ZA200603031B - Fused heterocyclic componds as serotonin receptor modulators - Google Patents

Fused heterocyclic componds as serotonin receptor modulators Download PDF

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ZA200603031B
ZA200603031B ZA200603031A ZA200603031A ZA200603031B ZA 200603031 B ZA200603031 B ZA 200603031B ZA 200603031 A ZA200603031 A ZA 200603031A ZA 200603031 A ZA200603031 A ZA 200603031A ZA 200603031 B ZA200603031 B ZA 200603031B
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phenyl
triaza
hexahydro
azulene
substituted
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ZA200603031A
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Nicholas I Carruthers
Deng Xiaohu
Annette K Kwok
Mani Neelakandha
Victoria D Wong
Chai Wenying
Curt A Dvorak
Jimmy T Liang
Dale A Rudolph
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Janssen Pharmaceutica Nv
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Description

FUSED HETEROCYCLIC COMPOUNDS
Field of the Invention
There is provided by the present invention compounds that are serotonin receptor modulators. More particularly, there is provided by the present invention fused heterocyclic compounds that are serotonin receptor modulators useful for the treatment of disease states mediated by serotonin receptor activity.
Background of the Invention
Serotonin (5-hydroxytryptamine, 5-HT) is a major neurotransmitter eliciting effects via a multiplicity of receptors. To date, at least fifteen different 5-HT receptors have been identified, largely as the result of cloning cDNA’s, and these receptors have been grouped into seven families (5-HT, through 5-
HT) (Hoyer, D. et al. Pharmacol. Biochem. Behav. (2002) 71, 533-554).
Fourteen of the fifteen cloned 5-HT receptors are expressed in the brain. 5-HT is implicated in many disease states, particularly conditions of the central nervous system including; depression, anxiety, schizophrenia, eating disorders, obsessive compulsive disorder, learning and memory dysfunction, migraine, chronic pain, sensory perception, motor activity, temperature regulation, nociception, sexual behavior, hormone secretion and cognition. The identification of multiple 5-HT receptors has provided the opportunity to characterize existing therapeutic agents thought to act via the serotonergic system. Consequently, this has led to the realization that many drugs have non-selective properties (Roth, B.L. et al. Neuroscientist (2000) 6(4) 252-262).
For example, the antipsychotic drugs, clozapine, chlorpromazine, haloperidol and olanzapine exhibit affinities for multiple serotonin receptors in addition to other families of receptors. Similar behavior has been noted for antidepressants, including imipramine, nortriptaline, fluoxetine and sertraline.
Similarly, the anti-migraine agent sumatriptan exhibits high affinity for several serotonin receptors. While the lack of selectivity often contributes to a favorable therapeutic outcome, it can also cause undesirable and dose-limiting side effects (Stahl, S.M. Essential Psychopharmacology, 2™ ed., Cambridge
University Press, Cambridge, U.K., 2000). Thus, the inhibition of serotonin and norepinephrine uptake together with 5-HT. receptor blockade is responsible for the therapeutic effects of the tricyclic antidepressants. In contrast, their blockade of histamine Hs, muscarinic and alpha-adrenergic receptors can lead to sedation, blurred vision and orthostatic hypertension respectively. Likewise, the atypical antipsychotics, including olanzapine and clozapine, are considered to have positive therapeutic effects attributable to their actions at 5-HTz, D2 and 5-HT; receptors. Conversely, their side effect liability is due to their affinities at a range of dopaminergic, serotonergic and adrenergic receptors.
More selective ligands therefore have the potential to ameliorate untoward pharmacologies and provide novel therapies. More importantly the ability to obtain compounds with known receptor selectivities affords the prospect to target muitiple therapeutic mechanisms and improve clinical responses with a single drug.
Summary of the Invention
The invention features a compound of formulae (1), (1) and (111):
R? CYCHALK)q
CYC-ALK GN SA YOANN Ar 'e ) — y= a Sr SR a
Tw RN "hw (I) (I) (1) wherein mis0,1o0r2 nis1,2or3; pis 1, 2 or 3, with the proviso that where mis 1, pis not 1; m+n is less than or equal to 4; m+p is less than or equal to 4; qisOort; ris0, 1,2, 3, 4,05;
R® is -C1aalkyl, allyl, propargyl, or benzyl, each optionally substituted with -C.salkyl, “OH, or halo;
Ar is an aryl or heteroaryl ring selected from the group consisting of: a) phenyl, optionally mono-, di- or tri-substituted with R' or di-substituted on adjacent carbons with -OC1.4alkyleneO-, -(CHz)2.3NH-, -(CHz)1.2NH(CHo)-, (CH2)2.9N(C1.salkyl)- or -(CH2)1.2N(C1.salkyl)(CHz)-;
R' is selected from the group consisting of —OH, -C1-salkyl, -OC.salkyl, -C2.salkenyl, -OCagalkenyl, -Cz.galkynyl, -OCa alkynyl, -CN, -NO., -N(R*)R* (wherein RY and R* are independently selected from H or Cq_salkyl), -(C=O)N(R")R?, -(N-R)COR!, -(N-RYSO2Cy-ealkyl (wherein R'is H or Cs.ealkyl), -(C=0)C;.¢alkyl, -(S=(O)n)-C1-s2lkyl (wherein n is selected from 0, 1 or 2), -SO.N(R")R?, -SCFs3, halo, -CFs, -OCFs, -COOH and -COOCgalkyl; b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered ! aromatic ring, which moiety has one carbon atom replaced by >0, >S, >NH or >N(C1.salkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R'; c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R’; d) naphthyl, optionally mono-, di- or tri-substituted with R’; e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C1.salkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R'; and f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- of di-substituted with R* and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R" g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di- or tri-substituted with R';
ALK is a branched or unbranched Cs.salkylene, C..salkenylene, Cosalkynylene or Cascycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -OC4 alkyl, -OCascycloalkyl, -CN, -NO, -N(R*R® (wherein R* and R® are independently selected from H, C1.alkyl or Cz.ealkenyl), (C=O)N(R*R", -(N-R)COR®, -(N-R)SO.C, alkyl (wherein RC is H or Cy.salkyl), -(C=0)C.¢alkyl, -(S=(0)s)-C1-salkyl (wherein d is selected from 0, 1 or 2), -SO,N(R®)R®, -SCFs3, halo, -CF3, -OCF3, -COOH and -COOCgalkyl,
CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of: i) phenyl, optionally mono-, di- or tri-substituted with R® or di-substituted on adjacent carbons with -OC+.4alkyleneO-, -(CHg)2.aNH-, -(CHa)1.2NH(CHz)-, -(CHz)23N(C1.salkyl)- or -(CHz)12N(C1-4alkyl)(CHz)-;
RY is selected from the group consisting of OH, -C1.salkyl, : -OC;.salkyl, -Cascycloalkyl, -OCsecycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO, -N(R*)R" (wherein R" and RP are independently selected from H, Cy.salkyl or C2.¢alkenyl, or R® and R® may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O,
=N-, >NH or >N(C.salkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=O)N(R*)R”, -(N-R°)COR’, -(N-R%)SO:C1.calkyl (wherein R® is H or Cs.calkyl or two R® in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N-(SO2C1.calkyl)z, -(C=0)C.salkyl, -(S=(0)q4)-Cr-salkyl (wherein d is selected from 0, 1 or 2), -SON(R?)R®, -SCFs, halo, -CFs, -OCFs, -COOH and
-COOCgalkyl;
ii) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, >NH or >N(C1«alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY; iii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY;
iv) naphthyl, optionally mono-, di- or tri-substituted with RY v) a monocyclic aromatic hydrocarbon group having five ring atoms, : having a carbon atom which is the point of attachment, having one carbon atom replaced by >O, >S, >NH or >N(C;.4alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R? and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R%;
vi) a monocyclic aromatic hydrocarbon group having six ring atoms,
having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with RY; vii) a 3-8 membered non-aromatic carbocyclic of heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 t0 5 substituents RY and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents R%; and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents RY;
R' is selected from the group consisting of H, C.7alkyl, Co7alkenyl, Co7alkynyl,
Ca.7cycloalkyl, CazcycloalkylCi.7alkyl, Ca scycloalkenyl,
Ca7cycloalkenylCy.7alkyl and benzo-fusedCa.7cycloalkyl, each optionally mono-, di-, or tri-substituted with RP;
RP is selected from the group consisting of —OH, -OC4 alkyl, -Caecycloalkyl, -OCa.cycloalkyl, -CN, -NOz, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®)R" (wherein R® and R" are independently selected from H or Cysalkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C4-alkyl) and optionally having one or two unsaturated bonds in the ring), -(C=0)N(R*)R", -(N-R¥)CORY, -(N-R")SO:C.¢alkyl (wherein R' is H or Cy.¢alkyl or two
RY in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C1.salkyl, -(S=(0)n)-C1-galkyl (wherein n is selected from 0, 1 or 2), -SON(R®)R", -SCF3, halo, -CF3, -OCF;3, -COOH and -COOC;.salkyl, wherein the foregoing phenyl, pyridyl, thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: OH, -Ci.salkyl, -OC1.ealkyl, -CN, -NO., N(R®)R" (wherein R® and R® are independently selected from H, C1.salkyl or
Cz-salkenyl), -(C=O)N(R®R", -(N-R°)COR?®, -(N-R°)SO2C1-salkyl (wherein R® is H or C1.¢alkyl), -(C=0)C1.galkyl, -(S=(0)q)-C1-salkyl (wherein d is selected from 0, 1 or 2), -SO.N(RYR", -SCF3, halo, -CF,, -OCF3, -COOH and -COOC, ¢alkyl;
R? is selected from the group consisting of H, Cy.7alkyl, C..zalkenyl, Co.7alkynyl and Ca.rcycloalkyl; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof.
Similarly, isomeric forms of the compounds of formulae (n, (11), and (I), and of their pharmaceutically acceptable salts, esters, and amides, are encompassed within the present invention, and reference herein to one of such isomeric forms is meant to refer to at least one of such isomeric forms. One of ordinary skill in the art will recognize that compounds according to this invention may exist, for example in a single isomeric form whereas other compounds may exist in the form of a regioisomeric mixture.
The invention also features pharmaceutical compositions containing such compounds and methods of using such compositions in the treatment or prevention of disease states mediated by the serotonin receptors, particularly, 5-HT; and/or 5-HT; receptor subtypes.
Detailed Description
Preferably, mis 1 or 2 and most preferably, mis 1.
Preferably, nis 1 or 2.
Preferably, pis 1 or 2.
Preferably, m+n is 2 or 3.
Preferably, m+p is 2 or 3.
Preferably, gis 1. :
Preferably, ris 0, 1, or 2.
Preferably, ris 4.
Preferably R®, optionally substituted, is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, allyl, propargyl, and benzyl.
Preferably, R® is methyl.
Preferably Ar, optionally substituted, is selected from the group consisting of: a) phenyl, 5-, 6-, 7-, 8-benzo-1,4-dioxanyl, 4-, 5-, 6-, 7-benzo-1,3- dioxolyl, 4-, 5-, 6-, 7-indolinyl, 4-, 5-, 6-, 7-isoindolinyl, 1,2,3,4-tetrahydro- . 15 quinolin-4, 5, 6 or 7-yl, 1,2,3,4-tetrahydro-isoquinolin-4, 5, 6 or 7-yl, b) 4-, 5-, 6- or 7-benzoxazolyl, 4-, 5-, 6- or 7-benzothiophenyl, 4-, 5-, 6- or 7-benzofuranyl, 4-, 5-, 6- or 7-indolyl, 4-, 5-, 6- or 7-benzthiazolyl, 4-, 5-, 6- or 7-benzimidazolyl, 4-, 5-, 6- or 7-indazolyl, imidazo[1,2-alpyridin-5, 6, 7 or 8- yl, pyrazolo[1,5-alpyridin-4, 5, 6 or 7-yl, 1H-pyrrolo[2,3-b]pyridin-4, 5 or 6-yl, 1H-pyrrolo[3,2-c]pyridin-4, 6 or 7-yl, 1H-pyrrolo[2,3-c]pyridin-4, 5 or 7-yl, 1H-pyrrolo[3,2-b]pyridin-5, 6 or 7-yl, c) 5-, 6-, 7- or 8-isoquinolinyl, 5-, 6-, 7- or 8-quinolinyl, 5-, 6-, 7- or 8- quinoxalinyl, 5-, 6-, 7- or 8-quinazolinyl, d) naphthyl, e) furanyl, oxazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiophenyl, thiazolyl, isothiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 3-indoxazinyl, 2- benzoxazolyl, 2- or 3-benzothiophenyl, 2- or 3-benzofuranyl, 2- or 3-indoiyl, 2- benzthiazolyl, 2-benzimidazolyl, 3-indazolyl, f) pyridinyl, pyridinyl-N-oxide, pyrazinyl, pyrimidinyl, pyridazinyl, 1-, 3- or 4-isoquinolinyl, 2-, 3- or 4-quinolinyl, 2- or 3-quinoxalinyl, 2- or 4-quinazolinyl, [1,5], [1,6], [1,7], or [1,8]naphthyridin-2-, 3-, or 4-yl, [2,5], [2.6], [2,7], [2,8]naphthyridin-1-, 3-, or 4-yl, and g) biphenyl, 4-tetrazolylphenyl.
More preferably, Ar, optionally substituted, is selected from the group consisting of phenyl, pyridyl, thiophen-2-yl and thiophen-3-yl.
Specific Ar may be selected from the group consisting of phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-ethyiphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chloropheny!, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyt, 2-trifluoromethyiphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 3-cyanophenyl, 4-cyanophenyl, 3-acetylphenyl, 4-acetylphenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 2,3-difluorophenyl, 2,3-dichlorophenyl, 2,4-difluorophenyt, 2,4-dichlorophenyl, 3-nitrophenyl, 4-nitrophenyl, 3-chloro-4-fluorophenyl, 3-fluoro-4-chlorophenyi, benzo[1,3]dioxol-4 or 5-yl, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-hydroxy-2- methylphenyl, 4-hydroxy-3-fluorophenyl, 3,4-dihydroxyphenyl,4- dimethylaminophenyl, 4-carbamoylphenyl, 4-fluoro-3-methylphenyl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, 5-chlorothiophen-2-yl, 5- methylthiophen-2-yl, 5-chlorothiophen-3-yi, 5-methylthiophen-3-yl, 4'- chiorobiphenyl, and 4-tetrazolyiphenyl.
Preferably, ALK, optionally substituted, is selected from the group consisting of methylene, ethylene, propylene, butylene, tert-butylene, pentylene, 1-ethylpropylene, 2-ethylpropylene, 2-ethylbutylene, isopropylene, but-3-enylene, isobutylene, 3-methylbutylene, allylene, and prop-2-ynylene.
Specific ALK may be selected from the group consisting of methylene, trifluoromethylmethylene, methoxycarbonylmethyl, methylcarbamoylmethyl, ethylene, propylene, 3-methoxycarbonyl propylene, 3-carboxy propylene, butylene, tert-butylene, 4-hydroxybutylene, 4-methoxycarbonyl butylene, 4- carboxy butylene, pentylene, 5-hydroxypentylene, 1-ethylpropylene, 2- ethylpropylene, 2-ethylbutylene, isopropylene, but-3-enylene, isobutylene, 3- methylbutylene, prop-2-ynylene, 2-dimethylaminoethylene, and 2- cyanoethylene.
Preferably CYC, optionally substituted, is hydrogen or is selected from the group consisting of:
i) phenyl, 5-, 6-, 7-, 8-benzo-1 ,4-dioxanyl, 4-, 5-, 6-, 7-benzo-1,3-dioxolyl, 4-, 5. 6-, 7-indolinyl, 4-, 5-, 6-, 7-isoindolinyl, 1,2,3,4-tetrahydro-quinolin-4, 5, 6 or 7-yl, 1,2,3,4-tetrahydro-isoquinolin-4, 5, 6 or 7-yl, ii) 4-, 5-, 6- or 7-benzoxazolyl, 4-, 5-, 6- or 7-benzothiophenyl, 4-, 5-, 6- or 7-benzofuranyl, 4-, 5-, 6- or 7-indolyl, 4-, 5-, 6- or 7-benzthiazolyl, 4-, 5-, 6- or 7-benzimidazolyl, 4-, 5-, 6- or 7-indazolyl, imidazo[1 ,2-a)pyridin-5, 6, 7 or 8- yl, pyrazolo[1,5-a]pyridin-4, 5, 6 or 7-yl, 1H-pyrrolo[2,3-b]pyridin-4, 5 or 6-yl, 1H-pyrrolo[3,2-c]pyridin-4, 6 or 7-yl, 1H-pyrrolo[2,3-c]pyridin-4, 5 or 7-yl, 1H-pyrrolo[3,2-b]pyridin-5, 6 or 7-y, iii) 5-, 6-, 7- or 8-isoquinolinyl, 5-, 6-, 7- or 8-quinolinyl, 5-, 6-, 7- or 8- quinoxalinyl, 5-, 6-, 7- or 8-quinazolinyl, iv) naphthyl, v) furanyl, oxazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiophenyl, thiazolyl, isothiazolyi, pyrroiyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 3-indoxazinyl, 2- benzoxazolyl, 2- or 3-benzothiophenyl, 2- or 3-benzofuranyl, 2- or 3-indolyl, 2- benzthiazolyl, 2-benzimidazolyl, 3-indazolyl, vi) pyridinyl, pyridinyl-N-oxide, pyrazinyl, pyrimidinyl, pyridazinyl, 1-, 3- or 4-isoquinolinyl, 2-, 3- or 4-quinolinyl, 2- or 3-quinoxalinyl, 2- or 4-quinazolinyl, [1,5], [1,6], [1,7], or [1,8]naphthyridin-2-, 3-, or 4-yl, [2,5], [2,6], [2,7), [2,8]naphthyridin-1-, 3-, or 4-yl, vii) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, ~ cycloheptyl, cyclooctyl, adamantyl, pyrrolinyl, pyrrolidinyl, pyrazolinyl, piperidinyl, homopiperidinyl, azepanyl, tetrahydrofuranyl, tetrahydropyranyl, piperazinyl, morpholinyl, thiomorpholinyl, piperidinonyl, indanyl, dihydroindolyl, oxindolyl, dihydropyrrolopyridinyl, and viii) bicyclo[4.1 .0Jheptane, octahydroindolyl, octahydroisoindolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydropyrrolopyridinyl, and octahydropyrrolopyrrolidinyl.
More preferably, CYC, optionally substituted, is selected from the group consisting of hydrogen, phenyl, indolyl, benzthiazolyl, isoquinolyl, quinazolinyl, naphthalen-1 or 2-yl, thiophen-2-yl, thiophen-3-yl, furan-2-yi, furan-3-yi, pyridinyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, piperidin-
2,3 or 4-yl, 2-pyrrolin-2, 3, 4 or 5-yl, 3-pyrrolin-2 or 3-yl, 2-pyrazolin-3, 4 or 5-yi, morpholin-2, 3, 5 or 6-yl, thiomorpholin-2, 3, 5 or 6-yl, piperazin-2, 3, 5 or 6-yl, pyrrolidin-2 or 3-yl, homopiperidinyl, adamantanyl, and octahydroindoiyl.
Most preferably, CYC, optionally substituted, is selected from the group consisting of hydrogen, phenyl, pyridyl, cyclobutyl, cyclopentyl, cyclohexyl, thiophen-2-yl, thiophen-3-yl, tetrahydropyranyl, furan-2-yl, furan-3-yl and naphthalen-1 or 2-yl.
Specific CYC may be selected from the group consisting of hydrogen, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-methyliphenyl, 3-methylphenyl, 4-methyiphenyl, 4-ethylphenyl, 2-chlorophenyi, 3-chlorophenyi, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3-trifluoromethoxyphenyi, 4A-trifluoromethoxyphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3-acetylphenyl, 4-acetylphenyl, 3,4-difluorophenyl, 3,4-dichiorophenyl, 2,3-difluorophenyl, 2,3-dichlorophenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 2,6-difluorophenyl, 2,6-dichlorophenyi, 2,6-dimethylphenyl, 2,4 6-trifluorophenyl, 2,4,6-trichlorophenyl, 3,4,5-trimethoxyphenyl, cyclobutyl, cyclohexyl, cyclopentyl, 4-fluoro-3-methylphenyl, 3-nitrophenyl, 4-nitrophenyl, 4-methyl-3-fluorophenyl, 3,4-dimethylphenyl, 4-methoxy-3-fluorophenyl, 4- methoxy-2-methylphenyl, 3-aminophenyl, 4-aminophenyl, 4- carbomethoxyphenyl, 3-methanesulfonylamino-phenyl, 4-methanesulfonylamino-phenyl, 3-dimethanesulfonylamino-phenyi, y 4-dimethanesulfonylamino-phenyl, thiophen-2-yl, thiophen-3-yl, 5- chlorothiophen-2-yl, benzo[1,3]dioxol-4 or 5-yl, tetrahydropyran-2,3 or 4-yl, furan-2-yl, furan-3-yl, 5-carboxyethyl-furan-2-yl, naphthalen-1 or 2-yl, 3,4- bisbenzyloxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-hydroxy-2-methyliphenyl, 4-hydroxy-3-fluorophenyl and 3,4-dihydroxyphenyl.
Preferably, R' is selected from the group consisting of hydrogen,
Ci-zalkyl, Cosalkenyl, Cogalkynyl, Caecycloalkyl, CascycloalkylC,.aalkyl,
Cs-scycloalkenyl, benzo-fusedCs ecycloalkyl, each optionally mono-, di-, or tri- substituted with R®.
More preferably, R', optionally RP substituted, is selected from the group consisting of hydrogen, methyl, ethyl, propyl, and isopropyl.
Specific R'-may be selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, 3-hydroxypropyl, benzyl, 3,4-dimethoxybenzyl, methoxycarbonylmethyl, carbamoyimethyl, phenethyl, phenpropyl, and hydroxyethyl.
Preferably, R? is hydrogen, Cq.salkyl, Czalkenyl, C.4alkynyl, or
Caecycloalkyl.
More preferably, R? is hydrogen or methyl. lt is understood that some compounds referred to herein are chiral and/or have geometric isomeric centers, for example E- and Z- isomers. The present invention encompasses all such optical, including stereoisomers and racemic mixtures, diastereomers, and geometric isomers that possess the activity that characterizes the compounds of this invention. In addition, certain compounds referred to herein can exist in solvated as well as unsolvated forms. It is understood that this invention encompasses all such solvated and unsolvated forms that possess the activity that characterizes the compounds of this invention. :
Compounds according to the present invention that have been modified to be detectable by some analytic technique are also within the scope of this invention. The compounds of the present invention may be labeled with radioactive elements such as '%°1, *F, ''C, Cu, and the like for use in imaging or for radioactive treatment of patients. An example of such compounds is an isotopically labeled compound, such as an '8F isotopically labeled compound that may be used as a probe in detection and/or imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Preferably, compounds of the present invention labeled with 'F or *'C may be used as a positron emission tomography (PET) molecular probe for studying serotonin-mediated disorders. Another example of such compounds is an isotopically labeled compound, such as a deuterium and/or tritium labeled compound that may be used in reaction kinetic studies.
The compounds described herein may be reacted with an appropriate functionalized radioactive reagents using conventional chemistry to provide radiolabeled compounds.
Pharmaceutically acceptable salts, esters, and amides include carboxylate salts (e.g., Ci.salkyl, Ca.sCycloalkyl, aryl, C..1oheteroaryl, or Cz-10 non-aromatic heterocyclic), amino addition salts, acid addition salts, esters, and amides that are within a reasonable benefit/risk ratio, pharmacologically effective and suitable for contact with the tissues of patients without undue toxicity, irritation, or allergic response. Representative addition salts for compounds of formula (1) displaying basic functionality include hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactiobionate, and laurylsulfonate. Representative addition salts for compounds of formula (1) displaying acidic functionality are those that form non-toxic base salts with such compounds. These salts may include alkali metal and alkali earth cations such as sodium, potassium, calcium, and magnesium, as well as non-toxic ammonium, quaternary ammonium, and amine cations such as tetramethyl ammonium, methylamine, trimethylamine, and ethylamine. See example, S.M. Berge, et al., “Pharmaceutical Salts,” J.
Pharm. Sci., 1977, 66:1-19, which is incorporated herein by reference.
Representative pharmaceutically acceptable amides of the invention include those derived from ammonia, primary Ci. alkyl amines and secondary di(C,.salkyl) amines. Secondary amines include 5- or 6-membered heterocyclic or heteroaromatic ring moieties containing at least one nitrogen atom and optionally between 1 and 2 additional heteroatoms. Preferred amides are derived from ammonia, C1.salkyl primary amines, and di(C1.calkyl)amines.
Representative pharmaceutically acceptable esters of the invention include
C1.7alkyl, Cs.scycloalkyl, phenyl, and phenyl(C1.e)alkyl esters. Preferred esters include methyl esters.
Preferred compounds, which are fused pyrroles, are selected from the group consisting of:
x omewoanwe 1 “Benzyl-3-(4-nitro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- 1 “Benzyl-3-(3-chloro-4-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H- 2 | pyrrolo[3,2-cjpyridine; 1 “Benzyl-3-(4-trifluoromethoxy-phenyl)-4,5,6,7-tetrahydro-1 H 1 “Benzy!-3-(5-chioro-thiophen-2-yl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-
Lo
Ut Cl a clpyridine; 1-Benzyl-3-(3-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolof3,2- 3-(4-Chloro-phenyl)-1 -(2-fluoro-benzyl)-4,5,6,7-tetrahydro-1H-
Rl ei pyrrolo[3,2-c]pyridine; cJpyridine, pyrrolo[3,2-cjpyridine; clpyridine; . clpyridine; pyrrolo[3,2-c]pyridine; 1-(2,4-Dichloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-
ET
1 “Benzyl-2-methyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- 1-Be nzyl-3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- clpyridine; 3-Benzo[1,3)dioxol-5-yl-1-be nzyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- clpyridine,; cJpyridine; pyrrolof3,2-clpyridine; cJpyridine;
I I a i ds cJpyridine; 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahyd ro-pyrrolo[2,3-
EE
1-Benzyl-3-(5-chloro-thiophen-2-yl)-1 .4,5,6,7,8-hexahydro-pyrrolof2,3-
EE
1-(4-Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-
EE dlazepine; 1-Benzyl-3-(3-chloro-phenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-
EB c)pyridine; cJpyridine;
1 “Benzyl-3-(a-chioro-phenyl)-5-ethyl-4,5,6,7-tetrahydro-1 H- pyrrolo[3,2-clpyridine; 1-Benzyl-3-(4-chioro-phenyl)-5-isopropyl-4,5,6,7-tetrahydro-1H- 3-[1-Benzyl-3-(4-chloro-phenyl)-1 4.6,7-tetrahydro-pyrrolo[3,2- 1 ~Benzyl-3-(4-chloro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1 H 1-Benzyl-3-(3-chloro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1 H- 1 -Benzyl-3-(3-chioro-4-fluoro-phenyi)-5-methyl-4,5,6,7-tetrahydro-1 H
El : and . 1-Benzyl-5-isopropyl-3-phenyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-
ET
Preferred compounds, which are fused 1-substituted pyrazoles, are selected from the group consisting of: triaza-azulene; azulene, 1-Benzyl-3-(3-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- [TE azulene; 1-Benzyl-3-(2,3-difluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-
1 “Benzyl-3-(3,4-dichloro-phenyl)-1 4,5,6,7,8-hexahydro-1 ,2,6-triaza- azulene; 1-[4-(1-Benzyl-1,4,5,6,7,8-hexahydro-1 2 6-triaza-azulen-3-yl)- 1-Benzyl-3-(4-trifluoromethoxy-phenyl)-1 4.5,6,7,8-hexahydro-1,2,6- 1-Benzyl-3-(3-chloro-phenyl)-1 4.5 6,7,8-hexahydro-1,2,6-triaza- — 3-(1-Benzyl-1,4,5,6,7,8-hexahydro-1 .2,6-triaza-azulen-3-yl)- 4-(1-Benzyl-1,4,5,6,7,8-hexahydro-1 2,6-triaza-azulen-3-yl)- — 1-(4-Chloro-benzyl)-3-phenyl-1 ,4,5,6,7,8-hexahydro-1,2,6-triaza- 1-(4-Chloro-benzyl)-3-(4-chloro-phenyl)-1 ,4,5,6,7,8-hexahydro- vr azulene, 1-Benzyl-6-isopropyl-3-phenyi-1 4,5,6,7,8-hexahydro-1 ,2,6-triaza- 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- eT 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1 ,2,5-triaza- ro | EE azulene; 3-(4-Chloro-phenyl)-1-ethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- [Lo | TEmm———__— 3-(4-Chloro-phenyl)-1-propyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- oo | TE fa azulene;,
3-(4-Chloro-phenyl)-1 -(2-cyclohexyl-ethyl)-1 4,5,6,7,8-hexahydro- a 3-(4-Chloro-phenyl)-1 -phenethyl-1 4.5,6,7,8-hexahydro-1,2,6-triaza- 3-(4-Chloro-phenyl)-1 -(4-fluoro-3-methyl-benzyl)-1 ,4,5,6,7,8- 3-(4-Chioro-phenyl)-1 -(3-methyl-benzyl)-1 4,5,6,7,8-hexahydro- 3-(4-Chloro-phenyl)-1 -(4-fluoro-benzyl)-1 4.5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 3-(4-Chioro-phenyl)-1 ~(3-fluoro-benzyl)-1 4.5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 3-(4-Chioro-phenyl)-1 -(4-methyl-benzyl)-1 ,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 1,2,6-triaza-azulene; triaza-azulene; 3-(4-Chloro-phenyl)-1 -(3-fluoro-4-methyl-benzyl)-1,4,5,6,7,8- ers 1,2,6-triaza-azulene; 5-[3-(4-Chloro-phenyl)-5,6,7 8-tetrahydro-4 1 ,2,6-triaza-azulen-1- arenes 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1 ,2,6-triaza-azulen-1- yl]-pentanoic acid; yl}-pentan-1-ol; yi]-butyric acid methyl ester; yl]-butyric acid;
4-[3-(4-Chloro-phe nyl)-5,6,7,8-tetrahydro-4 H-1 ,2,6-triaza-azulen-1- yl]-butan-1-ol; 3-(4-Chloro-phenyl)-1 -(3-fluoro-4-methoxy-benzyl)-1 ,4,5,6,7,8-
El Birnie 3-(4-Chloro-phenyl)-1 -(4-nitro-benzyl)-1 4.5,6,7,8-hexahydro-1,2,6-
El ie 4-(3-Phenyl-5,6,7 8-tetrahydro-4 H-1 2 6-triaza-azulen-1-ylmethyl)-
I =
N-[4-(3-Phenyl-5,6,7 8-tetrahydro-4 H-1 ,2,6-triaza-azulen-1- yimethyl)-phenyl}-methanesulfonamide;
N,N-[4-(3-phenyl-5,6,7,8-tetrahydro-4 H-1 ,2,6-triaza-azulen-1- yimethyl)-phenyl]-dimethanesulfonamide; 1,2,6-triaza-azulene; azulene; 1,2,6-triaza-azulene; 1,2,6-triaza-azulene; 1,2,6-triaza-azulene; 1,2,6-triaza-azulene; 1,2,6-triaza-azulene; 1,2,6-triaza-azulene; azulene;
1-(2-Bromo-benzyl)-3-(4-chioro-phenyl)-1,4.,5.6,7,8-hexahydro- 1,2,6-triaza-azulene; 113 , ‘ no 1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-1-(2-ethyl-butyl)-1 ,4.5,6,7,8-hexahydro-1,2,6- triaza-azulene; 3-(4-Chloro-phenyl)-1 -(5-chloro-thiophen-2-yimethyl)-1,4,5,6,7,8- 1,2,6-triaza-azulene; ; 1,2,6-triaza-azulene; azulene; hexahydro-1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-1-(tetrahydro-pyran-4-ylmethyl)-1,4,5,6,7,8- rr 1,2,6-triaza-azulene; 1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-1-(3-methyl-butyl)-1,4,5,6,7,8-hexahydro-1,2,6- [Ee hexahydro-1,2,6-triaza-azulene hexahydro-1,2,6-triaza-azulene, triaza-azulene; hexahydro-1,2,6-triaza-azulene;
3-(4-Chloro-phenyli)-1 -(2,4,6-trifluoro-benzyl)-1 ,4,5,6,7,8- 2.[3-(4-Chloro-phenyl)-5,8,7,8-tetrahydro-4H-1 ,2,6-triaza-azulen-1- 3-(4-Chloro-phenyl)-1 -naphthalen-2-ylmethyl-1,4,5,6,7,8- 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1 ,2,6-triaza-azulen-1- yimethyl}-furan-2-carboxylic acid ethyl ester; 3-(4-Chloro-phenyl)-1-naphthalen-1-ylmethyl-1 ,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; [3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1 ,2,6-triaza-azulen-1-ylj- acetic acid methyl ester; 2-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1 ,2,6-triaza-azulen-1-
I nie 3-(4-Chloro-phenyl)-1-(3,4,5-trimethoxy-benzyl)-1 ,4,5,6,7,8- re 3-(4-Chloro-phenyl)-1-(2,6-dimethyl-benzyl)-1 ,4,5,6,7,8-hexahydro- en 1-(3,4-Bis-benzyloxy-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8- soe yimethyl]-phenol; yimethyl]-phenol; yimethyl]-3-methyl-phenol; ylmethyl]-benzene-1,2-diol; yimethyl]-2-fluoro-phenol; yimethyl]-phenol;

Claims (1)

  1. What is claimed is:
    1. A compound having serotonin receptor modulating activity of formula (1), (11), or (I): R? CYC-(ALK), J CYCHALKI—N A CY CHALK) NA '¢ ) Ar SE " kr " Wi " |N (1) (1) (1m) wherein mis 0, 10r2; nis1,2or3; pis 1, 2 or 3, with the proviso that where mis 1, p is not 1; m+n is less than or equal to 4; m+p is less than or equal to 4, : qisOori; ris0, 1,2, 3, 4, or 5; R3 is -C,alkyl, allyl, propargyl, or benzyl, each optionally substituted with
    -C1.3alkyl, —OH, or halo; Ar is an aryl or heteroaryl ring selected from the group consisting of: a) phenyl, optionally mono-, di- or tri-substituted with R' or di-substituted on adjacent carbons with -OC;4alkyleneO-, -(CH2)2.aNH-, -(CH2)1.2NH(CHa)-, -(CH2)23N(C14alkyl)- or -(CHz)1.2N(C14alkyl)(CH2)-; R' is selected from the group consisting of -OH, -Cssalkyl, -OC;.galkyl, -Cosalkenyl, -OCa.galkenyl, -Casalkynyl, -OCssealkynyl, -CN, -NO,, -N(R*)R? (wherein R’ and R* are independently selected from H or Cy.galkyl), -(C=O)N(R¥)R?, -(N-R)COR!, -(N-R")SOC;.salkyl (wherein R'is H or C1ealkyl), -(C=0)C;.ealkyl, -(S=(O)n)-C1-6alkyl (wherein n is selected from
    0, 1 or 2), -SO.N(R")R? -SCF;, halo, -CF, -OCF3, -COOH and © -COOC, alkyl; b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, >NH or >N(Csalkyl) and which moiety has up to one additional : carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R"; c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R'; d) naphthyl, optionally mono-, di- or tri-substituted with R"; . e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one "carbon atom replaced by >0, >S, >NH or >N(C,alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R and i} &@ monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R" g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, : where the resultant substituted moiety is optionally further mono-, di-
    substituent independently selected from the group consisting of: -OH,
    -OC.calkyl, -OCa.scycloalkyl, -CN, -NOa, -N(R*)R" (wherein R® and R are independently selected from H, C1.ealkyl or Czealkenyl), -(C=O)N(R®*)R®, -(N-R%)COR?®, -(N-R°)SO.C1.salkyl (wherein R® is H or Cy.¢alkyl), -(C=0)C1.¢alkyl, -(S=(0)q)-C1.salkyl (wherein d is selected from 0, 1 or 2),
    -SO.N(R%)R®, -SCF3, halo, -CF3, -OCF3, -COOH and -COOC;.galkyl; CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of: i) phenyl, optionally mono-, di- or tri-substituted with R? or di-substituted on adjacent carbons with -OC,.4alkyleneO-, -(CHz)2.sNH-, -(CHz)1.2NH(CHz)-, -(CHz)2.aN(C14alkyl)- or -(CHg)1.2N(C1-4alkyl)(CHg)-; RY is selected from the group consisting of —OH, -C1.galkyl, -0C, alkyl, -Csecycloalkyl, -OCsgcycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C,.¢alkyl or Co¢alkenyl, or R® and R may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C,.qalkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=O)N(R*)R®, -(N-R°)COR®, -(N-R®)SO,C1.¢alkyl (wherein R® is H or Cy.galkyl or two RC in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N-(SO2C1.salkyl)z, -(C=0)C,.salkyl, -(S=(0)q)-C1-6alkyl (wherein d is selected from 0, 1 or 2), -SO.N(R*)R®, -SCF3, halo, -CF3, -OCFs, -COOH and -COOC, alkyl; ii} phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >0, >S, >NH or >N(C;.salkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY,
    iii) pheny! fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring,
    which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R%:
    iv) naphthyl, optionally mono-, di- or tri-substituted with RY;
    v) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >O, >S, >NH or >N(C,.4alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R%,;
    vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with RY,
    vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR9, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 to 5 substituents R® and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents R% and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR9, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents R%; R' is selected from the group consisting of H, C+.7alkyl, C2.7alkenyl, Co7alkynyl,
    Ca.scycloalkyl, CascycloalkylC,.7alkyl, Cs.,cycloalkenyl,
    Cs.7cycloalkenylC.7alkyl and benzo-fusedCa scycloalkyl, each optionally mono-, di-, or tri-substituted with RP; RP is selected from the group consisting of —-OH, -OC;salkyl,
    -Ca.scycloalkyl, -OCsecycloalkyl, -CN, -NO,, phenyl, pyridyl, thieny!l, : furanyl, pyrrolyl, -N(R®)R" (wherein R® and R" are independently selected from H or Cy.salkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, =N-, >NH or >N(C,.4alkyl) and optionally having one or two unsaturated bonds in the ring), -(C=0)N(R®)R", -(N-R")COR", -(N-R")SO.C;.salkyl (wherein R" is H or C.¢alkyl or two R" in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)Cjgalkyl, -(S=(0)n)-C1ealkyl (wherein n is selected from 0, 1 or 2), -SO2N(R®*)R", -SCF3, halo, -CF3, -OCF3, -COOH and -COOC;.galkyl,- wherein the foregoing phenyl, pyridyl, thienyl, furany! and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C1.¢alkyl, -OC1.¢alkyl, -CN, -NO,, -N(R*)R® (wherein R? and R® are independently selected from H, C,.salkyl or C-salkenyl), -(C=0)N(R?)R", -(N-R°)COR?®, -(N-R°)SO.C.galkyl (wherein R® is H or Cy_galkyl), -(C=0)C1.galkyl, -(S=(0)q)-C1-alkyl (wherein d is selected from 0, 1 or 2), -SON(R*R®, -SCF3, halo, -CF3, -OCF3, -COOH and -COOC alkyl;
    R? is selected from the group consisting of H, Ci.7alkyl, Ca7alkenyl, C.7alkynyl and Ca.rcycloalkyi; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof.
    2. The compound of claim 1 wherein mis 1 or 2.
    3. The compound of claim 1 wherein mis 1.
    4. The compound of claim 1 wherein nis 1 or 2.
    5. The compound of claim 1 wherein pis 1 or 2.
    6. The compound of claim 1 wherein m+n is 2 or 3.
    7. The compound of claim 1 wherein m+p is 2 or 3.
    8. The compound of claim 1 wherein q is 1.
    9. The compound of claim 1 whereinris 0, 1, or 2.
    10. The compound of claim 1 wherein r is 4.
    11. The compound of claim 1 wherein R®, optionally substituted, is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, allyl, propargyl, and benzyl.
    12. The compound of claim 1 wherein R® is methyl.
    13. The compound of claim 1 wherein Ar, optionally substituted, is selected from the group consisting of:
    a) phenyl, 5-, 6-, 7-, 8-benzo-1,4-dioxanyl, 4-, 5-, 6-, 7-benzo-1,3- dioxolyl, 4-, 5-, 6-, 7-indolinyl, 4-, 5-, 6-, 7-isoindolinyl, 1,2,3,4-tetrahydro- quinolin-4, 5, 6 or 7-yl, 1,2,3,4-tetrahydro-isoquinolin-4, 5, 6 or 7-yl, b) 4-, 5-, 6- or 7-benzoxazolyl, 4-, 5-, 6- or 7-benzothiophenyl, 4-, 5-, 6- or 7-benzofuranyl, 4-, 5-, 6- or 7-indolyl, 4-, 5-, 6- or 7-benzthiazolyl, 4-, 5-, 6- or 7-benzimidazolyl, 4-, 5-, 6- or 7-indazolyl, imidazo[1,2-a)pyridin-5, 6, 7 or 8- yl, pyrazolo[1,5-a)pyridin-4, 5, 6 or 7-yl, 1H-pyrrolo[2,3-b]pyridin-4, 5 or 6-yl, 1H-pyrrolo[3,2-c]pyridin-4, 6 or 7-yl, 1H-pyrrolo[2,3-c]pyridin-4, 5 or 7-yl, 1H-pyrrolo[3,2-b]pyridin-5, 6 or 7-yl, c) 5-, 6-, 7- or 8-isoquinolinyl, 5-, 6-, 7- or 8-quinolinyl, 5-, 6-, 7- or 8- quinoxalinyl, 5-, 6-, 7- or 8-quinazolinyl, d) naphthyl, e) furanyl, oxazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, © 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiophenyl, thiazolyl, isothiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 3-indoxazinyl, 2- benzoxazolyl, 2- or 3-benzothiophenyl, 2- or 3-benzofuranyl, 2- or 3-indolyl, 2- benzthiazolyl, 2-benzimidazolyl, 3-indazolyl, f) pyridinyl, pyridinyl-N-oxide, pyrazinyl, pyrimidinyl, pyridazinyl, 1-, 3- or 4-isoquinolinyl, 2-, 3- or 4-quinolinyl, 2- or 3-quinoxalinyl, 2- or 4-quinazolinyl, [1,5], [1,6], [1,7], or [1,8]naphthyridin-2-, 3-, or 4-yl, [2,5], [2,6], [2,7], [2,8]naphthyridin-1-, 3-, or 4-yl, and g) biphenyl, 4-tetrazolylphenyl.
    14. The compound of claim 1 wherein Ar, optionally substituted, is selected from the group consisting of phenyl, pyridyl, thiophen-2-yl and thiophen-3-yl.
    15. The compound of claim 1 wherein Ar is selected from the group consisting of phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methyiphenyl, 4-ethyiphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyi, 4-trifluoromethyiphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 3-cyanophenyl,
    4-cyanophenyl, 3-acetylphenyl, 4-acetylphenyl, 3,4-diflucrophenyi, 3,4-dichlorophenyl, 2,3-difluorophenyl, 2,3-dichlorophenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 3-nitrophenyl, 4-nitrophenyl, 3-chloro-4-fluorophenyl, 3-fluoro-4-chlorophenyl, benzo[1,3]dioxol-4 or 5-yl, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-hydroxy-2-methylphenyl, 4-hydroxy-3-fluorophenyl, 3,4- dihydroxyphenyl,4-dimethylaminophenyl!, 4-carbamoylphenyl, 4-fluoro-3- methylphenyl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, 5- chlorothiophen-2-yl, 5-methyithiophen-2-yl, 5-chiorothiophen-3-yi, 5- methyithiophen-3-yl, 4'-chlorobiphenyl, and 4-tetrazolylphenyl.
    16. The compound of claim 1 wherein ALK, optionally substituted, is selected from the group consisting of methylene, ethylene, propylene, butylene, tert-butylene, pentylene, 1-ethylpropylene, 2-ethylpropylene, 2- ; ethylbutylene, isopropylene, but-3-enylene, isobutylene, 3-methylbutylene, allylene, and prop-2-ynylene.
    17. The compound of claim 1 wherein ALK is selected from the group consisting of methylene, trifluoromethylmethylene, methoxycarbonyimethyl, methylcarbamoylmethyl, ethylene, propylene, 3-methoxycarbony! propylene, 3- carboxy propylene, butylene, tert-butylene, 4-hydroxybutylene, 4- methoxycarbonyl butylene, 4-carboxy butylene, pentylene, 5-hydroxypentylene, 1-ethylpropylene, 2-ethylpropylene, 2-ethylbutylene, isopropylene, but-3- enylene, isobutylene, 3-methylbutylene, prop-2-ynylene, 2- dimethylaminoethylene, and 2-cyanoethylene.
    18. The compound of claim 1 wherein CYC, optionally substituted, is hydrogen or is selected from the group consisting of: i) phenyl, 5-, 6-, 7-, 8-benzo-1,4-dioxanyl, 4-, 5-, 6-, 7-benzo-1,3-dioxolyl, 4-, 5-, 6-, 7-indolinyl, 4-, 5-, 6-, 7-isoindolinyl, 1,2,3,4-tetrahydro-quinolin-4, 5, 6 or 7-yl 1,2,3,4-tetrahydro-isoquinolin-4, 5, 6 or 7-yl, ii) 4-, 5-, 6- or 7-benzoxazolyl, 4-, 5-, 6- or 7-benzothiophenyl, 4-, 5-, 6- or 7-benzofuranyl, 4-, 5-, 6- or 7-indolyl, 4-, 5-, 6- or 7-benzthiazolyl, 4-, 5-, 6- or 7-benzimidazolyl, 4-, 5-, 6- or 7-indazolyl, imidazo[1,2-a]pyridin-5, 6, 7 or 8-
    yl, pyrazolo[1,5-a}pyridin-4, 5, 6 or 7-yl, 1H-pyrrolo[2,3-b]pyridin-4, 5 or 6-yl, 1H-pyrrolo[3,2-c]pyridin-4, 6 or 7-yl, 1H-pyrrolo[2,3-c]pyridin-4, 5 or 7-yl, 1H-pyrrolo[3,2-blpyridin-5, 6 or 7-yl, iii) 5-, 6-, 7- or 8-isoquinolinyl, 5-, 6-, 7- or 8-quinolinyl, 5-, 6-, 7- or 8- quinoxalinyl, 5-, 6-, 7- or 8-quinazolinyl, iv) naphthyl, v) furanyl, oxazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazoly|, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiophenyl, thiazolyl, isothiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 3-indoxazinyl, 2- benzoxazolyl, 2- or 3-benzothiophenyl, 2- or 3-benzofuranyl, 2- or 3-indolyl, 2- benzthiazolyl, 2-benzimidazolyl, 3-indazolyl, vi) pyridinyl, pyridinyl-N-oxide, pyrazinyl, pyrimidinyl, pyridazinyl, 1-, 3- or 4-isoquinolinyl, 2-, 3- or 4-quinolinyl, 2- or 3-quinoxalinyl, 2- or 4-quinazolinyl, [1,5], [1,6], [1,7], or [1,8]naphthyridin-2-, 3-, or 4-yl, [2,5], [2,6], [2,7], [2,8]naphthyridin-1-, 3-, or 4-yl, vii) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, adamantyl, pyrrolinyl, pyrrolidinyl, pyrazolinyl, piperidinyl, homopiperidinyl, azepanyl, tetrahydrofuranyl, tetrahydropyranyl, piperazinyl, morpholinyl, thiomorpholinyl, piperidinonyl, indanyl, dihydroindolyi, oxindolyl, dihydropyrrolopyridinyl, and viii) bicyclo[4.1.0]heptane, octahydroindolyl, octahydroisoindolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydropyrrolopyridinyl, and octahydropyrrolopyrrolidinyl.
    19. The compound of claim 1 wherein CYC, optionally substituted, is selected from the group consisting of hydrogen, phenyl, indolyl, benzthiazolyl, isoquinolyl, quinazolinyl, naphthalen-1 or 2-yl, thiophen-2-yl, thiophen-3-yl, furan-2-yl, furan-3-yl, pyridinyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, piperidin-2,3 or 4-yl, 2-pyrrolin-2, 3, 4 or 5-yl, 3-pyrrolin-2 or 3-yl, 2- pyrazolin-3, 4 or 5-yl, morpholin-2, 3, 5 or 6-yl, thiomorpholin-2, 3, 5 or 6-yl, piperazin-2, 3, 5 or 6-yl, pyrrolidin-2 or 3-yl, homopiperidinyl, adamantanyl, and octahydroindolyl.
    20. The compound of claim 1 wherein CYC, optionally substituted, is selected from the group consisting of hydrogen, phenyl, pyridyl, cyclobutyl, cyclopentyl, cyclohexyl, thiophen-2-yl, thiophen-3-yl, tetrahydropyranyl, furan-2- yl, furan-3-yl and naphthalen-1or 2-yl. -
    21. The compound of claim 1 wherein CYC is selected from the group consisting of hydrogen, phenyl, 2-methoxyphenyi, 3-methoxyphenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-ethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromopheny!, 3-bromophenyl, 4-bromophenyt, 2-trifluoromethylphenyi, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3-trifluoromethoxyphenyl, 4-trittuoromethoxyphenyi, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3-acetylphenyl, 4-acetylphenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 2,3-difluorophenyl, 2,3-dichlorophenyl, 16 2,4-difluorophenyl, 2,4-dichiorophenyl, 2,6-difluorophenyl, 2,6-dichlorophenyl, 2,6-dimethylphenyl, 2,4,6-trifluorophenyl, 2,4,6-trichiorophenyl, 3,4,5-trimethoxyphenyl, cyclobutyl, cyclohexyl, cyclopentyl, 4-fluoro-3- methylphenyl, 3-nitrophenyl, 4-nitrophenyl, 4-methyl-3-fluorophenyl, 3,4- dimethylphenyl, 4-methoxy-3-fluorophenyl, 4-methoxy-2-methylphenyl, 3-aminophenyl, 4-aminophenyl, 4-carbomethoxyphenyl, 3-methanesulfonylamino-phenyl, 4-methanesulfonylamino-phenyl, 3-dimethanesulfonylamino-phenyl, 4-dimethanesulfonylamino-phenyl, thiophen-2-yl, thiophen-3-yl, 5-chiorothiophen-2-yl, benzo[1,3]dioxol-4 or 5-yl, tetrahydropyran-2,3 or 4-yl, furan-2-yl, furan-3-yl, 5-carboxyethyl-furan-2-yl, naphthalen-1 or 2-yl, 3,4-bisbenzyloxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-hydroxy-2-methylphenyl, 4-hydroxy-3- fluorophenyl and 3,4-dihydroxyphenyl.
    22. The compounds of claim 1 wherein R' is selected from the group consisting of hydrogen, Cy.aalkyl, Co4alkenyl, Ca.salkynyl, Csecycloalkyl, Ca. scycloalkylC,.aalkyl, Csecycloalkenyl, benzo-fusedCs.ecycloalkyl, each optionally mono-, di-, or tri-substituted with RP.
    23. The compound of claim 1 wherein R', optionally RP substituted, is selected from the group consisting of hydrogen, methyl, ethyl, propyl, and isopropyl.
    24. The compound of claim 1 wherein R'is selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, 3-hydroxypropy!, benzyl, 3,4-dimethoxybenzyl, methoxycarbonylmethyl, carbamoyimethyl, phenethyl, phenpropyl, and hydroxyethyl.
    25. The compound of claim 1 wherein R? is hydrogen, Ci.salkyl, Co4alkenyl, Caalkynyl, or Caecycloalkyl.
    26. The compound of claim 1 wherein R? is hydrogen or methyl.
    27. The compound of claim 1 selected from the group consisting of: EX CHEMICAL NAME 1 1-Benzyl-3-(4-nitro-phenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- cJpyridine; 2 1-Benzyl-3-(3-chloro-4-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H- pyrrolo[3,2-c]pyridine; 3 4-(1-Benzyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridin-3-yl)-phenol; 4 1-Benzyl-3-(4-trifluoromethoxy-phenyl)-4,5,6,7-tetrahydro-1 H pyrrolo[3,2-c]pyridine; 5 1-Benzyl-3-(5-chloro-thiophen-2-yl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- clpyridine; 6 1-Benzyl-3-thiophen-2-yl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-clpyridine; 7 1-(3-Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- clpyridine; 8 1-Benzyl-3-(3-fluoro-phenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- Clpyridine; 9 3-(4-Chloro-phenyl)-1-(2-fluoro-benzyl)-4,5,6,7-tetrahydro-1 H- pyrrolo[3,2-c]pyridine;
    1-(3-Chloro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1H- pyrrolo[3,2-c]pyridine; 11 1-(2-Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- clpyridine; 12 1-(4-Chloro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H- pyrrolo[3,2-c]pyridine; 13 1-Benzyl-3-(2,4-dichloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- clpyridine; 14 1-(4-Methoxy-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- clpyridine; 1-(2-Chloro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H- pyrrolo[3,2-c]pyridine; 16 1-(2,4-Dichloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- clpyridine; 17 1-Benzyl-2-methyl-3-phenyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- clpyridine; 18 1-Benzyl-3-p-tolyl-4,5,6,7-tetrahydro-1 H-pyrrolo{3,2-c]pyridine; 19 1-Benzyl-3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- Clpyridine; 3-Benzo[1,3]dioxol-5-yl-1-benzyl-4,5,6,7-tetrahydro-1 Hpyrrolo[3,2- clpyridine; 21 1-Benzyl-3-(4-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- clpyridine; 22 1-Butyl-3-p-tolyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine; 23 1-Benzyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2- clpyridine; . 24 1-Benzyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H- pyrrolo[3,2-c]pyridine; 1-Benzyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- cJpyridine; 26 1-Benzyl-3-phenyl-1,4,5,6,7,8-hexahydro-pyrrolo[2,3-dlazepine;
    27 1-Benzyl-3-(5-methyl-thiophen-2-yl)-4,5 6,7-tetrahydro-1H-pyrrolo[3,2- cJpyridine; 28 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-pyrrolo[2,3- dlazepine; 29 1-Benzyl-3-(5-chloro-thiophen-2-yl)-1,4,5,6,7,8-hexahydro-pyrrolo[2,3- dlazepine; 1-(4-Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- clpyridine; 31 1-Benzyl-3-phenyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine; 32 1-Benzyl-3-(3-chloro-phenyl)-1,4,5,6,7,8-hexahydro-pyrrolo[2,3- dlazepine; 33 1-Benzyl-3-(3-chloro-phenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- clpyridine; 34 1-Benzyl-3-(4-methoxy-phenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- Clpyridine; 1-Benzyl-3-(4-chloro-phenyl)-5-ethyl-4,5,6,7-tetrahydro-1H- pyrrolo[3,2-c]pyridine; 36 1-Benzyl-3-(4-chloro-phenyl)-5-isopropyi-4,5,6,7-tetrahydro-1 H- pyrrolo[3,2-c]pyridine; 37 3-[1-Benzyl-3-(4-chioro-phenyl)-1,4,6,7-tetrahydro-pyrrolo[3,2- cJpyridin-5-yl]-propan-1-ol; 38 1-Benzyl-3-(4-chloro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1 +H pyrrolo[3,2-c]pyridine; 39 1-Benzyl-3-(3-chloro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1 H- pyrrolo[3,2-clpyridine; 40 1-Benzyl-3-(3-chloro-4-fluoro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1 H- pyrrolo[3,2-clpyridine; 41 1,5-Dibenzyl-3-phenyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-clpyridine; and 42 1-Benzyl-5-isopropyl-3-phenyi-4,5,6,7-tetrahydro-1H-pyrrolo[3,2- clpyridine.
    28. The compound of claim 1 selected from the group consisting of: EX CHEMICAL NAME 1-Benzyl-3-(4-trifluoromethyl-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6- 43 triaza-azulene; 44 1-Benzyl-3-phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 45 1-Benzyl-3-(2-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 46 1-Benzyl-3-(3-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulens; 47 1-Benzyl-3-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- : azulene; 48 1-Benzyl-3-(2,3-difluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 49 1-Benzyl-3-(3,4-dichloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 50 1-]4-(1-Benzyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- phenyl]-ethanone; 51 1-Benzyl-3-(4-trifluoromethoxy-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; - 1-Benzyl-3-(3-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 53 3-(1-Benzyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- benzonitrile; ” 4-(1-Benzyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- benzonitrile; 55 1-(4-Chioro-benzyl)-3-phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 56 1-(4-Chloro-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 57 1-Benzyl-3-phenyl-6-propyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene, 5g 1-Benzyl-6-isopropyl-3-phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene;
    1-Benzyl-3-(4-chloro-phenyi)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- > azulene; 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,5-triaza- °0 azulene; 3-(4-Chloro-phenyl)-1-methyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- ® azulene; 3-(4-Chloro-phenyl)-1-ethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- 83 azulene; 65 3-(4-Chloro-phenyl)-1-propyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; &7 1-Butyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 69 3-(4-Chloro-phenyl)-1-(2-cyciohexyl-ethyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 74 3-(4-Chloro-phenyl)-1-phenethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 73 3-(4-Chiloro-phenyl)-1-(4-fluoro-3-methyl-benzyl)-1,4,5,6,7,8- : hexahydro-1,2,6-triaza-azulene; 74 3-(4-Chloro-phenyl)-1-(3-methyl-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 75 3-(4-Chloro-phenyl)-1-(4-fluoro-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 76 3-(4-Chloro-phenyl)-1-(3-fluoro-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 77 3-(4-Chloro-phenyl)-1-(4-methyl-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 78 3-(4-Chloro-phenyl)-1-(3,4-difluoro-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 79 3-(4-Chloro-phenyl)-1-(3-nitro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 80 3-(4-Chloro-phenyl)-1-(3-fluoro-4-methyl-benzyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene;
    3-(4-Chloro-phenyl)-1-(3,4-dimethyl-benzyl)-1,4,5,6,7,8-hexahydro- 81 1,2,6-triaza-azulene; 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1- 85 yl]-pentanoic acid methyl ester; 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H1,2,6-triaza-azulen-1- 86 yl]-pentanoic acid; 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- 87 yl]-pentan-1-ol; 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- 58 yl)-butyric acid methyl ester; o1 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1- yl]-butyric acid; 93 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- yl}-butan-1-ol; 56 3-(4-Chloro-phenyl)-1-(3-fluoro-4-methoxy-benzyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; o8 3-(4-Chloro-phenyl)-1-(4-nitro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 4-(3-Phenyl-5,6,7,8-tetrahydro-4 H-1 ,2,6-triaza-azulen-1-yimethyl)- 9 phenylamine; 100 N-[4-(3-Phenyl-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- yimethyl)-phenyl]-methanesulfonamide; 101 N,N-{4-(3-phenyl-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1- yimethyl)-phenyl}-dimethanesulfonamide; 102 1-Benzyl-3-p-tolyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 103 3-(4-Chloro-phenyl)-1-thiophen-2-yimethyl-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 104 1-Benzyl-3-thiophen-2-yl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 105 3-(4-Chioro-phenyl)-1-(3-methoxy-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 106 3-(4-Chloro-phenyl)-1-(2-fluoro-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene;
    3-(4-Chloro-phenyl)-1-(2-methyl-benzyl)-1,4,5,6,7,8-hexahydro- 107 1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-1-(2,4-difiuoro-benzyl)-1,4,5,6,7,8-hexahydro- 108 1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-1-(2-methoxy-benzyl)-1,4,5,6,7,8-hexahydro- 109 1 2,6-triaza-azulene; 1-(2-Chloro-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro- 110 1,2,6-triaza-azulene; 1-But-3-enyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- ha azulenes; 112 1-(2-Bromo-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 113 1-(4-Bromo-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 114 3-(4-Chloro-phenyl)-1-(2-ethyl-butyl)-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 115 3-(4-Chloro-phenyl)-1-(5-chloro-thiophen-2-yimethyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 116 1-(3-Bromo-benzyl)-3-(4-chioro-phenyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; ; 17 3-(4-Chloro-phenyl)-1-cyclohexylmethyl-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 118 3-(4-Chloro-phenyt)-1-isobutyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 119 1-Benzo[1,3]dioxol-5-yimethyl-3-(4-chloro-phenyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 120 3-(4-Chloro-phenyl)-1-(tetrahydro-pyran-4-ylmethy!)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 121 '3-(4-Chloro-phenyl)-1-(2,6-difluoro-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 123 3-(4-Chloro-phenyl)-1-(4-methoxy-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene;
    3-(4-Chloro-phenyl)-1-(3-methyl-butyl)-1,4,5,6,7,8-hexahydro-1,2,6- 124 triaza-azulene; 3-(4-Chloro-phenyt)-1-(2-trifluoromethyl-benzyl)-1,4,5,6,7,8- 125 hexahydro-1,2,6-triaza-azulene 3-(4-Chloro-phenyl)-1-(4-methoxy-2-methyl-benzyl)-1,4,5,6,7,8- 128 hexahydro-1,2,6-triaza-azulene; 134 3-(4-Chloro-phenyl)-1 -prop-2-ynyl-1 ,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 3-(4-Chloro-phenyl)-1-pentafluorophenyimethyl-1,4,5,6,7,8- 195 hexahydro-1,2,6-triaza-azulene; 137 3-(4-Chloro-phenyl)-1-(2,4,6-trifluoro-benzyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 138 2-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- yimethyl}-benzonitrile; 142 3-(4-Chloro-phenyl)-1-naphthalen-2-ylmethyl-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; a4 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- yimethyl]-furan-2-carboxylic acid ethyl ester; . 145 3-(4-Chioro-phenyl)-1-naphthalen-1-yimethyl-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 147 [3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1-yl}- acetic acid methyl ester; 148 2-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- yl]-N-methyl-acetamide; 150 3-(4-Chloro-phenyl)-1-(3,4,5-trimethoxy-benzyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 152 3-(4-Chloro-phenyl)-1-(2,6-dimethyl-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 154 1-(3,4-Bis-benzyloxy-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 156 3-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- ylimethyl]-phenol;
    4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- 157 ylimethyl}-phenol; 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1- 158 yimethyl]-3-methyl-phenol; 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- 159 yimethyl]-benzene-1,2-diol; 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H1,2,6-triaza-azulen-1- 160 ylmethyl]-2-fluoro-phenol; 2-[3-(4-Chioro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- 162 ylmethyl}-phenol; 165 1-Benzyl-3-(4-chloro-phenyl)-6-methyl-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 166 1-Benzyl-3-(4-chloro-phenyl)-6-ethyl-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 167 3-(4-Chloro-phenyl)-6-(3,4-dimethoxy-benzyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 168 1-Butyl-3-(4-chloro-phenyl)-6-(3,4-dimethoxy-benzyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 169 1-Benzyl-3-(4-chloro-phenyl)-6-(3,4-dimethoxy-benzyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 170 [1-Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza- azulen-6-yl)-acetic acid methyl ester; 171 2-[1-Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H+1,2,6-triaza- azulen-6-yl]-ethanol; 172 3-(4-Chloro-phenyl)-1-phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 173 3-(4-Chloro-phenyl)-1-(2-methyl-benzyl)-4,5,6,7,8,9-hexahydro-1 H- 1,2,6-triaza-cyclopentacyclooctene; 174 3-(4-Chloro-phenyl)-1-(2-methyl-benzyl)-4,5,6,7,8,9-hexahydro-1 H- 1,2,7-triaza-cyclopentacyclooctene; 475 3-(4-Chloro-phenyl)-1-(2-methyl-benzyl)-4,5,6,7-tetrahydro-1 H- pyrazolo[3,4-c]pyridine;
    {4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1- 280 ylmethyl]-phenyl}-methyl-amine; 3-(4-Chloro-phenyl)-1-cyclobutyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- 237 azulene; 3-(4-Chloro-phenyl)-1-cyclohexyi-1,4,5,6,7,8-hexahydro-1,2,6- 239 triaza-azulene; 0854 3-(4-Chloro-phenyl)-1-cycloheptyl-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 256 3-(4-Chloro-phenyl)-1-cyclooctyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; ova 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene citrate salt; 316 3-(4-Chloro-phenyl)-1-pyridin-4-ylmethyl-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 317 3-(4-Chloro-phenyl)-1-pyridin-2-ylmethyl-1,4,5,6,7,8-hexahydro- : 1,2,6-triaza-azulene; 319 3-(4-Chloro-phenyl)-1-pyridin-3-ylmethyl-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 320 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1- ylmethyl]-benzoic acid methyl ester; 391 3-(4-Chloro-phenyl)-1-(tetrahydro-pyran-4-yl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 322 3-(4-Chloro-phenyl)-1-(4-methyl-cyclohexyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 323 {2-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1- yl]-ethyl}-dimethyl-amine. 304 3-(4-Chloro-phenyl)-1-(1-oxy-pyridin-2-yimethyl)-1,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 305 2-[1-Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza- azulen-6-yl]-acetamide; 326 3-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1- yl}-propionitrile.
    a3 1-(4-Chloro-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro- 1,2,5-triaza-azulene; 308 3-(4-Chloro-phenyl)-1-(4-methyl-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,5-triaza-azulene; 334 3-(4-Chloro-phenyl)-1-(3,4-difluoro-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,5-triaza-azulene; oy 3-(4-Chloro-phenyl)-1-(3-methyl-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,5-triaza-azulene; 208 3-(4-Chloro-phenyl)-1-(3-fluoro-4-methyl-benzyl)-1,4,5,6,7,8- hexahydro-1,2,5-triaza-azulene; and 237 3-(4-Chloro-phenyl)-1-(4-fluoro-3-methyi-benzyl)-1,4,5,6,7,8- ~ hexahydro-1,2,5-triaza-azulene.
    29. The compound of claim 1 selected from the group consisting of: EX CHEMICAL NAME 62 3-(4-Chloro-phenyl)-2-methyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 64 3-(4-Chloro-phenyl)-2-ethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 66 3-(4-Chloro-phenyl)-2-propyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 68 2-Butyl-3-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 3-(4-Chloro-phenyl)-2-(2-cyclohexyl-ethyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 70 3-(4-Chloro-phenyl)-2-phenethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 82 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-2- yll-pentanoic acid methyl ester; 83 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-2- yl]-pentanoic acid; 84 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4/+1,2,6-triaza-azulen-2- yll-pentan-1-ol;
    4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4+1,2,6-triaza-azulen-2- 89 yl}-butyric acid methyl ester; 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2- 90 yl]-butyric acid; 4-[3-(4-Chloro-phenyl)-5,6,7 ,8-tetrahydro-4 H-1,2,6-triaza-azulen-2- 92 yl}-butan-1-ol; 3-(4-Chloro-phenyl)-2-(3,4-difluoro-benzyl)-2,4,5,6,7,8-hexahydro- 94 1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-2-(4-methyl-benzyl)-2,4,5,6,7,8-hexahydro- 9% 1,2,6-triaza-azulene; 97 3-(4-Chloro-phenyl)-2-(3-fluoro-4-methoxy-benzyl)-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 122 3-(4-Chloro-phenyl)-2-cyclohexylmethyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene, 126 3-(4-Chloro-phenyl)-2-(2-methyl-benzyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 127 2-Benzyl-3-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 129 3-(4-Chloro-phenyl)-2-(2,4-difluoro-benzyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 130 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-2- ylmethyl]-furan-2-carboxylic acid ethyl ester; 131 3-(4-Chloro-phenyl)-2-isobutyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 130 3-(4-Chloro-phenyl)-2-(2-methoxy-benzyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 133 2-Benzyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 136 3-(4-Chloro-phenyl)-2-thiophen-2-ylmethyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 139 3-(4-Chloro-phenyl)-2-(5-chloro-thiophen-2-ylmethyl)-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 140 3-(4-Chloro-phenyl)-2-(2,6-difluoro-benzyl)-2,4,5,6,7,8-hexahydro- : 1,2,6-triaza-azulene; :
    3-(4-Chloro-phenyl)-2-(2-trifluoromethyi-benzyl)-2,4,5,6,7,8- 141 hexahydro-1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-2-(2-ethyl-butyl)-2,4,5,6,7,8-hexahydro-1,2,6- 143 triaza-azulene; 2-Benzo[1,3]dioxol-5-yimethyl-3-(4-chloro-phenyl)-2,4,5,6,7,8- 146 hexahydro-1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-2-pentafluorophenyimethyl-2,4,5,6,7,8- 149 hexahydro-1,2,6-triaza-azulene; 151 3-(4-Chloro-phenyl)-2-naphthalen-1-ylmethyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 153 3-(4-Chloro-phenyl)-2-(3,4,5-trimethoxy-benzyl)-2,4,5,6,7,8- } hexahydro-1,2,6-triaza-azulene; 155 2-(3,4-Bis-benzyloxy-benzyl)-3-(4-chioro-phenyl)-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 161 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-2- ylmethyl]-2-fluoro-phenol; 163 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1 ,2,6-triaza-azulen-2- ylmethyl]-3-methyi-phenol; 164 2-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2- yimethyl]-phenol; 176 2,3-Diphenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 177 2-Cyclohexyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 178 3-(4-Chloro-phenyl)-2-cyclohexyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 179 2-Cyclohexyl-3-(4-trifluoromethyl-phenyi)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 180 2-Cyclopentyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 181 3-(4-Chloro-phenyl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 182 2-Cyclopentyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 183 2-(1-Ethyl-propyl)-3-(3-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene;
    2-(1-Ethyl-propyl)-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- 184 triaza-azulene; 2-(1-Ethyl-propyl)-3-thiophen-3-yl-2,4,5,6,7,8-hexahydro-1,2,6- 185 triaza-azulene, 2-(1-Ethyl-propyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- 186 azulene; 3-(4-Chloro-phenyl)-2-(2,2,2-trifluoro-ethyl)-2,4,5,6,7,8-hexahydro- 187 1,2,6-triaza-azulene; 188 2-(2,2,2-Trifluoro-ethyl)-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 189 2-Isopropyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 190 3-(4-Fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 191 2-(1 -Ethyl-propyl)-3-thiophen-2-y}-2,4,5,6,7,8-hexahydro-1 ,2,6- triaza-azulene; 192 2-Cyclopentyl-3-thiophen-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 193 2-Ethyl-3-phenyi-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 194 2-Ethyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 196 2-Ethyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 196 2-(3-Chloro-phenyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza- azulene; 197 2+(3-Fluoro-phenyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza- azulene; 198 2-(2-Chloro-phenyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 199 2-Phenyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 200 3-(4-Fluoro-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 201 3-(4-Chloro-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene;
    3-(3-Chloro-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- 202 azulene; 203 2-Phenyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 204 2,3-Diphenyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine; 3-Phenyl-2-(3-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- 205 triaza-azulene; 3-(4-Methoxy-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- 208 azulene; 507 2-(4-Chloro-phenyl)-3-pheny-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza- azulene; 208 6-Methyl-2,3-diphenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 209 2-lsopropyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 290 3-(4-Ethyl-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 11 3-(4-Chloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- . azulene; 212 4-(2-Isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- benzonitrile; 13 2-Isopropyi-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 214 2-Ethyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 215 2-tert-Butyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 016 2-tert-Butyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 217 2-Cyclopentyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 218 2-Cyclopentyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 219 3-(3-Chloro-phenyl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 220 2-Cyclopentyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 01 2-(3,3-Dimethyl-cyclopentyl)-3-pheny!-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene;
    2-(3,3-Dimethyl-cyclopentyl)-3-(4-fluoro-phenyi-2,4,5,6,7,8- 222 hexahydro-1,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-2-(3,3-dimethyl-cyclopentyl)-2,4,5,6,7,8- 223 hexahydro-1,2,6-triaza-azulene; 004 2-Cyclohexyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; p05 2-Cyclohexyl-3-(3,4-difluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 226 2-Cyclohexyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 007 2-Cyclohexyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 228 4-(2-Cyclohexyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- benzonitrile; 009 3-(3-Chloro-phenyl)-2-cyclohexyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 031 3-(4-Fluoro-phenyl)-2-isopropyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3- c]pyridine; 032 2-Cyclopentyl-3-furan-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 033 2-Cyclopentyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 034 2-tert-Butyl-3-thiophen-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 235 2-tert-Butyl-3-furan-3-yi-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 236 2-Cyclopentyl-3-(3,4-difluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 038 3-(4-Chloro-phenyl)-2-cyclobutyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 240 2-tert-Butyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 041 3-(3-Chloro-4-fluoro-phenyl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene;
    ” 2-Isopropyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 043 2-1sopropyl-3-(4-trifluoromethoxy-phenyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 044 2-1sopropyl-3-(4-isopropyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- . triaza-azulene; 045 3-(4-tert-Butyl-phenyl)-2-isopropyl-2,4,5,6,7 ,8-hexahydro-1,2,6- triaza-azulene; 246 2-Isopropyl-3-m-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 247 2-Isopropyl-3-o-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 048 3-(3,4-Dichloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulens; 049 2-Benzyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 250 2-Isopropyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza- azulene; 051 3-(2-Chloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 052 1-[4-(2-1sopropyl-2,4,5,6,7 ,8-hexahydro-1,2,6-triaza-azulen-3-yl)- phenyl]-ethanone; 053 2-Isopropyl-3-(4-nitro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 056 2-Benzyl-3-(4-chloro-phenyi)-2,4,5,6,7,8-hexahydro-1,2,5-triaza- azulene; ] 057 2-Ethyl-3-(4-ethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 058 4-(2-Ethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- benzonitrile; 059 3-(4-Fluoro-phenyl)-2-isopropyl-6-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 260 3-(4-Fluoro-phenyl)-2,6-diisopropyl-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene;
    2-Ethyl-3-(4-isopropyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- 261 azulene; 2-Ethyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- 262 azulene; 2-Ethyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- 263 triaza-azulene; 264 2-Ethyl-3-o-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 065 3-(2-Chloro-phenyl)-2-ethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 266 2-Ethy}-3-(2-fluoro-pheny)-2,4.5,6,7,8-hexahydro-1 ,2,6-triaza- azulene; 067 3-(2,4-Dichloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 268 [4-(2-Ethyl-2,4,5,6,7,8-hexahydro-1 2,6-triaza-azulen-3-yl)-phenyl]- dimethyl-amine; 269 6-Benzyl-3-(4-fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 270 3-(4-Fluoro-phenyl)-2-isopropyl-6-(3-phenyi-propyl)-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 071 3-(4-Fluoro-phenyl)-2-isopropyl-6-phenethyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; and 270 3-(4-Fluoro-phenyl)-2-isopropyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza- azulene-6-carboxylic acid tert-butyl ester. 074 3-(4'-Chloro-biphenyl-4-yl)-2-(2,2,2-trifluoro-ethyl)-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 278 3-(4'-Chloro-biphenyl-4-yl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 276 2-Cyclobutyt-3-phenyi-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 077 2-Cyclobutyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 278 2-Cyclobutyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 579 2-Cyclobutyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene;
    4-(2-Cyclobutyl-2,4,5,6,7, 8-hexahydro-1,2,6-triaza-azulen-3-yl)- 280 benzonitrile 281 2-Cyclopropyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 2-Cyclopropyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- 262 triaza-azulene; 2-(1-Ethyl-propyl)-3-(4-fluoro-3-methyl-phenyl)-2,4,5,6,7,8- 283 hexahydro-1,2,6-triaza-azulene; 284 2-Cyclopropyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 285 2-Cyclopropyl-3-thiophen-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 286 4-(2-Cyclopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- benzonitrile; 087 6-Benzyl-2-isopropyl-3-phenyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4- clpyridine; 288 2-Isopropyl-3-phenyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine; 289 6-Benzyl-2-isopropyl-3-thiophen-3-yl-4,5,6,7-tetrahydro-2H- pyrazolo[3,4-c]pyridine; 290 6-Benzyl-2-isopropy!-3-p-tolyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4- clpyridine. 091 6-Benzyl-3-(4-fluoro-phenyl)-2-isopropyl-4,5,6,7-tetrahydro-2H- pyrazolo[3,4-c]pyridine; ap 3-(4-Fluoro-phenytl)-2-isopropyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4- clpyridine; 293 2-lsopropyl-3-p-tolyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine; 094 2-Cyclopentyl-3-(4-fluoro-phenyl)-5,5,7,7-tetramethyl-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 005 2-Cyclopentyl-5,5,7,7-tetramethyl-3-phenyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 096 2-lsopropyl-5,5,7,7-tetramethyl-3-phenyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 097 3-(4-Fluoro-phenyl)-2-isopropyl-5,5,7,7-tetramethyl-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 298 2-sec-Butyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene;
    2-sec-Butyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- 299 azulene; 300 2-sec-Butyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 2-sec-Butyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- 801 triaza-azulene; 2-Cyclopentyl-3-(4-fluoro-phenyl)-6-methyl-2,4,5,6,7,8-hexahydro- 302 1,2,6-triaza-azulene; 4-(2-lsopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- 803 benzamide; 304 2-Isopropyl-3-[4-(1H-tetrazol-5-yl)-phenyl]-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 305 6-Benzyl-3-(4-fluoro-phenyl)-2-isopropyl-8-methyl-2,4,5,6,7,8- hexahydro-1,2,6-triaza-azulene; 306 3-(4-Fluoro-phenyl)-2-isopropyl-8-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 307 3-(4-Fluoro-phenyl)-2-isopropyl-4-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 308 2-Cyclopentyi-3-(4-fluoro-phenyl)-7-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 309 2-Cyclopentyl-3-(4-fluoro-phenyl)-5-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 310 2-Cyclopentyl-7-methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 311 2-Isopropyl-7-methyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 312 2-1sopropyl-5-methyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 313 3-(4-Fluoro-phenyl)-2-isopropyl-7-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 314 3-(4-Fluoro-phenyl)-2-isopropyl-5-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 315 2-lsopropyl-7-methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene;
    3-(4-Chloro-phenyl)-2-pyridin-2-yimethyl-1,4,5,6,7,8-hexahydro- 318 1,2,6-triaza-azulene; 3-[3-(4-Chioro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2- 327 yl]-propionitrile; 3-(4-Chloro-phenyl)-2-cycloheptyl-2,4,5,6,7,8-hexahydro-1,2,6- 328 triaza-azulene; 3-(4-Chloro-phenyl)-2-cyclooctyl-2,4,5,6,7 ,8-hexahydro-1,2,6-triaza- 329 azulene; 3-(4-Chioro-phenyl)-2-(4-methyl-cyclohexyl)-2,4,5,6,7,8-hexahydro- 330 1,2,6-triaza-azulene; 2-Benzyl-3-(4-chioro-phenyl)-2,4,5,6-tetrahydro-pyrrolo[3,4- 331 clpyrazole; and 338 3-(4-Fluoro-phenyl)-2-isopropyl-5,7-dimethyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene.
    80. The compound of claim 1 selected from the group consisting of: EX CHEMICAL NAME 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- 59 azulene; 74 3-(4-Chloro-phenyl)-1-(3-methyl-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 75 3-(4-Chloro-phenyl)-1-(4-fluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 76 3-(4-Chloro-phenyl)-1-(3-fluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 103 3-(4-Chloro-phenyl)-1-thiophen-2-ylmethyl-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 104 1-Benzyl-3-thiophen-2-yl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 108 3-(4-Chloro-phenyl)-1-(2,4-difluoro-benzyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 160 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen-1- yimethyl]-2-fluoro-phenol;
    1-Benzyl-3-(4-chloro-phenyl)-6-methyl-1,4,5,6,7,8-hexahydro-1,2,6- 165 triaza-azulene; 1-Benzyl-3-(4-chloro-phenyl)-6-ethyl-1,4,5,6,7,8-hexahydro-1,2,6- 166 triaza-azulene; 214 2-Ethyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 2-Ethyl-3-(4-ethyl-phenyl)-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza- 257 azulene; and 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- 273 azulene citrate salt.
    31. The compound of claim 1 selected from the group consisting of: EX CHEMICAL NAME 1a1 3-(4-Chloro-phenyl)-2-isobutyi-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 133 2-Benzyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 177 2-Cyclohexyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 178 3-(4-Chloro-phenyl)-2-cyclohexyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azuiene; 181 3-(4-Chloro-phenyl)-2cyclopentyl-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 182 2-Cyclopentyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 183 2-(1-Ethyl-propyl)-3-(3-fiuoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 184 2-(1-Ethyl-propyl)-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 186 2-(1-Ethyl-propyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 191 2-(1-Ethyl-propyl)-3-thiophen-2-yi-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 215 2-tert-Butyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene: 16 2-tert-Butyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene;
    217 2-Cyclopentyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene; 2-Cyclopentyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro- 218 1,2,6-triaza-azulene; 2-Cyclopentyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- 220 triaza-azulene; 2-Cyclopentyl-3-(3,4-difluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- 236 triaza-azulene; 038 3-(4-Chloro-phenyl)-2-cyclobutyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 041 3-(3-Chloro-4-fluoro-phenyl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 042 2-sopropyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 077 2-Cyclobutyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; : 278 2-Cyclobutyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 079 2-Cyclobutyl-3-(4-triflucromethyl-phenyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; : 284 2-Cyclopropyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 300 2-sec-Butyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 302 2-Cyclopentyl-3-(4-fluoro-phenyl)-6-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; 306 3-(4-Fluoro-phenyl)-2-isopropyl-8-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene; and 310 2-Cyclopentyl-7-methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene.
    32. . The compound of claim 1 selected from the group consisting of: EX CHEMICAL NAME 47 1-Benzyi-3-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 64 3-(4-Chloro-phenyl)-2-ethyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza- azulene;
    118 3-(4-Chloro-phenyl)-1-isobutyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 180 2-Cyclopentyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 190 3-(4-Fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 192 2-Cyclopentyl-3-thiophen-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 209 2-1sopropyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 210 3-(4-Ethyl-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 011 3-(4-Chloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 212 4-(2-Isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)- benzonitrile; 213 2-1sopropyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6- triaza-azulene; 030 2-Cyclopentyl-3-furan-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 233 2-Cyclopentyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene; 284 2-Cyclopropyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene; 300 2-sec-Butyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; and 315 2-Isopropyl-7-methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza- azulene.
    33. The compound of claim 1 wherein said pharmaceutically acceptable salt is an effective amino addition salt.
    34. The compound of claim 1 wherein said pharmaceutically acceptable sait is selected from the group consisting of hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate,
    succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactiobionate, and laurylsulfonate.
    35. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of compound having serotonin receptor modulator activity of formula (1), (11), or (Ill): : R2 CYC-(ALK), CYCHALKIN NA" CYC-ALK)—N NA N y ) Ar ES BY BS ES (I (11) (II) wherein mis 0, 1or2; nis1,2o0r3; pis 1, 2 or 3, with the proviso that where m is 1, p is not 1; m+n is less than or equal to 4; : m+p is less than or equal to 4; qisOor1; ris0,1,2,3,4,0r5; R%is -Ci4alkyl, allyl, propargyi, or benzyl, each optionally substituted with -C1aalkyl, —OH, or halo; Ar is an aryl or heteroaryl ring selected from the group consisting of: a) phenyl, optionally mono-, di- or tri-substituted with R" or di-substituted on adjacent carbons with -OC4alkyleneO-, -(CHa)o.sNH-, -(CH2)1.2NH(CHy)-, -(CHy)2.3N(C1-qalkyl)- or ~(CH2)1.2N(C1.4alkyl)(CHo)-; R'is selected from the group consisting of OH, -C+ alkyl, -OC;.galkyl, -Cz.¢alkenyl, -OCs alkenyl, -Ca.galkynyl, -OCsealkynyl, -CN, -NO,, -N(R*)R? (wherein RY and RZ are independently selected from H or Cy.salkyl), -(C=O)N(R")R?, -(N-R)COR, -(N-R")SO-C.salkyl (wherein R'is H or Cy.alkyl),
    -(C=0)C1alkyl, -(S=(O)n)-C,.calkyl (wherein n is selected from 0, 1 or 2), -SO2N(R*)R?, -SCF3, halo, -CF3, -OCF3, -COOH and -COOC.¢alkyl; b) pheny! or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, >NH or >N(C.4alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R"; c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R'; d) naphthyl, optionally mono-, di- or tri-substituted with R';
    "15 e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C4alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R'; and fy a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R';
    g) phenyl! or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di- or tri-substituted with R";
    ALK is a branched or unbranched C,.galkylene, Cz.salkenylene, Czsalkynylene or Cascycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -OC1salkyl, -OCsscycloalkyl, -CN, -NO,, -N(R®)R® (wherein R* and R® are independently selected from H, C1 .alkyl or Coealkenyl), (C=0)N(R*R®, -(N-R°)COR®, -(N-R%)SO.C1.salkyl (wherein R® is H or Ci.galkyl), -(C=0)C1.ealkyl, -(S=(0)q)-C1salkyl (wherein d is selected from 0, 1 or 2),
    -SO.N(R)R®, -SCF3, halo, -CF3, -OCF3, -COOH and -COOC alkyl; CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of: i) phenyl, optionally mono-, di- or tri-substituted with R® or di-substituted on adjacent carbons with -OC,.salkyleneO-, -(CHz)2.3NH-, -(CH2)1.2NH(CH2)-, -(CHz)2-3N(C1alkyl)- or ~(CHz2)1.2N(C14alkyl)(CH)-; R% is selected from the group consisting of —OH, -C1.salkyl, -OC1.galkyl, -Cs.ecycloalkyl, -OCa.gcycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO,, -N(R*)R® (wherein R® and R® are independently selected from H, C.alkyl or Co¢alkenyl, or R? and R® may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C,4alkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=0)N(R*R®, ~(N-R°)COR®, -(N-R°)S02C;.¢alkyl (wherein R® is H or Cyalkyl or two R® in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N-(SO2C,.salkyl)z, -(C=0)C.salkyl, -(S=(0)q4)-C1-salky! (wherein d is selected from 0, 1 or 2), -SO,N(R*)R®, -SCFs3, halo, -CF3, -OCFa, -COOH and -COOC, galkyl; ii) phenyl! or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, NH or >N(C,4alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R%,
    iii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY,
    iv) naphthyl, optionally mono-, di- or tri-substituted with RY;
    v) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >8, >NH or >N(C,.alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with RY;
    vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or , two carbon atoms replaced by —N=, optionally mono- or di-substituted with RY and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R%;
    vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR9, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 to 5 substituents R% and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents R% and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NRY, having 0, 1 or 2 unsaturated bonds,
    having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having O to 5 substituents R%; R'is selected from the group consisting of H, C,.7alkyl, Co.7alkenyl, Ca.7alkynyl,
    Cs.zcycloalkyl, CarcycloalkylC4.7alkyl, Ca scycloalkenyl,
    Cs.7cycloalkenylCs.7alkyl and benzo-fusedC,.scycloalkyl, each optionally mono-, di-, or tri-substituted with RP; RP is selected from the group consisting of -OH, -OC4.alkyl, -Cs-ecycloalkyl, -OCsgcycloalkyl, -CN, -NO,, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®)R" (wherein R® and R" are independently selected from H or Cyealkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C4alkyl) and optionally having one or two unsaturated bonds in the ring), -(C=O)N(R®)R", -(N-R")COR", -(N-R")SO.C;salkyl (wherein R" is H or C,.galkyl or two R" in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C.galkyl, -(S=(O)n)-C1-salkyl (wherein n is selected from 0, 1 or 2), -SO2N(R®*)R", -SCF3, halo, -CFa, -OCFs, -COOH and -COOC,.galkyl, wherein the foregoing phenyl, pyridyl, thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C,ealkyl, -OC;.galkyl, -CN, -NO», -N(R*)R® (wherein R® and R® are independently selected from H, Ci-ealkyl or Ca-salkenyl), -(C=0)N(R*)R®, -(N-R°)COR®, -(N-R%)S0O,C, salkyl (wherein R® is H or C.galkyl), -(C=0)C1.salkyl, -(S=(0)q)-C.calkyl
    PCT/US2004/030190 ® (wherein d is selected from 0, 1 or 2), -SO,N(R?*)R®, -SCF,, halo, - CF;, -OCF,, -COOH and —COOC, salkyl; R? is selected from the group consisting of H, C, ;alkyl, C, alkenyl, C,,alkynyl and C, cycloalkyl; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof.
    36. Use of a compound having serotonin receptor modulator activity of formula (I), (II), or (lll): R? CYC{ALK), CYCHALK)g—N Ar CYC-ALK)—N" "NS Ar % § ) Ar m Vr m Ls ” Lar (1) (I) (11) wherein mis 0, 1 or 2; nis 1, 2or3; pis 1, 2 or 3, with the proviso that where mis 1, pis not 1; m+n is less than or equal to 4; m+p is less than or equal to 4; qisOorf1; riso,1,2,3,4,orb5; R? is -C, alkyl, allyl, propargyl, or benzyl, each optionally substituted with
    -C,.;alkyl, —OH, or halo; Aris an aryl or heteroaryl ring selected from the group consisting of: a) phenyl, optionally mono-, di- or tri-substituted with R" or di-substituted on adjacent carbons with -OC, alkyleneO-, -(CH,), ;NH-, «(CH,)1.,NH(CH,)-, -(CH,),.sN(C, salkyl)- or -(CH,),..N(C,alky)(CH,)~; R'is selected from the group consisting of —-OH, -C, alkyl, -OC, salkyl, -C, alkenyl, -OC, alkenyl, -C, alkynyl, -OC,qalkynyl, -CN, -NO,, -N(R*)R? (wherein R’ and R* are independently selected from H or C, salkyl), -(C=0)N(R")R?, - 285 - AMENDED SHEET
    PCT/US2004/030190 ® -(N-R"YCOR, -(N-R")S0,C, salkyl (wherein R'is H or C, alkyl), -(C=0)C, alkyl, -(5=(0),)-C, ;alkyl (wherein n is selected from 0, 1 or 2), -SO,N(R")R?, -SCF;, halo, -CF,, -OCF,, -COOH and -COOC, alkyl;
    b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >0O, >S, >NH or >N(C, alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R";
    c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R';
    d) naphthyl, optionally mono-, di- or tri-substituted with R;
    e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R’; and f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R;
    g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di- or tri-substituted with R"; - 286 - AMENDED SHEET
    PCT/US2004/030190 ® ALK'is a branched or unbranched C.salkylene, C,salkenylene, C,salkynylene or C;4cycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -OC, alkyl, -OC, sCycloalkyl, -CN, -NO,, -N(R*)R® (wherein R? and R® are independently selected from H, C,salkyl or C, salkenyl), (C=0)N(R3R®, -(N-R°)COR®, -(N-R°)SO,C, alkyl (wherein R° is H or C, alkyl), -(C=0)C, zalkyl, -(8=(0),)-C, salky! (wherein d is selected from 0,1o0r2), -SO,N(R?)R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOQC, salkyl; CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of: i) phenyl, optionally mono-, di- or tri-substituted with R? or di-substituted on adjacent carbons with -OC, jalkyleneO-, -(CH,),sNH-, (CH). NH(CH,)-, -(CH,), ;N(C, alkyl)- or “(CHZ):oN(C, ,alkyl)(CH,)-; R%is selected from the group consisting of —OH, -C, salkyl, -OC, salkyl, -C; ¢Cycloalkyl, -OC; scycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C alkyl or C,salkenyl, or R? and R® may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C, alkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=0O)N(R*R?, «(N-R°)COR®, -(N-R)S0O,C, salkyl (wherein Ris H or C, alkyl or two R® in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N-(SO,C, calkyl),, ~(C=0)C, alkyl, -(8=(0),)-C, alkyl (wherein d is selected from 0, 1 or 2), -SO,N(R*)R®, -SCF,, halo, -CF,, -OCF;, -COOH and -COOC, ;alkyl; if) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >0, >S, >NH or >N(C, alkyl) and which moiety has up to one additional - 287 - AMENDED SHEET I —
    J —— EE.
    PCT/US2004/030190 ® carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with Re: iii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with Re: iv) naphthyl, optionally mono-, di- or tri-substituted with R®: Vv) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0O, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by ~N=, optionally mono- or di-substituted with R? and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with Re: vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R* and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R®: vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NRSY having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 to 5 substituents R® and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents R% and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NRS, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or - 288 - AMENDED SHEET J ———
    PCT/US2004/030190 ® an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NR", having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents RY;
    R'is selected from the group consisting of H, C, ;alkyl, C, alkenyl, C, alkynyl, C,,cycloalkyl, C;,cycloalkylC, alkyl, C, cycloalkenyl, C,,cycloalkenylC, ;alkyl and benzo-fusedC, ;cycloalkyl, each optionally mono-, di-, or tri-substituted with R®;
    RP is selected from the group consisting of —OH, -OC, salkyl, -C, cycloalkyl, -OC, scycloalkyl, -CN, -NO,, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®)R" (wherein R®* and R" are independently selected from H or C, zalkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, =N-, >NH or >N(C, ,alkyl) and optionally having one or two unsaturated bonds in the ring), -(C=0)N(R®*)R®, -(N-R)CORY, -(N-R")SO,C, alkyl (wherein R" is H or C, salkyl or two
    RY in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C, zalkyl, -(S=(0),)-C,¢alkyl (wherein n is selected from 0, 1 or 2), -SO,N(R°)R", -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, zalkyl, wherein the foregoing phenyl, pyridyl,
    thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C, alkyl, -OC, alkyl, -CN, -NO,, -N(R*)R® (wherein R® and R® are independently selected from H, C, salkyl or C,salkenyl), (C=0)N(R*R®, -(N-R*)COR®, -(N-R°)SO,C, ;alkyl
    (wherein Ris H or C, salkyl), (C=0)C, salkyl, -(S=(0)4)-C, alkyl (wherein d is selected from 0, 1 or 2), -SO,N(R*)R®, -SCF;, halo, -CF,, -OCF,, -COOH and -COOC, salkyl,
    R? is selected from the group consisting of H, C, ;alkyl, C, alkenyl, C, alkynyl and C, cycloalkyl;
    - 289 - AMENDED SHEET
    PCT/US2004/030190 ® and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof; in the preparation of a medicament for the treatment or prevention of a CNS disorder selected from the group consisting of: sleep disorders, depression/anxiety, generalized anxiety disorder, schizophrenia, bipolar disorders, psychotic disorders, obsessive-compulsive disorder, mood disorders, post-traumatic stress and other stress-related disorders, migraine, pain, eating disorders, obesity, sexual dysfunction, metabolic disturbances, hormonal imbalance, alcohol abuse, addictive disorders, nausea, inflammation, centrally mediated hypertension, sleep/wake disturbances, jetlag, and circadian rhythm abnormalities in mammals, suffering therefrom.
    37. Use of claim 36 wherein said CNS disorder is selected from the group consisting of: depression/anxiety, sleep disorders, and circadian rhythm abnormalities.
    38. Use of a compound having serotonin receptor modulator activity of formula (1), (11), or (11): R? CYC-(ALK), N N CYCHALK)N SA" cyC-(ALK)—NT SA 4 ) Ar — RY), = R%), Mn BE Je " Mn Tk Tk Tk (1) (I) (III) wherein mis0,1or2; nis1,2or3; pis 1, 2 or 3, with the proviso that where mis 1, p is not 1; m+n is less than or equal to 4; m+p is less than or equal to 4; qisOorf; ris0,1,2,3,4,or5; - 290 - AMENDED SHEET
    PCT/US2004/030190 ® R? is -C, 4alkyl, allyl, propargyl, or benzyl, each optionally substituted with
    -C, ;alkyl, —OH, or halo;
    Aris an aryl or heteroaryl ring selected from the group consisting of: a) phenyl, optionally mono-, di- or tri-substituted with R" or di-substituted on adjacent carbons with -OC,_alkyleneO-, -(CH,), ;NH-, -(CH,), ,NH(CH,)-, (CH,),sN(C, _alkyl)- or -(CH,),,N(C,_ alkyl )}(CH,)-; R'is selected from the group consisting of —OH, -C, salkyl, -OC, qalkyl, -C, salkenyl, -OC, ;alkenyl, -C, alkynyl, -OC, alkynyl, -CN, -NO,, -N(R")R* (wherein RY and R* are independently selected from H or C, salkyl), (C=0O)N(R")R?, -(N-R")COR, -(N-R"YSO,C, salkyl (wherein R'is H or C, salkyl), -(C=0)C, 4alkyl, -(S=(0),)-C, alkyl (wherein n is selected from 0, 1 or 2), -SO,N(RY)R?, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, alkyl;
    b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >0O, >S, >NH or >N(C, ,alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R’;
    c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —-N=, the fused rings optionally mono-, di- or tri-substituted with R’;
    d) naphthyl, optionally mono-, di- or tri-substituted with R';
    e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R; and
    -291 - AMENDED SHEET
    PCT/US2004/030190 ® f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R";
    g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di-
    or tri-substituted with R';
    ALK is a branched or unbranched C, ;alkylene, C,alkenylene, C, alkynylene or C,scycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH,
    -OC,4alkyl, -OC, (cycloalkyl, -CN, -NO,, -N(R*R® (wherein R* and R® are independently selected from H, C, ;alkyl or C, alkenyl), -(C=0)N(R*R®,
    -(N-R°)COR®, -(N-R%)SO,C, alkyl (wherein R® is H or C, zalkyl),
    -(C=0)C, galkyl, -(S=(0),)-C,calkyl (wherein d is selected from 0, 1 or 2),
    -SO,N(R*R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, salkyl;
    CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of:
    i) phenyl, optionally mono-, di- or tri-substituted with R® or di-substituted on adjacent carbons with -OC, ,alkyleneO-, -(CH,), ;NH-, «(CHo)1.NH(CH,)-, (CH), ,N(C, 4alkyl)- or -(CH,); ,N(C; salky)(CHo)-; R? is selected from the group consisting of —OH, -C, salkyl,
    -0OC, salkyl, -C, scycloalkyl, -OC, ;cycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C, salkyl or C, alkenyl, or R® and R® may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, =N-, >NH or >N(C, ,alkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=0)N(R*)R®, -(N-R°)COR¢, -(N-R%)SO,C, alkyl (wherein R® is H or C, salkyl or two R° in the
    -292 - AMENDED SHEET
    PCT/US2004/030190 ® same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N-(SO,C, salkyl),, -(C=0)C, alkyl, -(S=(0),)-C, salkyl (wherein d is selected from 0, 1 or 2), -SO,N(R?)R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, qalkyl,
    ii) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O,
    >S, >NH or >N(C, alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY;
    iii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring,
    which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R¢;
    iv) naphthyl, optionally mono-, di- or tri-substituted with RS,
    v) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0O, >S, >NH or >N(C, ,alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with RY and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R?,
    vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with RS;
    vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NRS, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally
    -293 - AMENDED SHEET
    PCT/US2004/030190 ® having one carbon member which forms a bridge, having 0 to 5 substituents R® and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents R? and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NRS, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents RS; R' is selected from the group consisting of H, C, ;alkyl, C, alkenyl, C, alkynyl, C, cycloalkyl, C, ;cycloalkylC, alkyl, C, cycloalkenyl, C,cycloalkenylC, ;alkyl and benzo-fusedC, ;cycloalkyl, each optionally mono-, di-, or tri-substituted with R®; RP” is selected from the group consisting of —OH, -OC, zalkyl, -C, cycloalkyl, -OC, (cycloalkyl, -CN, -NO,, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®*)R" (wherein R® and R" are independently selected from H or C, salkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, =N-, >NH or >N(C, alkyl) and optionally having one or two unsaturated bonds in the ring), -(C=0)N(R°)R", -(N-R")CORY, -(N-R")SO,C, salkyl (wherein R" is H or C, salkyl or two RY in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C, salkyl, -(S=(0),)-C, alkyl (wherein n is selected from 0, 1 or 2), -SO,N(R*)R", -SCF,, halo, -CF,, -OCF;, -COOH and -COOC, zalkyl, wherein the foregoing phenyl, pyridyl, - 294 - AMENDED SHEET
    PCT/US2004/030130 ® thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C, alkyl, -OC, salkyl, -CN, -NO,, -N(R*)R" (wherein R® and R® are independently selected from H, C, ;alkyl or C, alkenyl), (C=0)N(R*)R®, -(N-R°)COR®, -(N-R)SO,C, alkyl (wherein R® is H or C, salkyl), -(C=0)C, salkyl, -(S=(0),)-C, salky! (wherein d is selected from 0, 1 or 2), -SO,N(R*)R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, zalkyl; R? is selected from the group consisting of H, C, alkyl, C, alkenyl, C, alkynyl and C, cycloalkyl; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof; in the preparation of a medicament for the treatment or prevention of a disease or condition selected from the group consisting of. hypotension, peripheral vascular disorders, cardiovascular shock, renal disorders, gastric motility, diarrhea, spastic colon, irritable bowel disorders, ischemias, septic shock, urinary incontinence, and other disorders related to the gastrointestinal and vascular systems in mammals, suffering therefrom.
    39. Use of a compound having serotonin receptor modulator activity of formula (I), (II), or (I): R? CYCAALK)q CYCHALK)—N" SA" oye (ALK) —N NA % N ) Ar ) kr : Rr i Rk! (1) (11) (I) wherein mis 0, 1 or 2; nis 1, 2or3; pis 1, 2or3, with the proviso that where mis 1, pis not 1; m+n is less than or equal to 4; m+p is less than or equal to 4; - 295 - AMENDED SHEET
    PCT/US2004/030190 ® qgisOor1, ris0,1,2, 3,4, or5; R? is -C, alkyl, allyl, propargyl, or benzyl, each optionally substituted with -C, alkyl, —OH, or halo; Aris an aryl or heteroaryl ring selected from the group consisting of:
    a) phenyl, optionally mono-, di- or tri-substituted with R" or di-substituted on adjacent carbons with -OC, _alkyleneO-, -(CH,), ;NH-, -(CH,),.,NH(CH,)-, -(CH,),3N(C, alkyl)- or -(CH,),,N(C, ,alkyl)(CH,)-; R'is selected from the group consisting of -OH, -C, salkyl,
    -0OC, zalkyl, -C, alkenyl, -OC, calkenyl, -C, salkynyl, -OC, alkynyl, -CN, -NO,, -N(R")R? (wherein RY and R* are independently selected from H or C, alkyl), -(C=O)N(R")R?, -(N-R)COR, -(N-R")SO,C, salkyl (wherein R'is H or C, alkyl), -(C=0)C, alkyl, -(S=(0),)-C, alkyl (wherein n is selected from 0, 1 or 2), -SO,N(R")R?, -SCF,, halo, -CF;, -OCF;, -COOH and -COO0C, qalkyl;
    b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O,
    >S, >NH or >N(C, alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R";
    c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring,
    which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R";
    d) naphthyl, optionally mono-, di- or tri-substituted with R',
    e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >O, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or
    - 296 - AMENDED SHEET
    ET.
    PCT/US2004/030190 ® pyridofused moiety is optionally mono-, di-, or tri-substituted with R": and f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by ~N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R'; g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di- or tri-substituted with R": ALK is a branched or unbranched C.salkylene, C,salkenylene, C,salkynylene or C; gcycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -OC, salkyl, -OC, <Cycloalkyl, -CN, -NO,, -N(R*)R’ (wherein R? and R® are independently selected from H, C,salkyl or C,salkenyl), ~(C=O)N(R*R®, -(N-R°)COR, «(N-R)SO,C, alkyl (wherein R® is H or C, alkyl), -(C=0)C, salkyl, «(S=(0)y)-C, alkyl (wherein d is selected from 0, 1 or 2), -SO,N(R*)R®, -SCF,, halo, -CF;, -OCF,, -COOH and -COOC, alkyl: CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of: i) phenyl, optionally mono-, di- or tri-substituted with R® or di-substituted on adjacent carbons with -OC,alkyleneO-, -(CH,),.sNH-, -(CH,), ,NH(CH,)-, «(CH,),sN(C,_alkyl)- or -(CH,),.N(C, <alkyl)(CH,)-; R%is selected from the group consisting of OH, -C, calkyl, -OC, alkyl, -C; cycloalkyl, -OC, cycloalkyl, phenyl, -Ophenyi, benzyl, -Obenzyl, -CN, -NO,, -N(R*R® (wherein R® and R® are independently selected from H, C, alkyl or C.salkenyl, or R® and R® may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C, alkyl), optionally having one carbon substituted with -OH, and optionally having one or two - 297 - AMENDED SHEET J ———
    PCT/US2004/030190
    ® unsaturated bonds in the ring), -(C=0O)N(R?*R®, -(N-R°)COR¢, -(N-R%)SO,C, salkyl (wherein R® is H or C, alkyl or two R® in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring,
    said ring having 4 to 6 members), -N-(SO,C, qalkyl),, -(C=0)C, alkyl, -(S=(0),)-C,alky! (wherein d is selected from O, 1 or 2), -SO,N(R®*)R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, alkyl; ii) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, >NH or >N(C, alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY;
    iii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY;
    iv) naphthyl, optionally mono-, di- or tri-substituted with R¥,
    v) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0O, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R* and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R?,
    vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with RS;
    vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected - 298 - AMENDED SHEET
    PCT/US2004/030190 ® from O, S, -N=, >NH or >NR9, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 to 5 substituents R? and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents R% and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NR9, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents RY; R' is selected from the group consisting of H, C, alkyl, C, alkenyl, C, alkynyl, C, cycloalkyl, C,,cycloalkylC, alkyl, C, cycloalkenyl, C,,cycloalkenylC, ,alkyl and benzo-fusedC, ;cycloalkyl, each optionally mono-, di-, or tri-substituted with RP; RP is selected from the group consisting of -OH, -OC, salkyl, -C, (cycloalkyl, -OC, ccycloalkyl, -CN, -NO,, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®)R" (wherein R® and R* are independently selected from H or C, ;alkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, =N-, >NH or >N(C, alkyl) and optionally having one or two unsaturated bonds in the ring), -(C=0O)N(R®*)R", -(N-R")CORY, -(N-R")SO,C, salkyl (wherein R" is H or C, salkyl or two Rin the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C, salkyl, -(S=(0),)-C, alkyl! (wherein - 299 - AMENDED SHEET
    PCT/US2004/030190 ® n is selected from 0, 1 or 2), -SO,N(R®)R", -SCF,, halo, -CF;, -OCF,, -COOH and -COOC, qalkyl, wherein the foregoing phenyl, pyridyl, thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C, alkyl, -OC, salkyl, -CN, -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C, alkyl or C,salkenyl), -(C=0)N(R®)R®, -(N-R°)COR®, -(N-R°)SO,C, salkyl (wherein R® is H or C, alkyl), -(C=0)C, alkyl, -(S=(0),)-C, salkyl (wherein d is selected from 0, 1 or 2), -SO,N(R*)R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, 4alkyl, R? is selected from the group consisting of H, C, ;alkyl, C, alkenyl, C,,alkyny! and C, cycloalkyl; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof; in the preparation of a medicament for the treatment or prevention of an ocular disorder selected from the group consisting of. glaucoma, optic neuritis, diabetic retinopathy, retinal edema, and age-related macular degeneration in mammals suffering therefrom.
    40. Use of a compound having serotonin receptor modulator activity of formula (1), (II), or (il): R? CYCAALK)q CYCAALK)—N" NA" oye (ALK)—N" NAT oe N ) Ar Tk Tw Tk (1) (11) (11) wherein mis 0, 1 or 2; nis 1,2 or3; pis 1, 2or3, with the proviso that where mis 1, p is not 1; m+n is less than or equal to 4; m+p is less than or equal to 4; - 300 - AMENDED SHEET
    PCT/US2004/030190 ® qisOori; ris0,1,2,3,4,0r5; R3 is -C, alkyl, allyl, propargyl, or benzyl, each optionally substituted with -C, alkyl, —OH, or halo; Aris an aryl or heteroaryl ring selected from the group consisting of:
    a) phenyl, optionally mono-, di- or tri-substituted with R" or di-substituted on adjacent carbons with -OC, jalkyleneO-, -(CH,), ;NH-, (CH,),.,NH(CH,)-, (CH,),.;N(C_alkyl)- or (CH), .N(C, salkyl)(CH,)-; R" is selected from the group consisting of —OH, -C, alkyl,
    -0OC, ¢alkyl, -C, alkenyl, -OC, salkenyl, -C,salkynyl, -0C,¢alkynyl, -CN, -NO,, -N(R")R? (wherein R* and R* are independently selected from H or C, alkyl), -(C=O)N(R")R?, -(N-R)COR!, (N-R)SO,C, salkyl (wherein R'is H or C,zalkyl), -(C=0)C, salkyl, -(S=(0),)-C, alkyl (wherein n is selected from 0,
    1 or 2), -SO,N(R")R?, -SCF,, halo, -CF,, -OCF;, -COOH and -COOC, zalkyl;
    b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O,
    >S, >NH or >N(C, alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R";
    c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring,
    which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R';
    d) naphthyl, optionally mono-, di- or tri-substituted with R';
    e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0O, >S, >NH or >N(C, ,alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or - 301 - AMENDED SHEET
    PCT/US2004/030190 ® pyridofused moiety is optionally mono-, di-, or tri-substituted with R": and f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R"; g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di- or tri-substituted with R": ALK is a branched or unbranched C,salkylene, C,salkenylene, C, salkynylene or C; gcycloalkenylene, optionally mono-, di-, or tri-substituted with a 16 substituent independently selected from the group consisting of: -OH, -OC, zalkyl, -OC;¢cycloalkyl, -CN, -NO,, -N(R*)R® (wherein R®* and R® are independently selected from H, C, alkyl or C, salkenyl), -(C=0O)N(R*R, -(N-R*)COR®, «(N-R)SO,C, alkyl (wherein R® is H or C, alkyl), ~(C=0)C, salkyl, «(8=(0),)-C, salky! (wherein d is selected from 0, 10r2), -SO,N(R?)R®, -SCF,, halo, -CF;, -OCF;, -COOH and -COOC, qalkyl; CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of: i) phenyl, optionally mono-, di- or tri-substituted with R? or di-substituted on adjacent carbons with -OC, alkyleneO-, -(CH,), ;NH-, ~(CH,); ,NH(CH,)-, -(CH,),,N(C,_jalkyl)- or -(CH,),.,N(C, salkyl)(CH,)-; Ris selected from the group consisting of —OH, -C, alkyl, -OC, alkyl, -C, sCycloalkyl, -OC,; ¢cycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO,, -N(R*)R"® (wherein R? and R® are independently selected from H, C, alkyl or C,salkenyl, or R® and R® may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C, alkyl), optionally having one carbon substituted with -OH, and optionally having one or two - 302 - AMENDED SHEET I —
    PCT/US2004/030190 ® unsaturated bonds in the ring), -(C=0)N(R*)R?, -(N-R°)COR®, -(N-R)SO,C, salkyl (wherein R® is H or C, alkyl or two Re in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N-(SO,C, alkyl), -(C=0)C, alkyl, «(8=(0),)-C, alkyl (wherein d is selected from 0, 1 0r2), -SO,N(R*)R?, -SCF;, halo, -CF,, -OCF;, -COOH and -COOC, 4alkyl: if) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >0, >S, >NH or >N(C, 4alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY;
    iii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —-N=, the fused rings optionally mono-, di- or tri-substituted with RS;
    iv) naphthyt, optionally mono-, di- or tri-substituted with R*:
    Vv) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >O, >S, >NH or >N(C_alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R9:
    vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R? and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R*: vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ning having 0, 1 or 2 non-adjacent heteroatom members selected - 303 - AMENDED SHEET I ———
    PCT/US2004/030190 ® from O, S, -N=, >NH or >NRS®, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 to 5 substituents R® and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents RY and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR?Y, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NR?9, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents R®; R'is selected from the group consisting of H, C, alkyl, C, alkenyl, C, alkynyl, C,cycloalkyl, C,,cycloalkylC, ;alkyl, C, cycloalkenyl, C,cycloalkenylC, ;alkyl and benzo-fusedC, cycloalkyl, each optionally mono-, di-, or tri-substituted with RP; RP is selected from the group consisting of —OH, -OC, salkyl, -C, scycloalkyl, -OC, cycloalkyl, -CN, -NO,, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®*)R" (wherein R®* and R" are independently selected from H or C, salkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, =N-, >NH or >N(C, jalkyl) and optionally having one or two unsaturated bonds in the ring), -(C=0)N(R®)R", -(N-R")CORY, -(N-R%)S0O,C, salkyl (wherein R" is H or C, alkyl or two R" in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C, salkyl, -(S=(0),)-C, salkyl (wherein - 304 - AMENDED SHEET
    EEE. PCT/US2004/030190 ® nis selected from 0, 1 or 2), -SO,N(R*)R?, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, salkyl, wherein the foregoing phenyl, pyridyl, thienyl, furany! and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C, salkyl, -OC, alkyl -CN, -NO,, -N(R?)R® (wherein R® and R? are independently selected from H, C, alkyl or C,salkenyl), -(C=O)N(R*)R?, -(N-R°)COR®, -(N-R°)SO,C, salky! (wherein R° is H or C, alkyl), -(C=0)C, alkyl, +(8=(0),)-C, calkyl (wherein d is selected from 0.10r2), -SO,N(R*R®, -SCF;, halo, -CF,, -OCF,, -COOH and -COOC, zalkyl; R? is selected from the group consisting of H, C, ,alkyl, C.,..alkenyl, C,.;alkynyl and C, ;cycloalkyl; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof: in the preparation of a medicament for the treatment or prevention of a disease or condition selected from the group consisting of: depression/anxiety, sleep/wake disturbances, jetlag, migraine, urinary incontinence, gastric motility, and irritable bowel disorders in mammals, suffering therefrom.
    41. Useofa compound having serotonin receptor modulator activity of formula (I), (II), or (IH): R? CYCLALK), CYCHALK)—N" Ny —Ar CYCHALK)—N" Ar '¢ ) Ar ER RR EER (1) (11) (III) wherein mis 0, 1 or 2; nis 1, 2or3; : pis 1, 2or3, with the proviso that where mis 1, pis not 1: m+n is less than or equal to 4; m+p is less than or equal to 4; - 305 - AMENDED SHEET I —
    EE EE, PCT/US2004/030190 ® qisOor1: ris0, 1,2, 3, 4, or 5; R®is -C, alkyl, allyl, propargyl, or benzyl, each optionally substituted with
    -C,.salkyl, —OH, or halo: Arisanarylor heteroaryl ring selected from the group consisting of: a) phenyl, optionally mono-, di- or tri-substituted with R" or di-substituted on adjacent carbons with -0C, ,alkyleneO-, -(CH,), ;NH-, “(CH,);..NH(CH,)-, -(CH,).sN(C, ,alkyl)- or (CH): .N(C,Lalkyl)(CH,)-; R'is selected from the group consisting of —~OH, -C, alkyl, -OC, alkyl, -C, salkenyl, -OC, salkenyl, -C, alkynyl, -OC, alkynyl, -CN, -NO,, -N(R")R? (wherein RY and R? are independently selected from H or C, alkyl), ~(C=O)N(R")R?, -(N-R')COR, -(N-R')SO,C, salkyl (wherein R'is H or Ci zsalkyl), <(C=0)C, alkyl, «(8=(0),)-C, alkyl (wherein n is selected from 0, 1 or 2), -SO,N(RYR?, -SCF;, halo, -CF,, -OCF;, -COOH and -COOC, 4alkyl; b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >Q, >S, >NH or >N(C, alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R’; c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R"; d) naphthyl, optionally mono-, di- or tri-substituted with R" e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or - 306 - AMENDED SHEET I — --
    EE —— PCT/US2004/030190 ® pyridofused moiety is optionally mono-, di-, or tri-substituted with R": and f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R" g) phenyl! or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di- or tri-substituted with R"; ALK is a branched or unbranched Cisalkylene, C, salkenylene, C, alkynylene or C,4cycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -OC, zalkyl, -OC, 4cycloalkyl, -CN, -NO,, -N(R*)R® (wherein R? and R? are independently selected from H, C, alkyl or C, salkenyl), -(C=0)N(RR?, -(N-R°)CORS, -(N-R°)SO,C, salkyl (wherein R® is H or C, alkyl), -(C=0)C,zalkyl, «(S=(0),)-C, salky! (wherein d is selected from 0, 1 or 2), -SO,N(R®)R?, -SCF,, halo, -CF;, -OCF,, -COOH and -COOC, alkyl; CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of: i) phenyl, optionally mono-, di- or tri-substituted with R® or di-substituted on adjacent carbons with -0OC, ,alkyleneO-, -(CH,), ,NH-, «(CH,), .NH(CH,)-, -(CH,),3N(C, 4alkyl)- or -(CH,),.N(C, <alkyl)(CH,)-; R%is selected from the group consisting of ~OH, -C alkyl, -OC,zalkyl, -C, sCycloalkyl, -OC, sCycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO,, -N(R*)R® (wherein R? and R® are independently selected from H, C,salkyl or C, salkenyl, or R? and R® may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, =N-, >NH or >N(C, alkyl), optionally having one carbon substituted with -OH, and optionally having one or two - 307 - AMENDED SHEET IE ———
    EE aE EEE, PCT/US2004/030190 ® unsaturated bonds in the ring), «(C=O)N(R*)R®, -(N-R)COR, «(N-R%)SO,C, salkyi (wherein R¢ is H or C,salkyl or two RC in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N-(SO,C, salkyl),, -(C=0)C, alkyl, -(8=(0)y)-C, salkyl (wherein d is selected from 0, 1 0r2), -SO,N(R*R", -SCF;, halo, -CF,, -OCF;, -COOH and -COOC, alkyl; if) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >0,
    >S, >NH or >N(C, alkyl) and which moiety has up to one additional carbon atom optionaily replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RS;
    ii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by -N= the fused rings optionally mono-, di- or tri-substituted with R®;
    iv) naphthyl, optionally mono-, di- or tri-substituted with RS;
    Vv) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R?;
    vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by ~N=, optionally mono- or di-substituted with R? and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R: vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected - 308 - AMENDED SHEET I ——————
    PCT/US2004/030190 ® from O, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 to 5 substituents R® and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents R? and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR?", having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl! and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NR?, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents RS, R'is selected from the group consisting of H, C, ;alkyl, C, alkenyl, C, alkynyl, C, cycloalkyl, C, ;cycloalkylC, ;alkyl, C, cycloalkenyl,
    C,.,cycloalkenylC, ;alkyl and benzo-fusedC, cycloalkyl, each optionally mono-, di-, or tri-substituted with R®; RP” is selected from the group consisting of —OH, -OC, alkyl, -C, cycloalkyl, -OC, ;cycloalkyl, -CN, -NO,, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®*)R" (wherein R®* and R" are independently selected from H or C, zalkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C, alkyl) and optionally having one or two unsaturated bonds in the ring), -(C=0O)N(R®*)R", -(N-R")CORY, -(N-R")SO,C, alkyl (wherein R" is H or C, salkyl or two RY in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C, alkyl, -(S=(0),)-C, salkyl (wherein - 309 - AMENDED SHEET
    Ee —— PCT/US2004/030190 nis selected from 0, 1 or 2), -SO,N(R)RY, -SCF;, halo, -CF,, -OCF,, -COOH and -COOC, (alkyl, wherein the foregoing phenyl, pyridyl, thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C, salkyl, -OC, ,alkyl, -CN. -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C, alkyl or
    C.salkenyl), -(C=O)N(R?)R?, -(N-R°)COR, «(N-R")SO,C, alkyl (wherein R° is H or C,salkyl), -(C=0)C,salkyl, «(§=(0),)-C, salky! (wherein d is selected from 0, 1 or 2), -SO,N(R*R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, alkyl; R? is selected from the group consisting of H, C, alkyl, C..,alkenyl, C, alkynyl and C, ,cycloalkyl; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof; in the preparation of a medicament for the treatment or prevention of a disease or condition selected from the group consisting of: depression/anxiety, generalized anxiety disorder, schizophrenia, bipolar disorders, psychotic disorders, obsessive-compulsive disorder, mood disorders, post-traumatic stress disorders, sleep disturbances, sexual dysfunction, eating disorders, migraine, addictive disorders, and peripheral vascular disorders in mammals suffering therefrom.
    42. A method of making a compound of formula (XVI) comprising the step of reacting a compound of formula (XXXV) with a compound of formula (XIV): Hn NOTE CYC-ALK)—N otf 5 = CYC-(ALK)4-X 5 )= (R ol, (XIV) (R = ON oT - G G 05 OX) (XVI) wherein Gis -C, alkyl, -COOC, ;alkyl, -(C=0)C, alkyl, or benzy! unsubstituted or substituted with -OC, ;alky! or -C,salkyl; Xis Cl, Br, I, OMs, or OTs: mis0, 1or2; -310 - AMENDED SHEET J —— -
    PCT/US2004/030190 ® pis 1, 2 or 3, with the proviso that where mis 1, p is not 1; m+p is less than or equal to 4; qisOor1; ris0,1,2,3,4,or5; R’is-C,alkyl, allyl, propargyl, or benzyl, each optionally substituted with
    -C, ;alkyl, —OH, or halo;
    ALK is a branched or unbranched C, ;alkylene, C, alkenylene, C,zalkynyiene or C,4cycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH,
    -OC, salkyl, -OC, scycloalkyl, -CN, -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C, salkyl or C, alkenyl), -(C=0)N(R®)R®, -(N-R°)COR, -(N-R°)SO,C, salkyl (wherein R° is H or C, galkyl),
    -(C=0)C, alkyl, -(S=(0),)-C, salkyl (wherein d is selected from 0, 1 or 2),
    -SO,N(R*)R®, -SCF,, halo, -CF;, -OCF,, -COOH and -COOC, zalkyl;
    16 CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of:
    i} phenyl, optionally mono-, di- or tri-substituted with R® or di-substituted on adjacent carbons with -OC, ,alkyleneO-, -(CH,),,;NH-, -(CH,),,NH(CH,)-, (CH,),.;N(C,_alkyl)- or -(CH,),,N(C, _4alkyl)(CH,)-;
    R" is selected from the group consisting of —OH, -C, salkyl,
    -OC, zalkyl, -C, scycloalkyl, -OC, cycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO,, -N(R*)R® (wherein R* and R°® are independently selected from H, C, calkyl or C, alkenyl, or R® and R° may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C, alkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), (C=0)N(R*)R®, -(N-R°)COR®,
    -(N-R%)SO,C, salkyl (wherein Ris H or C, calkyl or two R°® in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N-(SO,C, salkyl),, -(C=0)C, salkyl, -(S=(0),)-C,salkyl (wherein d is selected from 0, -311 - CLEAN COPY
    EEE PCT/US2004/030190 ® 1 or2), -SO,N(R*)R®, -SCF,, halo, -CF;, -OCF,, -COOH and -COOC, zalkyt:
    ii) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O,
    >S, >NH or >N(C, alkyl) and which moiety has up to one additional carbon atom optionally replaced by —-N=, the fused rings optionally mono-, di- or tri-substituted with RY;
    iii) phenyl fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R%;
    iv) naphthyl, optionally mono-, di- or tri-substituted with RY Vv) a monocyclic aromatic hydrocarbon group having five ring atoms,
    having a carbon atom which is the point of attachment, having one carbon atom replaced by >O, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R? and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with RS; vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with Re:
    vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NRS, having 0, 1 or 2 unsaturated bonds,
    having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having Oto 5 substituents R? and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents RS and
    -312 - CLEAN COPY J —,————— -
    PCT/US2004/030190 ® viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR", having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from 0, S, -N=, >NH or >NRSY, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents RY, and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof.
    43. The method of claim 42 wherein said compound of formula (XXXV) is H HN =O wd, (=N G prepared by treating a compound of formula (XII), (Xi) with a triflating agent.
    44. The method of claim 42 wherein said compound of formula (XVI) is subsequently reacted in at least one step to produce a compound of formula (i): CYCHALK)—N Ar nt CN R (In wherein Aris an aryl or heteroaryl ring selected from the group consisting of: -313 - CLEAN COPY
    PCT/US2004/030190 ® a) phenyl, optionally mono-, di- or tri-substituted with R" or di-substituted on adjacent carbons with -OC, jalkyleneO-, -(CH,), ;NH-, -(CH,),,NH(CH,)-, -(CH,),sN(C,_,alkyl)- or -(CH,),.,N(C,_salkyl)}(CH,)-; R" is selected from the group consisting of —OH, -C, alkyl, -OC, zalkyl, -C, alkenyl, -OC, salkenyl, -C,salkynyl, -OC, alkynyl, -CN, -NO,, -N(R")R* (wherein R¥ and R* are independently selected from H or C, alkyl), -(C=0)N(R")R?, -(N-R)COR!, -(N-R")SO,C, alkyl (wherein R'is H or C, salkyl), -(C=0)C, alkyl, -(S=(0),)-C, galkyl (wherein n is selected from O, 1 or 2), -SO,N(R")R?, -SCF;, halo, -CF,, -OCF,, -COOH and -COO0C, alkyl;
    b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O,
    >S, >NH or >N(C,_ alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R';
    c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring,
    which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R';
    d) naphthyl, optionally mono-, di- or tri-substituted with R’;
    e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C, ,alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R";
    and f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent
    - 314 - CLEAN COPY
    PCT/US2004/030190 @® carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R’; g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di- or tri-substituted with R'; and R' is selected from the group consisting of H, C, ;alkyl, C,,alkenyl, C, alkynyl, C, ;cycloalkyl, C,,cycloalkylC, ;alkyl, C, cycloalkenyl, C, ,cycloalkenylC, alkyl and benzo-fusedC, ;cycloalkyl, each optionally mono-, di-, or tri-substituted with R?; RP is selected from the group consisting of —OH, -OC, alkyl, -C, ,cycloalkyl, -OC, scycloalkyl, -CN, -NO,, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®)R* (wherein R®* and R" are independently selected from H or C, salkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, =N-, >NH or >N(C, alkyl) and optionally having one or two unsaturated bonds in the ring), (C=0)N(R®)R", -(N-RY)CORY, -(N-R")SO,C, alkyl (wherein R" is H or C, salkyl or two RY in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C, alkyl, -(S=(0),)-C, salkyl (wherein n is selected from 0, 1 or 2), -SO,N(R®)R", -SCF,, halo, -CF,, -OCF,, . -COOH and -COOC, zalkyl, wherein the foregoing phenyl, pyridyl, thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C, salkyl, -OC, alkyl, -CN, -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C, salkyl or C,¢alkenyl), (C=0)N(R*R®, -(N-R°)COR®, -(N-R°)SO,C, zalkyl (wherein R°® is H or C, zalkyl), -(C=0)C, alkyl, -(S=(0),)-C, alkyl (wherein d is selected from 0, 1 or 2), -SO,N(R*R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, ¢alkyl; - 315 - CLEAN COPY
    PCT/US2004/030190 ® 45. A method of making a compound of formula (XXXV) comprising the step of reacting a compound of formula (Xl) with a triflating agent: . oN 0 in Ns OTE Ne a (Xi) (XXXV) wherein Gis -C,zalkyl, -COOC, zalkyl, -(C=0)C, salkyl, or benzyl unsubstituted or substituted with -OC, salkyl or -C, salkyl; mis 0, 1 or 2; pis 1, 2 or 3, with the proviso that where mis 1, pis not 1; m+p is less than or equal to 4; ris0,1,2,3,4,0r5; R® is -C,_4alkyl, allyl, propargyl, or benzyl, each optionally substituted with -C, alkyl, —OH, or halo; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof.
    46. The method of claim 45 wherein said compound of formula (XXXV) is subsequently reacted in at least one step to produce a compound of formula (in: CYC-ALK);—N ay Ar (RYH~L (1 wherein qgisQorf; Ar is an ary! or heteroaryl ring selected from the group consisting of: a) phenyl, optionally mono-, di- or tri-substituted with R" or di-substituted on adjacent carbons with -OC,_jalkyleneO-, -(CH,),;NH-, -(CH,), ,NH(CH,)-, -(CH,),,N(C, ,alkyl)- or -(CH,), ,N(C,_alky!)(CH,)-; - 316 - CLEAN COPY
    PCT/US2004/030190 ® R" is selected from the group consisting of —OH, -C, salkyl, -0C, salkyl, -C, alkenyl, -OC, zalkenyl, -C, alkynyl, -0OC; alkynyl, -CN, -NO,, -N(R")R? (wherein R* and R* are independently selected from H or C, salkyl), -(C=0O)N(RY)R?, -(N-R)COR, -(N-R"'SO,C, salkyl (wherein R'is H or C, salkyl),
    -(C=0)C, galkyl, -(S=(0),)-C,qalky! (wherein n is selected from 0, 1 or 2), -SO,N(R")R?, -SCF,, halo, -CF,, -OCF;, -COOH and -COOC, alkyl;
    b) phenyl or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, >NH or >N(C, ,alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R";
    c) phenyl fused at two adjacent ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with R';
    d) naphthyl, optionally mono-, di- or tri-substituted with R";
    e) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C, alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with R'; and f) a monocyclic aromatic hydrocarbon group having six ring atoms, having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R" and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R';
    -317 - CLEAN COPY
    PCT/US2004/030190 ® g) phenyl or pyridyl, substituted with a substituent selected from the group consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di- or tri-substituted with R";
    ALK s a branched or unbranched C, alkylene, C, alkenylene, C, jalkynylene or C, qcycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -OC, salkyl, -OC, (cycloalkyl, -CN, -NO,, -N(R*)R® (wherein R?* and R® are independently selected from H, C, salkyl or C, salkenyl), -(C=0)N(R?*)R",
    -(N-R®)CORS, -(N-R®)SO,C, calkyl (wherein Ris H or C, alkyl),
    -(C=0)C, alkyl, -(S=(0)4)-C, alkyl (wherein d is selected from 0, 1 or 2), -SO,N(R*R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, salky!;
    CYC is hydrogen or a carbocyclic, heterocyclic, aryl or heteroaryl ring selected from the group consisting of:
    i) phenyl, optionally mono-, di- or tri-substituted with R? or di-substituted on adjacent carbons with -OC,_alkyleneO-, -(CH,), ;NH-, ~(CH,);,NH(CH,)-, (CH,),.sN(C,_alkyl)- or -(CH,), ,N(C, salkyl(CH,)-; Reis selected from the group consisting of —OH, -C, salkyl,
    -OC, salkyl, -C, scycloalkyl, -OC, cycloalkyl, phenyl, -Ophenyl,
    benzyl, -Obenzyl, -CN, -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C, zalkyl or C, alkenyl, or R® and R® may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O,
    =N-, >NH or >N(C, ,alkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=0)N(R*R®, -(N-R°)COR?®, -(N-R%)SO,C, alkyl (wherein R° is H or C,zalkyl or two R° in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring,
    said ring having 4 to 6 members), -N-(SO,C, salkyl),, -(C=0)C, alkyl, -(S=(0),)-C, salkyl (wherein d is selected from 0, 1 or 2), -SO,N(R*R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, 4alkyl; -318 - CLEAN COPY
    PCT/US2004/030190 @® ii) phenyl! or pyridyl fused at two adjacent carbon ring members to a three membered hydrocarbon moiety to form a fused five membered aromatic ring, which moiety has one carbon atom replaced by >O, >S, >NH or >N(C, ,alkyl) and which moiety has up to one additional carbon atom optionally replaced by —N=, the fused rings optionally mono-, di- or tri-substituted with RY;
    iii) phenyl! fused at two adjacent carbon ring members to a four membered hydrocarbon moiety to form a fused six membered aromatic ring, which moiety has one or two carbon atoms replaced by —-N=, the fused rings optionally mono-, di- or tri-substituted with R¥,
    iv) naphthyl, optionally mono-, di- or tri-substituted with R¢;
    v) a monocyclic aromatic hydrocarbon group having five ring atoms, having a carbon atom which is the point of attachment, having one carbon atom replaced by >0, >S, >NH or >N(C,_alkyl), having up to one additional carbon atoms optionally replaced by —N=, optionally mono- or di-substituted with R* and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with RY,
    vi) a monocyclic aromatic hydrocarbon group having six ring atoms,
    having a carbon atom which is the point of attachment, having one or two carbon atoms replaced by —N=, optionally mono- or di-substituted with R® and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with R%;
    vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected from O, S, -N=, >NH or >NR9, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl, optionally having one carbon member which forms a bridge, having 0 to 5 substituents R® and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety has 0, 1, 2 or 3 substituents R?, and viii) a 4-7 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected
    -319 - CLEAN COPY
    PCT/US2004/030190 ® from O, S, -N=, >NH or >NRSY, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member which forms a bridge, the heterocyclic ring fused at two adjacent carbon atoms forming a saturated bond or an adjacent carbon and nitrogen atom forming a saturated bond to a 4-7 membered carbocyclic or heterocyclic ring, having 0 or 1 possibly additional heteroatom member, not at the ring junction, selected from O, S, -N=, >NH or >NR?Y, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents R% and R'is selected from the group consisting of H, C, alkyl, C, ,alkenyl, C, alkynyl, C, ,cycloalkyl, C, ;cycloalkylC, ;alkyl, C, cycloalkenyl, C,,cycloalkenylC, ;alkyl and benzo-fusedC, ,cycloalkyl, each optionally mono-, di-, or tri-substituted with RP; RP is selected from the group consisting of —OH, -OC, galkyl, -C, cycloalkyl, -OC, 4cycloalkyl, -CN, -NO,, phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(R®*)R" (wherein R®* and R" are independently selected from H or C, zalkyl, or may be taken together with the nitrogen of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >O, =N-, >NH or >N(C, alkyl) and optionally having one or two unsaturated bonds in the ring), (C=0)N(R®)R", -(N-R")CORY, ~(N-R")SO,C, alkyl (wherein R" is H or C, alkyl or two RY in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=0)C, salkyl, -(S=(0),)-C, salky! (wherein n is selected from 0, 1 or 2), -SO,N(R®)R", -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, salkyl, wherein the foregoing phenyl, pyridyl, thienyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the group consisting of: -OH, -C, ;alkyl, -OC, alkyl, -CN, -NO,, -N(R*)R® (wherein R* and R® are independently selected from H, C, zalky! or C,salkenyl), -(C=0)N(R?)R®, (N-R°)COR¢, -(N-R°)SO,C, calkyl (wherein R® is H or C, salkyl), -(C=0)C, salkyl, -(S=(0),)-C, salkyl - 320 - CLEAN COPY
    PCT/US2004/030190 ® | (wherein d is selected from 0, 1 or 2), -SO,N(R*)R®, -SCF,, halo, -CF,, -OCF,, -COOH and -COOC, alkyl;
    47. A compound of claim 1 isotopically-labelled to be detectable by PET or SPECT.
    48. A method for studying serotonin-mediated disorders comprising the step of using an '®F-labeled or "C-labelled compound of claim 1 as a positron emission tomography (PET) molecular probe.
    49. A compound as claimed in claim 1 or claim 47, substantially as herein described with reference to and as illustrated in any of the examples.
    50. A pharmaceutical composition as claimed in claim 35, substantially as herein described with reference to and as illustrated in any of the examples.
    51. Use as claimed in any one of claims 36, or 38 to 41, substantially as herein described with reference to and as illustrated in any of the examples.
    52. A method as claimed in claim 42, substantially as herein described with reference to and as illustrated in any of the examples.
    53. A method as claimed in claim 48, substantially as herein described with reference to and as illustrated in any of the examples. -321- AMENDED SHEET
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