 H), 2.39 (d, J=1.4 Hz, 3 H), 3.43 (m", 4 H), 3.65 (rn, 2 H), 3.77 (dd, J=11.7, 2.9 Hz, 2 H), 3.95 (m, 2 H), 7.22 (d, J=8.1 Hz, 4 H), 7.57 (m, 6 H), 7.67 (m, 4 H); MS (DCI/NH3) m/z 281 (M+H)+; Anal, calculated for drHaoN^CTHaOaS: C, 59.59; H, 5.81; M, 8.97. Found: C, 59.35; H, 5.74; N, 8.81. 87 Example 86A 1)FB 2)RA 3)S1 2-Methy|-5-(5-methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole bis-p-toluenesulfonate 'H NMR (300MHz. CD3OD) 8 ppm 2.35 (s, 6 H), 2.39 (s, 3 H). 2.99 (s, 3 H), 3.16 (m. 2 H), 3.48 (m, 2 H), 3.89 (m, 6 H). 7.22 (d, J=8.1 Hz, 4 H), 7.58 (m. 6 H), 7.68 (m, 4 H); MS (DCI/NH3) m/z 295 (M+H)*; Anal, calculated for Ci8H22N4'2.25C7He03S-H20: C, 57.92; H, 6.05; N, 8.01. Found: C, 57.55; H, 5.96; N. 8.31. 88 Example 86B 1)FB 2)S5 2-(4-Methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-cjpyrrole bis-L-tartrate'H NMR (300 MHz. CD3OD) 8 ppm 2.50 (d. J=0.7 Hz, 3 H), 3.31 (m, 4 H). 3.60 (m, 4 H), 3.71 (m, 2 H), 4.45 (s, 4 H), 7.48 (m, 3 H), 7.80 (d, J=0.7 Hz, 1 H), 7.95 (m, 2 H); MS (DCI/NH3) m/z 281 (M+H)*; Anal, calculated for C,7H2ON4'2C4H6OB: C, 51.72; H, 5.56; N, 9.65. Found: C, 51.89; H, 5.47; N, 10.22.1 89 Example 86B 1)FB 2)RA 3)S2 2-Methyl-5-(4-methyl-6-phenyl~pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole fumarate). 1H NMR (300 MHz, CD3OD) 5 ppm 2.50 (d, J=0.7 Hz, 3 H), 2.91 (s, 3 H). 3.25 (m, 4 H). 3.48 (m. 2 H), 3.64 (m, 2 H), 3.71 (d, J=11.2 Hz, 2 H), 6.68 (s, 2 H), 7.48 (m, 3 H), 7.81 (d, J=1.0 Hz. 1 H), 7.95 (m, 2 H); MS (DCI/NH3) m/z 295 (M+H)*; Anal, calculated for dsH^-C^O^O: C. B4.09; H, 6.41; N, 13.59. Found: C, 63.78; H. 6.32; N, 13.27. Examples 90-110 Example 90 5-(6-Chloro-pyridazin-3-vl)-hexahvdro-pvrrolor3.4-c1pvrrole-2-carboxvlicacid tert- butyl ester -107- WO 2005/028477 PCT/US2004/030735 The product of Example 6c (1.5 g, 7.1 mmol) was dissolved in 1,4-dioxane (35 mL). 3,6-Dichloropyridazine (Aldrich, 1.37 g, 9.2 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 0.28 g, 0.31 mmol), 1,3- bis(2,6-di-i-propylphenyl)imidazolium chloride (Strem, 0.38 g, 0.90 mmol), and CS2CO3 (6.97 g, 21.2 mmol) were added and the mixture was stirred at 85 °C for 18 h, then cooled to room temperature, filtered, and concentrated under vacuum. The residue was triturated with 80% EtOAc-hexanes (50 mL) and the resulting solid was filtered and dried under vacuum to give 0.81 g of the title compound (2.5 mmol, 35% yield). MS (DCI/NH3) m/z 325 (M+H)+. ' Examples 91-110 The General Procedures for preparing compounds described in Examples 91-110 are described below. General Procedure for Suzuki Coupling Method G: The The aryl chloride from Example 90 (5 mmol) and the listed arylboronic acid (6 mmol) were dissolved in 1,4-dioxane (50 mL). Cesium carbonate (14 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 0.3 mmol) and 1,3-bis(2,6-di-i-propylphenyl)imidazolium chloride (Strem, 0.8 mmol) were added, and the mixture was stirred at 85 °C and for 20 h. The reaction was then cooled to room temperature and concentrated under vacuum. The residue was purified by column chromatography to provide the arylated pyridazine. Deprotection and/or N-methylation, followed by salt formation according to the procedures previously described in Example 31, provided the title compounds. Method H: The aryl chloride from Example 90 (1.5 mmol) and the listed arylboronic acid (3 mmol) were stirred in toluene (25 mL). Aqueous Na2C03 (2M, 2.5 mL), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 0.06 mmol) and 1,3-bis(2,6-di-i-propylphenyl)imidazolium chloride (Strem, 0.15 mmol) were added, and the mixture was stirred at 85 °C for 16 h. The mixture was then cooled to ambient temperature, filtered through diatomaceous earth and concentrated under reduced pressure. The residue was purified by column chromatography to provide the ^ WO 2005/028477 PCT/US2004/030735 arylated pyridazine. Deportection and/or N-methylation, followed by sal formation according to the procedures previously described in Example 31, provided the title compounds. Method I: The aryl chloride from Example 90 (0.6 mmol) and the listed arylboronic acid (0.66 mmol) were combined in dioxane (15 ml_). Cesium carbonate (0.72 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 9 u.mol) and Bu3P (Strem, 70 ul of 10 wt% in hexanes, 24 u.mol) were added, and the mixture was warmed to 95 °C for 18 h. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth and concentrated under reduced pressure. The crude material was purified by column chromatography to provide the arylated pyridazine. Deprotection and/or N-methylation, followed by salt formation according to the procedures previously described in Example 31, provided the title compounds. TNI Method MW: The aryl halide from Example 90 (0.5 mmol) and the arylboronic acid or arylboronic ester (1.5 mmol) were dissolved in dioxane-ethanol (1:1,2 ml_). Dichlorobis(triphenylphosphine)-palladium(ll) (Aldrich, 0.05 mmol) and 2-(dicyclohexylphosphino)biphenyl (Strem, 0.0125 mmol) were added followed by 1 N Na2CC>3 (aq) (1 mL)and the suspension was stirred for 5 minutes. The reaction mixture was heated in a sealed tube to 150 °C at 330 Watts for 10 min. in an Emry Creator microwave. The reaction was then cooled to room temperature and concentrated under vacuum. The residue was purified by HPLC (Xterra C-i830, X 100 mm). The salt was prepared according to the procedures previously described in Example 31, to provide the title compounds. Example Boronic Acid Conditions Resulting Compound 1)H 2-(6-o-To!yl-pyridazin-3-y!)-octahydro-pyrrolo[3,4- 91 o-to!yl boronic acid 2)FB c]pyrrole bis-trifluoroacetate 3)S4 'H NMR (300 MHz, CD3OD) 5 2.36 (s, 3 H), 3.25 (m, 2 H). 3.39 [m, 2 H), 3.66 (en; 2 H),-3.75 (dd, J= 11.7.3.2 Hz. 2 H), 3.90 (m, -109- WO 2005/028477 PCT7US2004/030735 (m. 2 H), 3.66 (m, 2 H), 3.75 (dd. J=11.7. 3.2 Hz. 2 H), 3.90 (m. 2 H), 7.39 (m. 4 H). 7.52 (d, J=9.5 Hz. 1 H), 7.89 ppm (d, J=9.5 Hz, 1 H); MS (DCI/NH3) m/z 281 (M+Hf; Anal, calculated for Ci7H2oN4'2CF3C02H: C. 49.61; H, 4.36; N, 11.02. Found: C, 50.09; H. 4.47; N, 11.24. 92 m-tolyl boronic acid DG2)FB3)S4 2-(6-(3-methylphenyl)pyridazin:3ryl)-octahydro-pyrro!o[3,4-c]pyrroleBis(trifluoroacetate)'H NMR (CH3OH-d4, 300 MHz) 8 2.44 (m. 3H), 3.30 (m. 1H), 3.40 (m, 3H), 3.66 (m, 2H), 3.76 (m, 2H). 3.91 (m, 2H). 7.36 (m, 1H), 7.43 (m, 1H), 7.54 (d. J=9.8 Hz, 1H). 7.70 (m, 1H), 7.79 (m. 1H), 8.22 (d. J=9.8 Hz. 1H); MS (DCI/NH3) m/z 281 (M+Hf; Anal. C,7H2oN4'2CF3C02H: C, H, N. 93 p-tolyl boronic acid 1)G2)FB3)S4 2-(6-p-Tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole trifluoroacetate'H NMR (300 MHz. CD3OD) 8 2.42 (s, 3 H), 3.40 (m. 4 H), 3.66 (m, 2 H). 3.75 (dd, J=11.9. 3.4 Hz, 2 H), 3.91 (m. 2 H). 7.36 (m, 2 H). 7.54 (d, J=9.6 Hz, 1 H). 7.85 (m, 2 H), 8.22 ppm (d. J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 281 (M+Hf; Anal, calculated forC17H20N4- 1.9CF3C02H: C, 50.27; H, 4.44; N, 11.27. Found: C, 50.23; H, 4.52; N, 11.57. 94 3,5-dimethylphenylboronicacid 1)G2)FB3)S4 2-[6-(3,5-Dimethyl-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole trifluoroacetate'H NMR (300 MHz. CD3OD) 8 ppm 2.40 (S, 6 H). 3.38 (m, 4 H), 3.66 (m, 2 H), 3.75 (dd, J=11.7. 3.2 Hz, 2 H), 3.92 (m, 2 H), 7.20 (s, 1 H), 7.56 (d, J=9.5 Hz, 1 H), 7.56 (s, 2 H), 8.23 (d, J=9.5 Hz. 1 H); MS (DCI/NH3) m/z 295 (M+Hf; Anal, calculated for CeH^N,- 2CF3C02H: C, 50.58; H, 4.63; N, 10.72. Found: C, 50.66; H, 4.56; N. 10.66. 95 p-methoxyphenyl boronic add 1)H 2)FB 3) S3 2-[6-(4-Methoxy-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole hydrochloride'H NMR (CH30H-d4. 300 MHz) 8 3.35 (m, 2H). 3.43 (m, 2H), 3.66 (m, 2H), 3.77 (m, 2H), 3.88 (s, 3H), 3.97 (m, 2H>, 7.11 (m, 2H), 7.72 (d. J=9.8 Hz, 1H). 7.93 (m, 2H). 8.37 (d, J=9.8 Hz, 1H); MS (DCI/NH3) m/z 297 (M+Hf; Anal, calculated for C17H20N4-3HCI: C, 50.32; H, 5.71; N, 13.81. Found: C. 50.42; H. 6.11; N, 13.71. 96 Furan-3-yl boronic acid 1)H2)FB3)S4 2-(6-Furan-3-yl-pyridazin-3-yl)-octahydro-3yrrolo[3,4-c]pyrrolebis-trifluoroacetate'H NMR (300 MHz. CO3OD) 8 ppm 3.39 (m, 4 H), 3.65 (m, 2 H), 3.74 (dd, J=11.7, 3.2 Hz. 2 H), 3.92 (m, 2 H). 7.00 (dd. J=1.7. 0.7 Hz, 1 H), 7.56 (d, J=9.8 Hz, 1 H). 7.69 (t, J=1.7 Hz, -110- WO 2005/028477 PCT/US2004/030735 1 H). 8.10 (d, J=9.5 Hz, 1 H), 8.29 (m, 1 H); MS (DCI/NH3) m/z 257 (M+H)*; Anal, calculated for C4H16N40 2CF3C02H: C. 44.64; H, 3.75; N, 11.57. Found: C, 44.49; H, 3.70; N, 11.42. 97 Thiophen-3-yl boronic acid 1)H2)FB3)S1 2-(6-Thiophen-3-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrolep-toluenesulfonate'H NMR (300 MHz, CD3OD) 5 ppm 2.33 (s. 3 H). 3.32 (m, 4 H), 3.64 (m, 2 H), 3.71 (m, 2 H), 3.82 (m, 2 H), 7.21 (m. 2 H), 7.27 (d, J=9.5 Hz, 1 H), 7.56 (dd, J=5.1, 3.1 Hz, 1 H), 7.68 (m, 3 H), 8.00 (m, 2 H); MS (DCI/NH3) m/z 273 (M+H)*; Anal, calculated for C14H16N4S-C7HBO3S-0.5H2O: C, 54.53; H, 5.42; N, 10.38. Found: C, 54.58; H, 5.25; N, 10.58. 98 Thiophen-3-yl boronic acid 1)H 2)FB 3)RA 4)S1 2-Methyl-5-(6-thiophen-3-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole p-toluenesulfonate'H NMR (300 MHz, CD3OD) 5 ppm Z36 (s, 3 H), 2.94 (s, 3 H), 3.26 (m, 2 H). 3.38 (m, 2 H), 3.64 (m, 4 H), 3.77 (m, 2 H), 7.14 (d, J=9.5 Hz, 1 H). 7.22 (m, 2 H), 7.53 (dd, J=5.1, 3.1 Hz, 1 H), 7.70 (m, 3 H), 7.88 (d, J=9.5 Hz, 1 H), 7.93 (dd, J=2.9, 1.2 Hz. 1 H); MS (DCI/NH3) m/z 287 (M+H)*; Anal, calculated for C15H1BN4S'C7H803S: C, 57.62; H, 5.71; N. 12.22. Found: C. 57.49; H, 5.71; N, 12.07. 99 5-indolyl boronic acid 1)12)FB3)S1 5-[6-(Hexahydro-pyrrolo[3,4-c]pyrroI-2-yl)-pyridazin-3-yl]-1 H-indole Bis(p-toluenesulfonate)'H NMR (CH3OH-d4, 300 MHz) 8 ppm 2.31 (s, 7.5 H), 3.23 -3.50 (m, 4 H), 3.58 - 3.72 (m, 2 H), 3.78 (dd. J=11.7, 2.2 Hz. 2 -I), 3.95 (dd, J=11.2, 6.8 Hz. 2 H). 6.63 (d. J=3.1 Hz, 1 H), 7.19 (d, J=7.8 Hz, 5 H), 7.39 (d, J=3.1 Hz, 1 H). 7.59 (d, J=8.8 Hz. 1 H). 7.64 - 7.77 (m, 7 H), 8.19 (s, 1 H), 8.41 (d, J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 306 (M+H)*; Anal. CleH19N5'2.3C7HB03S: C, -I, N. 100 N-=methylindol-5-yl boronic acid 1)12)FB3)S2 5-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1 -methyl-1 H-indole Fumarate1H NMR (CH3OH-d4, 300 MHz) 8 ppm 3.19 - 3.39 (m. 4 H), 3.56 - 3.79 (m, 6 H), 3.84 (s, 3 H), 6.52 (dd, J=3.1, 0.7 Hz, 1 H). 6.67 (s, 3 H), 7.12 (d, J=9.5 Hz, 1 H), 7.21 (d, J=3.1 Hz, 1 H), 7.48 (d, J=8.8 Hz, 1 H). 7.78 (dd, J=8.5,1.7 Hz, 1 H), 7.92 (d, J=9.5 Hz, 1 H). 8.09 (d, J=1.4 Hz. 1 H); MS (DCI/NH3) m/z 320 (M+H)*; Anal. CsHziNs'l .3C4H4O4-NH40: C, H. N. 102 o-tolyl boronic acid 1)H2)FB3)RA 2-Methyl-5-(6-o-tolyI-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole bis- L-tartrate'H NMR (300 MHz, CD3OD) 8 ppm 2.31 (s. 3 H), 2.94 (s, 3 H), 3.26 (m, 2 H), 3.40 (m, 2 H), 3.67 (m, 4 H), 3.80 (m. 2 H), 4.45 -111- WO 2005/028477 PCT/US2004/030735 4)S5 (s, 4 H), 7.17 (d, J=9.5 Hz, 1 H), 7.32 (m. 4 H), 7.56 (d. J=9.5 Hz. 1 H); MS (DCI/NH3) m/z 295 (M+Hf; Anal, calculated for CieH22N4-2 C4H606: C. 52.52; H, 5.76; N, 9.42. Found: C, 52.29; H, 5.82; N, 9.42. 103 m-tolyl boronic acid 1)G 2)FB 3)RA 4) S3 2-Methyl-5-(6-(3-methy|phenyl)pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrroledihydrochloride'H NMR (CH3OH-d4, 300 MHz) 5 Z45 (s, 3H). 2.96 and 3.02 [rotamers, 3H), 3.20 (m, 1H), 3.48 (m, 2H), 3.61 (m, 1H), 3.79 (m, 1H). 3.98 (m, 5H), 7.44 (m, 2H), 7.81 (m, 3H), 8.41 and B.44 (rotamer d, J=9.8 Hz, 1H); MS (DCI/NH3) m/z 295 (M+Hf; *nal. C1BH22lV2.5HO0.5H20: C, H, N. 104 p-to!yl boronic acid . 1)G 2) S3 2-Methyl-5-(6-p-toiyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole di-hydrochloride'H NMR (300 MHz, CD3OD) S ppm 2.43 (s, 3 H), 2.97 (s, 3 H), 3.17 (m, 2 H), 3.54 (m, 2 H), 3.93 (m, 6 H), 7.40 (d, J=7.8 Hz, 2 H), 7.76 (m, 1 H), 7.88 (m, 2 H), 8.38 (d. J=9.5 Hz, 1 H); MS (DCI/NHa) m/z 295 (M+Hf; Anal, calculated for C«H;BN«« 2HCM.7H20: C, 54.33; H, 6.94; N, 14.08. Found: C. 54.79; H, 7.01; N, 13.65. 105 3,5-dimethylphenyl boronic acid 1)G 2)FB 3)RA 4) S3 2-[6-(3,5-Dimethyl-pheny!)-pyridazin-3-yl]-5-methyl-octahydro-pyrTolo[3,4-c]pyrrole di-hiydrochloride1H NMR (300 MHz, CD3OD) 8 ppm 2.41 (s, 6 H), 2.97 (s, 3 H), 3.17 (m, 1 H), 3.52 (m, 3 H), 3.91 (m, 6 H), 7.25 {s, 1 H), 7.58 (s, 2 H), 7.78 (t, J=9.2 Hz, 1 H), 8.39 (m, 1 H); MS (DCI/NH3) m/z 309 (M+H)*; Anal, calculated for C19HJ4N4' 2HCM.7H20: C, 55.39; H, 7.19; N, 13.60. Found: C, 55.21; H, 7.37; N, 13.51. 106 Furan-3-yl boronic acid 1)H 2)FB 3)RA 4)S1 2-(6-Furan-3-yl-pyridazin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrolebis-p-toiuenesulfonate'H NMR (300 MHz, CD3OD) 8 ppm £32 (s. 6 H), 2.99 (s, 3 H), 3.19 (m, 1 H), 3.49 (m, 3 H), 3.91 (m, 6 H), 6.97 (m, 1 H), 7.19 (d, J=8.1 Hz, 4 H), 7.65 (m, 5 H), 7.72 (m, 1 H), 8.12 (dd, J=27.8, 9.8 Hz, 1 H), 8.32 (d, J=5.8 Hz, 1 H); MS (DCI/NH3) m/z 271 (M+H)*; Anal, calculated for CsH^O^CTHgOaS: C, 56.66; H, 5.57; N, 9.11. Found: C, 56.61; H, 5.56; N, 8.81. 107 1 -(4-methylbenzene-sulfonyl)indol-5-boronic acid 1) I2) FB3) S1 5-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1 -(toluene-4-sulfonyl)-1 H-indole -112- WO 2005/028477 PCT/US2004/030735 'H NMR (300 MHz, CD3OD) 6 2.27 (s, 6 H), 2.35 (s, 3 H), 3.37 - 3.51 (m, 4 H), 3.57 - 3.72 (m, 2 H), 3.80 (dd, J=11.9. 2.0 Hz, 2 H). 3.99 (dd, J=11,2. 6.8 Hz. 2 H), 6.86 (d. J=3.7 Hz, 1 H), 7.17 (d, J=8.1 Hz, 4 H). 7.34 (d, J=8.8 Hz, 2 H), 7.65 (d, J=8.1 Hz, 4 H), 7.71 (d, J=9.8 Hz, 1 H), 7.79 (d, J=3.7 Hz, 1 H), 7.86 (d, J=8.5 Hz, 2 H), 7.92 (dd, J=8.8,1.7 Hz, 1 H), 8.11 - 8.20 (m, 2 H). 8.34 ppm(d. J=9.8 Hz. 1 H); MS (DCI/NH3) m/z 460 (M+H)+; Anal, calculated for CsHaNsC^S^.SCrHoOaS: C, 57.69; H, 5.11; N, 8.18. Found: C. 57.34; H, 4.82; N 8.41. 108 p-methoxyphenyl boronic acid DH 2)FB 3)RA 4)S1 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane L-tartrate1H NMR (300 MHz. CD3OD) 8 ppm 2.22 (m, 1 H), 2.50 (m, 1 -1). 2.80 (m. 1 H). 2.88 (s, 3 H), 3.00 (m, 1 H), 3.24 (dd, J=13.9, 3.4 Hz, 1 H). 3.55 (m, 1 H). 3.75 (dd, J=7.3,1.9 Hz, 1 H). 4.07 (m, 2 H), 4.39 (s, 2 H), 4.68 (m, 1 H), 7.07 (d, J=9.5 Hz, 1 H), 7.49 (m, 3 H). 7.92 (m. 2 H), 7.94 (d. J=9.2 Hz. 1 H); MS (DCI/NH3) m/z 281 (M+Hf; Anal, calculated for CITHZONVI^HSCVI H20: C, 54.32; H. 6.15; N, 11.71. Found: C, 54.94; H, 6.54; N, 11.37. Example 114-128 Example 114 A 2-(6-Chloro-pvridazin-3-vl)-octahvdro-pyrrolor3,4-clpvrrole The product from Example 90 (1.5 g, 4.6 mmol) was deprotected using Method FB to give 1.02 g of the title compound (4.6 mmol, 100% yield). 1H NMR (300 MHz, CD3OD) 5 2.78 (dd, J=11,4 Hz, 2 H) 2.97 - 3.06 (m, 2 H) 3.09 - 3.18 (m, 2 H) 3.42 (dd, J=11,4 Hz, 2 H) 3.63 - 3.75 (m, 2 H) 7.02 (d, J=9 Hz, 1 H) 7.40 ppm (d, J=9 Hz, 1 H). MS m/z 225 (M+H)+. Example 114B 2-(6-Chloro-pyridazin-3-vl)-5-methvl-octahvdro-pvrrolor3.4-clpvrrole The product from Example 114A (1.0 g, 4.5 mmol) was N-methylated using method EC to give 1.0 g of the title compound (4.4 mmol, 96% yield). H NMR (300 MHz, CD3OD) 8 2.34 (s, 3 H) 2.52 (dd, J=10,4 Hz, 2H) 2.73 - 2.84 (m, 2 H) 3.01 -3.14 (m, 2 H) 3.47 (dd, J=11, 3 Hz, 2 H) 3.57-3.73 (m, 2 H), 7.03 (d, J=9 Hz, 1 H) 7.40 ppm (d, J=9 Hz, 1 H). MS (DCI/NH3) m/z 239 (M+H)+. -113- WO 2005/028477 PCT/US2004/030735 Examples 115-127 The aryl halide from Example 114B (0.5 mmol) and the arylboronic acid or arylboronic ester (1.5 mmol) were processed according to the procedure of method MW, and the product carried further through the listed procedures to provide-the title compounds. Example Boron ic Acid Conditions Resulting Compound 115 5-indolyl boronic acid (Frontier) 1.12.S2 5-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-y!)-pyridazin-3-yl]-1 H-indole fumarate'H NMR (CH3OH-d4, 300 MHz) 5 ppm 2.87 (s, 3 H), 3.18 - 3.43 (m, 4 H), 3.51 - 3.70 (m, 4 H). 3.72 - 3.81 (m, 2 H), 6.54 (d, J=3.4 Hz, 1 H), 6.69 S ppm3.30 (m, 2 H), 3.39 (m, 2 H), 3.69 (m, 6 H), 7.82 (m, 2 H), 7.89 (t, J=7.8 Hz, 1 H), 8.23 (d, J=8.5 Hz, 1 H), 8.28 (d, J=3.1 Hz, 1 H), 8.55 (d. J=9.5 Hz, 1 -I), 8.59 (dd, J=7.5,1.0 Hz, 1 H), 8.73 (dd, J=8.5,1.7 Hz, 1 H), 9.15 (dd, J=4.7,1.7 Hz. 1 H); MS (DCI/NH3) m/z 317 (M+Hf; Anal, calculated for C2oH2oN4' 3CF3C02H: C, 47.43; H, 3.52; N, 8.51. Found: C, 47.67; H, 3.55; N, 8.53. 166 3-aminophenyl boronic acid 1)G 2) FB 3)S4 3-[5-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yI)-pyridin-2-yl]-shenylamine trifiuoroacetate'H NMR (CH3OH-d4, 300 MHz) 6 3.27 (m, 1H), 3.34 (m, 3H) 3.57 (m, 4H), 3.64 (m, 2H), 7.07 (ddd, J=7.8, 2.4,1.7 Hz, 1H), 7.37 (m, 2H), 7.42 (m, 1H), 7.62 (dd, J=9.1. 3.1 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 8.00 (d, J=2.7 Hz, 1H); MS (DCI/NH3) m/z 281 (M+H)*; Anal, calculated for C17H20N4«2.7CF3CO2H: C, 45.74; H, 3.89; N, 9.5Z Found: C, 45.86; H, 3.90; N, 9.69. 167 2-naphthalene boronic acid 1) G2) FB3) S4 2-(6-Naphthalen-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole bis-trifluoroacetate 'H NMR (300 MHz. CD3OD) S ppm3.30 (m, 2 H), 3.37 (m. 2 H), 3.64 (m, 6 H), 7.59 (m. 2 H), 7.70 (dd, J=9.0, 2.9 Hz, 1 H), 7.92 (m. 1 H), 7.98 (m, 2 H), 8.05 (d, J=5.1 Hz, 1 H), 8.07 (S, 1 H), 8.15 (d, J=9.2 Hz, 1 H), 8.35 (m, 1 H); MS (DCI/NH3) m/z 316 (M+H)*; Anal, calculated forCziHz1N3- 2CF3C02H: C, 55.25; H, 4.27; N, 7.73. -125- WO 2005/028477 PCT/US2004/030735 Found: C, 55.16; H, 4.23; N, 7.63. 168 2-benzofuran boronic acid 1)G2) FB3) S4 2-(6-Benzofuran-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole bis-trifluoroacetate 'H NMR (300 MHz, CDaOD) 6 ppm3.31 (m, 4 H), 3.58 (m, 6 H). 7.30 (m, 4 H), 7.54 (d, J=8.8 Hz, 1 H), 7.63 (m, 1 H), 7.94 (d, J=8.8 Hz, 1 H), 8.06 (d, J=2.7 Hz, 1 H); MS (DCI/NH3) m/z 306 (M+H)+; Anal, calculated for Ci9H19N30 2CF3C02H: C, 51.r3rH, 3.97; N, 7:88. Found: C, 51.52; H, 3.71; N, 7.69. 169 Benzo[b]thiophen-2-yl boronic acid 1)1 2) FB 3)S4 2-(6-Benzo[b]thiophen-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrroletrif!uoroacetate'H NMR (CH3OH-d4, 300 MHz) 8 3.26 (m, 4H). 3.45 {m. 2H), 3.55 (m, 2H), 3.63 (m, 2H), 7.21 (dd, J=8.8, 3.1 Hz, 1H), 7.32 (m, 2H), 7.73 (brs, 1H), 7.78 (m, 1H), 7.83 (m, 2H), 8.03 (brd, J=2.7 Hz, 1H); MS (DCI/NH3) m/z 322 (M+H)*; Anal, calculated for CisHigNaS-LICFaCOzH: C, 56.98; H, 4.53; N, 9.40. Found: C, 57.11; H. 4.44; N, 9.21. 170 3-furanyl boronic acid 1)G2) FB3) S4 5-(6-Furan-3-yl-pyridin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrTole trifluoroacetate'H NMR (CH3OH-d4, 300 MHz) 5 3.25 (m, 2H), 3.33 (m, 2H), 3.55 (m, 4H), 3.64 (m, 2H), 6.97 (dd, J=2.0,1.0 Hz, 1H), 7.60 (dd, J=9.2, 3.1 Hz, 1H), 7.70 (dd, J=1.7,1.7 Hz, 1H), 7.87 (d, J=9.2 Hz, 1H), 7.91 (d. J=2.7 Hz, 1H), 3.19 (dd, J=1.4,1.0 Hz, 1H). MS (DCI/NH3) m/z 256 (M+H)*; Anal, calculated for CsHuNsO^CFsCC^H: C, 47.21; H, 3.96; N, 8.69. Found: C, 47.17; H, 4.01; N, 8.65 171 3-Biphenyl boronic acid DG2) FB3) RA4) S1 2-(6-Biphenyl-3-yl-pyridin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrolep-toluenesu!fonate'H NMR (CH3OH-d4, 300 MHz) 5 2.34 (s, 3H), 2.96 (s, 3H). 3.35 (m, 6H), 3.62 (m, 4H), 7.21 (m, 2H), 7.36 (m, 2H), 7.46 (m, 2H), 7.53 (m, 1H), 7.63 (ddd, J=7.8,1.7,1.0 Hz, 1H), 7.69 (m, 4H). 7.81 (ddd. J=7.8,1.7,1.0 Hz, 1H) 7.82 (m, 1H), 8.10 (dd. J=2.0,1.4 Hz, 1H), 8.15 (brd, J=2.7 Hz, 1H); MS (DCI/NH3) m/z 356 (M+Hf; Anal, calculated for Cz-iHKNa-CTHaOaS-O.SHzO: C, 69.38; H, 6.39; N, 7.83. Found: C, 69.24; H, 5.27; N, 7.78. 172 o-to!y! boronic acid 1) H2)FB3)S5 2-Methyl-5-(6-o-tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole bis- L-tartrate'H NMR (300 MHz, CD3OD) 8 ppm Z26 (s, 3 H), 2.93 (s, 3 H), 3.30 (m, 6 4), 3.66 (m. 4 H). 4.45 (m, 4 H), 7.26 (m, 4 H), 7.34 (m, 2 H), 8.11 (m, 1 H); MS (DCI/NH3) mfe 294 (M+H)*; Anal, calculated for C,9H»N3'2. C4H606: C, 54.08; H. 5.90; N, 6.90. Found: C, 53.91; H, 5.72; N, 6.51. 173 m-tolyl boroic acid DH 2)FB 2-Methyl-5-(6-m-tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole bis- L-tartrate1H NMR (300 MHz, CD3OD) 8 ppm 1.24 (m. 2 H). 2.41 (s. 3 H), 2.93 (s, 3 -126- WO 2005/028477 PCT/US2004/030735 3) RA4) S5 H), 3.31 (m, 4 H), 3.62 (d, J=8.8 Hz, 2 H), 3.69 (m, 2 H), 4.45 (s, 4 H). 7.18 (d, J=7.5 Hz, 1 H). 7.31 (m, 2 H). 7.61 (d, J=7.8 Hz, 1 H), 7.66 (s, 1 H), 7.70 (d, J=8.8 Hz, 1 H), 8.11 (d, J=2.7 Hz, 1 H); MS (DCI/NH3) m/z 294 (M+Hf; Anal, calculated for CgHaNj^.SCHsOs: C, 53.04; H, 5.81; N, 6.58. Found: C, 52.65; H, 6.16; N, 6.28. 174 m-(trifluoro-methyl)phenyl 1)12) FB3) RA4) S5 2-Methy!-5-iB-(3-trifluoromethyl-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrroleL-tartrate'H NMR (CH3OH-d4, 300 MHz) 8 2.93 (s, 3H), 3.34 (m, 6H) 3.65 (m. 4H), 4.44 (s, 4H), 7.30 (dd, J=8.8. 3.1 Hz, 1H), 7.63 (m, 2H), 7.81 (d, J=8.8 Hz. 1H). 8.12 (m, 1H), 8.17 (brd, J=3.1 Hz, 1H) 8.19 (m, 1H); MS (DCI/NH3) m/z 348 (M+Hf; Anal. CgHzoFaNs-ZIC^Os : C, H, N. 175 Phenyl boronic acid 1)G2) FB3) RA4) S5 2-Methyl-5-(6-phenyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-cjpyrrole L-tartrate1H NMR (300 MHz, CD3OD) S ppm 2.87 (s, 3 H). 3.30 (m, 6 H), 3.60 (m, 4 H), 4.40 (s, 2 H). 7.29 (dd, J=8.8, 2.7 Hz, 1 H), 7.35 (m, 1 H). 7.44 (m, 2 H), 7.71 (d, J=8.5 Hz, 1 H), 7.83 (m, 2 H), 8.12 (d, J=3.1 Hz, 1 H); MS (DCI/NH3) m/z 280 (M+Hf; Anal, calculated for C18H,8N3F3CM.05 C^eCte C, 61.02; H, 6.30; N, 9.62. Found: C, 61.00; H. 5.99; N, 9.46. 176 3-methoxyphenyl boronic acid 1)62) FB3) RA4) S5 2-[6-(3-Methoxy-phenyl)-pyridin-3-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrolebis-L-tartrate'H NMR (300 MHz, CD3OD) 8 ppm 2.93 (s, 3 H), 3.30 (m, 6 H), 3.61 (m, 2 H), 3.70 (m, 2 H), 3.85 (m, 3 H), 4.44 (m, 4 H). 6.92 (m, 1 H), 7.32 (m, 4 H), 7.71 (d, J=8.8 Hz, 1 H), 8.12 (d, J=3.1 Hz. 1 H); MS (DCI/NH3) m/z 310 (M+Hf; Anal, calculated for 0,^23^02.25 C4H6Os-H20: C, 50.56; H, 5.83; N, 6.32. Found: C, 50.47; H, 5.92; N, 6.45. 177 3-trtfIuoromethoxy-phenyl boronic acid 1)G 2) FB 3)RA 4) S5 2-Methyl-5-[6-(3-trifluoromethoxy-phenyl)-pyridin-3-yr]-octahydro-pyrrolo[3,4-c]pyrrole bis-L-tartrate'H NMR (300 MHz, CD3OD) 8 ppm 2.93 (s, 3 H), 3.33 (m, 6 H), 3.63 (d. J=8.5 Hz, 2 H). 3.70 (m, 2 H), 4.45 (s, 4 H). 7.25 (m, 1 H), 7.28 (dd. J=8.8, 3.1 Hz, 1 H), 7.52 (t, J=8.1 Hz, 1 H), 7.77 (d, J=8.5 Hz. 1 H), 7.80 (m. 1 H), 7.86 (d, J=8.1 Hz, 1 H), 8.16 (d, J=3.1 Hz, 1 H); MS (DCI/NH3) m/z 364 (M+Hf; Anal, calculated for drtoNaO^ C4H606: C, 48.87; H, 4.86; N, 3.33. Found: C, 48.54; H. 4.89; N, 6.22., 178 3-nitrophenyl boronic acid DG2) FB3) RA4) S1 2-Methyl-5-[6-(3-nitro-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole 3-toluenesulfonate'H NMR (300 MHz, CD3OD) 8 ppm 2.35 (s, 3 H), 2.94 (s, 3 H). 3.26 (m, 3 H), 3.43 (m. 3 H). 3.68 (m, 3 H), 3.99 (m. 1 H). 7.22 (m, 2 H). 7.33 (m, 1 H), 7.69 (m, 3 H), 7.88 (d, J=8.8 Hz. 1 H). 8.21 (m, 2 H). 8.28 (m, 1 H). 8.77 (dd, J=1.9.1.9 Hz, 1 H); MS (DCI/NH3) m/z 325 (M+Hf; Anal, calculated For C,BH2ON402' C7H803S-H20: C, 58.35; H, 5.88; N, 10.89. Found: C, 58.19; H, 5.64; N, 10.64. -127- WO 2005/028477 PCT/US2004/030735 179 Thiophen-3-yl boronic acid DG 2)FB 3)RA 4)S1 2-Methyl-5-(6-thiophen-3-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrolep-toluenesulfonate 1H NMR (300 MHz, CD3OD) 5 ppm £36 (s. 3 H), 2.93 (s, 3 H), 3.30 (m, 6 H), 3.59 (m. 4 H), 7.22 (d, J=7.8 Hz, 2 H). 7.27 (dd. J=8.8, 3.1 Hz, 1 H), 7.47 (dd, J=5.1, 3.1 Hz, 1 H), 7.58 (dd. J=5.1,1.4 Hz, 1 H), 7.68 (m. 3 H), 7.77 (dd, J=2.9,1.2 Hz, 1 H), 8.05 (d, J=2.7 Hz, 1 H); MS (DCI/NH3) m/z 286 (M+H)*; Anal, calculated for Ci$H19N3S' C7HB03S: C, 60.37; H, 5.95; N, 9.18. Found: C, 60.12; H, 5.92; N, 9.03. 181 8-quino!ine boronic acid 1)G 2)FB 3) RA 4) S1 B-[5-(5-Methyl-hexahydrc-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-quinolinep-toluenesulfonate 1H NMR (300 MHz, CD3OD) 8 ppm 2.35 (s, 3 H), 2.93 (s. 3 H). 3.33 (m, 6 H), 3.61 (m, 4 H), 7.22 (d, J=7.8 Hz, 2 H). 7.37 (dd, J=8.6. 2.9 Hz, 1 H), 7.57 (dd. J=8.3,4.2 Hz, 1 H), 7.71 (m. 3 H), 7.86 (d, J=8.8 Hz, 1 H), 7.98 (ddd, J=14.1, 7.6.1.4 Hz, 2 H), 8.19 (d, J=2.7 Hz, 1 H), 8.42 (dd, J=8.5, 1.7 Hz, 1 H), 8.87 (dd, J=4.2,1.9 Hz, 1 H); MS (DCI/NH3) mfe 331 (M+H)*; Anal, calculated for C^HJBN,' C7H803S: C, 66.91; H, 6.02; N, 11.15. Found: C, 66.80; H. 5.91; N, 11.14. 182 2-naphthalene boronic acid 1)G 2) FB 3) RA 4)S1 2-Methyl-5-(6-naphthalen-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole >toluenesulfonate 'H NMR (300 MHz, CD3OD) 5 ppm 2.35 (s, 3 H), 2.95 (s, 3 H), 3.34 (m, 6 H), 3.64 (m, 4 H). 7.22 (m. 2 H). 7.34 (dd, J=8.8.2.7 Hz, 1 H), 7.50 (m, 2 H), 7.70 (m, 2 H), 7.90 (m, 4 H). 8.02 (dd, J=8.5,1.7 Hz, 1 H), 8.18 (d, 1=2.7 Hz, 1 H), 8.32 (m, 1 H); MS (DCI/NH3) m/z 330 (M+H)*; Anal, calculated for C^H^Ns* CTHSOSS: C, 69.43; H, 6.23; N, 8.38. Found: C. 59.06; H, 5.86; N, 8.05. 183 Benzo[b]thiophen-2-yl boronic acid Dl 2) FB 3)RA 4)S4 2-(6-Benzo[b]thiophen-2-yl-pyridin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrolep-toluenesulfonate 'H NMR (CH3OH-CI4. 300 MHz) 8 2.36 (s, 3H), 2.93 and 2.98 (rotamer s, 3H), 3.27 (m, 2H), 3.29 (m, 2H), 3.42 (m. 2H), 3.65 (m, 3H), 3.98 (m, 1H), 7.22 (m, 2H). 7.32 (m, 3H). 7.70 (m. 2H), 7.75 (br s, 1H), 7.78 (m, 1H), 7.84 (dd, J=7.1.2.0 Hz, 1H), 7.85 (br d. J=8.5 Hz, 1H), 8.07 (br d. J=2.4 Hz, 1H); MS (DCI/NH3) m/z 322 (M+H)*; Anal, calculated for C2oH2iN3S«1.2C7He03S«H20: C. 60.90; H, 5.87; N, 7.50. Found: C, 60.93; H, 5.74; N, 7.31. 184 3-furanyl boronic acid 1)G 2) FB 3) RA 4)S1 2-(6-Furan-3-yl-pyridin-3-yl)-5-methyi-octahydro-pyrrolo[3,4-c]pyrrole p-toluenesulfonate 'H NMR (CH3OH-d4. 300 MHz) 8 2.35 (s. 4H) 2.95 (m, 4H). 3.29 (m, 3H). .42 (m, 3H), 3.64 (m. 3H). 6.93 (dd, J=2.0,1.0 Hz. 1H), 7.21 (m, 3H), 7.47 (m. 1H), 7.64 (dd, J=1.7,1.7 Hz, 1H), 7.68 (m. 3H), 7.72 (m. 1H), 7.97 (m. 1H). 8.11 (dd, J=1.4.1.0 Hz, 1H). MS (DCl/NH3) mfe 270 (M+H)*; Anal, calculated for CsHuNaOLSCyHaOzS: C. 60.32; H, 5.92; N, 7.96. Found: C, 60.34; H. 6.00; N. 8.11. -128- WO 2005/028477 PCT/US2004/030735 Examples 185-187 The product of Example 156 was processed according to the method EC to afford 2-(6-chloropyridin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole, which was coupled with the specified boronic acid and converted to the title salts according to the methods listed in the table. Example Boronic Acid Conditions Resulting Compound 185 * 5-indolyi boronic acid Di2)S2 5-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yi]-1 H-indole Trifluoroacetate'H NMR (CHjOH-d*. 300 MHz) 5 ppm 2.97 (s. 3 H), 3.33 - 3.83 (m, 10 H), 6.62 (d, J=3.1 Hz, 1 H). 7.40 (d, J=3.1 Hz. 1 H), 7.54 (dd, J=8.7,1.6 Hz, 1 H), 7.61 (d, J=8.7 Hz, 1 H), 7.86 (dd, J=9.0, 2.2 Hz, 1 H), 7.93 (s. 1 H), 8.05 (s, 1 H), 8.12 (d, J=9.4 Hz, 1 H); MS (DCI/NH3) m/z 319 (M+Hf; Anal. CaoH^N^.ICzFaHOz: C, H, N. 186 4-indolyl boronic acid 1)12)S2 4-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-1 H-indole Trifluoroacetate'H NMR (CH3OH-d«, 300 MHz) 8 ppm 2.98 (s, 3 H), 3.13 - 4.11 (m, 10 H), 6.65 (dd, J=3.2, 0.8 Hz. 1 H), 7.27 - 7.37 (m, J=3.7, 3.7 Hz, 2 H), 7.44 - 7.50 (m. 1 H), 7.58 - 7.67 (m, 1 H), 7.82 - 7.93 (m, 1 H), B.06 (s, 1 H), 8.14 (d, J=9.2 Hz, 1 H); MS (DCI/NH3) m/z 319 (M+Hf; Anal. CajHzzN^CzFsHOz: C, H, N. 187 5-quinoline boronic acid 1)1 2) S3 5-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-quinoline Hydrochloride'H NMR (CH3OH-d4, 300 MHz) 8 ppm 3.00 (d. J=12.2 Hz, 3 H). 3.03 -3.41 (m. 2 H). 3.41 - 3.82 (m. 8 H), 4.03 (dd, J=12.0.7.3 Hz. 1 H), 7.68 - 7.77 (m, 1 H), 7.93 (dd, J=8.8,1.7 Hz. 1 H). 7.97 - 8.09 (m, 2 HI), 8.17 - 8.25 (m. 1 H), 8.26 - 8.37 (m, 2 H), 9.10 (d, J=8.8 Hz, 1 H), 9.21 (d, J=5.1 Hz, 1 H); MS (DCI/NH3) m/z 331 (M+Hf; Anal. C21H22N4'3.5HCI«C2H60: C, H, N. Example 188 6a-Methvl-5-(6-m-tolvl-pvridin-3-vl)-octahvdro-pyrrolof3.4-blpvrrolefumarate The diamine from Example 20G was coupled to 5-bromo-2-chloropyrdine according to the procedure of Example 156A. The product was in turn coupled with m-tolyl boronic acid according to the procedure of method G, and further processed -129- WO 2005/028477 PCT/US2004/030735 according to methods PD and S2 to provide the title compound: 1H NMR (MeOH-d4, 300 MHz) 5 1.66 (s, 3H), 2.06-2.13 (m, 1H), 2.40 (s, 3H), 2.44-2.54 (m, 1H), 2.84-2.93 (m, 1H), 3.35-3.62 (m, 4H), 4.00 (d, J=11.2Hz, 1H), 6.69 (s, 2.2H), 7.19-7.34 (m, 3H), 7.59-7.72 (m, 3H), 8.09 (d, J=2.4Hz, 1H); MS (DCI/NH3) m/z 294 (M+H)+; Anal. Ci9H23N3'l"lC4H404: C, H, N. Examples 191-197: The product of Example 10 was reacted with 3,6-dichloropyridazine according to the procedure of Example 90, and the material was in turn coupled to the boronic acid and processed further according to the conditions listed in the table below: Example Boronic Acid Conditions Resulting Compound 191 p-tolyl boronic acid 1)H2)FB3)S1 (1R, 5R)-3-(6-p-Tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptanebis(p-toluenesulfonate)'H NMR (MeOH-D<, 300 MHz) 8 2.32 (s, 6 H), 2.45 (s, 3H). 3.38 -3.99 (m, 4 H). 4.28-4.40 (m, 2 H), 4.56 (d, J=13.6 Hz, 1 H), 5.03 -5.34 (m, 1 H), 7.19 (d, J=7.8 Hz, 4 H), 7.44 (m, 2 H) 7.66 (d, J=8.1 Hz, 4 H) 7.76 - 8.00 (m, 3 H) 8.37 (d, J=9.8 Hz. 1 H); MS (DCl/NH3; m/z 267 (M+H)*: Anal. Calculated for Ci6HiaN4-2.00C7H8SO3: C, 59.00; H, 5.61; N, 9.17. Found: C, 58.92; H, 5.54; N, 9.08. 192 o-tolyl boronic acid 1)H2)FB3)S1 (1R, 5R>- 3-(6-o-Toly!-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptanebis(p-toluenesulfonate)'H NMR (MeOH-D,, 300 MHz) 6 2.35 (s, 6 H), 2.39 (s, 3 H), 3.54 -3.80 (m, 3 H), 3.84 (dd, J=11.0, 5.3 Hz. 1 H), 4.17 - 4.43 (m, 2 H), 4.56 (d, J=13.9 Hz, 1 H), 5.19 (t, J=6.1 Hz, 1 H), 7.22 (d, J=8.1 Hz, i H) 7.33 - 7.59 (m, 2H) 7.68 (d, J=8.1 Hz, 4 H), 7.92 (d, J=9.5 Hz, 1 H), 8.11 (d, J=9.5 Hz, 1 H); MS (DCl/NH3) m/z 267 (M+Hf; Anal. Calculated for Cl6H,BN<-2.00C7HeSO»'1;00H2O: C, 57.31; H, 5.77; N.8.91. Found: C, 57.90; H, 5.60; N, 8.79. 193 m-tolyl boronic acid 1)H2)FB3)S1 (1R, 5R)- 3-(6-m-Tolyl-pyridazin-3-yl)-3,6-diaza->icyclo[3.2.0]heptanebis(p-toluenesulfonate)'H NMR (MeOH-D<, 300 MHz) 8 2.32 (s, 6 H), 2.48 (s, 3 H), 3.58 -3.99 (m. 4 H), 4.20 - 4.40 (m. 2 H), 4.58 (d, J=13.6 Hz, 1 H). 5.22 (t, J=6.3 Hz, 1 H), 7.19 {d, J=8.1 Hz. 4 H), 7.39 - 7.58 (m, 2 H) 7.66 (d, J=8.1 Hz, 4 H). 7.70 - 7.86 (m. 2 H) 7.94 (d, J=9.8 Hz, 1 H), 8.40 (d, J=9.5 Hz, 1 H); MS (DCI/NH3) m/z 267 (M+Hf; Anal. Calculated for C16H,6N<-2.10CjH8SO3'1.40HjO: C, 56.35; H. 5.79; N, 8.47. -130- WO 2005/028477 PCT/US2004/030733 Found: C. 56.60; H, 5.78; N, 8.13. 194 3,4-methylenedioxy-benzeneboronicacid 1)H2)FB3)S1 (1R, 5R)- 3-(6-Benzo[1,3]dioxol-5-yl-pyridazin-3-yl)-3,6-diazabicyclo[3.2.0]heptane bis(p-toluenesulfonate)'H NMR (MeOH-D4, 300 MHz) S 2.33 (s, 6H), 3.55-3.70 (m, 2H). 3.78 (dd, J=12.1, 5.8 Hz, 1H). 3.88 (dd, J=11.9. 5.1 Hz. 1H), 4.20-136 (m, 2H). 4.56 (d. J=12.9 Hz, 1H), 5.21 ft J=5.8 Hz, 1H), 6.11 [s, 2H). 7.04 (d, J=8.2 Hz, 1H), 7.20 (d, J=8.1 Hz. 4H). 7.46-7.52 (m, 2H), 7.65 (d, J=8.4 Hz, 4H). 7.88 {d. J=9.9 Hz, 1H), 8.33 (d, J=9.8 Hz, 1H); MS (DCI/NH3) m/z297 (M+Hf; Anal. Calculated for Ci6Hi6N4O2-2.00C7H8SO3: C, 56.24; H. 5.03; N, 8.74. Found: C, 56.01; H, 4.94; N, 8.51. 195 p-tolyl boronic acid 1)H 2)FB 3)RA 4)S1 (1R, 5R)- 6-Methyl-3-(6-p-tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptanefumarate'H NMR (MeOH-D4, 300 MHz) 6 2.40 (s, 3 H), 2.89 (s, 3 H), 3.31 -3.66 (m, 3 H), 3.91 (dd, J=10.7, 4.6 Hz, 1 H), 4.10-4.18 (m, 2H), *.50 (d, J=13.6 Hz, 1 H), 4.68 - 4.97 (m, 1 H), 6.68 (s, 2 H), 7.18 -7.44 (m, 3 H), 7.84 (d. J=8.5 Hz, 2 H), 7.95 (d, J=9.5 Hz, 1 H); MS (DCI/NH3) m/z 281 (M+H)*; Anal. Calculated for Ci7H2oN4'1.10C4H4Cv0.50H20: C, 61.90; H, 6.12; N, 13.49. Found: C, 61.97; H, 5.77; N, 13.72. 196 o-to!yl boronic acid 1)H 2)FB 3)RA 4)S1 (1R, 5R)- 6-Methyl-3-(6-o-tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptanebis(p-toluenesulfonate)J1H NMR (MeOH-D4, 300 MHz) 5 2.35 (s, 6 H), 2.38 (s, 3 H), 3.05 (s, 3 H), 3.58 - 3.85 (m, 3 H) 4.20 (d, J=6.4 Hz, 2 H), 4.30 (d, J=10.5 Hz, 1 H), 4.64 (d, J=14.6 Hz. 1 H) 4.98 - 5.18 (m, 1 H), 7.21 (d, J=7.8 Hz, 4 H), 7.35 - 7.59 (m, 4 H), 7.68 (d, J=8.1 Hz. 4 H) 7.95 (d. J=9.8 Hz, 1 H) 8.15 (d, J=9.8 Hz, 1 H); MS (DCI/NH3) nVz 281 (M+Hf; Anal. Calculated for drHaoNW.IOCzHeSOj'I.OOHjO: C. 57.69; H, 5.93; N, 8.49. Found: C, 57.50; H, 5.60; N. 8.79. 197 3,4-methylenedioxybenzeneboronicacid DH 2)FB 3)RA 4)S1 (1R, 5R)- 3-(6-Benzo[1,3]dioxol-5-yl-pyridazin-3-yl)-6-methyf-3,6-diaza-bicyclo[3.2.0]heptanebis(p-toluenesulfonate)'H NMR (MeOH-D4. 300 MHz) 8 2.31 (s. 6 H), 3.04 (s, 3 H), 3.52 ■ 3.79 (m, 3 H), 4.05 - 4.38 (m, 3 H), 4.61 (d, J=13.9 Hz, 2 H), 5.07 (t, J=6.3 Hz, 1 H), 6.10 (s, 2 H), 7.03 (d, J=7.8 Hz, 1 H), 7.18 (d, J=7.£ Hz, 4 H), 7.35 - 7.56 (m, 2 H), 7.64 (d, J=8.1 Hz, 4 H), 7.75 (d, J=9.5 Hz. 1 H). 8.22 (d. J=9.8 Hz, 1 H); MS (DCI/NH3) mfe 311 (M+Hf; Anal. Calculated for C,7H18N4O2-2.10C7H8SCy1.00H2O: C, 56.87; H, 5.23; N, 8.56. Found: C, 56.85; H, 5.37; N, 8.74. Examples 204 - 208: -131- WO 2005/028477 PCT/US2004/030735 The product of Example 8B was reacted with 3,6-dichloropyridazine according to the procedure of Example 90, and the material was in turn coupled to the boronic acid and processed further according to the conditions listed in the table below: Example Boronic Acid Conditions Resulting Compound 204 5-indolyl boronic acid 1) MW2) FB3) S2 (1S, 5S)-5-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole Fumarate'H NMR (CH3OH-d4, 300 MHz) 6 ppm 3.29 - 3.38 (m, 1 H), 3.45 [dd, J=13.6, 5.1 Hz, 1 H), 3.51 - 3.65 (m, 1 H), 3.78 (dd, J=11.4, 5.3 Hz, 1 H), 4.17 (d, J=11.2 Hz, 1 H), 4.30 (dd, J=11.0, 8.6 Hz. 1 H), 4.48 (d, J=13.6 Hz, 1 H), 5.10 (dd, J=7.1, 5.1 Hz. 1 H), 6.55 (d. J=2.4 Hz, 1 H), 6.71 (s, 2 H), 7.30 (d, J=3.4 Hz, 1 H), 7.34 (d, J=9.5 -lz, 1 H), 7.50 (d, J=8.5 Hz, 1 H), 7.75 (dd, J=8.5.1.7 Hz. 1 H), 8.02 (d, J=9.5 Hz, 1 H), 8.13 (s. 1 H); MS (APCI/NH3) m/z 292 (M+Hf; Anal. Ci7H17N5-1.5C4H«O«-0.5H2O: C, H, N. 205 5-indolyl boronic acid 1) MW2) RA3) S4 (1S, 5S^5-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole Bis(trifluoroacetate)'H NMR (CH3OH-d4, 300 MHz) 5 ppm 3.02 (s, 3 H), 3.43 - 3.72 (m. i H). 4.07 - 4.29 (m, 2 H), 4.53 - 4.66 (m, 1 H). 5.03 (s. 1 H), 6.64 (d, J=4.1 Hz, 1 H). 7.39 (d, J=3.4 Hz, 1 H), 7.57 - 7.64 (m, 1 H), T.67 - 7.73 (m, 1 H), 7.78 (d, J=9.8 Hz, 1 H), 8.20 (d, J=1.4 Hz, 1 H), 8.39 (d, J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 306 (M+H)*; Anal. C,eH19N5'2C2F3H02: C, H, N. 206 4-indolyl boronic acid 1) MW2) S4 (1S, 5S)-4-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole Bis(trifluoroacetate)'H NMR (CH3OH-d4, 300 MHz) 8 ppm 3.03 (s, 3 H), 3.45 - 3.73 (m, 4 H), 4.09 - 4.30 (m. 2 H), 4.63 (d. J=12.9 Hz, 1 H), 5.04 (s, 1 H), 6.81 (dd, J=3.4,1.0 Hz, 1 H), 7.32 (t, J=7.8 Hz, 1 H), 7.43-7.49 (m, 2 H), 7.63 (d, J=7.8 Hz, 1 H), 7.75 (d, J=9.5 Hz. 1 H), 8.33 (d, J=9.5 Hz, 1 H); MS (DCI/NH3) mfe 306 (M+H)*; Anal. Ci6H19N5'2.5C2F3H02: C, H, N. 207 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran 1) MW2) S4 (1S, 5S)-3-(6-Benzofuran-5-yl-pyridazin-3-yl)-6-methyl-3,6-diaza-bicyclo[3.2.0]heptaneBis(trifluoroacetate)H NMR (CH3OH-d4, 300 MHz) 5 ppm 3.03 (s, 3 H), 3.46 - 3.72 (m. 4 H), 4.09 - 4.29 (m, J=16.3 Hz, 2 H). 4.56 - 4.68 (m, 1 H). 5.04 (s, 1 H), 6.99 (dd, J=2.4,1.0 Hz. 2 H), 7.68 (d, J=5.4 Hz, 1 H), 7.71 (d, J=4.4 Hz, 1 H), 7.88 (d, J=2.4 Hz, 1 H), 7.93 (dd, J=8.8, 2.0 Hz, 1 H), 8.24 (d, J=1.7 Hz, 1 H), 8.30 (d, J=9.5 Hz, 1 H); MS (DCI/NH3) -132- WO 2005/028477 PCT/US2004/030735 m/z 307 (M+H)T; Anal. C(8H,aN40'2.5C2F3H02: C. H, N. 208 p-aminobenzene boronic acid D l2) FB3) S1 (1S, 5S)- 4-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yI]-phenylamine tri(p-toluenesulfonate)'H NMR (MeOH-D<, 300 MHz) S Z33 (s, 9 H), 3.76-4.05 (m, 4 H), 4.20-4.40 (ID, 2H), 4.58 (d. J=13.9 Hz, 1 H) 5.22 (t, J=5.9 Hz, 1 H) 7.20 (d, J=8.5 Hz, 6 H) 7.36 (d, J=8.5 Hz. 2 H) 7.67 (d, J=8.1 Hz, 6 H) 7.91 (d, J=9.8 Hz, 1 H) 8.01 (d, J=8.8 Hz, 2 H) 8.37 (d, J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 268 (M+H)*; Anal. Calculated for C,5HITN5'3.23C7HBSO3'0.50H2O: C, 54.26; H, 5.31; N, 8.41. Found: C, 53.93; H, 4.82; N, 8.02. Example 209-211 The product of Example 7 J was reacted with 3,6-dichloropyridazine according to the procedure of Example 90, and subjected to N-methylation according to method EC. The material was in turn coupled to the boronic acid and processed further according to the conditions listed in the table below: Example Boronic Acid Conditions Resulting Compound 209 3-thienyl boronic acid 1). MW 2) S4 (1R, 5S)- 3-[6-(3-MethyI-3,6-diaza-bicyclo[3.2.0]hept-6-/l)-pyridazin-3-yl]-thiophene trifluroacetate 'H NMR (CH3OH-d„, 300 MHz) 8 ppm 3.08 (s, 3 H), 3.19 - 3.38 (m, 2 H), 3.51 - 3.61 (m, 1 H), 3.91 (dd, J=8.6. 3.2 Hz, 1 H), 4.02 (dd, 25.1,12.2 Hz, 2 H), 4.30 (t, J=8.3 Hz, 1 H), 5.23 (dd, J=6.6, 3.6 Hz, 1 H). 7.01 (d, J=9.2 Hz, 1 H), 7.54 (dd, J=5.1, 2.7 Hz, 1 H), 7.71 (dd, J=5.1,1.4 Hz, 1 H), 7.92 (d, J=9.5 Hz, 1 H), 7r96 (dd, J=3.1,1.4 Hz, 1 H); MS (DCI/NH3) m/z 273 (M+H)*; Anal. C14Hi6N 300 MHz) 5 pprn 3.10 (s. 3 H). 3.30 - 3.41 (m, 2 H), 3.50 - 3.72 (m, 1 H), 3.99 - 4.09 (m. 2 H), 4.18 (d. J=12.9 Hz. 1 H), 4.45 (t, J=8.6 Hz, 1 H), 5.36 (dd, J=6.8,4.1 Hz, 1 H), 6.83 (dd, J=3.2, 0.8 Hz, 1 H), 7.25 - 7.32 (m, 1 H), 7.39 - 7.46 (m, 3 H), 7.60 (d, J=B.1 Hz, 1 H), 8.26 (d, J=9.5 Hz, 1 H): MS (DCI/NH3) mfe 306 (M+H)*; Anal. C,8H19N5'2.4CzF3HCy0.8H2O: C, H, N. Example 212 3-Methvl-5-r6-(5-methvl-hexahvdro-pvrrolof3.4-c1Pvrrol-2-vl)-pvridazin-3-vn-1H- indazole bisftrifluoroacetate) Example 212A 3-Methvl-5-trimethvlstannanvl-indazole-1-carboxylic acid tert-butvl ester Hexamethylditin (4.73 g, 14.4 mmol) was added to a mixture of 3-methyl-5-bromo-indazole-1-carboxylic acid tert-butyl ester (3.0 g, 9.6 mmol) and Pd(PPh3)4 (1.1 g, 0.96 mmol) in toluene (50 ml_). The solution was purged with nitrogen, and heated to 115 °C under nitrogen for 2 h. The black reaction mixture was cooled to room temperature, loaded onto a column od silica gel and eluted with EtOAc-Hexane (5 - 30%) to provide the title compound (3.06 g, 80% yield): MS (DCI/NH3) m/z 396 (M+H)+. Example 212B 3-Methvl-5-f6-(5-methvl-hexahvdro-pvrrolor3,4-clPvrrol-2-vl)-pvridazin-3-vn-1H- jndazole bisftrifluoroacetate) The product of Example 114 (120 mg, 0.5 mmol) was combined with the product of Example 212A (278 mg, 0.7 mmol). Dioxane (10mL), tris(dibenzylidene)-dipalladium (Pd2(dba)3, 24 mg, 0.025 mmol), Pd (Pbul3, 26 mg, 0.05 mmol) and CsF (152 mg, 1 mmol) were added, and the mixture was stirred at 100 °C under nitrogen for 16 h. The reaction was cooled to room temperature, diluted with ethyl acetate (30 ml_) and washed with water. The organic phase was concentrated under vacuum, and the resicdue was purified by column chromatography (10% MeOH-CH2CI2) to provide the free base (120 mg, 55% yield) which was converted to the title compound by method S4: 1H NMR (300 MHz, CH3OH-d4) 5 2.63 (s, 3 H), 2.99 (s, 3 H), 3.23-4.07 (m, 10 H), 7.58-7.70 (m, J=8.6, 8.6 Hz, 2 H), 8.03 (dd, J=8.8, 1.4 Hz, -134- WO 2005/028477 PCT/US2004/030735 1 H), 8.36 (s, 1 H), 8.42 ppm (d, J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 335 (M+H)+; Anal, calculated for dgHzjNe^SCaFsHOa: C, 47.61; H, 4.12; N, 14.14. Found: C, 47.26; H, 3.92; N 14.44. Example 213 (1S, 5SV 5-r6-(3,6-Diaza-bicvclor3.2.01hept-3-vl)-pyridin-3-vn-3-methvl-1 H-indazole tri(p-toluenesulfonate) The product of Example 9 was was reacted with 2,5-dibromopyridine according to the procedure of Example 128A, then coupled with the product of Example 212A according to the procedure of Example 212B. The resulting product was deprotected according to procedure FB and converted to the salt by method S4 toprovide the title compound: 1H NMR (MeOH-D4, 300 MHz) 5 2.32 (s, 9 H), 2.65 (s, 3 H) 3.67-3.73 (m, 2 H), 3.82 (dd, J=13.2, 5.8 Hz, 1 H), 3.90 (dd, J=11.2, 4.1 Hz, 1H), 4.25-4.37 (m, 2H), 4.58 (d, J=13.2 Hz, 1H), 5.24 (t, J=6.1 Hz, 1H), 7.20 (d, J=7.8 Hz, 6 H), 7.41 (d, J=9.2 Hz, 1 H), 7.64 - 7.70 (d, J=7.8 Hz, 6 H), 7.72 - 7.75 (dd, J=8.8,1.2 Hz, 1 H), 7.80 (dd, J=8.8,1.6 Hz, 1 H), 8.16 (m, 1 H), 8.26 (d, J=1.7 Hz, 1 H), 8.46 (dd, J=9.5, 2.4 Hz, 1 H); MS (DCI/NH3) m/z 306 (M+H)+; Anal. Calculated for Ci8H19N5'3.30C7H8SO3 »1.50H2O: C, 54.81; H, 5.42; N, 7.78. Found: C, 54.98; H, 5.30; N, 7.40. Example 224 (1R. 5S)-3-Phenyl-6-(6-phenvl-pyridazin-3-vl)-3,6-diaza-bicvclof3.2.01heptane bis(p- toluenesulfonate) The diamine from Example 9 was coupled with 3-chloro-6-phenylpyridazine according to the procedure of Method A. The product was deprotected by the procedure of Method PD, then coupled with bromobenzene according to the general procedure of Example 156A. The product was then converted to the salt with p-toluenesulfonic acid according to Method S1 to provide the title compound: 1H NMR (CD3OD, 300 MHz) 5 2.40 (s, 6 H), 2.99 - 3.22 (m, 2 H), 3.57 - 3.76 (m, 1 H), 3.99 (d, J=10.5 Hz, 1 H), 4.13 - 4.27 (m, 2 H), 4.48 - 4.64 (m, 1 H), 5.30 - 5.47 (m, 1 H), 6.89 (t, J=7.3 Hz, 1 H), 7.00 (d, J=8.1 Hz, 2 H), 7.12 - 7.36 (m, 7 H), 7.46 - 7.62 (m, 3 H), 7.69 (d, J=8.5 Hz, 4 H), 7.88 - 8.06 (m, 2 H), 8.33 (d, J=9.8 Hz, 1 H); MS WO 2005/028477 PCT/US2004/030735 (DCI/NH3) m/z 329 (M+H)+; Anal. Calculated for C2iH2oN4-2.00C7H8S03*1.50H20: C, 60.07; H, 5.62; N, 8.01. Found: C, 59.97; H, 5.55; N, 7.92. Examples 225 – 239 The product of Example 10 was was reacted with 5-bromo-2-chloropyridine according to the procedure of Example 156A, then coupled with the listed boronic acid and processed according to the procedures indicated in the table below. Example Boronic Acid Conditions Resulting Compound 225 4-acetylphenyl boronic acid 1.G 2. FB 3.S1 (1R, 5R)-1-{4-[5-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-phenyl}-ethanone p-toluenesulfonate'H NMR (CHjOH-d,, 300 MHz) 8 2.35 (s, 6H), 2.67 (s, 3H), 3.43 (dd, J,=12.9Hz, J;>=5.4Hz, 1H), 3.55-3.67 (m, 1H), 4.09 (d, J=11.2Hz, 1H), 4.26-4.37 (m, 2H), 5.14 (t, J=6.5Hz, 1H), 7.21 (d, J=7.8Hz, 4H), 7.68 (d, J=8.1Hz, 4H), 7.95-8.01 (m, 3H), 8.17-8.22 (m. 3H), 8.28 (d, J=3.1Hz, 1H); MS (DCI/NH3) m/z 294 (M+H)*; Anal. deH^O^CyHeOsS: C, H, N. 226 4-N.N-dimethylaminophenylboronic acid 1. G2. FB3. S1 [1R, 5RH4-[5-(3,6-Diaza-bicyclo[3.2.0]hept-3-y!)-pyridin-2-yl]-phenyI}-dimethyl-amine p-toluenesulfonate'H NMR (CH3OH-d4, 300 MHz) 8 ppm 2.34 (s, 6 H), 3.10 (s, 6 H), 3.23 (dd, J=10.5, 6.4 Hz, 1 H), 3.31 - 3.39 (m, 1 H), 3.51 -3.64 (m, 1 H), 3.79 (dd, J=11.0, 5.3 Hz. 1 H), 4.01 (d, J=10.9 Hz, 1 H), 4.21 - 4.35 (m, 2 H), 5.12 (dd, J=6.8, 5.4 Hz, 1 H), S.94 (d, J=9.2 Hz, 2 H), 7.21 (d, J=8.1 Hz, 4 H), 7.69 (d, J=8.5 Hz, 4 H), 7.73 (d, J=9.2 Hz, 2 H), 7.97 - 8.13 (m, 3 H): MS (DCI/NH3) m/z 295 (M+H)*; Anal. C18H22N4-2.4C7H9O3S-O.3H2O: C, H, N. 227 m-tolyl boronic acid 1. G2. FB3. RA4. S1 (1R, 5R)-6-Methyi-3-(6-m-tolyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane p-toluenesulfonate'H NMR (CH3OH-d4,300 MHz) 8 ppm 2.33 (s, 6 H), 2.48 (s, 3 H), 3.04 (s, 3 H). 3.32 - 3.38 (m, 1 H). 3.42 (dd, J=12.9,4.7 Hz, 1 H). 3.57 - 3.69 (m, 1 H), 4.08 (d. J=10.8 Hz, 1 H), 4.13 -4.21 (m, 2 H), 4.39 (d, J=12.9 Hz, 1 H), 5.01 (dd, J=7.3,4.6 Hz, 1 H). 7.20 (d, J=7.8 Hz, 4 H), 7.42 - 7.56 (m, 2 H), 7.58 -7.71 (m, 6 H), 7.99 - 8.06 ; MS (DCI/NH3) m/z 266 (M+H)*; Anal. Calculated for C17H,9N3'1.4C4H40,: C, H, N. 238 Pyridine-3-boronic acid 1. G2. FB3. RA4. S2 (1R, 5R)-5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-[2,3']bipyridinyl Fumarate'H NMR (CHsOH-d.,, 300 MHz) 8 ppm 2.91 (s, 3 H), 3.09 -3.23 (m, 2 H), 3.46 - 3.57 (m, 1 H), 3.89 - 4.01 (m, 2 H), 4.09 -4.19 (m, 1 H), 4.24 (d, J=12.9 Hz, 1 H). 4.85 - 4.90 (m, 1 H), 5.69 (s, 2 H), 7.45 (dd, J=8.6, 2.9 Hz. 1 H), 7.52 (ddd, J=8.1, 4.8, 0.7 Hz, 1 H), 7.87 (d, J=8.5 Hz, 1 H), 8.32 - 8.39 (m, 2 H), B.52 (dd, J=4.9.1.5 Hz, 1 H), 9.09 (dd, J=2.4, 0.7 Hz. 1 H); MS (DCI/NH3) m/z 267 (M+H)*; Anal. Calculated for C,6H,8N4'1.2C4H4OV C, H, N. 239 5-indolyl boronic acid 1) 12) FB3) S1 (1R, 5R)- 5-[5-(6-Methy!-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-1 H-indole p-toluenesulfonate'H NMR (MeOH-D4. 300 MHz) 8 Z34 (s. 3 H). 2.97 (s. 3 H), 3.07 (dd, J=10.3. 6.3 Hz, 1 H), 3.15 (dd, J=12.7,4.6 Hz. 1 H), 3.41 - 3.69 (m. 1 H). 3.96 (d, J=10.5 Hz, 1 H), 4.26 (d, J=12.5 Hz. 1 H). 4.90-5.02 (m, 1 H). 6.53 (d. J=2.4 Hz, 1 H). 7.21 (d, J=8.1 Hz, 2 H), 7.29 (d. J=3.4 Hz, 1 H), 7.48 (d. J=8.5 Hz, 1 4), 7.53 (dd, J=8.8,2.7 Hz, 1 H), 7.63 (dd, J=8.5,1.7 Hz, 1 H), 7.69 (d, J=8.1 Hz, 2 H), 7.82 (d, J=8.8 Hz, 1 H), 8.05 (d, J=1.4 te, 1 H), 8.22 (d, J=Z7 Hz, 1 H); MS (DCI/NH3) m/z 305 (M+H)*; Anal. Calculated for dsf-WVI^CrHeSOj '0.50H2O: C, 62.92; H, 5.89; N, 11.08. Found: C, 63.13; H, 5.87; N, 10.70. -139- WO 2005/028477 PCT/US2004/030735 Example 240 The product of Example 10 was was reacted with 5-bromo-2-chloropyridine according to the procedure of Example 156A, then coupled with the listed boronic acid and processed according to the procedures indicated in the table below. Example Boronic Acid Conditions Resulting Compound 240 5-indolyl boronic acid 1) I2) FB3) S1 (1S, 5S)- 5-[5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-1 H-indole p-toluenesulfonate'H NMR (MeOH-D4, 300 MHz) 8 2.34 (s, 3 H), 2.97 (s, 3 H), 3.07 (dd, J=10.3, 6.3 Hz, 1 H), 3.15 (dd, J=12.7,4.6 Hz, 1 H), 3.41 - 3.69 (m, 1 H), 3.96 (d, J=10.5 Hz, 1 H), 4.26 (d, J=12.5 Hz, 1 H), 4.90-5.02 (m, 1 H), 6.53 {d, J=2.4 Hz, 1 H), 7.21 (d, J=8.1 Hz, 2 H), 7.29 (d, J=3.4 Hz, 1 H), 7.48 (d, J=8.5 Hz. 1 H), 7.53 (dd, J=8.8, 2.7 Hz, 1 H), 7.63 (dd. J=8.5,1.7 Hz, 1 H). 7.69 (d, J=8.1 Hz, 2 H), 7.82 (d, J=8.8 Hz. 1 H), S.05 (d, J=1.4 Hz, 1 H), 8.22 (d, J=2.7 Hz, 1 H); MS (DCI/NH3) m/z 305 (M+Hf; Anal. Calculated for C^HaoN^I.^CrHeSOs '1.00H2O: Z, 62.56; H, 6.06; N, 10.87. Found: C, 62.75; H, 5.75; N, 10.48. Examples 243 - 246: The product of Example 8B was was reacted with 5-bromo-2-chloropyridine according to the procedure of Example 156A, then coupled with the listed boronic acid and processed according to the procedures indicated in the table below. Example Boronic Acid Conditions Resulting Compound 243 Phenyiboronic acid 1)H2)Pd3)S2 (1R, 5S)- 6-(6-Phenyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane fumarate'H NMR (MeOH-D,, 300 MHz) 8 3.20 (dd, J=12.5, 3.4 Hz, 1H), 3.32 - 3.39 (m, 1 H). 3.39 - 3.54 (m, 1 H) 3.67 - 3.80 (m. 2 H), 3.82 (dd, J=7.8. 2.7 Hz, 1 H). 4.07(t, J=7.8 Hz, 1 H), 4.89 - 5.03 (m, 1 H), 6.68 (s, 2 H) 7.10 (dd, J=8.6, 2.9 Hz, 1 H] 7.34 (t, J=7.3 Hz, 1 H) 7.39 - 7.48 (m, 2 H), 7.70 (d. J=8.5 Hz, 1 H). 7.78 - 7.86 (m, 2 H), 7.92 (d, J=2.7 Hz, 1 H); MS (DCI/NH3) m/z 252 (M+H)*; Anal. Calculated for Ci9H20N4-1.00C4H4O4 «0.10H2O: C, 65.06; H, 5.79; N, 11.38. Found: C, 64.79; H, 5.42; N, 11.24. -140- WO 2005/028477 PCT/US2004/030735 244 m-tolyl boronic acid 1)H2)Pd3)S2 (1R, 5S)- 6-(6-m-Tolyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane fumarate'H NMR (MeOH-D«, 300 MHz) 8 2.40 (s, 3 H), 3.18 (dd. J=12.5, 3.4 Hz, 1 H), 3.35 (d, J=7.5 Hz, 1 H), 3.38 - 3.52 (m, 1 H), 3.73 (dd, J=12.2, 9.8 Hz, 2 H), 3.81 (dd, J=8.0, 2.9 Hz, 1 H), 4.02 - 4.12 (m, -LHi 4.94 (dd, J=6.4, 3.4 Hz, 1 H), 6.68 (s, 2 H), 7.09 (dd, J=8.6, 2.9 Hz, 1 H), 7.17 (d, J=7.5 Hz, 1 H), 7.31 (t, J=7.6 Hz, 1 H), 7.55 - 7.66 -pyridin-3-yl]-1 H-indole bis(p-toluenesulfonate)'H NMR (MeOH-D4, 300 MHz) 8 2.29 (s, 1 H), 3.59-3.88 (m. 4 H), 4.23 (d, J=9.9 Hz. 1 H), 4.33 (dd, J=11.2, 8.8 Hz. 1H), *.50 (d, J=13.2 Hz. 1 H), 5.22 (t, J=6.1 Hz, 1 H). 6.55 (d, J=3.1 Hz. 1 H). 7.20 (t, J=8.1 Hz. 4 H), 7.29 - 7.43 (m, 3 H), 7.53 (d, J=8.5 Hz. 1 H). 7.66 (d, J=8.1 Hz. 4 H), 7.83 (d, J=1.7 Hz, 1 H). 8.14 (d. J=2.4 Hz. 1 H). 8.30 - 8.52 (m, 1 H); MS (DCI/NH3) m/z 291 (M+H)*; Anal. Calculated for C,8Hi8N4'2.00C7HBSO3 '1.50H2O: C. 58.76; H. 6.44; N, 7.61. Found: C, 58.58; H, 6.12; N, 7.50. 248 Phenylboronic acid 1) H2) FB3) S1 (1S, 5S)- 3-(5-Phenyl-pyridin-2-yl)-3,6-diaza-bicyclo[3.2.0]heptanebis(p-toluenesulfonate)'H NMR (MeOH-D,, 300 MHz) 6 2.38 (s. 6 H), 3.61 - 3.75 (m. 2 H), 3.79 (dd, J=13.6, 5.8 Hz, 1 H). 3.88 (dd. J=11.5, 4.7 Hz. 1H), 4.24 (d, J=10.2 Hz, 1 H), 4.27 - 4.39 (m. 1 H), 4.51 (d. J=13.2 Hz, 1 H). 5.22 (t, J=6.1 Hz, 1 H), 7.20 (d, J=7.8 Hz. 4 H), 7.37 (d, J=9.5 Hz. 1 H), 7.42 - 7.58 (m, 2 H), 7.59 - 7.78 (rn, 7 H). 8.16 (d. J=1.7 Hz, 1 H), 8.37 (dd, J=9.5,2.4 Hz, 1 H); MS (DCI/NH3) m/z 252 (M+H)*; Anal. Calculated for C16H,7N3'2.10C7H8SO3 '0.50H2O: C, 59.29; H, 5.64; N, 6.76. Found: C, 58.94; H. 5.87; N. 6.51. 249 Phenylboronic acid 1)H 2)FB 3)RA 4)S1 (1S, 5S)- 6-Methyl-3-(5-phenyl-pyridin-2-yl)-3,6-diaza-bicyclo[3.2.0]heptanefumarate^H NMR (MeOH-D4. 300 MHz) 8 2.93 (s. 3 H), 3.16 - 3.40 (m, 2 H), 3.40-3.54 (m. 1 H) 3.85 - 3.95 (m, 1 H) 4.01 - 4.06 (m. 1 H) 4.20 (d, J=20.3 Hz, 1 H) 4.43 (d. J=13.2 Hz, 1 H), 4.87 -5.00 (m, 1 H), 6.70 (s. 2H), 6.93 (d, J=8.8 Hz, 1 H), 7.32 (t, J=7.1 Hz, 1 H), 7.39 - 7.50 (m, 2 H), 7.52 - 7.66 (m, 2 H). 7.93 (dd, J=8.5,2.4 Hz, 1 H), 8.44 (d, J=2.7 Hz, 1 H); MS (DCI/NH3) m/z 266 (M+H)*; Anal. Calculated for Ci7Hi9N3'1.00C3 (3 mL), and the aqueous layer was further extracted with CH2CI2 (3x5 mL). The combined extract was washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The residue was purified via column chromatography to , provide the alkylated amine, which was converted to a salt by the listed procedure. Example N-alkylating Conditions Resulting Compound :Agent -154- WO 2005/028477 PCT/US2004/030735 Agent 265 Benzyl bromide 1)K 2) S3 2-Benzyl-5-(6-phenylpyridazin-3-yl)-octahydropyrrolo|3,4-c]pyrrole hydrochloride'H NMR (MeOH-d4, 300 MHz) 6 3.11-3.32 (m, 4 H), 3.56-3.87 (m, 6 H), 4.36 (s, 2 H). 7.17 (d, J=9 Hz, 1 H), 7.38-7.58 (m, 8 H), 7.86-7.99 (m, 3 H); MS (DCI/NH3) m/z 357 (M+Hf; Anal. C23H24N4-1.05HCl: C, H, N. 266 ,4-chloromethyl pyridine 1)K 2)S4 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-4-ylmethyl)-octahydropyrro!o[3,4~c]pyrrolebis(trifluoroacetate)'H NMR (MeOH-d4, 300 MHz) 6 3.13-3.52 (m, 6 H), 3.73-3.91 (m, 4 H), 4.30 (s. 2 H), 7.46-7.59 (m, 4 H), 7.66 (d. J=6 Hz, 2 H), 7.92-8.02 (m, 2 H), 8.18 (d, J=10 Hz, 1 H), 8.67 (d, J=5 Hz, 2 H); MS (DCI/NH3) m/z 358 [M+H)*; Anal.C22H23N52C2HF3O2: C, H, N. 267 2-chtoromethyl pyridine 1)K 2)S4 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-2-ylmethyl)-octahydropyrrolo[3,4-c]pyrrolebis(trifluoroacetate)'H NMR (MeOH-d«, 300 MHz) 6 3.36-3.51 (m. 4 H). 3.75-3.96 (m, 6 H), 4.61 (s, 2 H), 7.41-7.58 (m, 6 H). 7.90 (td. J=8, 2 Hz, 1 H), 7.93-7.99 (m. 2 H). 8.15 (d, J=10 Hz, 1 H), 8.67 (d, J=4 Hz, 1 H); MS (DCI/NH3) m/z 358 [M+Hr. Anal. CZZHZJNS^QHFSOJ: C, H, N. 268 2-chloro-5-chloromethylpyridine 1j\K 2) S3 2-(6-Chloropyridin-3-ylmethy!)-5-(6-phenylpyridazin-3-yl)-octahydropyrrolo[3,4-c]pyrrole hydrochloride'H NMR (MeOH-d4, 300 MHz) 5 3.04-3.22 (m, 2 H). 3.23-3.61 (m, 4 H), 3.65-3.83 (m, 4 H), 4.26 (s, 2 H), 7.26 (d, J=9 Hz, 1 H), 7.41-7.59 (m. 4 H), 7.89-8.03 (m, 4 H), 8.47 (d, J=2 Hz, 1 H); MS (DCI/NH3) m/z 392, 394 [M+H)*; Anal. CW-faCINsHCI: C, H, N. 269 3-Pyridylacetic acid DL 2)S4 2-(6-Phenylpyridazin-3-yl)-5-(2-pyridin-3-ylethyl)-octahydropyrrolo[3,4-c]pyrrolebis(trifluoroacetate)*H NMR (CD3OD. 300 MHz) 6 3.17 (m, 2 H), 3.38-3.61 (m, 4 H), 3.76-3.95 (m, J=2 Hz, 4 H), 7.47-7.61 (m, 5 H), 7.93-8.02 (rn, 3 H), 8.20 (d, J=10 Hz, 1 H), 8.54 (dd, J=5,1 Hz. 1 H), 8.58 (d, J=1 Hz, 1 H); MS (DCI/NH3) m/z 372 (M+Hf; Anal. 02^25^-2.0502^304: C, H, N. 270 3-bromomethylpyridine hydrobromide 1)K 2)S4 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl)-octahydropyrrolo[3,4-c]pyrrolebis(trifluoroacetate)'H NMR (MeOH-d*, 300 MHz) 6 3.40-3.54 (m. 4H), 3.63-3.76 (m, 2H), 3.82-3.95 (m, 4H), 4.49 (s, 2H), 7.54-7.58 (m, 3H). 7.60 (ddd, J=8,5.1 Hz, 1H), 7.66 (d, J=10 Hz, 1H). 7.93-8.01 (m. 2H), 8.09 (ddd. J=8, 2 Hz, 1H), 8.32 (d, J=10 Hz, 1H). 8.68 (dd, J=5,1-Hz, 1H). 8.73 (d, J=2 Hz, 1H); MS (DCI/NH3) m/z 358 (M+H)+; Anal. C22H23N5-2.5C2HF302: C, H, N. -155- WO 2005/028477 271 Allyl iodide 1)K 2)S1 2-Allyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-cjpyrrole bis-p-toluenesulfonate)'H NMR (300 MHz. CD3OD) 8 ppm 2.28 (s, 6 H). 3.24 (m, 1H), 3.50 (m, 3H). 3.89 (m,.8 H), 5.58 (m, 2 H), 6.03 (m, 1 H), 7.17 (d, J=8.1 Hz, 4 H), 7.58 (m, 3 H), 7.64 (d, J=8.1 Hz, 4 H), 7.73 (dd, J=27.5, 9.5 Hz, 1 H), 7.96 (m, 2 H), 8.30 (dd. J=23.9, 9.7 Hz, 1 H); MS (DCI/NH3) m/z 307 (M+H)*; Anal, calculated for dsH^^^CrHeOaS-O.SHzO: C, 60.07; H, 5.96; N, 8.49. Found: C. 60.37; H, 5.68; N, 8.5£ 272 Crotonaldehyde 1)M 2)S1 2-But-2-enyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c|pyrrole bis-p-toluenesulfonate'H NMR (300 MHz, CD3OD) 6 ppm 1.78 (d, J=5.8 Hz, 3 H), 2.31 (s. 6 H), 3.14 (m, 2 H), 3.48 (m, 2 H). 3.87 (m. 8 H). 5.83 (m, 2 H), 7.18 (d, J=7.8 Hz. 4 H). 7.58 (m. 3 H), 7.66 (m, 4 H). 7.73 (dd. J=25.1.10.2 Hz, 1 H). 7.97 (m, 2 H). 8.31 (dd, J=22.4, 9.8 Hz, 1 H); MS (DCI/NH3) m/z 321 [M+H)*; Anal, calculated for CzoH^N^CTHeOjS: C. 61.42; H, 6.06; N, 8.43. Found: C, 61.15; H, 5.83; N, 8.40. 273 Acetaldehyde 1)M 2)S1 2-Ethyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-cjpyrrole bis-p-toluenesulfonate'H NMR (300 MHz, CD3OD) S ppm 1.37 (q, J=7.7 Hz, 3 H), 2.30 (s, 6 H), 3.41 (m, 6 H), 3.94 (m, 6 H), 7.18 (d, J=7.8 Hz, 4 H). 7.58 (m. 3 H), 7.65 (d. J=8.1 Hz, 4 H), 7.74 (dd, J=28.1, 10.2 Hz, 1 H), 7.96 (d. J=3.7 Hz, 2 H), 8.32 (dd, J=27.0,10.0 Hz, 1 H); MS (DCI/NH3) m/z 295 (M+H)*; Anal, calculated for CoHz-N^C/HsOsS: C, 60.17; H, 6.00; N, 8.77. Found: C, 59.74; H. 5.98; N, 8.68. 274 Propionaldehyde 1)M 2)S1 2-(6-Phenyl-pyridazin-3-yl)-5-propyl-octahydro-pyrrolo[3,4-c]pyrrole tris-p-toluenesulfonate)'H NMR (300 MHz, CD3OD) 6 ppm 1.01 (q. J=7.5 Hz. 3 H), 1.76 (m, 1 H), 2.31 (s, 9 H), 3.33 (m, 6 H). 3.94 (m, 7 H), 7.19 (d. J=8.1 Hz, 6 H), 7.58 (m, 3 H), 7.66 (m, 6 H), 7.75 (m, J=30.8 Hz. 1 H), 7.97 (m. 2 H), 8.31 (dd. J=28.6, 9.7 Hz, 1 H); MS (DCI/NH3) m/z 309 (M+H)*; Anal, calculated for Ci9H24N4'3C7HeO3S-0.8NH3: C, 57.29; H, 6.06; N, 8.02. Found: C, 57.67; H, 5.58; N. 8.41. 275 Acetone 1)M 2)S1 2-lsopropyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolop^-clpyrrolebis-p-toluenesulfonate'H NMR (300 MHz, CD3OD) 8 ppm 1.40 (d, J=6.8 Hz, 3 H), 1.44 (d, J=6.£ Hz. 3 H), 2.30 (s, 6 H). 3.24 (m, 1 H). 3.51 (m, 4 H), 3.94 (m, 6 H), 7.18 (d. J=8.1 Hz. 4 H), 7.58 (m, 3 H), 7.65 (d, J=8.1 Hz, 4 H). 7.70 (m, 1 H), 7.97 (m, 2 H), 8.30 (dd. J=31.9. 9.8 Hz, 1 H); MS (DCI/NHj) m/z 309 (M+H)*; Anal, calculated fordsHWV 2C7H„03S: C. 60.71; H, 6.18; N, B.58. Found: C, 60.45; H, 5.99; N, 8.47. -156- WO 2005/028477 PCT/US2004/030735 Examples 276-281 5-aryl-2- benzenesulfanyl-1,3,4-oxadiazole derivatives were prepared from the commercially available 5-aryl-1,3,4-oxadiazolyl-2-thiols according to the following procedure: Example 276A 2-Benzvlsulfanyl-5-phenvl-ri,3,41oxadiazole 5-Phenyl-[1,3,4]oxadiazole-2-thiol (Aldrich, 3.1g, 17.4 mmol) was added to EtOH (30 mL) and cooled to 0°C while stirring. Diisopropylethylamine (3.1 mL, 17.4 mmol) was then added and the mixture became a clear solution. Benzyl bromide (2.08mL, 17.4 mmol) was added and the resulting mixture was allowed to warm to room temperature while stirring. After 45 min, a thick white precipitate formed. The mixture was stirred an additional 1hr followed by the addition of 1M NaOH (3mL). The mixture was filtered, washed with 1M NaOH (2 x 20mL), 3% citric acid (2 x 20 mL), H20 (2 x 20mL) and the precipitate was dried under vacuum to afford 4.31 g (92%) 2-benzylsulfanyl-5-phenyl-[1,3,4]oxadiazole as a white solid. 1H NMR (CDCI3, 300 MHz) 5 4.57 (sj 2H), 7.37 (m, 3H), 7.48 (m, 5H), 7.99 (m, 2H); MS (DCI/NH3) m/z.269 (M+H)+. Example 276B (3aR,6aR)-5-(5-PhenYl-f1,3,41oxadiazol-2-vl)-hexahvdro-pvrrolor3,4-b1pyrrole-1-carboxylic acid tert-butyl ester To provide the title compound, the product of Example 14H, 0.20 g, 0.95 mmol) and diisopropylethylamine (0.17 mL, 0.95 mmol) were dissolved in 1,2-dichlorobenzene (3 mL). The 2-benzylsulfanyl-5-aryl-[1,3,4]oxadiazole (0.23g, 0.86 mmol, prepared according to the procedure of Example 276A) was added and the mixture heated to 220°C under microwave irradiation for 15 min. After cooling, the reaction mixture was diluted with CH2CI2 (25 mL), washed successively with sat. NaHCO3(10 mL), H20 (10 mL), and brine (10 mL), dried (Na2S04) and concentrated under vacuum. The residue was purified by column chromatography (100% CH2CI2 WO 2005/028477 PCT/US2004/030733 to 95/5/0.5 CH2CI2:MeOH:NH4OH) to provide the title compound (56 mg, 18%) as a yellow solid: 1H NMR (CD3OD, 300 MHz) 5 1.48 (s, 9H), 1.78-1.93 (m, 1H), 2.04-2.21 (m, 1H), 3.16 (m, 1H), 3.42-3.57 (m, 3H), 3.68-3.90 (m, 3H), 4.42 (m, 1H), 7.51 (m, 3H), 7.89 (m, 2H); MS (DCI/NH3) m/z 357 (M+H)+. The product was carried through deprotection and/or salt formation steps as listed in the table below. Examples 276-281 General Coupling Procedure (OP): The diamine (1 mmol) and diisopropylethylamine (1-2 mmol) were dissolved in 1,2-dichlorobenzene (3 ml_). A 5-aryl-substituted 2-benzylsulfanyl-[1,3,4]oxadiazole (1-2 mmol) was added and the mixture heated to 220°C under microwave irradiation for 15 min. After cooling, the reaction mixture was diluted with CH2CI2 (25 mL), washed successively with sat. NaHCO3(10 ml_), H20 (10 mL), and brine (10 mL), dried (Na2S04) and concentrated under vacuum. The residue was purified by column chromatography. Examples 276-281 were prepared by reacting the 2-benzylsulfanyl-[1,3,4]oxadiazole derivative substituted at the 5-position with the listed aryl group and the corresponding diamine according to the conditions listed in the table below. Example Aryl . Diamine Conditions Resulting Compound 276 Phenyl Example 14H 1) OD2) FB (3aR,6aR)-5-(5-Phenyl-[1,3,4]oxadiazol-2-yl)-octahydro-pyrrolo[3,4-b]pyrrole'H NMR (CD3OD, 300 MHz) 8 1.72-1.83 (m, 1H), 2.02-2.18 [m, 1H), 2.88-3.06 (m. 3H). 3.40-3.46 (m, 1H), 3.57-3.63 [m, 1H), 3.71-3.81 (m, 2H), 3.94-4.00 (m, 1H), 7.52 (m, 3H), 7.90 (m, 2H); MS (DCI/NH3) mfe 257 (M+H)*; Anal. C,4H,6N,(O'0.67H2O: C, H, N 277 Phenyl Example 6C 1) B2) FB3) S3 2-(5-PhenyI-[1,3,4]oxadiazoI-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole bis hydrochloride'H NMR (DMSO-ds, 300 MHz) 5 3.06 - 3.25 (m, 4 H) 3.38-3.47 (m. 2 H) 3.52 - 3.63 {m, 2 H) 3.65 - 3.76 (m, 2 H) 7.51 - 7.58 (m. 3 H) 7.82 - 7.90 (m. 2 H) 9.17 (s, 2 H): MS (DCI/NH3) m/z 257 (M+Hf; Anal. CMH^O-LSHCI: C, H. -158- WO 2005/028477 PCT/US2004/030735 N. 278 p-methoxy phenyl Example 6C 1) B2) FB3) S4 2-[5-(4-Methoxy-phenyl)-[1,3,4joxadiazol-2-yl]-octahydro-pyrrolof3,4-c]pyrroletrifluoroacetate'H NMR (DMSO-d6,300 MHz) 6 3.08 - 3.21 (m, 4 H) 3.37 -3.49 (m, 2 H) 3.49 - 3.57 (m, 2 H) 3.61 - 3.71 (m. 2 H) 3.83 (s. 3 H) 7.06 - 7.14 (m, 2 H) 7.75 - 7.83 (m, 2 H) 8.88 (s, 2 H); MS (DCI/NH3) m/z 287 (M+Hf; Anal. C15HIBN402'C2HF302: C, H. N. 279 p-methoxy pheny Example 6C 1) B2) FB3) RA4) S3 2-[5-(4-Methoxy-phenyl)-[1,3,4]oxadiazo!-2-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrolehydrochloride'H NMR (DMSO-d6,300 MHz) 6 2.81 (del, J=6.6,4.9 Hz, 3 H) 2.86 - 2.96 (m, 1 H) 3.04 - 3.20 (m, 1 H) 3.23 - 3.36 (m, 2 H) 3.47 - 3.58 (m, 2 H) 3.59 - 3.66 (m, 2 H) 3.66 - 3.82 (m, 2 H) 3.83 (s, 3 H) 7.05 - 7.16 (m, 2 H) 7.75 - 7.86 (m, 2 H); MS (DCI/NH3) m/z 301 (M+Hf; Anal. Ci6H2oN402-1.3HCI: C, H, N. 280 p-chloro phenyl Example 6C D B2) FB3) S4 2-[5-(4-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-octahydro-pyrrolo[3,4-c]pyrroletrifluoroacetate'H NMR (DMSO-d6,300 MHz) § 3.11 - 3.22 (m, 4 H) 3.38 -3.49 {m, 2 H) 3.51 - 3.59 (m, 2 H) 3.64 - 3.74 (m, 2 H) 7.44 • 7.75 (m, 2 H) 7.79 - 8.00 (m, 2 H) 8.97 (s, 2 H); MS [DCI/NH3) mfe 291 (M+Hf; Anal. C14H15CIN4O3.7C2HF302: C, H. N. 281 Phenyl Example 5D 1) B2) S4 6-Methyl-3-(5-phenyl-[1,3,4]oxadiazol-2-yl)-3,6-diaza-bicyclo[3.2.1]octane bis trifluoroacetate1H NMR (MeOD-d4, 300 MHz) 8 2.07 - 2.28 (m, 1 H) 2.41 -2.56 (m, 1 H) 2.88 - 2.97 (m, 1 H) 2.99 (s, 3 H) 3.24 (dd, J=12.4, 5.6 Hz, 1 H) 3.35 - 3.59 (m, 2 H) 3.74 - 4.00 (m, 2 H) 4.01 - 4.31 (m, 2 H) 7.40 - 7.68 (m, 3 H) 7.84 - 8.07 (m, 2 H); MS (DCI/NH3) m/z 271 (M+Hf; Anal. C15H18N4O2.2C2HF302: C.H.N. Example 282 2-(2-Methoxv-blphenvl-4-vn-octahvdro-pvrrolof3,4-clpyrrole Example 282A -159- L WO 2005/028477 PCT/US2004/030735 5-(3-Methoxv-phenvl)-hexahvdro-pvrrolor3.4-clpvrrole-2-carboxvlicacidtert-butvl ester The product of Example 6C (1.0 g, 4.71 mmol), 3-bromoanisole (1.15 g, 6.12 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 86 mg, 0.094 mmol), racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP, Strem, 0.117 g, 0.188 mmol), and tert-BuONa (0.724 g, 7.54 mmol) were combined in 20 mL toluene. This mixture was warmed to 85 °C and stirred for 18 h then was cooled to ambient temperature, filtered and concentrated under reduced pressure. The crude residue was purified via flash column chromatography (Si02, 50% hexanes-EtOAc) to give 1.45 g of the title compound (4.6 mmol, 97% yield). MS (DCI/NH3) m/z 319 (M+H)+. Example 282B 5-(4-lodo-3-methoxv-phenvl)-hexahvdro-pvrrolo[3.4-clpvrrole-2-carboxvlicacid tert- butyl ester To the product of Example 282A (0.7 g, 2.2 mmol) in 30 mL CH2CI2 at ambient temperature was added 1.16 g of TIOAc (Aldrich, 4.4 mmol) as described in Pirrung, M., et al, JACS, 2001, 123, 3638-3643. This mixture was stirred for 5 min then l2 (0.67 g, 2.64 mmol) in CH2CI2 (70 mL) was added dropwise. Thallium (I) iodide formed a precipitate in the course of this reaction. This mixture stirred at ambient temperature for 2 h then was filtered. The filtrate was washed with 10% aqueous Na2S203 (15 mL), NaHC03 (10 mL),and saturated, aqueous NaCI (10 mL). The organic material was concentrated under reduced pressure and purified via flash column chromatography (Si02j 50% hexanes-EtOAc) to provide the title compound (0.68 g, 70% yield). MS (DCI/NH3) m/z 445 (M+H)+. Example 282C 5-(2-Methoxv-biphenvl-4-vl)-hexahydro-pvrrolof3,4-clpvrrole-2-carboxylicacid tert- butvl ester The product of Example 282B (0.68 g, 1.53 mmol), phenylboronic acid (Aldrich, 0.59 g, 3.07 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 56 mg, 0.061 mmol), 1,3-bis(2,6-di-i-propylphenyl)imidazolium chloride -160- WO 2005/028477 PCT/US2004/030735 (Strem, 65 mg, 0.15 mmol), and 2M Na2C03 (aq, 4 mL) were combined in toluene (20 mL). The mixture was warmed to 85 °C and stirred for 18 h; however, the mixture contained mostly starting material, so additional Pd2(dba)3 (56 mg, 0.061 mmol) and 1,3-bis(2,6-di-l-propylphenyl)imidazolium chloride (65 mg, 0.15 mmol) were added and the mixture stirred for another 18 h at 85 °C. The reaction was cooled to ambient temperature, filtered, concentrated under reduced pressure and purified by column chromatography (Si02, 50% hexanes-EtOAc) to give the title compound (0.17 g, 28% yield). MS (DCI/NH3) m/z 395 (M+H)+. Example 282D 2-(2-Methoxv-biphenvl-4-vl)-octahvdro-pvrrolor3,4-c1pvrroletrifluoroacetate To the product of Example 282C (0.17 g, 0.43 mmol) in 6 mL CH2CI2 was added 3 mL trifluoroacetic acid (TFA) according to the general procedure to give 0.122 g of the title compound (0.30 mmol, 69% yield). 1H NMR (CH3OH-d4, 300 MHz) 5 3.25 (m, 4H), 3.35 (m, 2H), 3.52 (m, 2H), 3.62 (m, 2H), 3.78 (s, 3H), 6.41 (dd, J=6.8, 2.4 Hz, 1H), 6.42 (s, 1H), 7.18 (m, 2H),7.31 (m. 2H), 7.42 (m, 2H); MS (DCI/NH3) m/z 295 (M+H)+; Anal, calculated for C19H22N2O CF3C02H: C, 61.76; H, 5.68; N, 6.86; Found: C, 62.03; H, 5.91; N, 7.02. Example 283 2-(2-Methoxv-biphenvl-4-vl)-5-methvl-octahvdro-pvrrolof3,4-c1pvrrole Example 283A 2-(2-Methoxv-biphenvl-4-yl)-5-methvl-octahvdro-pvrrolof3.4-clpvrrole To the product of Example 282D (0.102 g, 0.25 mmol) in 3 mL 37% aqueous HCHO was added 54 mg NaBH(OAc)3 (0.25 mmol). This material stirred at ambient temperature for 4 h then was quenched with 5 mL saturated, aqueous NaHC03. CH2CI2 (5 mL) was added, the layers separated and the aqueous layer was extracted 3 X 5 mL CH2CI2. The combined organics were dried over Na2S04, concentrated under reduced pressure and purified via flash column chromatography (Si02,1% NH4OH : 9% CH3OH : 90% CH2CI2) to give 69 mg of the title compound -161- WO 2005/028477 PCT/US2004/030735 (2.24 mmol, 90% yield) which was carried on to the next reaction without further purification. Example 283B 2-(2-Methoxv-bipheiwl-4-ylV5-methyl-octahvdro-pvrrolof3,4-c1pvrrolep- totuenesulfonate To the product of Example 283A (69 mg, 0.224 mmol) in 3 mL 10% EtOH in EtOAc was added p-toluenesulfonic acid (p-TsOH»H20, 45 mg, 0.24 mmol) in 2 mL 10% EtOH in EtOAc. Diethyl ether (1 mL) was added and the mixture stirred at ambient temperature until a precipitate formed. Filtration yielded 28 mg of the title compound (0.043 mmol, 19% yield). 1H NMR (CH3OH-d4, 300 MHz) 6 2.35 (s, 6H), 2.92 and 2.98 (rotamer s, 3H), 3.19 (m, 3H) 3.38 (m, 3H), 3.63 (m, 3H), 3.77 (s, 3H), 3.98 (m, 1H), 6.50 (m, 1H), 6.52 (s, 1H), 7.16 (m, 1H), 7.22 (m, 5H), 7.32 (m, 2H), 7.42 (m, 2H), 7.70 (m, 4H); MS (DCI/NH3) m/z 309 (M+H)+; Anal, calculated for C2oH24N20-2C7H803S: C, 62.55; H, 6.18; N, 4.29; Found: C, 62.17; H, 5.95; N, 4.18. Example 284 4- (Hexahvdro-pyrrolor3,4--c1pvrrol-2-yl)-biphenyl-2-oldi-bromide Demethylation Procedure (deMe): A solution of the product of Example 282C (0.28 g, 0.71 mmol) in CH2CI2 (15 mL) was cooled to -78 °C and BBr3 (2.8 mL of a 1 M solution in heptane, 2.8 mmol) was added dropwise via syringe. The mixture was stirred at -78 °C for 30 min then was allowed to warm to room temperature and stirred for an additional 3 h. The mixture was cooled to -78 °C and ~3 mL CH3OH was added dropwise and the mixture was allowed to warm to ambient temperature. After concentration under reduced pressure, 5 mL of 10% CH3OH in EtOAc was added. The resulting solids were isolated via filtration to give 0.25 g of the title compound (0.56 mmol, 80% yield). *H NMR (300 MHz, CD3OD) 5 ppm 3.32 (m, 6 H), 3.50 (dd, J=9.8,1.7 Hz, 2 H), 3.61 (m, 2 H), 7.16 (t, J=4.4 Hz, 1 H), 7.21 (m, 1 H), 7.33 (m, 3 H), 7.50 (m, 3 H); MS (DCI/NH3) m/z 281 (M+H)+; Anal, calculated for Ci8H20N2O» 2HBr; C, 48.89; H, 5.01; N, 6.34. Found: C, 48.53; H, 5.04; N, 6.14. Example 285 -162- WO 2005/028477 PCT/US2004/030735 4-(5-MethYl-hexahvdro-Pvrrolof3,4-c1pyrrol-2-vl)-biphenvl-2-ol bis-p-toluenesulfonate The product of Example 284 was processed according to the methods RA and S1 to prvide the title compound 7% yield). 1H NMR (300 MHz, CD3OD) 5 2.36 (s, 6 H), 2.91 (s, 3 H), 3.18 (m, 6 H), 3.52 (m, 4 H), 7.13 (m, 1 H), 7.22 (m, 5 H), 7.40 (m, 5 H), 7.69 ppm (m, 5 H); MS (DCI/NH3) m/z 295 (M+H)+; Anal, calculated for C19H22N20- 1.7C7H803S: C, 63.21; H, 6.11; N, 4.77. Found: C, 62.93; H, 5.68; N, 5.10. Example 286 Example 286A 5-r6-(3-Methoxv-phenvl)-pyridazin-3-vll-hexahvdro-pyrrolof3,4-c]pvrrole-2-carboxvlic acid tert-butvl ester The product of Example 90(0.50 g, 1.5 mmol), m-methoxy-phenylboronic acid (0.47 g, 3.1 mmol), aqueous Na2C03 (2M, 2.5 mL), tris(dibenzylideneacetone)dipa!ladium (0) (Pd2(dba)3, Strem, 56 mg, 0.062 mmol) and 1,3-bis(2,6-di-i-propylphenyl)imidazoIium chloride (Strem, 65 mg, 0.15 mmol) were combined in toluene (20 mL) were combined in toluene (20 mL). The mixture was deoxygenated by three vacuum/N2 purge cycles. The mixture was stirred under nitrogen at 85 °C for 18 h then cooled to room temperature, filtered, concentrated under reduced pressure and purified by column chromatography (Si02, 50% hexanes in ethyl acetate) to provide the title compound (0.51 g, 84% yield). MS (DCI/NH3) m/z 397 (M+H)+. Example 286B 3-r6-(Hexahvdro-pyrrolof3.4-c1pvrrol-2-vl>-pvridazin-3-vn-phenoldihvdrobromide The product of Example 286A (0.63 g, 1.6 mmol) was processed according to the procedure 'deMe' as described in Example 284 to provide the title compound (0.77 g) as a crude solid, suitable for the next reaction: MS (DCI/NH3) m/z 283 (M+H)+. Example 286C -163- WO 2005/028477 PCT/US2004/030735 5-[6-(3-Hvdroxv-phenvlVpyridazin-3-vll-hexahvdro-pyrrolof3.4-c1pvrrole-2-carboxvlic acid tert-butyl ester The product of Example 286B (-1.6 mmol) was dissolved in THF (15 mL). Aqueous NaHC03 (2M, 4 mL) was added, followed by di-tert-buty! dicarbonate (0.49 g, 2.2 mmol). This mixture was stirred at ambient temperature for 1 h then extracted CH2CI2 (2 x 5mL). The combined extract was washed with brine (3 mL), dried over anhydrous Na2SC>4, concentrated under reduced pressure and purified by column chromatography (Si02> 1% NH4OH : 9% CH3OH : 90% CH2CI2) to provide the title compound (0.34 g, 56% from Example 286A). MS (DCI/NH3) m/z 383 (M+H)+. Example 286D 3-[6-(Hexahvdro-pvrrolof3,4-clpvrrol-2-vl)-pvridazin-3-vn-phenoltri-hydrochloride The product of Example 286C was processed according to the methods FB and S3 to provide the title compound in 29% yield: 1H NMR (300 MHz, CD3OD) 8 ppm 3.31 (m, 4 H), 3.70 (m, 6 H), 6.86 (ddd, J=8.0, 2.4,1.2 Hz, 1 H), 7.12 (d, J=9.5 Hz, 1 H), 7.29 (t, J=7.8 Hz, 1 H), 7.37 (m, 2 H), 7.85 (d, J=9.5 Hz, 1 H); MS (DCI/NH3) m/z 283 (M+H)+; Anal, calculated for C16H18N40 3.8HO 1.3NH4OH: C, 41.20; H, 6.12; N, 15.91. Found: C, 40.90; H, 6.27; N, 16.26. Example 287 ' 4-f6-(Hexahvdro-pyrrolo[3.4-c1pvrrol-2-vl)-pvridazin-3-vll-Phenolbis-trifluoroacetate Example 287A 4-f6-(Hexahydro--pvrrolof3,4-clpvrrol-2-vl)-pvridazin-3-yn-phenol dihydrobromide The product of Example 95 was processed according to the procedure deME as described in Example 284 to provide the title compound as a crude salt in 89% yield: MS (DCI/NH3) m/z 283 (M+H)+. Example 287B 5-[6~(4-Hydroxv-phenvl)-pvridazin-3-vl]-hexahvdro-pyrrolof3,4-c1pyrrole-2-carboxylic acid tert-butyl ester -164- V WO 2005/028477 PCT/US2004/030735 The product of Example 287A was treated with di-tert-butyl dicarbonate according to the procedure Boc as described in Example 286C to provide the crude title compound: MS (DCI/NH3) m/z 383 (M+Hf. Example 287C 4-f6-(Hexahvdro-pvrrolo[3,4-c1pvrrol-2-vl)-pyridazin-3-vn-phenol bis-trifluoroacetate The product of Example 287B was processed according to the methods FB and S4 to provide the title compound in 87% yield: 1H NMR (300 MHz, CD3OD) 8 ppm 3.37 (m, 4 H), 3.66 (dd, J=11.5, 7.1 Hz, 2 H), 3.74 (dd, J=11.7, 3.2 Hz, 2 H), 3.93 (m, 2 H), 6.96 (m, 2 H), 7.65 (d, J=9.8 Hz, 1 H), 7.83 (m, 2 H), 8.29 (d, J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 282 (M+H)+; Anal, calculated for C16H18N40-2.4CF3C02H: C, 44.93; H, 3.70; N, 10.08. Found: C, 45.16; H, 3.61; N, 10.22. Example 288 Diethvl-(2-f3-f6-(hexahvdro-pyrrolof3,4-clpyrrol-2-yl)-pvridazin-3-vn-phenoxy}-ethvl)- amine bis-p-toluenesulfonate Example 288A 5-{6-f3-(2-Diethylamino-ethoxv)-phenyl]-pvridazin-3-vl)-hexahvdro-pyrrolop,4- clpyrrole-2-carboxylic acid tert-butyl ester Polymer-bound triphenylphosphine (Aldrich, 0.61 g, 1.8 mmol) was added to an ice-cooled solution of the product of Example 286C (0.28 g, 0.73 mmol) and N, N-diethylethanolamine (0.24 mL, 1.8 mmol) in CH2CI2. Di-iso-propyl-azodicarboxylate (Aldrich, 0.36 mL, 1.8 mmol) was added dropwise via syringe. This mixture was stirred at 0 °C for 1 h then kept at room temperature for 72 h. The reaction mixture was filtered through diatomaceous earth, concentrated under reduced pressure and purified by column chromatography (Si02,1% NH4OH : 9% CH3OH : 90% CH2CI2) to provide the title compound (0.19 g, 54% yield). MS (DCI/NH3) m/z 482 (M+H)+. Example 288B -165- WO 2005/028477 PCT/US2004/030733 Diethvl-(2-{3-r6-(hexahvdro-pvrrolor3,4-clDvrrol-2-vl)-Pvridazin-3-vn-phenoxv>-ethvn- amine bis-p-toluenesulfonate , The product of Example 288A (0.18 g, 0.37 mmol) was processed according to the methods FB and S1 to provide the title compound in 43% yield: 1H NMR (300 MHz, CD3OD) 8 ppm 1.39 (t, J= 7.3 Hz, 6 H), 1.38 (s, 6 H), 3.32 (m, 8 H), 3.71 (m, 8 H), 4.44 (dd, J=4.8 Hz, 2 H), 7.11 (dd, J=7.6, 2.2 Hz, 1 H), 7.21 (m, 5 H), 7.46 (t, J=8.0 Hz, 1 H), 7.57 (m, 1 H), 7.67 (m, 5 H), 7.97 (d, J=9.5 Hz, 1 H); MS (DCI/NH3) m/z 382 (M+H)+; Anal, calculated for C22H31N5O 2C7H803S» 1.1 H20: C, 57.98; H, 6.65; N, 9.39. Found: C, 57.67; H, 6.64; N, 9.11. Example 289 Diethyl-(2-l4-r6-(hexahvdro-pvrrolof3.4-c1pvrrol-2-vl)-pvridazin-3-vn-phenoxv>-ethv0- amine tris-trifluoroacetate The product of Example 287B was processed successively according to the procedures of Example 288A, FB, and S4 to provide the title compound: 1H NMR (300 MHz, CD3OD) 5 ppm 1.39 (t, J=7.3 Hz, 6 H), 3.37 (m, 8 H), 3.65 (m, 4 H), 3.76 (dd, J=11.2, 2.7 Hz, 2 H), 3.91 (m, 2 H), 4.45 (m, 2 H), 7.19 (m, 2 H), 7.53 (d, J=9.8 Hz, 1 H), 7.98 (m, 2 H), 8.21 (d, J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 382 (M+H)+; Anal, calculated for C22H31N5O 3CF3C02H: C, 46.48; H, 4.74; N, 9.68. Found: C, 46.56; H, 4.72; N, 9.55. Example 290 (2-(4-r6-(Hexahydro-pvrrolo[3,4-c1pvrrol-2-vl)-pvridazin-3-vl1-phenoxy)-ethyl)- dimethvl-amine tris-trifluoroacetate The product of Example 287B was coupled to N, N-dimethylethanolamine according to the procedure of Example 288A. The product was further processed according to the methods FB and S4 to provide the title compound: 1H NMR (300 MHz, CD3OD) 6 ppm 3.01 (s, 6 H), 3.39 (m, 4 H), 3.65 (m, 4 H), 3.76 (m, 2 H), 3.91 (m, 2 H), 4.44 (m, 2 H), 7.19 (m, 2 H), 7.53 (d, J=9.5 Hz, 1 H), 7.98 (m, 2 H), 8.20 (d, -166- WO 2005/028477 PCT/US2004/030733 J=9.8 Hz, 1 H); MS (DC!/NH3) m/z 354 (M+H)+; Anal, calculated for C20H27N5O 3CF3C02H: C, 44.90; H, 4.35; N, 10.07. Found: C, 44.85; H, 4.16; N, 9.92. Examples 291 - 294 The N-methyl derivatives of Examples 286 - 290 were prepared according to the methods indicated in the table below: Example Starting Material Conditions Resulting Compound 291 Example 286 1)RA 2) S3 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenol tri-hydrochloride 'HMMR (300 MHz. CD3OD) S ppm 2.96 (s, 3 H), 3.31 (m, 4 H), 3.61 (m, 6 H), 6.86 (ddd, J=7.9, 2.5.1.2 Hz, 1 H), 7.16 (d, J=9.5 Hz, 1 H). 7.29 (t, J=7.8 Hz, 1 H), 7.37 (m, 2 H). 7.86 (d, J=9.5 Hz, 1 H); MS (DCI/NHj) m/z 297 (M+H)*; \nal. calculated for C^H^O- 2.5HCI- 0.75H2O: C, 50.91; H, 6.03; N, 13.97. Found: C, 51.03; H, 6.36; N, 13.98. 292 Example 287 1)RA 2)S1 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenol bis-p-toluenesulfonate'H NMR (300 MHz, CD3OD) 6 ppm 2.31 (m, 6 H), 3.00 [s, 3 H), 3.20 (m, 1 H), 3.47 (m. 3 H), 3.89 (m, 6 H), 6.97 [m, 2 H), 7.19 (m, 4 H), 7.65 (m. 5 H), 7.81 (d, J=8.5 Hz, 2 H), 8.24 (dd, J=24.8,10.9 Hz, 1 H); MS (DCI/NH3) m/z 297 (M+H)*; Anal, calculated for C,7H2oN«0« 2C7H503S: C, 58.11; H, 5.66; N, 8.74. Found: C, 57.96; H, 5.56; N, 8.69. 293 Example 288 1)RA 2)S2 Diethyl-(2-{3-[6-(5-methyi-hexahydro-Dyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-ahenoxy}-ethyl)-amine bis-fumarate 1H NMR[300 MHz, CD3OD) 5 ppm 1.38 (t, J=7.3 Hz, 6 H), 2.88 (s. 3 H). 3.28 (m, 4 H), 3.35 (q, J=7.1 Hz, 4 H), 3.62 (m, 6 H), 3.78 (m, 2 H), 4.44 (dd, J=4.8 Hz, 2 H), 6.70 (s, 4 H), 7.09 [ddd. J=8,1.2.5,0.8 Hz, 1 H), 7.15 (d. J=9.5 Hz, 1 H), 7.45 (t, J=8.0 Hz. 1 H). 7.54 (m. 1 H), 7.65 (m, 1 H), 7.91 [d. J=9.5 Hz. 1 H); MS (DCI/NH3) m/z 396 (M+H)*; Anal, calculated for CaHaNsO- 204^0,* NH4OH: C, 56.18; H, 7.00; N, 12.68. Found: C, 56.40; H, 6.50; N. 12.94. -167- WO 2005/028477 PCT/US2004/030735 294 Example 289 1)RA 2)S1 Diethyt-(2-{4-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenoxy}-ethyi)-amine bis-p-toluenesulfonate'H NMR (300 MHz, C03OD) 6 ppm 1.38 (t, J=7.3 Hz, 6 H), 2.35 (s, 6 H), 2.94 (s, 3 H), 3.32 (m, 8 H), 3.64 (m. 6 H), 3.77 (m, 2 H), 4.41 (m, 2 H), 7.14 (m, 3 H), 7.22 (m, 4 H), 7.69 (m, 4 H), 7.87 (d, J=9.5 Hz, 1 H), 7.93 (m, 2 H); MS (DCI/NH3) m/z 396 (M+Hf; Anal, calculated for C23H33N5O'2CTH8OjS'0.25H2O: C, 59.70; H, 6.70; N, 9.41. Found: C, 59.41; H, 6.71; N, 9.36. Example 295A 5-[6-(4-Amino-phenvl)-pvridazin-3-vn-hexahvdro-pyrrolof3,4-c1pvrrole-2-carboxylic i acid tert-butvl ester The product of Example 90 (0.97 g, 3.0 mmol) and 4-aminophenylboronic acid, pinacol ester (TCI, 1.92 g, 7.5 mmol) were coupled according to the procedure of method (G, H, I) to provide the title compound (0.91 g, 2.39 mmol, 80% yield). MS (DCI/NH3)m/z181 (M+H)+. Examples 295 - 300 The product of Example 295A (164 mg, 0.43 mmol) and an acylating agent (0.86 mmol) were combined in CH2CI2 (2.0 mL) containing anhydrous pyridine (0.10 mL, 1.2 mmol) and stirred at rt to 40 °C for 2 - 18 h. The mixture was cooled to room temperature, partitioned with CH2CI2 (10 mL) and 1 N aq. NaOH (5 mL) and the layers were separated. The organic layer was washed with satd. aq. NH4CI (2X5 mL) and brine (5 mL), dried (Na2S04) and concentrated under reduced pressure to give the acylated product in 51%-84% yield. The crude materials were further processed as indicated below to provide the title compounds. Example Acylating Agentt Conditions Resulting Compound 295 Methanesulfonyl chloride 1)EC 2)S2 N-{4-l6-(5-Methyl-hexahydro-pyrro!o[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-methanesulfonamide fumarate'H NMR (D20,300 MHz) .5 2.89 (s, 3 H) 3.07 (s, 3 H) 3.22 ■ 3.56 (m, 4 H) 3.58 - 3.78 (m, 4 H) 3.82 - 4.05 (m, 2 H) 5.48 (s, 2 H) 7.18 (d, J=9.5 Hz, 1 H), 7.20 - 7.34 (m, 2 H) 7.66 - 7.80 (m, 2 H) 7.86 (d. J=9.5 Hz, 1 H); MS ■168- WO 2005/028477 PCT/US2004/030735 (DCI/NH3) m/z 374 (M+H)T; Anal. C^NsOjS-I.O C4H404'2.6H20: C,H, N. 296 Benzoyl chloride 1)FB 2)S2 N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yI]-phenyl}-benzamide fumarate'H NMR (MeOD-d*, 300 MHz) 8 3.12 - 3.21 (m, 2 H) 3.25 -3.30 (m, 2 H) 3.48 - 3.59 (m, 2 H) 3.62 - 3.71 (m/l H) 3.75 - 3.83 (m, 2 H) 6.72 (s, 1 H) 7.07 (d. J=8.9 Hz, 1 H) 7.48 - 7.55 (m, 2 H) 7.55 - 7.60 (d, J=8.9 Hz. 1 H) 7.70 -7.75 (m, 2 H) 7.83 - 7.90 (m, 2 H) 7.93 - 8.00 (m, 3 H); MS (DCI/NHa) m/z 386 (M+Hf; Anal. C^HoNsOO.? C4H4O4: C, H. KL 297 Methanesulfonyl chloride 1)FB 2)S2 N-{4-[6-(Hexahydropyrrolo[3,4-c]pyrrol-2-yI)-pyridazin-3-yQ-phenyl}-methanesuIfonamidefumarate'H NMR (D20.300 MHz) 5 3.04 (s, 3 H) 3.18 - 3.30 (m, 4 H) 3.47 - 3.55 (m, 2 H) 3.54 - 3.69 (m. 4 H) 6.41 (s, 1 H) 6.95 (d, J=9.5 Hz. 1 H) 7.19 - 7.25 (m, 2 H) 7.63 (d, J=9.8 Hz, 1 H) 7.65-7.70 (m, 2 H);MS (DCI/NHj) m/z 360 (M+H)*; Anal. Ci7H2,N5O2S'0.8 C4H4O4: C, H, N. 298 Dimethyl sulfamoyl chloride 1)FB 2)S2 N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl>-pyridazin-3-yl]-phenyl}-dimethylaminosulfonamide fumarate'H NMR (DzO, 300 MHz) 8 2.73 (s, 6 H) 3.20 - 3.31 (m, 2 H) 3.30 - 3.39 (m, 2 H) 3.56 - 3.67 (m, 4 H) 3.76 - 3.87 (m, 2 H) 6.49 (s, 4 H) 7.17 - 7.25 (m. 2 H) 7.29 (d. J=9.8 Hz. 1 H) 7.66 - 7.74 (m, 2 H) 7.89 (d, J*=9.8 Hz, 1 H); MS (DCI/NH3) m/z 389 (M+H)* 299 Acetic anhydride 1)FB 2)S4 ^4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-acetamidetrifluoroacetate'H NMR (MeOD-d<, 300 MHz) S £15 (s, 3 H) 3.26 - 3.40 (m, 4 H) 3.58 - 3.67 (m, 2 H) 3.67 - 3.74 (m, 2 H) 3.76 -3.86 (m, 2 H) 7.25 (d. J=9.6 Hz. 1 H) 7.66 - 7.75 (m. 2 H) 7.86 - 7.95 (m, 2 H) 8.00 (d, J=9.5 Hz, 1 H);MS PCI/NH3) TI/Z 324 (M+H)*; Anal. CwHaNsO-LSC^HFaOz: C, H, N. 300 Acetic anhydride 1)FB2)RA• 3)S4 N-{4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-acetamide trifluoroacetate -169- WO 2005/028477 PCT/US2004/030735 'H NMR (MeOD-cU, 300 MHz) S 2.15 (s, 3 H) 2.96 (s, 3 H) 3.33 - 3.43 (m, 4 H) 3.57 - 3.74 (m, 4 H) 3.75 - 3.84 (m, 2 H) 7.16 (d, J=9.5 Hz, 1 H) 7.65 - 7.72 (m, 2 H) 7.85 - 7.92 (m, 2 H) 7.90 (d, J=9.4 Hz. 1 H); MS (DCI/NH3) m/z 338 (M+Hf; Anal. CuHaNsO-CzHFaOj: C, H, N. Example 301 2-(2-Phenvl-pvrimidin-5-yl)-octahvdro-pvrrolor3,4-clpvrrole Example 301A 5-Pvrimidin-5-vl-hexahvdro-pyrrolor3,4-clpvrrole-2-carboxvlic acid tert-butvl ester A mixture of the product of Example 6C (2.045 g, 9.63 mmol), 5-bromopyrimidine (1.84 g, 11.6 mmol), tris(dibenzylideneacetone)dipalladium (0) Pd2(dba)3, Strem, 0.265 g, 0.29 mmol), racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP, Strem, 0.30 g, 0.48 mmol) and tert-BuONa (sodium tert-butoxide, 1.85 g, 19.3 mmol) in 75 mL PhCH3 was degassed three times with a N2 back-flush. The mixture was warmed to 85 °C, stirred for 48 h then was cooled, filtered and concentrated under reduced pressure. Purification by column chromatography (Si02, 50% hexanes-EtOAc) gave 2.68 g of the title compound (9.23 mmol, 95% yield). MS (DCI/NH3) m/z 291 (M+H)+. Example 301B 5-(2-Bromo-pvrimidin-5-vl)-hexahvdro-pvrrolof3,4-clpyrrole-2-carboxylic acid tert-butvl ester To a solution of the product of Example 301A (2.68 g, 9.23 mmol) in 75 mL of CH3CN at 0 °C was added N-bromosuccinimide (NBS, 1.64 g, 9.23 mmol) in 50 mL CH3CN portionwise via cannula. The mixture was allowed to warm to ambient temperature and stir for 16 h. The reaction mixture was quenched by the addition of 25 mL H2O then 50 mL CH2CI2 was added. The layers were separated and the aqueous layer was extracted 3 X 20 mL CH2CI2. The combined organic layers were washed with 10 mL saturated, aqueous NaCI (brine), then were dried over Na2SC>4, and concentrated under reduced pressure. Purification via column chromatography -170- WO 2005/028477 PCT/US2004/030733 (Si02) 75% hexanes-EtOAc) gave 1.2 g of the title compound (3.25 mmol, 35% yield). MS (DCI/NH3) m/z 369, 371 (M+H)+. Examples 301 - 304 The product of Example 301B was coupled with an aryl boronic acid and further processed by methods listed in the table below to provide the title compounds: Example Boronic Acid Conditions Resulting Compound 301 Phenyl boronic acid 1) H2) FB3) S1 2-(2-Phenyl-pyrimidin-5-yl)-octahydro-pyrrolo[3,4-c]pyrrolep-toluenesulfonate'H NMR (CHjOH-d,, 300 MHz) 8 2.35 (s, 3H). 3.27 (m, 4H), 3.45 (m, 2H), 3.59 (m, 4H), 7.20 (m, 2H), 7.42 (m, 3H). 7.69 (m, 2H), 8.22 (m, 2H), 8.30 (s, 2H); MS (DCI/NH3) mfe 267 (M+Hf; Anal, calculated for CwH^-I^SCrHeOaS: C, 61.73; H. 5.86; N, 11.63; Found: C, 61.47; H, 5.85; N, 11.71. 302 Phenyl boronic acid 1) H2) FB3) RA4) S1 2-Methyl-5-(2-phenyl-pyrimidin-5-yl)-octahydro-pyrrolo[3,4-c]pyrroIep-toluenesulfonate1H NMR (CH3OH-d4l 300 MHz) 5 2.35 (s, 3H). 2.95 (s, 3H), 3.30 (m, 2H), 3.35 (m. 4H), 3.65 (m, 4H), 7.21 (m, 2H). 7.43 (m, 3H), 7.69 (m, 2H), 8.23 (m, 2H). 8.36 (s, 2H); MS (DCI/NH3) m/z 281 (M+Hf; Anal, calculated for C17H2oN4-C7HB03S: C, 63.69; H. 6.24; N, 12.38; Found: C, 63.32; H, 6.12; N, 12.07. 303 o-methoxyphenyl boronic acid 1), H2) DeMe3) FB4) S1 2-[5-(Hexahydro-pyrrolo[3,4-c]pyrroI-2-yl)-pyrimidin-2-yl]-phenol p-to!uenesulfonate'H NMR (300 MHz, CD3OD) 8 ppm 0.93 (m. 1 H), 1.35 (m, 1 H), 2.35 (s, 3 H), 3.30 (m, 2 H). 3.56 (m, 6 H), 6.91 (m, 2 H), 7.22 (m, 2 H), 7.28 (ddd, J=8.1, 7.1,1.7 Hz, 1 H). 7.69 (m, 2 H), 8.30 (dd, J=8.1,1.7 Hz, 1 H), 8.37 (s, 2 H); MS (DCI/NH3) m/z 283 (M+H)*; Anal, calculated for dsH^O* 1.5CTHe03S-H20: C, 56.97; H, 5.77; N, 10.03. Found: C, 57.04; H, 5.44; N. 10.30. 304 o-methoxyphenyl boronic acid 1) H2) DeMe3) FB4) RA5) S1 2-f5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-yl]-phenoi p-toluenesulfonate 1HNMR (300 MHz, CD3OD) D ppm 2.35 (s, 3 H), 2.95 (s, 3 H), 3.28 (m, 4 H), 3.37 (m. 3 H), 3.67 (m, 3 H), 6.89 (m, 2 H), 7.22 (m, 2 H), 7.27 (dd, J=7.5,1.7 Hz, 1 H), 7.69 (m, 2 H), 8.30 (dd, J=8.3,1.9 Hz, 1 H). 8.40 (s, 2 H); MS (DCI/NH3) m/z 297 (M+H)*; Anal, calculated for CBHWNIO' C7H8O3S'0.25H2O: C, 60.93; H, 6.07; N, 11.84. Found: C, 60.84; H, 5.98; N, 11.58. Example 305 5-(4-Bromo-phenyl)-hexahvdro-pyrrolof3.4-clpyrrole-2-carboxvlic acid tert-butyl ester -171- WO 2005/028477 PCT/US2004/030735 The product of Example 6'C (0.75 g, 3.53 mmol), 1,4-dibromobenzene (0.83 g, 3.53 mmol), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3, Strem, 65 mg, 0.071 mmol), racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BiNAP, Strem, 88 mg, 0.14 mmol), and NaOt-Bu (0.54 g, 5.6 mmol) were combined in toluene (15 mL). This mixture was stirred at 100 °C for 24 h. The reaction mixture was cooled to ambient temperature, filtered, concentrated under reduced pressure and purified by column chromatography (Si02, 70% hexanes in EtOAc) to give the title compound (0.65 g, 1.8 mmol, 50% yield). MS (DCI/NH3) m/z 367 (M+H)+. Examples 306 - 309 The intermediate Example 305 was coupled with an aryl boronic acid and further processed by methods listed to provide the title compounds: Example Boronic Acid Conditions Resulting Compound 306 3-pyridinyl boronic acid D G2) FB3) S4 2-(4-Pyridin-3-yl-phenyl)-octahydro-pyrrolo[3,4-cjpyrrole bis- trifluoroacetate 'H NMR (300 MHz,CD3OD) 8 ppm 3.25 (m. 4 H). 3.45 (m, 2 H), 3.53 (m, 2 H). 3.63 (m, 2 H), 6.89 (m, 2 H). 7.67 (m. 2 H), 7.86 (dd, J=8.1. 5.4 Hz, 1 H), 8.56 (m. 2 H). 8.95 (s, 1 H); MS (DCI/NH3) m/z 266 (M+Hf; Anal, calculated for C,7Hi9N3- 2CF3C02H •0.5H2O: C, 50.20; H, 4.41; N, 8.38. Found: C, 50.51; H. 4.29; N, 8.1£ 307 3-pyridinyl boronic acid 1) G2) FB3) RA4) S1 2-Methyl-5-(4-pyridin-3-yl-phenyl)-octahydro-pyrrolo[3,4-c]pyrrole p-toluenesulfonate H NMR(300 MHz, CD3OD).S ppm 2.36 300 MHz) 8 2.87 (s, 3 H), 3.19 - 3.39 (m, 4 H), 3.52 - 3.68 (m, 4 H), 3.73 - 3.81 (m, 2 H), 3.84 (s, 3 H). 6.53 (d, J=3.1 Hz, 1 H), 6.68 (s, 2 H), 7.16 (d, J=9.5 Hz, 1 H), 7.22 (d, J=3.1 Hz, 1 H), 7.48 (d, J=8.5 Hz, 1 H), 7.79 (dd, J=8.8, 1.7 Hz, 1 H), 7.94 (d, J=9.5 Hz, 1 H), 8.10 ppm (d, J=1.4 Hz, 1 H); MS (DCI/NH3) m/z 334 (M+H)+; Anal. C2oH23N5*1.14C4H404: C, H, N. Example 311 Dimethyl-{5-f6-(5-methvl-hexahvdro-pvrrolof3,4-clpvrrol-2-vl)-pvridazin-3-vl1-1H- indol-3-vlmethyl)-amine fumarate The product of Example 115 was converted to the free base by method FB. The free base (90 mg, 0.28 mmol), 37% formaldehyde solution (34 mg, .0.42 mmol) and 2M dimethylamine solution in THF (0.21 ml, 0.42 mmol) were combined in dioxane (1 mL) and HOAc (1 mL), and the mixture was stirred at room temperature for 4 h. The mixture was concentrated, and the residue was purified by preparative HPLC (Xterra® column, NH4HCO3-CH3CN). The product was converted to thte title compound according to method S2 (81 mg, 50% yield): 1H NMR (CH3OH-d4, 300 MHz) 8 ppm 2.78 - 2.85 (m, 9 H), 3.32 - 3.41 (m, 4 H), 3.42 - 3.49 (m, 2 H), 3.61 (dd, J=10.8, 6.9 Hz, 2 H), 3.84 (d, J=11.9 Hz, 2 H), 4.50 (s, 2 H), 6.52 (s, 3 H), 7.08 (d, J=9.5 Hz, 1 H), 7.49 - 7.57 (m, 2 H), 7.78 (dd, J=8.7,1.4 Hz, 1 H), 7.85 (d, J=9.5 Hz, 1 H), 8.22 (s, 1 H); MS (DCI/NH3) m/z 377 (M+H)+; Anal. C^H^Ne'l .6C4H4(VH20: C, H, N. -173- WO 2005/028477 PCT/US2004/030735 Example 312 (1S, 5S)-6-r6-(6-Methyl-3,6-diaza-bicvdof3.2.01hept-3-vl)-pvridazin-3-vll-2,3,4,9- tetrahydro-1 H-carbazole Bis(trifluoroacetate) Example 312A v N-(4-f6-(6-Methvl-3,6-diaza-bicvclof3.2.01hept-3-vl)-pvridazin-3-vn-phenvl)-hydrazinecarboxylic acid tert-butvl ester The free base of the product of Example 85 (790 mg, 2 mmol), tert-butyl carbazate (317 mg, 2.4 mmol), cesium carbonate (910 mg, 2.8 mmol) and Cul (29 mg, 0.15 mmol) were combined in DMF (8 mL). The mixture was stirred at 80°C under N2 for 16 hours. The reaction mixture was purified via column chromatography (Si02,10% CH2CI2-MeOH) to give 0.6 g of the title compound (1.5 mol, 75% yield). 1H NMR (300 MHz, CD3OD) 5 1.52 (s, 9 H), 2.41 (s, 3 H), 3.18 - 3.41 (m, 4 H), 3.59 (dd, J=11.4, 8.3 Hz, 1 H), 3.94-4.03 (m, 2 H), 4.06 (dd, J=6.8, 4.4 Hz, 1 H), 7.15 (d, J=9.5 Hz, 1 H), 7.58 (d, J=8.8 Hz, 2 H), 7.85 - 7.94 ppm (m, J=9.2, 7.1 Hz, 3 H); MS (DC!/NH3) m/z 397 (M+H)+. Example 312B 6-f6-(6-Methvl-3,6-diaza-bicvclor3.2.01hept-3-vl)-pyridazin-3-vn-2,3,4,9-tetrahvdro- 1 H-carbazole bis (trifluoroacetate) The product of Example 312A (200 mg, 0.5 mmol), cyclohexanone (98 mg, 1 mmol) and p-toluenesulfonic acid (30 mg, 0.15 mmol) were combinedin EtOH (3 mL), and the mixture was heated in the microwave reactor to 150°C for 10 minutes. The crude reaction mixture was purified by preparative HPLC (Xterra® column, 0.1% TFA-CH3CN), to provide the title compound (19.9 mg, 6% yield). 1H NMR (300 MHz, CD3OD) 8 1.85 - 2.01 (m, 4 H), 2.72 - 2.82 (m, 5 H), 2.96 - 3.09 (m, 2 H), 3.43 - 3.70 (m, 4 H), 4.06 - 4.28 (m, 2 H), 4.52 - 4.64 (m, 1 H), 4.95 - 5.09 (m, 1 H), 7.46 (d, J=8.5 Hz, 1 H), 7.60 (dd, J=8.5, 2.0 Hz, 1 H), 7.80 (d, J=9.8 Hz, 1 H), 8.00 (d, J=1.7 Hz, 1 H), 8.42 ppm (d, J=9.8 Hz, 1 H); MS (DCI/NH3) m/z 360 (M+H)+; Anal, calculated for C22H25N5'2.5C2F3HO2*0.3H2O: C, 49.90; H, 4.36; N, 10.78. Found: C, 49.85; H, 4.51; N 10.89. Example 314 -174- Jfc WO 2005/028477 PCT/US2004/030735 2-(5-Phenvl-1H-pyrazol-3-vn-2,5-diaza-bicvclof2.2.nheptanebis-iP-toluenesulfonate Example314A 5-n-Methvlsulfanyl-3-oxo-3-phenvl-propenvl)-2,5-diaza-bicvclor2.2.nheptane-2- carboxylic acid tert-butyl ester 3,3-Bis-methylsulfanyl-1-phenyl-propenone (0.675 g, 3.0 mmol), was prepared according to literature procedure (Galli, f. et al WO 01/92251 A1) and was combined with the product of Example 24 (0.200 g, 1.0 mmol) in 10 mL MeOH. This mixture was warmed to 70 °C for 4 h then was cooled to ambient temperature, concentrated under reduced pressure and purified via column chromatrography (Si02) 10% CH3. OH - CH2CI2 with 1% NH4OH) to give 0.159 g of the title compound (0.38 mmol, 38% yield). MS (DCI/NH3) m/z 375 (M+H)+. Example314B 5-(5-Phenvl-1 H-pvrazol-3-yl)-2,5-diaza-bicvclof2.2.1lheptane-2-carboxylic acid tert-butyl ester The product of example 314B (0.143 g, 0.42mmol), hydrazinel .0M solution in THF (1.7mL , 1.7mmol), sodium acetate (0.13 g, 1.3 mmol) were combined in toluene (4mL), acetic acid (2ml_), water (0.5 mL), and ethanol. The mixture was heated to reflux for 8 h. The mixture was poured into saturated Aq sodium carbonate and extracted with EtOAc the organics were dried over MgS04 and concentrated under reduced pressure. The residue was purified by column chromatography (Si02,10% CH3OH - CH2CI2 with 1% NH4OH) to provide the title compound (0.088 g, 0.24 mmol, 57% yield). MS (DCI/NH3) m/z 356 (M+H)+. Example314C 2-(5-Phenvl-1H-pvrazol-3-vl)-2,5-diaza-bicvclof2.2.nheptanebis-p-toluenesulfonate The product of Example 314B was processed according to method FB, and S1 to provide the title salt. 1H NMR (CH3OH-d4, (300 MHz) 5 2.04 - 2.20 (m, 2 H) 2.26 -2.42 (m, 6 H) 3.35 - 3.44 (m, 1 H) 3.45 - 3.66 (m, 2 H) 3.66 - 3.86 (m, 1 H) 4.49 -4.72 (m, 2 H) 6.28 - 6.47 (m, 1 H) 7.14 - 7.30 (m, 5 H) 7.45 - 7.59 (m, 1 H) 7.62 - -175- PCT/US2004/030735 7.83 ppm (m, 7 H). MS (DCI/NH3) m/z 241 (M+H)+> Anal, calculated for Ci4Hi6N4-2.C7H8O3S-0.: C, 57.51; H, 5.52; N, 9.58. Found: C, 57.39; H, 5.19; N, 9.14 Example 315 Example 315A Benzyl (1S,5S)-6-(5-cvano-3-pvridinvl)-3.6-diazabicvclor3.2.01heptane-3-carboxvlate The product of Example 7J (830 mg, 3.58 mmol) in toluene (20 mL) was treated with Pd2(dba)3 (71.0 mg, 0.072 mmol), BINAP (134 mg, 0.214 mmol), Cs2C03 (2.32g, 7.16 mmol) and 3-bromo-5-cyanopyridine (0.98 g, 5.37 mmol). The mixture was heated at 100 °C under N2 for 10 hours and then allowed to cool to room temperature and diluted with ethyl acetate (100 mL). The brown solution was washed with water (2x10 mL) and concentrated under reduced pressure. The residue was purified by chromatography (SiC>2, EtOAc.hexane, 50:50, Rf 0.3) to provide the title compound (770 mg, 64% yield). 1H NMR (MeOH-d4, 300 MHz) 5 3.2(dd, J=12.9,4.Hz, 1H), 3.30-3.4(m, 2H), 3.6(dd, J=8.2, 3.Hz, 1H), 3.96-4.10 (m, 3H),4.74 (dd, J=6.1,4.0 Hz, 1H), 5.10 (m, 2H), 7.15 (dd, J=2.7,1.7 Hz, 1H), 7.25 (m, 3H), 7.35 (m, 2H), 7.96 (d, J=2.7 Hz, 1H), 8.15 (d, J=1.7 Hz, 1H); MS (DCI/NH3) m/z 335 (M+H)+. Example 315B Benzyl (1S,5S)-6-(6-bromo-5-cvano-3-pvridinvO-3,6-diazabicvclor3.2.01heptane-3- carboxylate The product of Example 315A was treated with N-bromosuccinimide in acetonitrile according to the method of Example 301B to provide the title compound: MS (DCI/NH3) m/z 413/415 (M+H)+. Example 315C Benzyl (1Sf5SV6-(6-f2-thienvn-5-cvano-3-pvridinvl)-3,6~diazabicvclof3.2.01heptane- 3-carboxylate The product of Example 315B was coupled with 2-thienyl boronic acid according to the procedure of method I to provide the title compound: MS (DCI/NH3) m/z417(M+H)+. -176- » WO 2005/028477 PCT/US2004/030735 Example 315D (1R. 5S)- 5-f3.6-Diaza-bicvclo[3.2.01hept-6-vn-2-thiophen-2-yl-nicotinonitrile trifluoroacetate The product of Example 315C was stirred in trifluoroacetic acid at 65 °C for-2 h, then cooled to room temperature and concentrated under vacuum. The residue was triturated with 10% methanol in ether to provide tht title compound: 1H NMR (MeOH-D4, 300 MHz) D 3.20 (dd, J=12.9, 3.8 Hz, 1 H), 3.33 - 3.42 (m, 1 H), 3.41 - 3.61 (m, 1 H), 3.66 - 3.89 (m, 3 H), 4.13 (t, J=8.1 Hz, 1 H), 5.01 (dd, J=6.6, 3.6 Hz, 1 H), 7.14 (dd, J=5.1, 3.7 Hz, 1 H), 7.36 (d, J=2.7 Hz, 1 H), 7.53 (d, J=5.1 Hz, 1 H), 7.95 (d, J=3.7 Hz, 1 H), 8.10 (d, J=3.1 Hz, 1 H); MS (DCI/NH3) m/z 283 (M+H)+; Anal. Calculated for C15H14N4S*1.i2CF3C02H '1.90H2O: C, 54.08; H, 5.64; N, 9.83. Found: C, 54.33; H, 5.30; N, 9.46. Example 316 (1R. 5S)- 5-(3-Methvl-3,6-diaza-bicvclo[3.2.01hept-6-vl)-2-thiophen-2-yl-nicotinonitrile fumarate The product of Example 315D was processed according to method RA, then converted to the salt according to method S2: 1H NMR (MeOH-D4, 300 MHz) 5 2.82 - 2.93 (m, 4 H), 3.00 (dd, J=11.7, 7.0 Hz, 1 H), 3.39 - 3.58 (m, 1 H), 3.73 (d, J=11.9 Hz, 1 H), 3.77 - 3.91 (m, 2 H), 4.10 (t, J=8.1 Hz, 1 H), 4.96 (dd, J=6.8, 3.4 Hz, 1 H), 6.69 (s, 2 H), 7.13 (dd, J=5.1, 3.7 Hz, 1 H), 7.30 (d, J=2.7 Hz, 1 H), 7.52 (d, J=5.1 Hz, 1 H), 7.93 (d, J=3.7 Hz, 1 H), 8.07 (d, J=3.1 Hz, 1 H); MS (DCI/NH3) m/z 297 (M+H)+; Anal. Calculated for C16H16N4S-1.10 C4 H404 -1.10H2O: C, 62.26; H, 6.25; N, 10.18. Found: C, 62.34; H, 6.31; N, 10.43. Example 318 (1S, 5SV 3-(4-Pvridin-3-vl-phenvl)-3,6-diaza-bicvclof3.2.01heptane bisfp- toluenesulfonate) Example 318A (1S. 5R)- 3-(4-bromophenyl)-3,6-diaza-bicvclof3.2.01heptane-6-carboxvlate -177- WO 2005/028477 PCT/US2004/030735 t-butyl ester The product of Example 8B was coupled with p-dibromobenzene according to the procedure of Example 128A to provide the title compound. Example!? 18B (1S, 5S)- 3-(4-Pvridin-3-yl-phenvO-3.6-diaza-bicvclor3.2.01heptane bis(p- toluenesulfonate) The product of Example 318A was coupled with pyridine-3-boronic acid according to the procedure of Method I. The product was further processed according to method FB and method S1 to provide tht title compound: 1H NMR (MeOH-D4, 300 MHz) 8 2.37 (s, 6 H) 3.02 (dd, J=10.5, 6.1 Hz, 1 H), 3.10 (dd, J=12.5,4.7 Hz, 1 H), 3.39 - 3.60 (m, 1 H), 3.75 (dd, J=11.0, 5.3 Hz, 1 H), 3.93 (d, J=10.9 Hz, 1H), 4.14 (d, J=12.5 Hz, 1 H), 4.25 (dd, J=10.8, 8.5 Hz, 1 H), 5.02 (dd, J=7.0, 4.9 Hz, 1 H), 6.93 - 7.16 (m, 2 H) 7.23 (d, J=8.1 Hz, 4 H) 7.47 (dd, J=8.0, 4.9 Hz, 1 H) 7.56 - 7.66 (m, 3 H) 7.64 - 7.80 (m, 4 H) 7.95 - 8.15 (m, 1 H) 8.44 (dd, J=4.9,1.5 Hz, 1 H) 8.75 (d, J=1.7 Hz, 1 H); MS (DCI/NH3) m/z 252 (M+H)+; Anal. Calculated for Ci6H17N3-2.20 C7H8S03 '0.50^0: C, 59.00; H, 5.61; N, 6.57. Found: C, 58.75; H, 5.72; N, 6.75. Example 319 (1S. 5S)- 6-Methyl-3-(4-pvridin-3-yl-phenvl)-3,6-diaza-bicvclor3.2.01heptane bis(p- toluenesulfonate) The product of Example 318A was coupled with pyridine-r3-boronic acid according to method I, and further processed according to methods FB, RA,a nd S1 to provide the title compound: 1H NMR (MeOH-D4, 300 MHz) 8 2.39 (S, 6 H), 2.89 -2.90 (m, 4 H), 3.11 (dd, J=13.2,4.7 Hz, 1 H), 3.38 - 3.62 (m, 1 H), 3.94 (d, J=9.8 Hz, 1 H), 4.01 - 4.16 (m, 2 H), 4.16 - 4.34 (m, 1 H), 4.72 - 5.05 (m, 1 H), 7.08 (d, J=8.5 Hz, 2 H), 7.22 (d, J=8.1 Hz, 4 H), 7.51 - 7.91 (m, 6 H) 8.35 (d, J=8.1 Hz, 1 H), 8.55 (d, J=3.7 Hz, 1 H), 8.89 (s (br.), 1 H); MS (DCI/NH3) m/z 266 (M+H)+; Anal. Calculated for Ci7H19N3«2.00 C7H8S03 '0.60^0: C, 60.00; H, 5.88; N, 6.77. Found: C, 59.92; H, 5.72; N, 6.74. -178- WO 2005/028477 PCT/US2004/030735 Example 320 (1S, 5S)- 5-r4-(3,6-Diaza-bicyclor3.2.01hept-3-vl)-phenvn-3-methvl-1H-indazole bis(p- toluenesulfonate) The product of Example 318A was coupled with the product of Example 212A according to the procedure of Example 212B. The product was further processed according to methods FB and S1 to provide the title compound: 1H NMR (MeOH-D4, 300 MHz) 5 2.28 (s, 6 H), 2.53 (s, 3 H), 2.59 (d, J=9.8 Hz, 1 H), 2.91 (dd, J=10.3, 5.9 Hz, 1 H), 3.02 (dd, J=11.7,4.9 Hz, 1 H), 3.33 - 3.44 (m, 1 H), 3.89 (d, J=10.5 Hz, 1 H) ,4.04 - 4.21 (m, 2 H), 4.87 - 5.05 (m, J=4.7 Hz, 1 H), 6.96 (d, J=8.5 Hz, 2 H), 7.10 (d, J=7.8 Hz, 4 H), 7.41 - 7.54 (m, 5 H), 7.56 - 7.69 (m, 3 H), 7.90 (s, 1 H); MS (DCI/NH3) m/z 305 (M+H)+; Anal. Calculated for C19H2oN4-2.00 C7H8S03 -0.60H2O: C, 59.84; H, 5.60; N, 8.46. Found: C, 60.04; H, 5.72; N, 8.70. Example 321 DETERMINATION OF BIOLOGICAL ACTIVITY To determine the effectiveness of representative compounds of this invention i as ct7 nAChRs, the compounds of the invention were evaluated according to the [3H]-methyllycaconitine (MLA) binding assay and considering the [3H]-cytisine binding assay, which were performed as described below. [3H]-Cvtisine binding Binding conditions were modified from the procedures described in Pabreza LA, Dhawan, S, Kellar KJ, [3H]-Cytisine Binding to Nicotinic Cholinergic Receptors in Brain, Mol. Pharm. 39:9-12,1991. Membrane enriched fractions from rat brain minus cerebellum (ABS Inc., Wilmington, DE) were slowly thawed at 4 °C, washed and resuspended in 30 volumes of BSS-Tris buffer (120 mM NaCI/5 mM KCI/2 mM CaCI2/2 mM MgCI2/50 mM Tris-CI, pH 7.4,4 °C). Samples containing 100-200 ug of protein and 0.75 nM [3H]-cytisine (30 C/mmol; Perkin Elmer/NEN Life Science Products, Boston, MA) were incubated in a final volume of 500 uL for 75 minutes at 4 °C. Seven log-dilution concentrations of each compound were tested in duplicate. Non-specific binding was determined in the presence of 10 uM (->-nicotine. Bound radioactivity was isolated by vacuum filtration onto prewetted glass fiber filter plates -179- WO 2005/028477 PCT/US2004/030735 (Millipore, Bedford, MA) using a 96-well filtration apparatus (Packard Instruments, Meriden, CT) and were then rapidly rinsed with 2 mL of ice-cold BSS buffer (120 mM NaCI/5 mM KCI/2 mM CaCI2/2 mM MgCI2). Packard MicroScint-20® scintillation cocktail (40 uL) was added to each well and radioactivity determined using a Packard TopCount® instrument. The IC50 values were determined by nonlinear regression in Microsoft Excel® software. Kj values were calculated from the IC50S using the Cheng-Prusoff equation, where Kj = IC5o/1+[Ligand]/KD]. r3H1-Methvlvcaconitine (MLA) binding Binding conditions were similar to those for [3H]-cytisine binding. Membrane enriched fractions from rat brain minus cerebellum (ABS Inc., Wilmington, DE) were slowly thawed at 4 °C, washed and resuspended in 30 volumes of BSS-Tris buffer (120 mM NaCI, 5 mM KCI, 2 mM CaCI2, 2 mM MgCI2, and 50 mM Tris-CI, pH 7.4, 22 °C). Samples containing 100-200 ug of protein, 5 nM [3H]-MLA (25 Cj/mmol; Perkin Elmer/NEN Life Science Products, Boston, MA) and 0.1% bovine serum albumin (BSA, Millipore, Bedford, MA) were incubated in a final volume of 500 uL for 60 minutes at 22 °C. Seven log-dilution concentrations of each compound were tested in duplicate. Non-specific binding was determined in the presence of 10 uM MLA. Bound radioactivity was isolated by vacuum filtration onto glass fiber filter plates prewetted with 2% BSA using a 96-well filtration apparatus (Packard Instruments, Meriden, CT) and were then rapidly rinsed with 2 mL of ice-cold BSS. Packard MicroScint-20® scintillation cocktail (40 uL) was added to each well and radioactivity was determined using a Packard TopCount® instrument. The IC50 values were determined by nonlinear regression in Microsoft Excel® software. Kj values were calculated from the IC50S using the Cheng-Prusoff equation, where Kj = IC50/1+[Ligand]/KD]. Compounds of the invention had Kj values of from about 1 nanomolar to about 10 micromolar when tested by the MLA assay, many having a Kj of less than 1 micromolar. [3H]-Cytisine binding values of compounds of the invention ranged from about 50 nanomolar to at least 100 micromolar. The determination of preferred compounds typically considered the Kj value as measured by MLA assay in view of the Kj value as measured by [3H]-cytisine binding, such that in the formula D = KJMLA/ -180- WO_2005/028477 PCT/US2004/030735 Ki 3H-cytisine» D is about 50. Preferred compounds typically exhibited greater potency at cc7 receptors compared to cc4p2 receptors. Compounds of the invention are a.7 nAChRs ligands that modulate function of oc7 nAChRs by altering the activity of the receptor. The compounds can be inverse agonists that inhibit the basal activity of the receptor or antagonists that completely block the action of receptor-activating agonists. The compounds also can be partial agonists that partially block or partially activate the a7 nAChR receptor or agonists that activate the receptor. It is understood that the foregoing detailed description and accompanying examples are merely illustrative and are not to be taken as limitations upon the scope of the invention, which is defined solely by the appended claims and their equivalents. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications, including without limitation those relating to the chemical structures, substituents, derivatives, intermediates, syntheses, formulations and/or methods of use of the invention, may be made without departing from the spirit and scope thereof. -181- WO 2005/028477 PCT/US2004/030735 We CLAIM.- 1. A compound of the formula (I): Z-Ari-Ar2 (I) or a pharmaceutical^ acceptable salt, ester, amide, or prodrug thereof, wherein: Z is a diazabicyclic amine of the formula: R2 CCH^T (CH2)0 (CH2);A^CH2>P R2 (II) An is a 5- or 6-membered aromatic ring of the formula (a) or (b): Y1 Y2 Y4- s / ^\ \ > -& Y3 (a) or (b) Ar2 is selected from the group consisting of an unsubstituted or substituted 5-or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl is substituted with 0,1, 2, or 3 substituents selected from the group consisting of alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, arylcarbonyl, alkylcarbonyioxy, alkylsulfonyl, alkylthio, alkynyl, carboxy, cyano, formyl, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, nitro, -NRARB, (NRARB)alkyl, (NRARB)carbonyl, (NRARB)sulfonyl, and phenyl; provided that when Y1 is O or S, Y2 is N, Y3 is -CR3 and R3 is hydrogen, and Y4 is C, then Ar2 is not 5-tetrazolyI; -182- WO 2005/028477 PCT/US2004/030733 Xi, X2l X3, and X4 are each independently selected from the group consisting of N and -CR3, provided that R3 is not hydrogen at least in one occurrence when Xi, X2, X3, and X4 are all -CR3; Yi, Y2, and Y3 are each independently selected from the group consisting of N, O, Brand -CR3; Y4 is selected from the group consisting of C and N, provided that when Y4 is C at least one of Y1, Y2, and Y3, is other than -CR3; I, m, n, o, and p are each independently selected from the group consisting of 0, 1, or 2, provided that the sum total of I, m, n, o, and p is 3, 4, or 5, and further provided that the sum of I and o is at least 1 and the sum of m and p is at least 1; R1 is selected from the group consisting of hydrogen, alkenyl, alkyl alkoxycarbonyl, arylalkyl, and heteroarylalkyl; R2 at each occurrence is independently selected from the group consisting of hydrogen, alkoxycarbonyl, and alkyl; R3 at each occurrence is independently selected from the group consisting of hydrogen and alkyl; RA and Rs are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, formyl and (NRcRo)sulfonyl; and Re and RD are each independently selected from the group consisting of hydrogen and alkyl. 2. The compound of claim 1, wherein Z is selected from the group consisting of: R1 -183- WO 2005/028477 PCTAJS2004/030735 3. The compound of claim 1, wherein An is selected from the group consisting of isoxazolyl, oxadiazolyl, oxazolyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, thiadiazolyl, isothiazolyl, thiazolyl, thienyl, and phenyl, wherein the pyridazinyl, pyridyl, and phenyl, are substituted with 0 or 1 substitutent selected from the group consisting of alkoxy, alkyl, cyano, and hydroxy. -184- 4. The compound of claim 1, wherein An is selected from the group consisting of: k WO 2005/028477 PCT/US2004/030735 Vs - • and R3 ' ^N wherein R3 is selected from the group consisting of hydrogen, alkoxy, alkyl, cyano, and hydroxy. 5. The compound of claim 1, wherein Ar2 is selected from the group consisting of benzofuranyl; benzothien'yl; carbazolyl; tetrahydrocarbazolyl; fury!; imidazolyl; 3-indolyl; 4- indolyl; 5-indolyl; isoxazolyl; naphthyl; pyrazolyl; pyridazinyl; pyridyl; pyrimidinyl; 2-pyrrolyl, 3-pyrrolyl; quinolinyl; thienyl; 3,4-(methylenedioxy)phenyl; and phenyl; wherein the phenyl is substituted with 0, 1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyi, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. -185- 6. The compound of .claim 1, wherein Ar2 is selected from the group consisting of: WO 2005/028477 PCTYUS2004/030735 R4 . R4 - and R4 • wherein R4 at each occurrence is independently selected from the group consisting of hydrogen, aikoxy, alkoxycarbonyl, alkyl, alkylcarbonyi, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB. (NRARB)alkyl, (NRARB)alkoxy, and phenyl. 7. The compound of claim 1, wherein Ar2 is selected from the group consisting of phenyl, para-acetylaminophenyl, meta-aminophenyl, para-aminophenyl, para(2-(diethylamino)ethoxy)phenyl, meta(2-(diethylamino)ethoxy)phenyl, para-(dimethylamino)phenyl, para-bromophenyl, meta-cyanophenyl, para-cyanophenyl, meta-hydroxyphenyl, para-hydroxyphenyl, para-iodophenyl, meta-methylphenyl, para-methylphenyl, 3,5-dimethylphenyl, meta-methoxyphenyl, para-methoxyphenyl, meta-trifluoromethoxyphenyl, meta-nitrophenyl, para-nitrophenyl, and meta-trifluoromethylphenyl. 8. The compound of claim 1, wherein Z is selected from the group consisting of -186- WO 2005/028477 PCT/US2004/030735 and ; and An is pyridazinyl. 9. The compound of claim 8, wherein Ar2 is phenyl substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. 10. The compound of claim 1, wherein Z is selected from the group consisting of X Rt—N \ and Ri -N- N—S- ; and An is selected from the group consisting of pyridazinyl and pyridyl. 11. The compound of claim 10, wherein Ar2 is selected from the group consisting of 3-indolyl, 5-indolyl; 1-methyl-3-indolyl, 1-methyl-5-indolyl, 3-methyl-5-indolyl, 3,4-(methylenedioxy)phenyl, and phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. 12. The compound of claim 1, wherein Z is R-N N-S- ; and API is pyridazinyl. -187- WO 2005/028477 PCT/US2004/030735 13. The compound of claim 12, wherein Ar2 is phenyl substituted with 0, 1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. 14. The compound of claim 1, wherein Z is Ri—N ; and An is pyridyl. 15. The compound of claim 14, wherein Ar2 is selected from the group consisting of heteroaryl and bicyclic heteroaryl, provided that Ar2 is not 1-pyrrolyl or 1-indolyl. 16. The compound of claim 14, wherein Ar2 is selected from the group consisting of furyl, benzothienyl, and phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. 17. The compound of claim 1, wherein Z is Ri_ N N-S- ; and An is selected from the group consisting of either isoxazolyl, oxadiazolyl, pyrazolyl, pyrimidinyl, thiadiazolyl, and thiazolyl. 18. The compound of claim 17, wherein Ar2 is selected from the group consisting of furyl and phenyl, wherein the phenyl is substituted with 0,1, or 2 substituents selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, -188- WO 2005/028477 PCT/US2004/030735 carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl, (NRARB)alkoxy, and phenyl. 19. The compound of claim 1, wherein Z is An is pyridazinyl, pyrimidinyl, or thiazolyl. 20. The compound of claim 19, wherein Ar2 is selected from the group consisting of 3,4-(methylenedidxy)phenyl and phenyl wherein the phenyl is substituted with 0, 1, or 2 substituents selected from the group consisting of alkbxy, alkoxycarbonyl, alkyl, alkylcarbonyl, carboxy, cyano, halogen, haloalkoxy, haloalkyl, hydroxy, nitro, -NRARB, (NRARB)alkyl. (NRARB)alkoxy, and phenyl. 21. The compound of claim 1, wherein n is 0. 22. The compound of claim 1, or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, selected from the group consisting of: 3-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[3.2.1]octane; 8-methyl-3-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[3.2.1]octane; 6-methyl-3-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.1]octane; 3-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 8-methyl-3-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 2-(6-phenyl-pyridazln-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-m-tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-methyl-5-(6-m-tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(4-methoxy-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-biphenyl-3-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-biphenyl-3-yl-pyridin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; -189- WO 2005/028477 PCT/US2004/030735 (1R, 5R)-1-{4-[5-(6-methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-phenyl}- ethanone; 6a-methyl-5-(6-m-tolyl-pyridin-3-yl)-octahydropyrroIo[3,4-b]pyrroie; 2-(5-phenyl-thiazo!-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-methyl-5-(5-phenyl-thiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 3-(6-Phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 8-(6-Phenyl-pyridazin-3-yI)-3I8-diaza-bicyclo[4.2.0]octane; 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[3.2.1]octane; 6a-Methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrroIo[3,4-b]pyrrole; 2-(6-Phenyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrrole-3a-carboxylicacid ethyl ester; 2,5-Bis-(6-phenyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c]pyrrole-3a-carboxylicacid ethyl ester; (1R, 5R)-6-(6-Phenyl-pyridazin-3-yl)-2,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-2-(6-Phenyl-pyridazin-3-yl)-2,6-diaza-bicyclo[3.2.0]heptane; Ethyl 2-Methyl-5-(6-phenyl-pyridazin-3-yl)-hexahydro-pyrrolo[3,4-c3pyrrole-3a- carboxylate; 5-Methyl-2-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c3pyridine; 1-Benzyl-6a-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-b]pyrrole; 3-Methyl-6-(6-phenyl-pyridazin-3-yl)-3,6-diaza-bicycIo[3.2.1]octane; 8-(6-Phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; S-Methyl-S^-phenyl-pyridazin-S-ylJ-S.S-diaza-bicyclo^^.Ojoctane; 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[3.2.1]octane; 1,6a-Dimethyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-b]pyrrole; 2-[6-(4-Bromo-phenyl)-pyridazin-3-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; (1S, 5S)- 3-[6-(4-Bromo-phenyl)-pyridazin-3-yl]-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)- S-te^-Bromo-phenylJ-pyridazin-S-yq-e-methyl-S.e-diaza- bicyclo[3.2.0]heptane; 3-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H-indole; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H-indole; (1R, 5R)-3-[6-(3,6-Diaza-bicyclot3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; -191- WO 2005/028477 PCT/US2004/030735 (1S, 5S)-3-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; (1R, 5R)-3-[6-(6-Methy!-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; 2-[6-(4-Nitro-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(2-Nitro1phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(3-Nitro-phenyi)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[6-(4-nitro-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[6-(3-nitro-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-lmidazol-1-yl-pyridazin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-lmidazol-1-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; (1R,5S)-6-[6-(4-lodo-phenyl)-pyridazin-3-yl]-3,6-diaza-bicyclo[3.2.0]heptane; (1S,5S)-3-[6-(4-lodo-phenyl)-pyridazin-3-yl]-3,6-diaza-bicyclo[3.2.0]heptane; (1S,5S)-3-[6-(4-lodo-phenyl)-pyridazin-3-yl]-6-methyl-3,6-diaza- bicyclo[3.2.0]heptane; 2-(5-Methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; . 2-(4-Methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(4-methyl-6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrroIe; 2-(6-o-ToIyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-p-Tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(3,'5-Dimethyl-phenyl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Furan-3-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Thiophen-3-yl-pyridazin-3-yl)-octahydro-pyrroIo[3,4-c]pyrroIe; 2-Methyl-5-(6-thiophen-3-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 5-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1 H-indole; 5-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1-methyl-1 H-indole; 2-Methyl-5-(6-o-tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-p-tolyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[6-(3,5-Dimethy(-phenyl)-pyridazin-3-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Furan-3-yl-pyridazin-3-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 3-Methyl-8-(6-phenyl-pyridazin-3-yl)-3,8-diaza-bicyclo[4.2.0]octane; 5-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1 H-indole; -192- WO 2005/028477 PCT/US2004/030735 3-Methyl-5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H- indole; 2-Methyl-5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]- phenylamine; 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenylamine; 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H-indole; 2-(6-Benzofuran-2-yl-pyridazin-3-yI)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 5-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-pyridin-2-ylamine; 2-Methyl-5-[6-(1H-pyrroI-3-yl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-thiophen-2-yl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[6-(1H-pyrazol-4-yl)-pyridazin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-9H-carbazole; 2-(6-Furan-2-yl-pyridazin-3-yl)-5-methyi-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-pyrimidin-5-yl-pyridin-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[5-(1H-pyrazol-4-yl)-pyridin-2-yl]-octahydro-pyrrolo[3,4-c]pyiTole; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-benzonitrile; 2-[5-(2-Methoxy-pyrimidin-5-yl)-pyridin-2-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-[5-(3,5-Dimethyl-1H-pyrazol-4-yl)-pyridin-2-yl]-5-rnethyl-octahydro-pyrrolo[3,4- c]pyrrole; 2-Methyl-5-[5-(1-methyl-1H-pyrazol-4-yl)-pyridin-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-[5-(3,5-Dimethyl-isoxazol-4-yl)-pyridin-2-yl]-5-methyl-octahydro-pyrrolo[3,4- c]pyrrole; 6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-[3,3']bipyridinyl; 6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-[3,4']bipyridinyl; 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-benzonltrile; 6,-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrro!-2-yl)-[3,3,]bipyridinyl-6-ylamine; 2-Methyl-5-[5-(1H-pyrrol-3-yl)-pyridin-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[5-(1H-pyrrol-2-yl)-pyridin-2-yl]-octahydro-pyrrolo[3I4-c]pyrrole; 6'-(5-Methyl-hexahydro-pyrrolo[3f4-c]pyrrol-2-yl)-[3,3^ipyridinyl-2-carbonitrile; 2-(5-Furan-3-yl-pyridin-2-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-thiophen-2-yl-pyridin-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(5-thiophen-3-yl-pyridin-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; -193- WO 2005/028477 PCT/US2004/030735 2-(5-Benzofuran-5-yl-pyridin-2-yl)-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-(5-Furan-2-yl-pyridin-2-yl)-5-methyl-octahydro-pyrro!o[3,4-c]pyrrole; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-9H-carbazole; 5-[6-(5-Methyl-hexahydro-pyrrolo[3)4-c]pyrrol-2-yl)-pyridin-3-yl]-1H-indole; 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-1H-indole; 2-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-3-yl]-2H-pyridazin-3-one; 2-(6-Phenyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-o-Tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-m-Tolyl-pyridin-3-yl)-octahydro-pyrrolo[3I4-c]pyrrole; 2-[6-(3-Methoxy-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole 2-[6-(3-Trifluoromethoxy-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Thiophen-3-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 8-[5-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-quinoline; 2-(6-Naphthalen-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Benzofuran-2-y!-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-o-tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-m-tolyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-phenyl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyiTole; 2-[6-(3-Methoxy-phenyl)-pyridin-3-yl]-5-methyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-[6-(3-trifIuoromethoxy-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4- cjpyrrole; 2-Methyl-5r[6-(3-nitro-phenyl)-pyridin-3-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(6-thiophen-3-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 8-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-quinoline; 2-Methyl-5-(6-naphthalen-2-yl-pyridin-3-yl)-octahydro-pyrrolo[3,4-c]pyiTole; 5-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-1H-indole; 4-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-1H-indole; 5-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridin-2-yl]-quinoline; (1R,5R)-3-(6-p-Tolyl-pyridazin-3-yl)-3I6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)- 3-(6-o-Tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)- 3-(6-m-Tolyl-pyridazin-3-yl)-3,6-diaza-bicydo[3.2.0]heptane; (1R, 5R)- 6-Methyl-3-(6-p-tolyl-pyridazin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; -194- WO 2005/028477 PCT/US2004/03073* (1R, 5R)- 6-Methyl-3-(6-o-tolyl-pyridazin-3-yl)-3,6-diaza-bicyc!o[3.2.0]heptane; (1S, 5S)-5-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; (1S, 5S)-5-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; (1S, 5S)-4-[6-(6-Methyl-3,6-diaza-bicyc!o[3.2.0]hept-3-yl)-pyridazin-3-yl]-1 H-indole; (1S, 5S)-3-(6-Benzofuran-5-yl-pyridazin-3-yl)-6-methyl-3,6-dlaza-bicyclo[3.2.0]heptane; (1S, 5S)- 4-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-phenylamine; (1R, 5S)- 3-[6-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-pyridazin-3-yl]-thiophene; (1R, 5S)- 5-[6-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-pyridazin-3-yl]-1 H-indole ; (1R, 5S)- 4-[6-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-pyridazin-3-yl]-1 H-indole ; 3-Methyl-5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrroi-2-yl)-pyridazin-3-yl]-1H-indazole; (1S, 5S)- 5-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-3-yl]-3-methyl-1 H-indazole; (1R,5R)-{4-[5-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-phenyl}-dimethyl-amine; (1R, 5R)-6-Methyl-3-(6-m-tolyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-6-Methyl-3-(6-p-tolyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-3-[5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-benzonitrile; (1R, 5R)-3-[6-(4-Ethyl-phenyl)-pyridin-3-yl]-6-methyl-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-Dimethyl-{4-[5-(6-methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-phenyl}-amine; (1R, 5R)-3-[6-(3-Methoxy-phenyl)-pyridin-3-yl]-6-methyl-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-3-(6-Benzo[1 .SJdioxol-S-yl-pyridin-S-yO-e-methyl-S.e-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-3-[6-(4-Methoxy-phenyl)-pyridin-3-yO-6-methyl-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-3-[6-(3,4-Dimethoxy-phenyl)-pyridin-3-yl]-6-methyl-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5R)-6-Methyl-3-(6-phenyl-pyridin-3-yl)-3(6-diaza-bicyclo[3.2.0]heptane; (1R, SRJ-S-CS-Methyl-S.e-diaza-bicyclotS^.Ojhept-S-yO-p.Slbipyridinyl; (1R, 5R)- 5-[5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-1 H-indole; -195- «i WO 2005/028477 PCT/US2004/030735 (1S, 5S)- 5-[5-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-2-yl]-1 H-indole; (1R, 5S)- 6-(6-Phenyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5S)- 6-(6-m-Tolyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5S)- 3-Methyl-6-(6-phenyl-pyridin-3-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1R, 5S)- 5-[5-(3--Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-pyridin-2-yl]-1 H-indole; (1S, 5S)- 5-[6-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-3-yl]-1 H-indole; (1S, 5S)- 3-(5-Phenyl-pyridin-2-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)- 6-Methyl-3-(5-phenyl-pyridin-2-yl)-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5S)-5-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridin-3-yl]-1 H-indole; 2-(4-Phenyl-thiophen-2-yl)-octahydro-pyrrolo[3I4-c]pyrrole; 2-Methyl-5-(5-phenyl-[1,3,4]thiadiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(2-Phenyl-thiazol-5-yl)-octahydro-pyrroIo[3,4-c]pyrrole; 2-Methyl-5-(2-phenyl-thiazol-5-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(4-Phenyl-thiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Benzyl-5-(6-phenylpyridazin-3-yl)-octahydropyrrolo[3,4-c]pyrrole; 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-4-ylmethyl)-octahydropyrrolo[3,4-c]pyrrole; 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-2-ylmethyl)-octahydropyrrolo[3,4-c]pyrrole; 2-(6-Chloropyridin-3-ylmethyl)-5-(6-phenylpyridazin-3-yl)-octahydropyrrolo[3,4-cjpyrrole; 2-(6-Phenylpyridazin-3-yl)-5-(2-pyridin-3-ylethyl)-octahydropyrrolo[3,4-c]pyrrole; 2-(6-Phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl)-octahydropyrrolo[3,4-c]pyrrole; 2-Allyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-But-2-enyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Ethyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-(6-Phenyl-pyridazin-3-yl)-5-propyl-octahydro-pyrrolo[3,4-c]pyrrole; 2-lsopropyl-5-(6-phenyI-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole; (3aR,6aR)-5-(5-Phenyl-[1,3,4]oxadiazol-2-yl)-octahydro-pyrrolo[3,4-b]pyrrole; 2-(5-Phenyl-[1,3,4]oxadiazol-2-yl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-[5-(4-Methoxy-phenyl)-[1I3,4]oxadiazol-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; 2-[5-(4-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-5-methyl-octahydro-pyrrolo[3,4-cjpyrrole; 2-[5-(4-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-octahydro-pyrrolo[3,4-c]pyrrole; -196- WO 2005/028477 PCT/US2004/030735 6-Methyl-3-(5-phenyl-[1,3,4]oxadiazol-2-yl)-3,6-diaza-bicyclo[3.2.1]octane; 4-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-biphenyl-2-ol; 4-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-biphenyl-2-ol; Diethyi-(2-{3-[6-(hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenoxy}-ethyl)- amine; 4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenol; Diethyl-(2-{4-[6-(hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenoxy}-ethyl)- amine; (2-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenoxy}-ethyl)- dimethyl-amine; 3-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyiTol-2-yl)-pyridazin-3-yl]-phenol; 4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenol; Diethyl-(2-{4-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]- phenoxy}-ethyl)-amine; , N-{4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}- methanesulfonamide; N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrroN2-yl)-pyridazin-3-yl]-phenyl}-benzamide; N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}- methanesulfonamide; N-{4-[6-(Hexahydro-pyrro!o[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}- dimethylaminosulfonamide; N-{4-[6-(Hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}-acetamide; N-{4-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-phenyl}- acetamide; 2-[5-(Hexahydro-pyrro!o[3,4-c]pyrrol-2-yl)-pyrimidin-2-yl]-phenol; 2-[5-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyrimidin-2-yl]-phenol; 2-(4-Pyridin-3-yl-phenyl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Methyl-5-(4-pyridin-3-yl-phenyl)-octahydro-pyrrolo[3,4-c]pyrrole; 2-Biphenyl-4-yl-octahydro-pyrrolo[3,4-c]pyrrole; 2-Biphenyl-4-y!-5-methy!-octahydro-pyrrolo[3,4-c]pyrrole; 1-Methyl-5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H- indole; -197- WO 2005/028477 PCT/US2004/03073s Dimethyl-{5-[6-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H- indol-3-y!methyl}-amine; (1S, 5S)-6-[6-(6-Methyl-3,6-diaza-bicyclo[3.2.0]hept-3-yl)-pyridazin-3-yl]-2,3,4,9- tetrahydro-1 H-carbazole; (1R, 5S)- 5-(3,6-Diaza-bicyclo[3.2.0]hept-6-yl)-2-thiophen-2-yl-nicotinonitrile; (1R, 5S)- 5-(3-Methyl-3,6-diaza-bicyclo[3.2.0]hept-6-yl)-2-thiophen-2-yl- nicotinonitrile; (1S, 5S)-3-(4-Pyridin-3-yl-phenyl)-3,6-diaza-bicyclo[3.2.0]heptane; (1S, 5Sy 6-Methyl-3-(4-pyridin-3-yl-phenyl)-3,6-diaza-bicyclo[3.2.0]heptane; and (1S, 5S)- 5-[4-(3,6-Diaza-bicyclo[3.2.0]hept-3-yl)-phenyl]-3-methyl-1 H-indazole. 23. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier. 24. A method of selectively modulating the effects of