AU2011253635B2 - Fused heterocyclic compounds - Google Patents

Abstract

Abstract Certain fused pyrazole-containing heterocyclic compounds are serotonin modulators useful in the treatment of serotonin-mediated diseases.

Description

- 1 AUSTRALIA PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT ORIGINAL Name of Applicant: Janssen Pharmaceutica, N.V. Actual Inventors: Wenying Chai and Xiaohu Deng and Annette K. Kwok and Jimmy T. Liang and Neelakandha Mani and Dale A. Rudolph and Victoria D. Wong and Nicholas I. Carruthers and Curt A. Dvorak Address for Service is: SHELSTON IP 60 Margaret Street Telephone No: (02) 9777 1111 SYDNEY NSW 2000 Facsimile No. (02) 9241 4666 CCN: 3710000352 Attorney Code: SW Invention Title: Fused heterocyclic compounds Details of Original Application No. 2004283196 dated 15 Sep 2004 The following statement is a full description of this invention, including the best method of performing it known to me/us: File: 49405AUP01 FUSED HETEROCYCLIC COMPOUNDS Field of the Invention 5 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. 10 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 1 through 5 15 HT 7 ) (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, 20 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 25 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. 30 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 nd ed., Cambridge University Press, Cambridge, U.K., 2000). Thus, the inhibition of serotonin and la norepinephrine uptake together with 5-HT2 receptor blockade is responsible for the therapeutic effects of the tricyclic antidepressants. In contrast, their blockade of histamine H,, muscarinic and alpha-adrenergic receptors can lead to sedation, blurred vision and orthostatic hypertension respectively. Likewise, the atypical antipsychotics, 5 including olanzapine and clozapine, are considered to have positive therapeutic effects attributable to their actions at 5-HT 2 , D2 and 5-HT 7 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 10 pharmacologies and provide novel therapies, More importantly the ability to obtain compounds with known receptor selectivities affords the prospect to target multiple therapeutic mechanisms and improve clinical responses with a single drug, Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common 15 general knowledge in the field. It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative. Summary of the Invention According to a first aspect, the present invention provides a compound having 20 serotonin receptor modulating activity of formula (1), (II), or (ll): CYC-(ALK), N r wherein m is 1 or 2; n is 1,2 or 3; 25 m+n is less than or equal to 4; q is 1; r is0, 1, 2, 3, 4, or 5; R3 is -C 4 aikyi, allyl, propargyl, or benzyl, each optionally substituted with -C 1 3 aIkyl, OH, or halo: 30 Ar is an aryl or heteroaryl ring selected from the group consisting of: 2 a) phenyl, optionally mono-, di- or tri-substituted with R'or di-substituted on adjacent carbons with -OCl-alkyleneC-, -(CH )NH-, -(CH 2

)

1

NH(CH

2 )-,

-(CH

2 )24 3

N(C

4 alkyl)- or -(CH 2

)

1 TN(Calkyl)(CH 2 )-; R is selected from the group consisting of -OH, -CO 6 alkyl, -OC-alkyl -C2 5 6 alkenyl, -OC 36 alkenyl, -Cu 6 alkynyl, -OC 3 ualkyny, -CN, -NO-, N(RY)R' (wherein RY and R- are independently selected from H or C 6 alkyl), -(C=0)N(R)R, -(N-R')COR. (N-R)S0 2

C

1 _alky (wherein Rt is H or C!6alkyl), -(C=0)C,alkyl, -(S=(O))-Ctsalky (wherein n is selected from 0, 1 or 2), -S0 2 N(Rv)Rz, -SCF3, halo, -CF, -OCF, -COOH and 10 -COOC .

6 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(CI-alky) and which moiety has up to one additional carbon atom optionally replaced by 15 -N=, the fused rings optionally mono-, di- or trn-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 tr-substituted with R'; 20 d) naphthyl, optionally mono-, di- or tr-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 1 ,aikyl), having up to one additional carbon atoms optionally replaced by -N= optionally mono- or di-substituted with R, 25 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

T

: 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 30 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, thiophen-2-y or thiophen-3-yl, oxazolyl and 35 tetrazolyl, where the 2a resultant substituted moiety is optionally further mono-, di- or tri-substituted with Rr; ALK is a branched or unbranched C 1

.

8 alkylene, C 2 ualkenylene, C 2

-

8 alkynylene or

C

3

.

8 cycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent 5 independently selected from the group consisting of: -OH, -OC 1 .ealkyl,

-OC

3 .ecycloalkyl, -CN, -NO 2 , -N(Ra)Rb (wherein R and Rb are independently selected from H, C 1 .6alkyl or C 2 .ealkenyl), -(C=O)N(R")Rb, -(N-Rc)CORc,

-(N-R')SO

2 C1.

6 alkyl (wherein Rc is H or C1.

6 alkyl), -(C=O)C 16 alkyl, -(S=(O)d)-C1.

6 alkyl (wherein d is selected from 0, 1 or 2), -SO 2 N(Ra)Rb, -SCF 3 , 10 halo, -CF 3 , -OCF 3 , -COOH and -COOC 1

.

6 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 RI or di-substituted on adjacent carbons with -OC 1

.

4 alkyleneO-, -(CH 2

)

2

-

3 NH-, -(CH 2

)

1

.

2

NH(CH

2 )-, 15 -(CH 2

)

2

-

3

N(C

1

.

4 alkyl)- or -(CH 2 )1- 2

N(C

1 .4alkyl)(CH 2 )-; RI is selected from the group consisting of -OH, -C 1 .ealkyl, -OC 1

.

6 alkyl, -C 3 6 cycloalkyl, -OC 3

.

6 cycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN,

-NO

2 , -N(Ra)Rb (wherein Ra and Rb are independently selected from H,

C

1 .6alkyl or C 2 .ealkenyl, or Ra and Rb may be taken together with the 20 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 1

.

4 alkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=O)N(Ra)Rb, -(N-Rc)CORc, 25 -(N-Rc)SO 2 C1.6alkyl (wherein R' is H or C 1

.

6 alkyl 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 2

C

1 .6alkyl)2, -(C=O)C 1 .salkyl, -(S=(O))-C1.

6 alkyl (wherein d is selected from 0, 1 or 2), -SO 2 N(Ra)Rb, -SCF 3 , halo, -CF 3 , 30 -OCF 3 , -COOH and -COOC 1

.

6 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(C1.

4 alkyl) and which moiety has up to one additional carbon atom 35 optionally replaced by -N=, the fused rings optionally mono-, di- or tri-substituted with Rq; 2b 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 Rq; 5 iv) naphthyl, optionally mono-, di- or tri-substituted with Rq; 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(Cl.

4 alkyl), having up to one additional carbon atoms optionally replaced by -N=, optionally mono- or di-substituted 10 with Rq and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with Rq; 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 15 atoms replaced by -N=, optionally mono- or di-substituted with R4 and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with Rq; vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 20 0, 1 or 2 non-adjacent heteroatom members selected from 0, S, -N=, >NH or >NRI, 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 R4 and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or 25 pyridofused moiety has 0, 1, 2 or 3 substituents R4; 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 0, S, -N=, >NH or >NRI, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member 30 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 >NRq, having 0, 1 or 2 unsaturated 35 bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents Rq; 2c R' is selected from the group consisting of H, Cqalkyl, C 2 -alkenyl. C;alkynyl, Cqcycloalkyi, C 3 7 cycloalkylC1alkyl, C 3 7 cycloalkenyl, C 3 7 cycloalkenylC 14 aIkyl and benzo-fusedC 44 cycloalkyl, each optionally mono-, di, or tri-substituted with RP 5 RP is selected from the group consisting of -OH, -OC 1 -alkyl, -C 36 cycloalkyl, -O% 6 cycloalkyl, -CN, -NO 2 , phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(Rs)R t (wherein R 5 and R' are independently selected from H or C 1 .alkyb 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 10 having one carbon replaced with >0, =N-, >NH or >N(Calkyl) and optionally having one or two unsaturated bonds in the ring), ~(C=0)N(R)R, -(N-R")CORv -(N-R")SOsCiealkyl (wherein R" is H or C 1 alkyl or two RV 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 15 members), (C=O)C 6 alkyl, -(S=(0),)-C..

6 alkyl (wherein n is selected from 0, I or 2), -SO 2 N(R)R", -SCF 3 , halo, -CFO, -OCF, -COOH and -COOCI 6 alky, 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 1 .- alkyl, 20 -OCealkyl, -CN, -NO 2 , -N(Ra)Rb (wherein R' and RW are independently selected from H, C 1

-

6 alkyl or C 2 .alkenyl), ~(C=O)N(R)R, -(N-R)COR,

-(N-.R)SO

2

C

1 alkyi (wherein R 0 is H or CO 1 alkyl), -(C=O)Calkyl -(S=(O)d)&Ci _alky1 (wherein d is selected from 0, 1 or 2), -SO 2

N(R")R

0 ,

-SCF

3 , halo, -CF;. -OCF 3 , -COOH and -COOC 6 alkyl 25 or an enantiomer, diastereomer, hydrate, solvate or pharmaceutically acceptable salt, ester or aide thereof. According to a second aspect, the invention provides a compound 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-Ch loro-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- ,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-pheny!)-2-(2-cyclohexyl-ethyl)-2 ,4,5,6,7,8-hexahydro-1,2,6 70 triaza-azulene; 72 3-(4-Chloro-phenyl)-2-phenethyl-2,4;5,6 ,7,8-hexahydro-1 ,2,6-triaza-azulene: 2d 82 54[3-(4-Ch lara-phenyl) >5,6,7 ,8-tet lahyd rc-4H4-1,2,6-triaza-azulen-2-y] pentanaic acid methyl ester; 5-[3-(4-Ch lara-phenyl >-,6 ,7,8-te Lrahyd ro-4H-1I,2.6-triaza-a9zulen-2-y] 83 pentanoic acid; 84 54[3-(4-Claro-pheniyl)-5 .6,7 .8-tetr,.ahyd ro-4H-l ,2 ,6-triaza-azu le n-2?-yl] pentan-1 -ol; 69 44[3-(4-Chla ra-pheny9)-5 ,6,7 ,8-te-tra hydrao-4H-i ,2,6-triaza-azuLen-2-yi]butyric acid methyl ester;, 90 4-f 3-(4-Chlora-phenyl )-5,6,7 8-tetra hyd ra-4H-1I,2,6-triaza-a zulen-2-yfl-butyric a cid; 924-f3-(4-Ch lorao-phenyl >5,6,7 ,8-tetra hyd ro-4-1 ,2 ,6-triaza-azu le n-2-yfl-butani 1-; 9. 3-(4-Chlara-phen yl)-2-(3,4-d ifluoro-benizyfl-2,4,5,6,7,8-hexahyd ro-1 ,2,6 triaza -azu lane; 953-(4-Ch a ra-pheniyl)-2-(4-methyl-benzyl)-2 .4,5,6.7,8-hexa hyd ra-i,2,6-triaza azuiene; 3-(4-Ohla ra-phe nyl )-2-(3-f lua ra-4-methax' v-ben-zyi >2,4,5,6 ,7,8-hexa hydra I 2,6-triaza-azulene; 123-(4-Ch lara-phe ny9)-2-cyclahexylmethyl--2,4,5,6,7 ,8-hexa hydra-I,2,6-triaza a zuleanea; 3-(4-Ch lara-phen~yl)-2-(2-methy[-benzyl)-2,4,5,6,7,8-hexahydra-i ,2,6-triaza 126 azuiene; 127 2-Benizyk-3-(4-ch lara-phanyl )-2 .4,5,6,7 ,8-hexa hydra,- 1,2 ,6-triaz. a-azu lane; 129 3-(4-Chiara-phenyl)-2-(2 ,4-difluara-benzyD)-2,4,56C,7,8-hexahydra,-I .2,6 triaza-azulerie, -130 54[3-(4-Chlara--phenyl)-5,6, 7,8-tetr-ah.ydra-4-i 1,2,6-triaza-azul en,-2-ymethyli turan-2-ca rhaxylic acid ethyl ester;, 131 3-(4-C hlara-phenyl)-2-isabutyl-2,4,.5,6,,7 8-hexahiydra-1I 2,6--triaza-azulene; 1323-(4-Chlaro-phenyl>-2-(2-me thaxy-ba-nzyl)-2 .4,5,6,7, 8-hexa hydra-i .2,6) tlriaza-azulene; 133 2-Benizyl-3-phenyl-2,4,5,6,7 .8-haxahydra- 1,2 .6-triaza-azuilena;e 136 3-(4-Ohlara-pheny}Y2-thiaphan-2-yn ethyl-2,4,5,-,6,7,8-haxal hydra -I.2.6 tnraza-azu lne; 3-(14-Ch ia ra-phe nyl )-2-(5-chlara-thiophen-2-ylmethyi)-2 ,4,5,6,7 .8-hexahyd ra 139 I .2,6-triaza-azulene; 140 3-(4-Ohloro-ph-eny},-2-(2 ,6-difluo ro-benzyl)-2,4,5,6,7 ,Stexa hyd ro-l ,2 ,6 triaza-azulene; 141 3-(4-Chloro-phenyl)-2-(2drifluorome'%hy l-ben zyW)2,4A 56,8-hexahydro-1,2,6 triaza-azulene;, 143 3-(4-Ch ho ro-phenyi)-2-(2-ethyl-bu tyl >2,4.5,6,7 .8-hexahyd ro-i ,2 ,6-trieze azu ene; 16 2-Benzo[1 ,3]dioxod-5-yirnethyl-3-(4-ch-loro-ohenyl)-2,4,5,6,7,8-hexahydro I .2,6-triaze-azulene: 149 3-(4-Chloro-pheniyl }2-pe ntat luo rephe nyimethyl-2,4,5,6.7 .8-hexalhyd re-I 2,6 triaza-azu lene,; 151 3-(4-Chlorc)-phenyl, >2-n.a phthalen -1 -ylmethyl-2 ,4,.5,6,7,.8-hexa hyd ro-1,2,6 triaza-azuilene; 153 3-(4-Chlere-phenyl)-2-(3,4,5-trimethexy-benzy)-2, 4,5,6,7, 8-hexahydre-1 .2,6 triaza-azulene; 155 2-(3,4-Bis -benzylexy-benzyl )-3-(4-chlere-phenyl )-2 9,4,5,6,7, 8-hexehyd re.

1,2, 6-tria za-ezulene; 161 4-[3-(4-Chlere-phenyl)-5 .8,7 ,8-tetra -hydre-4H-1 ,2,6--trieze-azulen-2-yl methyl] 24fluare-phenel; 134-[3-(4-Ghlere-phenyl'-S , 6 ,7,8-tetrahyd re-4H-1.2 ,6-triaza-azu len.-2--yl m.ethyl]- 3-mnethyl-phenol; 164 2-[3-(4-Ghlere.-phenyl)-5 ,6, 7,8-tae uhydre-4H--1.2 ,6-trieza-a-zu lenf-2-yl methyl] p h enrol; 176 2,3-Diphenyl--2,4,5,6,7,8-haxahydre-1,2,6-trieza-azulena; 177 2 -Cycle hex yl-3phefnyl-2 ,4,5 ,6,7,8-hexa hyd to-' 1,2,6-t ria ze-ezu le ne 1783-(4-Chiere,-phanyl)-2-cyclehexyl-2,4,5,6,7 .8-haxah ydre-1,2,6-triaze ezu 5ene:, 179 2-Cydeohexyl-3-(4-trilueremethyl-ph eny }-2,4,5.6,7, 6-haxahydre- 1,2 ,6-trieza azu lene; 180 2 -Cycle pe ntyl- 3-pha nyl-2 .4,5,6,8-he xe h yd re-i 1,2 6-tria za-ez ule na; 181 3-(4-Chlere-pheniy)-2-cy clepentyl-2,4,5,6,7,8-hexe hydrto- 1,2,6-Plaza azulane;, 182 2-Cyclepentyl-3-(44luem:-phen yl)-2.4,5,6 .7.8-hexehydre-1 2&.-triaze ezulene; 183 2-(1 Ethyl -prop yl)-3-(3-flue re-p henyl)-2,45,6,7,8--hexe hydro- 1 2,6 -trieze ezulena; 2f 142-(l1-E thyl-prepyl )-3-(4-f luere-phenyl )-2,4,5, 6,7,8-hexahyd re-I ,2 6-triaza azulene; 185 Z-( 1 -Ethyk-prepyl)-3-thicphen-3-y4-2,4 15,617 ,8-hexahydj re-i ,2,6-triaza azule-ne; 186 2-(l -Ethy4-prepy)-3-phenyi-,4,S.6,7,8-hexahyd re-I ,2,6-triaza-azulene;, 187 3-(4-Ch lere-phenyl )-2-(2 ,2 ,2-trif lucre-ethyl )-2 ,4,5 ,6 I,8-hexahydl re-i ,2,6 triaza-azulene; 182-(2,2.2-Trifluere-ethvQI-3-(4-triflue rerethyl-Dhe niyi)-24,5,6,7 ,8-hexah,,yd rO 1 ,2.6-triaza-azulene; 189 2-lseprepyl--3-phenyk2e-,4,5,6 ,7,8-hexahyd rn-I,2,6-triaza-azuene: 190 3-(4-Fluoro-phe.'riy1)-2-iseprepyl-2 ,4,5,6,7,8-hexahvd re-I,2,6-triaza-azulene; 191 ~2--(l1-Ethyk-propy})3-thriephen-2-yl-2,4,5,6,7,8-h:lexahydre-1 ,2 ,Sdriaza aZU lene: 192 2-Cyclopent ii-3-thieophen-3-yk-2 4,5,617,8-hiexahydre-1,2,6-triaza-azulene;, 193 2-Ethyl-3-pheniyl-2,4, 5,6,7,8-hexahydre-1 ,2,6-triaza-azuilene; 194 2-E thyl-3-(44flu oro-p hen yl,2 , 4,5,6,7 ,8-hexa hydre-I 1,2,6 -triaza-azu le ne; 195 2-E thyl-3-th iephen-2-yl-2,4,5,6, 7,8-hexa hyd r-, 12,6-triaza-azule-ne; 196 2-(3-C hloro-pheny',)-3 -phenyl-2 ,4.5,6,7,8-hexahydro-i ,2,6-triaza-azuilene; 197 2-(3-Fluero-phenyl)-3-phenyl-2, 4,5, 6,7,8-hexa hyd re,-I,2 ,6-triaza-azulene; 198 2-(2-Ohlcro-pheniyl )3-phenyl-2 ,4, 5,6,7,8-hexahiydrn-1 ,2,6-triaz-azulene.; 199 2-Phenyl-3-thiephen-2-yk-2 4,5,6,7 ,8-hexahydre,,-i,2,6-triaza.-azulenie; 200 3-(4-Fluere-phenryl)-2-phenfyl-2,4,5,6,7,8-hexa-:hyd re-i,2,6-triaza-azulene; 201 3-(4-Chlere-phenyl)-2-phenyl-2 14.5,6,7 ,8-he'<ahyd ro- 1,2 ,6-bl-aza-azu ie e 202 3-(3-Chlore-phenyl'-2-pheniyl-2 54, 5,6,7,8-hexahydlre-i,2,6-triaza-azule~e ; 203 2-Phenyl-3-p-telyi-2,4,5,6,7,8-hexahydre-l ,2 ,6-triaza-azulene;, 204 2, 3-Dipheny-4,5,6,7-tetrahydr-2H-pyrazl[4,3-cnyrid ne; 205 3-Pheriyl-2-(3-trifluerernethyl-phenyl)-2

A

1 5,617 ,8-hexahyd re-I, 2,6-rieze azutiene; 206 3-(4-Metheoxy-phenyl )-2-pheiy -2,4,.5,6,7,8-hexahyd re-I ,2,6-triaza-azuiene;, 207 2-(4-Ch loer-phle nyi)-3 -ph enyl-2 ,45,6,7,8-hexa hyd ro- 12 ,6-tria za -azuierla; 208 6-Methiyl-2 ,3-di phenyl-2,4,5,6 ,7,8-hexa hydro-I ,2,6-triaza-azulene; 209 2-lsepropyl-3-p-tely-2,4,5,6, 7,8-hexa hyd rei-I,2 ,6-tr-iaza-azulene: 210 3-(4-Ethyl- phenyQ'-2- isop repyl-2 54,556 ,7,8-he xa hyd re- 1,2,6-triaza-azu lene;, 211 3-(4-Chlere,.-phenyl)-2-iseprecpyl-2,4,5,6 ,7,8-heoxahydre)-I,2, 6-tilaza-azuler ai; 212 4-(2-lseprepyl-2 14,5.6,7 ,8-hexahydre-1I,2,6-triaza-azuian-3- 'l)-benzer btile; 2g 2^3 2-lsaprapyk.3-(4-trif luaraomethyl-phenyl)-2,4,5,6 ,7,8-hexa-hydra-1 .2,6-friez azuiene; 214 2-Ethyl-3-p-talyl-2,4, 5,61 ,8-hexahyd ra-1,2 ,64tr1az'a-azu lon-e; 215 2-tert-Butyl-3-phenyl-2 ,4,5,6,7,8-hexahydra-1 ,2,6-triaza-azulene,; 216 2-tert-Butyl-3-(4-fluaora-phenyl)-2,4,5,6,7,8-hexahy,/d ra-1 ,2,6-triaza-azulene; .217 2-Cyclapenityk3-p-taIcly-2, 4,5,6 ,7 , -hexa hydra-I ,2,6-triaza-azukmf- re; 218 2-Cyclapentyk-3-(4-trif lua rarnethyl-phenyl )-2 ,4,5,6,7, 8-hexahyd-ra- 1,2,6 triaze-azutene; 293-(3-Ohlara-phenyb-2-cycoapenY 1-2A4,5, 6,7, 8-hexahyd ro-1 ,2,6-trilaza ezu lone; 2-Cyclape ntyl-3-(4-mrehx 'k-p ,.,y-heniyl)-2 ,4,5,6,7, 8-hexahyd ra-1 :2 ,6-triaza 220 ezndene; 221 2-(3,3-Dimethyl-cydaopentA})-3-phenvi-2,4,5,6,7, 8-hexe iydri .,2,6-triaza ezulene; 222 2-(3,3-Di methyl-cyciapentyl)-3-(4-fIluara-phenyk-2:4,5,6 ,7,S-hexa hyd ra-1 ,2,6 triaza-ezulene; 223 ~3-(4-Chlara-phenyl )-2--3,3-dimethyl-cyclopentyl)-2,4.,5,6,7 ,8-hexehydra I,2,6Gdriaza-azulene;, 224 2-Cyclahexyl-3-(4-fluaro-.phenyl) -2 ,4,5,6,7,8-hexahyd ra-i,2,6-trilaza-azulene; 225 ~2-OyclIohexyi-3(3 4di Wlura-phenyl )-2,4.5,6,7 ,8-hexahydra-1 ,2 ,6-tri aza azulene; 226 2-Cyelahexyl-3-pda lyl-2 ,4,5,6,7 ,6-hexahydra-i 2,6-triaza-azulene; 227 2-yaey-3(-ehx-pheny )-2 ,4,5-,6,7, 8-hexeahydra-I1,2,6-triaza azulene; 228 4-(2-Cyclahexyi-2 ,4,5, 6,7,8- hexahyd ra-1 ,2,6-triaza-azulen-3-yl)-benzonitlile;, 229 34- '3-O-hlara-phenyl )-2-oyciahiexyl-2 :4,5,6,7 ,3-hexahyd ra-1, 2,6-triais azu lane;, 231 3-(4-Fl uara-p henyl)-2-isa pra pyl-4,5,6 ,7-tetrehyd ra-2 H- pyrazala 14,3 c]pyridine; 232 2-Cyclopentyl-3-fuiran-3-yk-2,4,5,6,7,&-hexahy,,dra- 1,2,6Atria.;fa-azilen e:, 2 33 2-Cyclapentyl-3-thiapheni-2-yl-2 ,4,5,6 ,7,8-hexahydra-,1 .2,6-triaza-azulene;, 234 2-tert4-Bu.tyl-3--thiaphen-3-yl-2 ,4,5,6,7,8-he-xahydra-1i,2,6-triaza-azulene; 235 2 -tert-Butyl-3-fura n -3-yl -2,4,5,6,7,8-hexa hyd ra-1 ,2,6-triaza-az ulente', 26 2-Cyclape ntyl-3-(3,4-d ifiluara-phenyl)-2,4-,5,6 ,7,8-hexahyd ra-1 ,2,6-tniaza 236 azuiene; 238 3-(4-C'i lara-phenyl )-2-cyclabuityl-2 ,4,5,6,7 ,6-hexahyd ro-I ,2 ,6-thaza-azu lene; 2h 240 24ert-BtyI-3-thiophen-2-yk2,4,5,6,7,8-hexahyd ro-1 ,2 ,6-triaza-azulene; 32(3-Chlor-4-fluoro-phenyl)-2-cyclopenty-2,4,5,6 ,78-hexahydro-1,2,6 241 imaza-azulene; 242 2-Isopropyl~3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexa hydro- ,26-triaza azulene; 243 2-Isopropyl3-(4-trifluoro methoxy-phenyl )-2,4,5,6,7 8-hexahyd ro- 1,2,6-triaza azulene; 244 2-isopropyk-3-(4-isopropyl-phenyl)-2 4,5,6,7 ,8-hexahyd ro-1 ,2,6-triaza azulene; 245, 3-(4-tert-Butyl-phenyl)-2-isopropyl-2,4,5,6 7 ,8-hexahydro-1,2,6-ftriaza azulene; 246 2-Isopropyl-3-m-toly-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 247 2-lsopropy3-o-toly-2,4,5,6,7,8-hexahydro-1 .2,6-triaza-azulene; 248 3-(3,4-Dichlora-phenyl)-2Aisopropy-2 ,4,5,6,7,8-hexahydra-1,2,6-triaza azuIene; 249 2-Benzyl-3-(4-fluora-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; 251 3-(2-Chloro-phenyl)-2-isopropyk2 4,5,6,7,8-hexahydro-1,2 ,6-triaza-azulene; 252 1 -[4-(2-isopropy-2 4,5,6,7 ,8-hexahydro-1i,26-riaza-azuen-3-yl)-phenyf] ethanone; 253 2-isopropyl-3-(4-nitro-pheny)-2,4,5,6,7 8-hexahydro-1 2,6-triaza-azulene; 256 2-Benzyl-3-(4 chloro-phenyl>2,4,5,6,7 ,8-hexahydro-i,2,55triaza-azulene; 257 2-Ethyl-3-(4-ethyi-phenyl)-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene; 258 4-(2-Ethyl-2,4,5,0A7,8-hexahydro-1 ,2 ,6-triaza-azuler-3-y)-benzonitrile; 259 3-(4-Fluoro-phenyl)-2- isopropyk6-methy-2,4,5,6 ,7,8-hexahyd ro-I 2,6-triaza azulene; 260 3-(4-Fluoro-phenyl)-2,6-diisopropyl~2,4,A,6,7,8-hexahydro-1 2,6-triaza azulene; 261 2-Ethyl-3-(4-isopropyl-phenyl)-2,45,6 ,7,8-hexahydro-1,2,6-triaza-azuliene; 262 2-Ethyl-3-(4-methoxy-phenyl )-2,4,5,6,7,8-hexahydro-I,2,6-triaza-azu lene; 263 2-Ethyl-3-(4-trifluoromethyl-phenyl-2,4,5,6,7,8-hexa hydro-1,2,6-triaza azulene; 264 2-Ethyl-3-o-toly-2,4,5,6,7,8-hexahydro-1 2,6-triaza-azulene; 265 3-(2-Chloro-phenyl)-2-ethyl-2;4,5,6,7,8-hexahydro-i1,2,6-triaza-azulene; 266 2-Ethyl-3-(2-fluoro-phenyl)-2,4,5,6,7.8-hexahydro-1 ,2,6-triaza-azulene; 2i 3-(2,4-Dichloro-phenyl)-2-isopropyl-2,4,5,6 ,7,8-hexahydro-1 ,2,6-triaza 267 azulene; 268 [4-(2-Ethyk2,4,5,6,7,8-hexahydro-1;2,6-triaza-azulen-3-yl)-phenyl]-dimethyk amine; 6-Benzyl-3-(4-fluoro-phenyl)-2-isopropyk24,5,6,7,8-hexahydro-1,2,6-triaza 269 azulene; 270 3-(4-Flu oro-phe nyl)-2-isopropyl-6(3-pheny-'propyl)-2,4,5,6 7,8-hexa hydr 1,2,6-triaza-azulene; 271 3-(4-Fluoro-phenyl)-2-isopropyk6-phenethyl-2 ,4,5,6,7 ,8-hexahydr-1,2 6 triaza-azulene; and 3-(4-Fluoro-phenyD)-2-isopropy-4,5,7,8-tetrahydro-2H-1,2 ,6--triaza-azu lene 272 6-carboxylic acid tert-butyl ester. 3-(4'-ChIora-biphenyl-4-yl)-2-(2,2,2-trifluoro-ethyl)-2,4,5,6,7,8-hexahydro 274 1,2,6-taza-azulene; 3-(4-Chlo re-b iphenyl-4-yl )2-cyclopentyl-2;4,5,6,7,8-hexahyd ro- 1,2,6-triaza 275 azulene; 276 2-Cyclobutyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 277 2-Cyclobutyl-3-(4-fluoro-pheny)-2, 5,6,7.8-hexahydro-I,2,6-triaza-azulene; 278 2-Cyclobuty -3-p-tolyl-2,4,5,6,7,8-hexahydro-1 ,26-,triaza-azulene; 279 2-Cyclobutyl-3-(4-trifluorrmethyl-phenyl)-2 ,4, 516,7,8-hexahydro-1,2 6-triaza azulene; 280 4-(2-Cyclobutyl-2,4,5,6,7, 8-hexahyd ro-1,2,6-triaza-azulen-3-yl)-benzonitrile 281 2-Cycl propyi-3-pheny1-2 ,4,5,6,7,8-hexahydro-1; 2,6-triaza-azulene; 282 2-Cyclopropyl-3-(4-fluoro-phenyl)-2,4,5,,7,8-hexahydrl-1 ,2,6-triaza azulene; 2 8321 2-(1-Ethyl-propyl)-3-(4-fluoro-3-methyl-phenyl)-2,4,5,6,7, 8-hexahydro-1,2, 6 triaza-azulene; 284 2-Cyclopropyl-3-p-tolyk2 4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 285 2-Cyclopropy-3-thiophen-3-yI-2 ,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene 286 4-(2-Cyclopropyl-2,4,5,6 ,7,8-hexahydrm-1 ,2,6-triaza-azulen-3-yl) benzonitrile; 287 6-Benzyl-2-isopro pyl-3-phenyl-4,5,6,7-tetrahyd ro-2 H-pyrazolo[3,4-c] pyrid ine; 288 2-1sopropy1-3-phenyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine; 289 6-Benzyl-2-ispreopyl-3-thiophen-3-y-4 ,5,6 ,7-tetrahyd ro-2H-pyrazOlo[3,4 cjpyridirre: 290 6-Benzyl-2-isopro pyl-3-p-to lyV4, 5,6 ,7-etra hyd r-2H-pyrazolo[3,4-c]pyrid ine. 2j 6 Benzyk3-(4~fluoro-pheny)~2 isopropyl4,5,A7-tetrahyd ro-2H-pyrazolo{3,4~ 291 c]pyridine; 292 3-(4-Fluoro-phenyl)-2lisopropyk4,5.6a7-tetrahydro-2Hpyrazolo[3,4 c]pyridine; 293 2-isopropy[-3-p-tolyb-4 5,6,7-tetrahyd ro-2 H-pyrazolo[3,4-c]pyridine; 294 2-Cyclopenty3(4-fluoro-phenyl )-55> ,7-tetramethyl-2,4,5,6,7,8-hexahyd ro 1,2,6-triaza-azulene; 295 2-Cyclopenty 5,5,7,7-ttramethy-3-phenyl-2,4,5 ,7 8-hexahyd ro-1, 2,6 triaza-azulene; 296 2-sopropyl-5,5>7,7-tetramnethyl-3-phenyl-2.4>5,6,7,8-hexahydro-1,2,6-triaza azulene; 3-(4-Fluoro-phenyl)-2-isopropyl-, 5,7,7-tetramethyl-2,4,5,67 ,8-hexahyd ro 297 1 ,2,6-triaza-azulene; 298 2-sec-Butyl-3-phenyl~2,4>56,7, 8-hexahydro-12,6-triaza-azulene; 299 2-sec-Butyb~3-(4-fluoro-phenyi)-2,4,5,6,7 8-hexahydro-1,2,6-triaza-azulene; 300 2-sec-Buty-3-p-tolyk2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene; 2-sec-Butyl-3-(4-trifluoromethyl-phenyi)-2 .,5,6,7,8-hexahydro-12,6-triaza 301 azulene; 302 2-Cyclopentyi-3-4-fluoro-phenyl)-6-methyl-2 A45,6,7>8-hexahiydro-1 2,6 triaza-azulene; 303 4-(2-Isopropyk2 ,4,5,6,7,8-hexahyd ro-1 2,6-triaza-azulen-3-y)-benzamide; 304 2-Isopropyl-3-4-(1 Hdtetrazol-5-yl)-phenya-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene; 305 6-Benzyl-3-(4-fluoro-phenyl)-2-isopro pyl-8-methyl-2 4,5,6,7 8-hexa hydro S,2,6-triaza-azuIene. 3-(4-Fluoro-phenyl)-2-isopropyl-8-methyl-2,4 5,6,7 8-hexahydro-1,2,6-triaza 306 azulene; 3-(4-Fluoro-phenyl)-2isopropyK-4methyl-2 4,5,6,7, 8hexahydr-1,2,6-triaza 307 azulene; 2-Cyclopentyl-3-(4-fluoro-phenyl)-7-methy-2 4,5,6,7,8-hexahydro-I 2,6 308 triaza-azulene; 2-Cyclopentyl-3-(4fluoro-phenyl)-5-methyk2 4,5>6>7,8-hexahydro-1,2,6- 309 triaza-azuiene; 310 2-Cyclopentyl-7-rnethyl-3-p-tolyl-2,456 7,8-hexahydro-12,6-triaza-azulene; 311 2-isopropyl-7-methyl-3-pheny[2,4,5,6 ,8-hexahydro-1,2,6-triaza-azulene; 312 2-Isopropyl-5-methyl-3-phenyl-2,4,5,6 7,8-hexahydro-1,2,6-triaza-azulene; 2k 313 3-(4-Fluoro-phenyl)-2-isopropyf7-methyb2,4,5,6 7,8-hexahydro-1 2,6-triaza azulene; 31 3-(4-Fluoro-phenyi)2-isopropyl-5-methyL2 4,5,6,78-hexahydro-1,2,6-triaza azulene; 315 2-Isopropyk7-methyk3~p-tolyi-2,45,6,7,8-hexahydro- 1,2,6-triaza-azulene; 3-(4-Chloro-pheny)-2-pyridin-2-ylmethy-i,4 5,6,7, 8-hexahydro- 1 ,2,6-triaza 318 azulene; 327 3-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1 ,2,6-triaza-azulen-2-yi]~ propionitrile; 3-(4-Chloro-phenyl)-2-cycloheptyl-2,4,5,6.7,8-hexa hydro-1,2,6-triaza 328 azulene; 329 3-(4-Chloro-pheny9-2-cycloocty-2,4,5,6 7,8-hexahydro-1 ,2,6-triaza-azulene; 3-(4-Chloro-phenyl)-2-(4-methyl-cyclohexyl )2,4,5,6,7, 8-hexahyd ro-1,2,6 3301 triaza-azulene; 3-(4-Fluoro-phenyl)-2-isopropyl-5,7-dimethyl-24,5,6,7 ,8-hexahydro-126 338 triaza-azulene. According to a third aspect, the invention provides a compound selected from the group consisting of: 214 2-Ethyi-3-p-tolyl-2,45,6,7,8-hexahydro-1 ,2 6-triaza--azulene; 257 2-Ethyl-3-(4-ethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6triaza-azulene; According to a fourth aspect, the invention provides a compound selected from 5 the group consisting of: EX CHEMICAL NAME 131 3-(4-Chloro-phenyi)-2-isobutyk2,4,5,6 ,7,8-hexahydro-1,2,6-triaza-azulene; 133 2-Benzyi-3-phenyl-2 ,4,5,6, 7,8-hexahydro-1,2,6-triaza-azulene; 177 2-Cycoohexyl-3-pheny-2,45,6,7,8-hexahydro-1,2,6-triaza-azulene; 178 3-(4-Chloro-phenyl)-2-cyclohexyk2,4,5,6,7,8-hexahydro-I,2,6-triaza azuIene; 181 3-(4-Chloro--phenyl)-2-cyclopenti-2,4,5,6, 78-hexahydro-1 2,6-triaza azulene; 182 2-Cyclopentyl-3-(4-fluoro-phenyl)-2,4,5,6,78-hexahydro-1 2,6-triaza azulene; 183 2-(1 -Ethy-propyl )-3-(3-fluoro-pheny)-2,4 ,5,6,7,8-he xahyd ro-1 :2 ,6-triaza azulene; 21 142-(l1-Ethyl-propyl )-3-(4-fluoro-phenyl)-2,4,5,6,7 ,8-hexahyd ro-1 ,2 ,Gtri'aza azulene;, 166 2-41 -Ethyk-propyl)-3-phenyl-2,4,5,6X78-hexahydro-1 ,2,G-triaza-azlene; 191 2-(1 -E thyl- pro pyl>--3-thiophen-2-yl-2 ,4,5,6 ,7, 8-hexa hyd r-I 1,2, 6-frieze azuIene: 215 2-trir-ButykS3-pi enyl-2 ,4,5,6,7.8-hexahydro-1,2,6-triaza-azulene;, 216 2-tert-Butyl-3-(4-fiLuoro-phieniyO-2,4,5,6,7 ,8-hexahydro-i ,2 ,6triaza-azulene; 2.17 2-Cyclopentyi-3-p-toly1-2, 4,5,6,7 ,8-hex, -ah,,vdro-i ,2,6-tLriza-azulenie; 28 2-CyciopenW l-3-(4-trifluorornethy [she nyQ-2,4,5,6,7, 8-hexehydro -i 2 t6 triaza-azuiene; 220 2-Cyolopenityl-3-(4-rnsthoxy-phenyD)-2,4,5,6,7,8-hexa hydmr-1,2 ,6-tria-a azulene;, 23 2-ydCopty-3hi-(3-d iflrobphety-24,5,6,7 ,8-hxahyd r-,2 ,6-riaz azulene; 241 3 -C loro-phenyapi}l-2-iouyk,,I, l- 2 ,4 ,5 ,6,78-ex hdrn-I a yd2,6 azulene; 241 3-(-Ghclorot--4 luorhny--o ylo PC ty, , 5, 6 .7, 8d-exahy6- 1,2, tzazulene; 2782-sopropy -~-toy-,4,5,6,,6,7x-hhydhydro6-1,az6-aine; 277 2-Cyclo butyl-3-(441 ifuo ro-p hyl>2 ,4 -, 5. ,,hexahyd ro- 1,2 ,6-tria traazuene; 28 2-Cydlobut~yl-3-p-tolyI-2,4,5,6,7,8-he;-xahydro- 1,2 ,6-triaza-azuiene; 302 2-Cyclobuntyl-3-(4-trfluororp-iny ethyl-heyl ,4,5,6 I ,8-hexahy in- 1,2,6 triaze-azuIene; 3023-yl o-pl-344-fluoropyl-6-rnethyl-2 ,4,5,6,7, 8-hexa hd in-i 1,2 ,6 triaza-azulen'e: 3102-Cyclope ntyl-7-meth' -3-p-toiV2 ,4 ,5,6,7 .8-hxya hyd. rn-I,2 ,6-tniazaazuldene; 2.m According to a fifth aspect, the invention provides a compound selected from the group consisting of: EX CHEMICAL NAME 64 3-(4-Chloro-phenyl)-2-ethy-2,4 ,5 6,78-hexahydro-1;2,6-triaza-azuiene; 180 2-Cyclopentyl-3-phenyl-2,4,5,6,7,8-hexahydro-1 2,6-triaza-azulene; 190 3-(4-Fluoro-phenyl)-2 -isopropyk2 ,4,5,6 ,7,8-hexahyd ro-1,2 ,6-triaza azu lene: 192 2-Cyclopenty-3-thiophen-3-y~2 4,5,6,7,8-,exahydro-1 2,6-triaza-azulene; 209 2-Isopropyl-3-p-toly2,4,5,67,8-hexahydro-1 2 ,6-triaza-azulene; 210 3--(4-Ethyl-phenyl)-2-isopropyl-24, 5,6,7,8-hexahydro-1,2 ,6-triaze-azulene; 3-(4-Chloro-phenyi)-2-isopropyk2,4, ,6,7,8-hexahydro-1,2 6-triaza 211 azulene; 212 4-(2-sopropy-2,4,5,6,7,8-hexahydro-1 2,6-triaza-azulen-3-yl)-benzonitrile; 213 2-isopropyl-3-(4-trifluoromethykpheny)-2,4,5,6,7,8-hexahydero-1 ,2,6-triaza azulene; 232 2-Cyclopentyl3-furan-3-y24,5,6 7,8-hexahydro-1,2,6-triaza-azuiene; 233 2-Cyclopentyl-3-thiophen-2-yV2,4,5,6,7 8-hexahydro-1,2,6-triaza-azulene; 284 2-Cyclopropyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-traza-azu lene; 300 2-sec-Butyl-3-p-toly-2,4,5,6,7,8-hexahyd ro-1,2,6-triaza-azulene; 315 2-Isopropy1-7-methyl-3-p-tolyi-2,4,5,6 ,78-hexahydro-1 2,6-triaza-azulene; According to a sixth aspect, the invention provides a compound selected from 5 the group consisting of: 182 2-Cyclopenty-3-(4-fluoro-phenyi)-24,5,6,7,8-hexahydro-1,2,6-triaza azulene and pharmaceutically acceptable salt thereof. According to a seventh aspect, the invention provides a compound selected from the group consisting of: 3-(4-Fluoro-phenyl)-2-isopropy-2,4,5,6,7,8-hexahydro-i,2,6-triaza-azulene 190 and a pharmaceutically acceptable salt thereof. 10 According to an eighth aspect, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of compound according to the first aspect. According to a ninth aspect, the present invention provides a compound according to the first aspect for the treatment or prevention of a CNS disorder selected 2n 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, 5 hormonal imbalance, alcohol abuse, addictive disorders, nausea, inflammation, centrally mediated hypertension, sleep/wake disturbances, jetlag. and circadian rhythm abnormalities in mammals. According to a tenth aspect, the present invention provides a compound according to the first aspect for the treatment or prevention of a disease or condition 10 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. According to an eleventh aspect, the present invention provides a compound 15 according to the first aspect for the treatment or prevention of an ocular disorder selected from the group consisting of: glaucoma, optical neuritis, diabetic retinopathy, retinal edema, and age-related macular degeneration in mammals. According to a twelfth aspect, the present invention provides a compound according to the first aspect for the treatment or prevention of a disease or condition 20 selected from the group consisting of: depression/anxiety, sleep/wake disturbances, jetlag, migraine, urinary incontinence, gastric motility, and irritable bowel disorders in mammals. According to a thirteenth aspect, the present invention provides a compound according to the first aspect for the treatment or prevention of a disease or condition 25 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, additive disorders, and peripheral vascular disorders in mammals. 30 According to an fourteenth aspect, the present invention provides a compound of the first aspect isotopically-labelled to be detectable by PET or SPECT. According to a fifteenth aspect, the present invention provides a method for studying serotonin-mediated disorders comprising the step of using an 1 F-abeled or 1 C-labelied compound of the first aspect as a positron emission tomography (PET) 35 molecular probe, 2o According to a sixteenth aspect, the present invention provides use of a compound according to the first aspect 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, 5 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. 10 According to a seventeenth aspect, the present invention provides use of a compound according to the first aspect 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 15 disorders related to the gastrointestinal and vascular systems in mammals. According to an eighteenth aspect, the present invention provides use of a compound according to the first aspect 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. 20 According to a nineteenth aspect, the present invention provides use of a compound according to the first aspect 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. 25 According to a twentieth aspect, the present invention provides use of a compound according to the first aspect 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 30 dysfunction, eating disorders, migraine, addictive disorders, and peripheral vascular disorders in mammals. According to a twenty first aspect, the present invention provides a method of treatment or prevention of a ONS disorder selected from the group consisting of: sleep disorders, depression/anxiety, generalized anxiety disorder, schizophrenia, bipolar 35 disorders, psychotic disorders, obsessive-compulsive disorder, mood disorders, post traumatic stress and other stress-related disorders, migraine, pain, eating disorders, 2p obesity, sexual dysfunction, metabolic disturbances, hormonal imbalance, alcohol abuse, addictive disorders, nausea, inflammation, centrally mediated hypertension, sleep/wake disturbances, jetlag, and circadian rhythm abnormalities comprising administering to a mammal in need thereof a compound according to the first aspect. 5 According to a twenty second aspect, the present invention provides a method of 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 10 vascular systems comprising administering to a mammal in need thereof a compound according to the first aspect. According to a twenty third aspect, the present invention provides a method of treatment or prevention of an ocular disorder selected from the group consisting of: glaucoma, optic neuritis, diabetic retinopathy, retinal edema, and age-related macular 15 degeneration comprising administering to a mammal in need thereof a compound according to the first aspect. According to an twenty fourth aspect, the present invention provides a method of treatment or prevention of a disease or condition selected from the group consisting of: depression/anxiety, sleep/wake disturbances, jetag, migraine, urinary incontinence, 20 gastric motility, and irritable bowel disorders in mammals comprising administering to a mammal in need thereof a compound according to the first aspect. According to a twenty fifth aspect the present invention provides a method of treatment or prevention of a disease or condition selected from the group consisting of: depression/anxiety, generalized anxiety disorder, schizophrenia, bipolar disorders, 25 psychotic disorders, obsessive-compulsive disorder, mood disorders, post-traumatic stress disorders, sleep disturbances, sexual dysfunction, eating disorders, migraine, addictive disorders, and peripheral vascular disorders comprising administering to a mammal in need thereof a compound according to the first aspect Unless the context clearly requires otherwise, throughout the description and the 30 claims, the words "comprise", "comprising", and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to". The invention features a compound of formulae (I), (ii) and (IlI): 2q R2

CYC-(ALK)

0 CYC-(ALK)C 7 A CYCALK)qAr Ar ( ) (11)r wherein m isO 1 or2: n is 1,2 or3; 5 p is 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; q is0or1; r is 0 1, 2 3 4, or 5 --------------- 2r R9 is -C 1

.

4 alkyl, allyl, propargyl, or benzyl, each optionally substituted with -C1.

3 alkyl, -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 Rr or di-substituted 5 on adjacent carbons with -OC1.

4 alkyleneO-, -(CH 2

)

2

-

3 NH-,

-(CH

2

)

1

-

2

NH(CH

2 )-, -(CH2) 2 -sN(C1.

4 alkyl)- or -(CH2)1- 2 N(C1.

4 alkyl)(CH 2 )-; Rr is selected from the group consisting of -OH, -C1.

6 alkyl, -OC1- 6 alkyl, -C 2

-

6 alkenyl, -OC.

6 alkenyl, -C 2 -ealkynyl, 10 -OCs.

6 alkynyl, -CN, -NO 2 , -N(RY)Rz (wherein RY and Rz are independently selected from H or Ci 6 alkyl), -(C=O)N(RY)Rz, -(N-R)CORt, -(N-R)SO 2 C1.

6 alkyl (wherein R' is H or CI.

6 alkyl), -(C=O)C1.

6 alkyl, -(S=(O)n)-C1.

6 alkyl (wherein n is selected from 0, 1 or 2), -SO 2 N(RY)Rz, -SCF 3 , halo, -CF 3 , -OCF 3 , -COOH and 15

-COOC

1

.

6 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 >0, >S, >NH or >N(C 1

.

4 alkyl) and which moiety has up to one additional 20 carbon atom optionally replaced by -N=, the fused rings optionally mono-, di- or tri-substituted with Rr 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 25 fused rings optionally mono-, di- or tri-substituted with Rr; d) naphthyl, optionally mono-, di- or tri-substituted with Rr; 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 1

.

4 alkyl), having up to 30 one additional carbon atoms optionally replaced by -N=, optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or 3 pyridofused moiety is optionally mono-, di-, or tri-substituted with Rr; 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 5 carbon atoms replaced by -N=, optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with Rr; g) phenyl or pyridyl, substituted with a substituent selected from the group 10 consisting of phenyl, pyridyl, thiophenyl, oxazolyl and tetrazolyl, where the resultant substituted moiety is optionally further mono-, di or tri-substituted with Rr; ALK is a branched or unbranched Ci.

8 alkylene, C2.

8 alkenylene, C2.ealkynylene or C3-8cycloalkenylene, optionally mono-, di-, or tri-substituted with a 15 substituent independently selected from the group consisting of: -OH,

-OC

1

.

6 alkyl, -OC3.6cycloalkyl, -CN, -NO 2 , -N(Ra)Rb (wherein Ra and Rb are independently selected from H, C 1

.

6 alkyl or C 2 -ealkenyl), -(C=O)N(Ra)R b, -(N-Rc)CORc,

-(N-R)SO

2 C1.ealkyl (wherein Rc is H or C1.

6 alkyl),

-(C=O)C

1

.

6 alkyl, -(S=(O)d)-C1.

6 alkyl (wherein d is selected from 0, 1 or 2), 20 -SO 2 N(Ra)Rb, -SCF 3 , halo, -CF 3 , -OCF 3 , -COOH and -COOC1.ralkyl; 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 Rq or di-substituted on adjacent carbons with -OC 1

.

4 alkyleneO-, -(CH 2

)

2 -3NH-, 25 -(CH 2

)

1

-

2

NH(CH

2 )-, -(CH2)2-3N(C1.4alkyl)- or -(CH2)1- 2 N(C1.

4 alkyl)(CH 2 )-; Rq is selected from the group consisting of -OH, -C1.

6 alkyl,

-OC

1 6 alkyl, -C 3 -ecycloalkyl, -OC 3

.

6 cycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl, -CN, -NO 2 , -N(Ra)Rb (wherein Ra and Rb are 30 independently selected from H, C 1

.

6 alkyl or C2.

6 alkenyl, or Ra 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, 4 =N-, >NH or >N(Cl.

4 alkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=O)N(Ra)R, -(N-R)CORc,

-(N-R)SO

2

CI.

6 alkyl (wherein Rc is H or C 1

.

6 alkyl or two Rc in the 5 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-(S02C1 6 alkyl) 2 , -(C=0)C 1 salkyl, -(S=(O)d)-C1.6alkyl (wherein d is selected from 0, 1 or 2), -SO 2 N(Ra)Rb, -SCF 3 , halo, -CF 3 , -OCF 3 , -COOH and 10 -COOC 1

.

6 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(C1- 4 alkyl) and which moiety has up to one additional 15 carbon atom optionally replaced by -N=, the fused rings optionally mono-, di- or tri-substituted with Rq; 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 20 fused rings optionally mono-, di- or tri-substituted with Rq; iv) naphthyl, optionally mono-, di- or tri-substituted with Rq; 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 1

.

4 alkyl), having up to 25 one additional carbon atoms optionally replaced by -N=, optionally mono- or di-substituted with Rq and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with Rq; vi) a monocyclic aromatic hydrocarbon group having six ring atoms, 30 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 Rq and optionally benzofused or pyridofused at 5 two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with Rq; vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 0, 1 or 2 non-adjacent heteroatom members selected 5 from 0, S, -N=, >NH or >R4, 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 RI and optionally benzofused or pyridofused at two adjacent carbon atoms where the benzofused or pyridofused moiety 10 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 0, S, -N=, >NH or >NRq, having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally 15 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 20 0, S, -N=, >NH or >Rq, 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 Rq;

R

1 is selected from the group consisting of H, C 1

.

7 alkyl, C 2

.

7 alkenyl, C 2

-

7 alkynyl,

C

3

.

7 cycloalkyl, C3-7cycloalkylCl.

7 alkyl, C- 7 cycloalkenyl, 25 C~cycloakenylC 1

.

7 alkyl and benzo-fusedC 4

.

7 cycloalkyl, each optionally mono-, di-, or tri-substituted with RP; RP is selected from the group consisting of -OH, -OC 1 .alkyl,

-C

3

-

6 cycloalkyl, -OC 3

-

6 cycloalkyl, -CN, -NO 2 , phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(Rs)Ru (wherein Rs and Ru are independently 30 selected from H or C 1 6 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 1

.

4 alkyl) and optionally having 6 one or two unsaturated bonds in the ring), -(C=O)N(Rs)Ru, -(N-Rv)CORv, -(N-RV)SO 2 C1.

6 alkyl (wherein RV is H or C1.ealkyl or two RV in the same substituent may be taken together with the amide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring 5 having 4 to 6 members), -(C=O)C1.ralkyl, -(S=(O)n)-C1.

6 alkyl (wherein n is selected from 0, 1 or 2), -SO 2 N(Rs)Ru, -SCF 3 , halo, -CF 3 , -OCF 3 , -COOH and -COOC1.

6 alkyl, wherein the foregoing phenyl, pyridyl, thlenyl, furanyl and pyrrolyl substituents are optionally mono-, di-, or tri-substituted with a substituent independently selected from the 10 group consisting of: -OH, -C 1

.

6 alkyl, -OC 1

.

6 alkyl, -CN, -NO 2 , -N(Ra)R' (wherein Ra and Rb are independently selected from H, C 1

.

6 alkyl or C2.

6 alkenyl), -(C=O)N(Ra)Rb, -(N-Rc)CORc, -(N-RC)SO 2 C16.alkyl (wherein Rc is H or C 1

.

6 alkyl), -(C=O)C 1

.

6 alkyl, -(S=(O)d)-C1.

6 alkyl (wherein d is selected from 0, 1 or 2), -SO 2 N(Ra)Rb, -SCF 3 , halo, 15 -CF 3 , -OCF 3 , -COOH and -COOC16.alkyl;

R

2 is selected from the group consisting of H, C 1

.

7 alkyl, C 2

.

7 alkenyl, C2.

7 alkynyl and C3.

7 cycloalkyl; and enantiomers, diastereomers, hydrates, solvates and pharmaceutically acceptable salts, esters and amides thereof, 20 Similarly, isomeric forms of the compounds of formulae (1), (II), and (Ill), 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 25 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, 30 5-HT 7 and/or 5-HT 2 receptor subtypes. Detailed Description Preferably, m is 1 or 2 and most preferably, m is 1. 7 Preferably, n is 1 or 2. Preferably, p is 1 or 2. Preferably, m+n is 2 or 3. Preferably, m+p is 2 or 3. 5 Preferably, q is 1. Preferably, r is 0, 1, or 2. Preferably, r is 4. Preferably R 3 , optionally substituted, is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, allyl, propargyl, and benzyl. 10 Preferably, R 3 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-isolndolinyl, 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-indazoly, imidazo[1,2-a]pyridin-5, 6, 7 or 8 yl, pyrazolo[1,5-a]pyridin-4, 5, 6 or 7-yl, 1 H-pyrrolo[2,3-b]pyridin-4, 5 or 6-yl, 20 1 H-pyrrolo[3,2-c]pyridin-4, 6 or 7-yl, 1 H-pyrrolo[2,3-c]pyridin-4, 5 or 7-yl, 1 H-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, 25 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, 30 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 8 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, 5 2-methoxyphenyl, 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-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3-trifluoromethoxyphenyl, 10 4-trifluoromethoxyphenyl, 3-cyanophenyl, 4-cyanophenyl, 3-acetylphenyl, 4-acetylphenyl, 3,4-difluorophenyl, 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 15 methylphenyl, 4-hydroxy-3-fluorophenyl, 3,4-dihydroxyphenyl,4 dimethylaminophenyl, 4-carbamoylphenyl, 4-fluoro-3-methylphenyl, furan-2-yi, furan-3-yl, thiophen-2-yl, thiophen-3-yl, 5-chlorothlophen-2-yl, 5 methylthiophen-2-yl, 5-chlorothlophen-3-yl, 5-methylthiophen-3-yl, 4' chlorobiphenyl, and 4-tetrazolylphenyl. 20 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, 25 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 30 methylbutylene, prop-2-ynylene, 2-dimethylaminoethylene, and 2 cyanoethylene. Preferably CYC, optionally substituted, is hydrogen or is selected from the group consisting of: 9 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 5 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-yI, 1 H-pyrrolo[2,3-b]pyridin-4, 5 or 6-yl, 1 H-pyrrolo[3,2-c]pyridin-4, 6 or 7 -yl, 1 H-pyrrolo[2,3-c]pyridin-4, 5 or 7-yl, 1 H-pyrrolo[3,2-b]pyridin-5, 6 or 7-yl, 10 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, isothiazolyl, pyrrolyl, 15 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, pyrldinyl-N-oxide, pyrazinyl, pyrimidinyl, pyridazinyl, 1-, 3- or 4-isoquinolinyl, 2-, 3- or 4-quinolinyl, 2- or 3-quinoxalinyl, 2- or 4-quinazolinyl, 20 [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, 25 piperazinyl, morpholinyl, thiomorpholinyl, piperidinonyl, indanyl, dihydroindolyl, oxindolyl, dihydropyrrolopyridinyl, and viii) bicyclo[4.1 .]heptane, octahydroindolyl, octahydroisoindolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydropyrrolopyridinyl, and octahydropyrrolopyrrolidinyl. 30 More preferably, CYC, optionally substituted, is selected from the group consisting of hydrogen, phenyl, indolyl, benzthiazoyl, 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 10 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. Most preferably, CYC, optionally substituted, is selected from the group 5 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-methylphenyl, 10 3-methylphenyl, 4-methylphenyl, 4-ethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 15 3-acetylphenyl, 4-acetylphenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 2,3-difluorophenyl, 2,3-dichlorophenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 2,6-difluorophenyl, 2,6-dichlorophenyl, 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, 20 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 25 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-methylphenyl, 4-hydroxy-3-fluorophenyl and 3,4-dihydroxyphenyl. Preferably, R 1 is selected from the group consisting of hydrogen, 30 C1.

3 alkyl, C2.

4 alkenyl, C 2

.

4 alkynyl, C 3

.

6 cycloalkyl, C3-6cycloalkylC a alkyl,

C

5 rcycloalkenyl, benzo-fusedCs9ecycloalkyl, each optionally mono-, di-, or tri substituted with RP. 11 More preferably, R , optionally RP substituted, is selected from the group consisting of hydrogen, methyl, ethyl, propyl, and isopropyl. Specific R 1 -may be selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, 3-hydroxypropyl, benzyl, 3,4-dimethoxybenzyl, 5 methoxycarbonylmethyl, carbamoylmethyl, phenethyl, phenpropyl, and hydroxyethyl. Preferably, R 2 is hydrogen, C1.

3 alkyl, C2.

4 alkenyl, C 2

.

4 alkynyl, or C3.ecycloalkyl. More preferably, R 2 is hydrogen or methyl. 10 It 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 15 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 20 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 125 1 1 F, 11C, 64Cu, 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 'F Isotopically labeled compound 25 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 30 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 12 functionalized radioactive reagents using conventional chemistry to provide radiolabeled compounds. Pharmaceutically acceptable salts, esters, and amides include carboxylate salts (e.g., C 1

.

8 alkyl, C38cycloalkyl, aryl, C 2

-

1 oheteroaryl, or C2-10 5 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, 10 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 15 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. 20 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 C1-6 alkyl amines and secondary di(C 1 .6alkyl) amines. Secondary amines include 5- or 6-membered heterocyclic or heteroaromatic ring moieties containing at least one nitrogen atom and 25 optionally between 1 and 2 additional heteroatoms. Preferred amides are derived from ammonia, C 1

.

3 alkyl primary amines, and di(C 1

.

2 alkyl)amines. Representative pharmaceutically acceptable esters of the invention include

C

1

.

7 alkyl, C5.7cycloalkyl, phenyl, and phenyl(C 1

.

6 )alkyl esters. Preferred esters include methyl esters. 30 Preferred compounds, which are fused pyrroles, are selected from the group consisting of: 13 EX CHEMICAL NAME 1 1 -Benzyi-3-(4-nitro-pheny)-4,5 ,6,7-tetrahydro-1 H-pyrrolo[3,2 cipyridine; 2 1 -Benzyk-3-(3-chloro-4-fluoro-pheny)-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-clpyridin-3-yi)-phenol; 41 -Benzyl-3-(4-trif Juoromethoxy-phenyl)-4,5,6 ,7-tetrahyd ro- 1 H ____ pyrrolo[3,2-c]pyridine; 5 1-Benzyl-3-(5-chloro-thiophen-2-y)-45,6,7-tetrahydrol1 H-pyrrolo[3,2 c]pyridine; 6 1 -Benzyl-3-thiophen-2-yI-4,5,6,7-tetrahydro.1 H-pyrrolo[3,2-c]pyridine; 71 -(3-Oh Ioro-benzyl)-3-phe nyl-4,5,6,7-tetrahyd ro- 1 H-p yrrolo[3,2 c] pyridine; 81-Be nzyl-3-(3-f Iuoro-phenyl)-4,5,6,7-tetrahydro-l1H-pyrrolo[3, 2 c] pyridine; 9 3-(4-Chioro-phenyi)- 1 -(2-fluoro-benzyl)-4, 5 ,6,7-tetrahydro- 1 H pyrrolo[3,2- clpyridine; 1 1 -(3-Chloro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro.1

H

pyrrolo[3,2-c]pyridine; 11 1-(2-Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro.1 H-pyrrolo[3,2 c] pyridine; 12 1-(4-Chloro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro.1

H

pyrrolo[3,2-c]pyridine; 13 1 -Benzyt-3-(2,4-dic .hloro-phenyl)-4,5,6,7.tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 141-(4-Methoxy-benzyl)-3-phenyl-4,5 ,6,7-tetrahyd ro- 1 H-pyrrolo[3,2 % c]pyridine; 15 1-( 2 -Chioro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro.1

H

pyrroto[3,2-c]pyridine; 16 1-( 2 ,4-Dichloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 14 1 -Benzyl-2-methyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 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 c]pyridine; 20 3-Benzo[1,3]dioxol-5-yl-1 -benzyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 21 1 -Benzyl- 3 -(4-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo(3,2 c]pyridine; 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 c]pyridine; 24 1 -Benzyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1

H

pyrrolo[3,2-c]pyridine; 25 1 -Benzyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 26 1 -Benzyl-3-phenyl-1, 4 ,5,6,7,8-hexahydro-pyrrolo[2,3-djazepine; 27 1 -Benzyl-3-(5-methyl-thiophen-2-yl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 28 1 -Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-pyrrolo[2,3 djazepine; 29 1 -Benzyl-3-(5-chloro-thiophen-2-y)-1,4,5,6,7,8-hexahydro-pyrrolo[2,3 oazepine; 30 1-( 4 -Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 31 1 -Benzyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine; 32 1 -Benzyl-3-(3-chloro-phenyl)- 1,4,5,6,7,8-hexahydro-pyrrolo[2,3 djazepine; 33 1 -Benzyl-3-(3-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 34 1 -Benzyl- 3 -(4-methoxy-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine; 15 3 -Benzyl-3-( 4 -chloro-phenyl)5-ethyl -4,5,6,7-tetrahydro-1

H

pyrrolo[3,2-c]pyridine; 1-Be nzyl-3-(4-chloro-phenyl)-5-isopropyl-4,5,6,7-tetrahydro- 1 H 36 pyrrolo[3,2-c]pyridine; 3-[1 -Benzyl-3-(4-chloro-phenyl)-1,4,6,7-tetrahydro-pyrrolo[3,2 c]pyridin-5-yi]-propan-1 -ol; 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-c]pyridine; 40 1-Benzyl-3-(3-chloro-4-fluoro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1

H

pyrrolo[3,2-c]pyridine; 41 1,5-Dibenzyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine; and 1 -Benzyl-5-isopropyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 42 c]pyridine. Preferred compounds, which are fused 1-substituted pyrazoles, are selected from the group consisting of: EX CHEMICAL NAME 43 1 -Benzyl-3-(4-trifluoromethyl-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6 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-flupro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 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; 16 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) phe nyl]-eth a none; 51 1-Benzyl-3-(4-trifluoromethoxy-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene; 52 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; 54 4-(1 -Benzyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl) benzonitrile; 55 1-(4-Chloro-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-Be nzyl-3-phenyl-6-propyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 58 1 -Benzyl-6-isopropyl-3-phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 59 1 -Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 60 1 -Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,5-triaza azulene; 61 3-(4-Chloro-phenyl)-1 -methyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 63 3-(4-Chloro-phenyl)-1 -ethyl-i1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 65 3-(4-Chloro-phenyl)-1 -propyl-i1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 67 1 -Butyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 17 69 3-(4-Chloro-phenyl)-i -(2-cyclohexyl-ethyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 713-(4-Chloro-phenyl)-i -phenethyl-1 ,4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 73 3-(4-Chloro-phenyl)-1 -(4-fluoro-3-methyl-benzyl)-1 ,4,5,6,7,8 hexahydro- 1,2,6-triaza-azu lene; 74 3-(4-Chloro-phenyl)-i -(3-methyl-benzyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 75 3-(4-Chioro-phenyl)-1 -(4-fluoro-benzyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 76 3-(4-Chloro-phenyl)-1 -(3-f Iuoro-benzyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 77 3-(4-Chloro-phenyl)-l -(4-methyl-benzyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 78 3-(4-Chloro-phenyl)-l -(3,4-dif luoro-benzyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 793-(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; 81 3-(4-Chloro-phenyl)-l -(3,4-dimethyl-benzyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 85 5-[3-(4-C hlo ro-ph enyl)-5,6,7,8 -tetra hydro-4 H- 1,2,6-triaza-azu le n-1 yI]-pentanoic acid methyl ester; 86 5-[3- (4-C hlo ro-ph enyi)-5,6,7,8 -tetra hyd ro-4 H-1, ,2,6-triaza-azu len -1 yl]-pentanoic acid; 87 5-[3-(4-Chloro-phenyi)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 yl]-pentan-1 -ol; 88 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1 ,2,6-triaza-azulen-1 yl]-butyric acid methyl ester; 91 4-[3-(4-C hlo ro-p he nyI)-5,6,7,8 -tetra hydro-4H-1 ,2,6-triaza-azu len- 1 yl]-butyric acid; 18 934-[3-(4-Chloro-phe nyl) -5,6 ,7,8 -tetra hyd ro-4 H- 1,2,6-triaza-azulen-1 YI]-buta n-i -ol; 96 3-(4-Chloro-phenyl)-1 -(3-fluoro-4-methoxy-benzyl)-1,4,5,6,7,8 hexahydro-1 ,2,6-triaza-azulene; 98 3-(4-Chloro-phenyi)-l -(4-nitro-benzyl)-1 ,4,5,6,7,8-hexahydro-1 ,2,6 triaza-azulene; 99 4-(3-Phenyt-5,6,7,8-tetra hydro-4H- 1,2,6-tr iaza-azulen-1 -ylmethyl) phenylamine; 100 N-[4-(3-Phenyl-5,6,7,8-tetrahydro-4H--1 ,2,6-triaza-azulen-1 ylm ethyl) -phe nyl]-methanesuIf on ami de; 101NN-[4-(3-phenyl-5,6,7,8-tetrahydro-4H-1 ,2,6-triaza-azulen-1 ylmethyl) -phe nyl]-dimethanesu Ifonam ide; 102 1 -Benzyl-3-p-toly-1 ,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azuiene; 103 3-(4-Chloro-phenyl)-1 -thlophen-2-ylmethyl-1 ,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 1041 -Benzyl-3-thiophen-2-y-1 ,4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 105 3-(4-Chloro-phenyl)-1 -(3-methoxy-benzyl)-1,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 106 3-(4-Chloro-pheny)-1 -(2-fluoro-benzyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 107 3-(4-Chloro-phenyl)-1 -(2-methyl-benzyl)-1 ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 108 3-(4-Chloro-phenyl)-l -(2,4-difluoro-benzyl)-1 ,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 109 3-(4-Chloro-phenyl)-1 -(2-methoxy-benzyl)-1 ,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 110 1 -. (2-Chloro-benzyl)-3-(4-chloro-phenyl)-1 ,4,5,6,7,8-hexahydro 1,2,6-triaza-azuiene; 1 -But-3-enyl-3-(4-chloro-phenyl)-1 ,4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 19 12 1 -(2-Bromo-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro 112 1,2,6-triaza-azulene; 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-ylmethyl)-1,4,5,6,7,8 hexahydro-1,2,6-triaza-azulene; 116 1-(3-Bromo-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 11 3-(4-Chloro-phenyl)-1 -cyclohexylmethyl-1,4,5,6,7,8-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; 1 -Benzo[1, 3 ]dioxol-5-ylmethyl-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-ylmethyl)-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; 124 3-(4-Chloro-phenyl)-1 -(3-methyl-butyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene; 125 3-(4-Chloro-phenyl)-1 -(2-trifluoromethyl-benzyl)-1,4,5,6,7,8 hexahydro-1,2,6-triaza-azulene 128 3-(4-Chloro-phenyl)-1 -(4-methoxy-2-methyl-benzyl)-1,4,5,6,7,8 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; 135 3-(4-Chloro-phenyl)-1 -pentafluorophenylmethyl-1,4,5,6,7,8 hexahydro-1,2,6-triaza-azulene; 20 1373-(4-Chloro-phenyl)-1 -(2,4,6-trifluoro-benzyl)-1 3,5,6,7,8 hexahydro-1 ,2 1 6-triaza-azu lene; 18 2 -[3-(4-Chloro-phenyI)-5,6,7,8-tetrahydro-4H-1 ,2,6-triaza-azulen-1 ylmethyi]-benzonitrule; 142 3-(4-Chioro-phenyl)-1 -naphtha le n-2-ylm ethyl -1 , 45,6,7,8 hexahydro- 1,2,6-triaza-azulene; 144 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro..4H-1,2,6-triaza-azulen-1 ______ylmethyfl-furan-2-carboxylic acid ethyl ester; 145 3-(4-Ghioro-phenyl)-1 -naphthalen-1 -ylmethyl-1 ,4,5,6,7,8 hexahydro- 1,2,6-triaza-azu le ne; 147 [ 3

-(

4 -Chloro-phenyl)-5,6,7,8..tetrahydro-4H.1 ,2,6-triaza-azulen-1 -yI] acetic acid methyl ester; 148 2

-[

3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro..4H-1,2,6-triaza-azulen-1 yl] -N-methyl-acetam ide; 150 3-(4-Chloro-phenyl)-1 -(3,4,5 -tri met hoxy-b enzyl)- 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; 1541-( 3

,

4 -Bis-benzyloxy-benzyl)-3-(4-chloro.phenyl).i,4,5,6,7,8 hexahydro-1 ,2,6-triaza-azulene; 15 3

-[

3 -(4-Chloro-phenyl)-,6,7,8-tetrahydro4Hl ,2,6-triaza-azulen-1 ylmethyl]-phenol; 157 4 -[3- (4-Ch lo ro-phenyl)-5,6,7,8 -tetra hyd ro4H 1,2,6-triaza-azu len- 1 _______yimethyl]-phenol; 158 4

-[

3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1 ,2,6-triaza-azuen-1 ylmethyl]-3-methyl-phenol; 159 4

-[

3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H.1 ,2,6-triaza-azulen-1 ylmethyl]-benzene-1 ,2-diol; 160 4

-[

3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro4Hl ,2,6-triaza-azulen-1 ylmethyll-2-fluoro-phenol; 162 2

-[

3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H.1 ,2,6-triaza-azulen-1 _______ylmethyl]-phenol; 21 1 -Benzyl-3-(4-chloro-phenyl)-6-methy..1,4,5,6,7,8-hexahydro-1 ,2,6 165 triaza-azulene; 16 1 -Benzyl-3-(4-chioro-phenyl)-6-ethyl-1 ,4,5,6,7,8-hexahydro-1 ,2,6 triaza-azulene; 167 3-(4-Chloro-phenyl)-6-(3,4-dimethoxy-benzy).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 I hexahyciro- 1,2,6-triaza-azulene; 16 1- .BenzyI-3-(4-choropheny)6(3,4-dimethoxy-benzyl)-1,4,5,6,7,8 hexahyciro- 1,2, 6-triaza-azulene; 170 (1 -Benzyl-3-(4-choro-phenyl)4,5,7,8-tetrahydro-1 H-i ,2,6-triaza azulen-6-yi]-acetic acid methyl ester; 171 2-[1 -BenzyI-3-(4-chloro-phenyl)-4,5,7,8tetrahydro-1 H-i ,2,6-triaza azulen-6-yi]-ethanol; 172 3-(4-Chloro-phenyl)-l -phenyl-1 ,4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 173 3-(4-Chloro-phenyl)-1 -( 2 -m ethyl- be nzyi)-4,5,6,7,8, 9 -hexahydrol H 1, 2

,

6 -triaza -oyc lope ntacycl oocten e; 174 3-(4-Chloro-phenyl)-l -( 2 -methyi-benzyl)-4,5,6,7,8,9-hexahydro.1 H 1 2 2 ,7-triaza-oyc lope ntacycloocte ne; 175 3-(4-Chloro-phenyl)- 1 -( 2 -methyl-benzyl)-4,5,6,7-tetrahydro.1 H _______pyrazolo[3,4-c]pyridine; 230 { 4

-[

3 -(4-Chor-pheny)-5,6,7,8-tetrahydro4Hl ,2,6-triaza-azulen-1 ylmethyl]-phenyl)-methyf -amine; 237 3-(4-Chloro-phenyl)-1 -cyclobutyl-1 4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 239 3-(4-Chloro-phenyl)-l -cyclohexyl-1 ,4,5,6,7,8-hexahydro-1 ,2,6 triaza-azulene; 254 3-(4-Chloro-phenyl)-l -cycloheptyl-1 ,4,5,6,7,8-hexahydro-1 ,2,6 triaza-azulene; 255 3-(4-Chloro-phenyl)-l -cyclooctyl-1 ,4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 22 23 1 -Benzyl-3-(4-chloro-phenyl)-i ,4,5,6,7,8-hexahydro-i ,2,6-triaza azulene citrate salt; 316 3-(4-Chloro-phenyl)-1 -pyridin-4-ylmethyl-i ,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 317 3-(4-Chloro-phenyl)-1 -pyrid in-2-yl methyl- 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-hexa hydra 1 ,2,6-triaza-azulene; 320 4 -[3-(4-Chlara-phenyl)-5,6,7,8-tetrahydr-4H-1 ,2,6-triaza-azulen-1 ylmethyl]-benzoic acid methyl ester; 321 3-(4-Chlora-phenyl)-i -(tetrahydro-pyran-4-yl)-1 ,4,5,6,7,8 hexa hydra-i ,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-Chlaro-phe nyl)-5 ,6,7,8-tetrahydra-4H-1 ,2 ,6-triaza-azulen- 1 yl]-ethyll-dimethyl-amine. 324 3-(4-Chloro-phenyl)-i -(1 -oxy-py rid in-2-yl methyl) -1, 4,5,6,7,8 hexahydro-1 ,2,6-triaza-azulene; 325 2-[1 -Benzyl-3-(4-chlara-phenyl)-4,5,7,8-tetrahydro-1 H-i 1 2,6-triaza azulen-6-yl]-acetamide; 36 3

-[

3 -(4-Chloro-phenyl)-5,6,7,8..tetrahydro..4H-i ,2,6-triaza-azulen-1 yl]-propionitrile. 3321 -( 4 -Chloro-benzyl)-3-(4-chloro-phenyl)-i ,4,5,6,7,8-hexahydra 1 ,2,5-triaza-azulene; 333 3-(4-Chloro-phenyl)-i -(4-methyl-benzyl)-i ,4,5,6,7,8-hexahydro 1 ,2,5-triaza-azulene; 34 3-(4-Chlaro-phenyl)-1 -(3,4-difluora-benzyl)-1 ,4,5,6,7,8-hexahydra 1 ,2,5-triaza-azulene; 335 3-(4-Chlora-phenyl)-i -(3-methyl-benzyl)-i ,4,5,6,7,8-hexahydro 1 ,2,5-triaza-azulene; 336 3-(4-Chloro-phenyl)-i -(3-fluoro-4-methyl-benzyl)-i ,4,5,6,7,8 336 hexa hydra-i ,2,5-t .riaza-azulene; and 23 337 3-(4-Chloro-phenyl)-1 -(4-fluoro-3-methyl-benzyl)-1,4,5,6,7,8 hexahydro-1 ,2,5-triaza-azulene. Preferred compounds, which are fused 2-substituted pyrazoles, are 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; 70 3 -(4-Chloro-phenyl)-2-(2-cyclohexyl-ethyl)-2,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 72 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-4H-1,2,6-triaza-azulen-2 yl]-pentanoic acid methyl ester; 83 5-[ 3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2 yl]-pentanoic acid; 84 5-[ 3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2 yl]-pentan-1 -ol; 89 4

-[

3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2 yl]-butyric acid methyl ester; 90 4

-[

3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2 yl]-butyric acid; 92 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2 yl]-butan-1 -ol; 94 3

-(

4 -Chloro-phenyl)-2-(3,4-difluoro-benzyl)-2,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 24 95 3(4-YC)2(4mp etylbenz4-otyl b )245678hexahydro 1,2,6-triaza-azu le ne; 973-(4-Ch loro-phenyl)-2-(3.f luo ro-4-meth oxy-be nzyl)-2,4,5,6, 7,8 h exahyd ro-1, ,2,6-triaza-azu le ne; 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)-2,4,5,6,7,8Thexahydro 1 ,2,6-triaza-azulIe ne; 127 2 -Be nzyl- 3 -(4 -c hloro-phenyl)-2,4,56,7,8 -hexahyd rol 1,2,6-triaza azu len e; 129 3

-(

4 -Ch loro-p he nyI)-2- (2,4-dif Iuoro-be nzyl)..2,4,5,6,7,8- hexahydro. 1 ,2,6-triaza-azulene; 1 30 5-[3-(4-Chloro-phenyl)-5,6 ,7,8-tetrahydro-4H- 1 ,2,6-triaza-azu Ien-2 ylm ethyl]-furan-2-carboxylic acid ethyl ester; 131 3

-(

4 -Chloro-phenyl)-2-isobutyl-2,4,5,6,78hexahydro-1,2,6-triaza azulene; 132 3

-(

4 -Chloro-phenyl)-2-(2-methoxy-benzyl)-2,4,5,6,7,8.hexahydro 1 ,2,6-triaza-azulene; 1 33 2-Benzyl-3-phenyl-2,4,5,6,7,8 -hexahydro.1 ,2,6-triaza-azulene; 136 3

-(

4 -Chloro-phenyl)-2-thbophen-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-difluorobenzyl)245678hexahydro 1 ,2,6-triaza-azulene; 141 3

-(

4 -Chloro-phenyl)-2-(2-trifluoromethy-benzyl)-2,4,5,6,78 hexahydro-1 ,2,6-triaza-azulene; 143 3

-(

4 -Ghloro-phenyl)-2-(2-ethylbutyl)2,4,5,6,7,8hexahydro-1,2,6 triaza-azulene; 146 2-Be nzo[1 , 3 ]dioxol-5-ylmethyl-3-(4-chloro.phenyl).2456,78 hexahydro-i ,2,6-triaza-azulene; 25 19 3

-(

4 -ChNo ro-p he nyl)..2.pe ntaf luorophenyl methyl2,4,56,7,8 hexahydro- 1 ,2,6-triaza-azu le ne; 151 3-(4-Chloro-phenyl)-2-naphthalen- 1 -yimethyl-2,4 ,5,6 ,7, 8-hexahydro 1 ,2,6-triaza-azu le ne; 153 3-( 4 -C h oro-p he ny)-2(3,45 tri methoxy.be nzy)2456,78 hexahydro-1 ,2,6-triaza-azulene; 155 2 -(3,4- Bis-be nzyl oxy-be nzyl) -3-(4-ch loro-phe nyl) -2,45,6,78 hexahydro-1, ,6-triaza-azu Ie ne; 1 61 4

-[

3

-(

4 -C hloro-ph enyl)-5,6,7,8-tetra hydro4H- 1,2,6-tri aza-azu len-2 yl methyl]-2-f luo ro-phe no 1; 163 4

-[

3

-(

4 -Chioro-ph enyl)-5,6,7,8-tetrahydro4 H- ,2,6-triaza-azulen-2 ____ yimethyl]-3-methyl-phenol; 164 2 -[3-( 4 -Ch loro-p hen y1) -5,6,7,8 -tetra hyd ro4H- 1, ,6-triaza-azd le n-2 y m ethyl]-phe n 1; 176 2 ,3-Diphenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 177 2 -Cyciohexyl-3-pheny-2,4,5,6,7,8hexahydrol ,2,6-triaza-azulene; 1 78 3

-(

4 -Chloro-phenyl)-2-cycohexyl.2,4,5,6,7,8hexahydrol ,2,6-triaza azulene; 17 2 -Cyclohexyl-3-(4-trif luoromethyphenyl)2,4,5,6,7,8hexahydro 1 ,2,6-triaza-azulene; 1 80 2 -Cyclopentyl-3-phenyl-2,4,5,6,7,8hexahydrol ,2,6-triaza-azulene; 181 3-( 4 -C hloro-p he nyl)-2-cyc lope ntyl.2,4,5,6,7,8- h exa hyd ro- 12,6 triaza-azulene; 1 82 2 -Cyclopentyl-3-(4-f luoro.phenyl)2,4,5,6,7,8hexahydro-1,2,6-triaza azulene; 183 2-(1 -Ethyl- propyl) -3-(3-f I uo ro-phenyl)-2,4,5,6,7,8-hexa hydrol1 ,2,6 triaza-azulene; 1 84 2-(1 -Ethyl -p ropyl) -3- (4-f luoro-p he nyl)-2,4,5,6,7, 8 -hexa hydro- 1,2,6 triaza-azulene; 15 2-(1 -Ethyl-propyl)-3.thiophen.3.yI2,4,5,6,7,8hexahydro-1,2,6 triaza-azulene; 26 186 2-(1 -Ethyl-propyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 187 3

-(

4 -Chloro-phenyl)-2-(2,2,2-trifluoro-ethyl)-2,4,5,6,7,8-hexahydro 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-sopropyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene; 191 2-(1 -Ethyl-propyl)-3-thiophen-2-yl-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-phenyl-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; 195 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-yI-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; 202 3

-(

3 -Chloro-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 203 2-Phenyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 27 204 2, 3-Dip he nyl-4,5 ,6,7-tetrahyd ro-2 H-pyrazo lo[4,3-c] pyridi ne; 205 3-Phenyl-2-(3-trif luoromethyl-phenyl)>2,4,5,6,7,8-hexahydro.1,2,6 triaza-azulene; 206 3-(4-Methoxy-phe nyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 207 2 -(4-Chloro-phenyl)-3-phenyl-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 -I1sop ropyl- 3-p-tolyl-2,4,5,6,7,s- hexahydro.1 ,2,6-t riaza-azule ne; 210 3

-(

4 -Ethyl-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro.1 ,2,6-triaza azulene; 211 3

-

4 -Chloro-phenyl)-2-isopropyl-2,4,5,6,7,8-.hexahydro.1 ,2,6-triaza 7 azulene; 212 4

-(

2 -Isopropyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulen-3-yi) benzonitrile; 232-I sopropyl-3-(4-trifluoromethyl-phe nyl)-2,4,5 ,6,7,8-hexahydro-1 ,2, 6 triaza-azulene; 214 2- Ethyl -3- p-to lyl1-2,4,5,6,7,8 -he xahyd ro-1, ,2,6-triaza-azu le ne; 215 2-tert-ButyI-3-phenyl-2,4,5,6,7,8-hexahydro.1 ,2,6-triaza-azulene; 2-tert-Butyl-3-(4-fluoro-phenyl)-2,4,5 ,6,7 ,8-hexahydro-1 ,2,6-triaza 216 azulene; 217 2 -Cyclopentyl-3-p-tolyl-2,4,5,6,7,8-hexahydrol ,2,6-triaza-azulene; 21 8 2 -CyclopentyI-3-(4trif uoromethyI.pheny).24,67,8hexahydr.. 1,2,6-triaza-azulene; 219 3

-(

3 -Chloro-phenyl)-2-cyclopentyl-2,4,5,6,7,8hexahydro-1,2,6 triaza-azulene; 220 2 -Cyclopentyl-3-(4-methoxy-pheny)-2,4,5,6,78hexahydrol ,2,6 triaza-azulene; 221 2

-(

3

,

3 -D imethy-cyc ope nty) -3-p heny-24567,8hexahyd ro- 1 ,2,6 triaza-azulene; 222 2 -(3,3-Dimethyl-cyclopentyl)-3-(4.fluoro.phenyI.2456,7,8 hexahydro-1 ,2 ,6-triaza-azulene; 28 223 3

-(

4 -Chloro-phenyl)-2-(3,3-dimethyl-cyclopentyl)-2,4,5,6,7,8. hexa hyd ro-1, ,2,6-triaza-azu le ne; 224 2 -Cyc lohexyl-3-(4-f luoro-phe nyl).2,4,5,6,7,8hexahydro.1 ,2,6-triaza azulene; 225 2 -Oycloh exyl-3-(3,4-dif luoro-phenyl)2456,78hexa hyd ro- 12,6 triaza-azulene; 226 2 -Cyclohexyl-3-p-tolyl-2,4,5,6,7,8-hexahydro.1 ,2,6-triaza-azulene; 227 2 -Cyc lo hexy1- 3- (4- met hoxy-p he nyl) -2,4,5,6,7,8hexahyd ro- 1,2,6 triaza-azulene; 228 4

-(

2 -Cyclohexyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azuien-3-y) benzonitrile; 229 3

-(

3 -C hIo ro-phe nyl)-2-cyclo hexyl -2,4,5,6,7,8 -hexahydro- 1 2,6-triaza azulene; 231 3

-(

4 -Fluo ro-phenyl)-2-isopropyl-4,5,6,7..tetrahydro..2H-pyrazolo[4,3 clpyridine;, 232 2 -Cyclopentyl-3-f uran-3-y-2,4,5,6,78hexahydro-1,2,6-triaza azulene; 233 2 -Cyclopentyl-3-thiophen-2-yI-2,4,5,6,7,8-hexahydro.1 ,2,6-triaza azulene; 24 2 -te rt- Buty-3-thiop he n-3-yi-2,4,,6,7,8hexahydro- 1,2,6-triaza azulene; 235 2-te rt-Butyi-3-f uran -3-yl-2 ,4,5,6,7,8 8-hexahyd ro- 1,2,6-t riaza-azu le ne; 236 2 -Cyclopentyl-3-(3,4-dif luoro-phenyl).2,4,,678hexahydro-1,2,6 triaza-azulene; 238 3

-(

4 -C h oro-phe nyI)-2-cyclobut-I2,4,5,6,7,8-hexahyd ro1 ,2,6-triaza azulene; 240 2 -te rt-B utyI-3-th iop he n-2-y-2,4,5,6,7,8-h exahyd ro 1 ,2,6-triaza azulene; 21 3

-(

3 -Chlo ro-4-fI u oro- phe ny).2-cyc ope nty 2,4,5,6,7,8 -he~alhyd ro 1 ,2,6-triaza-azulene; 242 2 -1sop r 6 pyI- 3 -(4-m ethoxy- phe nyl) -2,4,5,6,7,8-h exahyd ro 1, ,2,6 triaza-azu le ne; 29 23 2 -I1sop ropyl- 3 -(4-trifuo romethoxyphenyl)-2,4,5,6,7,8- h exa hyd ro 1 ,2,6-triaza-azule ne; 244 2 -Isopropyl-3-(4-isopropylphenyl)-2,4,5,6,7,8-hexahydro.1 ,2,6 triaza-azulene; 245 3

-(

4 -tert-ButyI-phenyI)-2isopropyI.2,4,,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-azuiene; 247 2- Isop ropyl1-3-o-tolyl -2,4,5,6,7, 8- hexahydro- 1,2,6-triaza-azu le ne; 28 3

-(

3

,

4 -Dichloro-phenyl)-2-isopropy24567,8hexahydro-1,2,6 triaza-azu lene;I 29 2 -Benzyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8..hexahydro-1,2,6-triaza azulene; 250 2 -Isopropyl-3-thiophen-2-yI-2,4,s ,6,7,8-hexahydro-1,2,6-triaza azulene; 213-(2-Chloro-phenyl)-2-isopropyl-2,4,5,6,7 ,8-hexahydro-1 ,2,6-triaza azulene; 22 1 -[ 4

-(

2 -Isopropyl-2,4,5,6,7,8.hexahydro.1 ,2,6-triaza-azulen-3-yI) ____ phenyi]-ethanone; 253 2 -I1sop ropyl- 3 -(4- nitro-p he nyl)-2,4,5,6,7,8hexahyd ro- 1 2,6-triaza azulene; 256 2 -Benzyl-3-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro.1 ,2,5-triaza azulene; 257 2 -Ethyl-3-(4-ethyl-phenyl)-2,4,5,6,7,8.hexahydro-1,2,6-triaza azulene; 258 4 -(2-Ethyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulen-3-y) be nzon itrile; 259 3

-(

4 -Fluoro-phenyI)-2-isopropyl-6-methyI.2,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 260 3

-(

4 -Fluoro-phenyl)-2,6-diisopropyl2,4,5,,78hexahydro-1,2,6 triaza-azulene; 261 2 -Ethyl- 3

-(

4 -isopropy-phenyl)2,4,5,6,7,8..hexahydro-1,2,6-triaza azulene; 30 262 2 -EthyI- 3

-(

4 -methoxy-phe ny)2,4,5,6,7,8- hexahyd ro-1 ,2,6-triaza azulene; 263 2 -Ethyl- 3 -(4-trif uoromethy-pheny)2,4,5,6,7,8hexahydro-1 ,2,6 triaza-azuje ne; 24 2 -EthyI-3-o-tolyl-2,4,5,6,7,8-hexa hyd ro- 1, 2,6-triaza-azu le ne; 265 3

-(

2 -C hlo ro-phe nyI)-2-ethy-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 266 2 -Ethyl-3-(2-fluoro-phe nyl)2,4,5,6,7,8- hexa hydrol1 ,2,6-triaza azulene; 267 3

-(

2

,

4 -Dic h oro-p henyl)-2- isop ropy 2,4,5,6,7,8-.hexa hyd ro- 1,2,6 triaza-azulene; 268 [4-(2- Ethyl-2,4,5,6,7,8-hexa hyd ro- 1 ,2,6-triaza-azu le n-3-yI) -phe nyl] dimethyl-amine; 269 6 -Benzyl- 3

-(

4 -fiuoro-phenyl)2.iso pro pyI-2,4,5,6,7,8- hexahyd ro 1 ,2,6-triaza-azulene; 270 3-(4- Fl uoro-phe nyl)-2-isopropyl..6-(3-phe nyl-p ropyl)-2,4,5, 6,7,8 hexahydro-1, ,2,6-triaza-azu le ne; 21 3

-(

4 -Fluoro-pheny)2isopropy6phenethyI2,4,5,67,8hexahydro 1,2,6-triaza-azulene; and 272 3

-(

4 -Fluoro-phenyl)2-isopropyl.4,5,7,8.tetrahydro.2H.1 ,2,6-triaza azulene-6-carboxylic acid tert-butyl ester. 274 3

-(

4 '-Chloro-biphenyI-4-yl)-2-(2,2,2-trifluoro..ethyl)..2,4,5,6,7,8 hexahydro-1 ,2,6-triaza-azulene; 275 3

-(

4 '-Chloro-biphenyl-4-y)-2-cyclopentyl2,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 276 2-Cyclobutyl-3-phenyl-2 ,4 ,5,6,7, 8-hexahydro-1 ,2,6-triaza-azuiene; 277 2 -CYclobuty-3-(4-fluoro-phenyl)-2,4,5,6,7,8..hexahydro-1,2,6-triaza azulene; 278 2 -CycIobutyl-3-p-tolyl-2,4,5,6,7,8..hexahydro-1 ,2,6-triaza-azulene; 279 2 -CyclobutyI-3-(4-trifluoromethyI-pheny)..2,4,5 ,6,7,8-hexahydro 1,2,6-triaza-azulene; 31 280 4-( 2 -CYClobuty-2,4,-5.6,7,8- hexa hyd ro- 1 ,2,6-triaza-azul en-3-y) benzonitrile 281 2 -Cyclop ropyl-3-phe ny-2,4,5,6,7,8-h exahyd ro- 12,6-triaza-azu le ne; 282 2 -Gyclopropyl-3-(4-fluoro-phnyl)2,4,5,6,7,8hexahydrol 1,2,6 triaza-azulene; 283 2-(1 -EthyI-propyI)-3-(4-fuoro-3-methyl-pheny)2,4,5,6,7,8 hexahydro-1 ,2,6-triaza-azulene; 284 2 -Cyc lop ropy-3- p-tolyl-2,4,5,6,78- hexa hyd ro- 1 2,6 -t riaza-azu le ne; 285 2 -Gyclopropyi-3-thiophen-3-yt-2 ,4,5,6,7, 8-hexahydro-1 ,2,6-triaza azulene; 286 4

-(

2 -Cyc lop ropyl -2,4,5,6,7,8 -h exa hyd ro- 1,2,6 -triaza-azu le n-3-y) benzonitrile; 287 6 -Benzyl1-2-isopropyl-3-phenyl-4,5,6,7tetrahydro..2H-pyrazolo[3,4 c]pyridine; 288 2-I1sop ropyi-3-ph enyl-4,5, 6,7-tetra hyd ro-2 H-py razol o[3,4-c]pyrid ine; 2896-Be nzyl-2-isopropyl-3-thiophen-3-yJ-4,5 ,6,7-tetrahydro-2H pyrazolo[3,4-c]pyridine; 290 6 -Benzyl-2-isopropyi-3-p-tolyl-4,5,6,7-tetrahydro.2 H-pyrazolo[3,4 c]pyridine. 291 6 -Benzyl-3-(4-f luoro-phenyl)-2-isopropyl..4,5,6,7tetrahydro.2H. pyrazolo[3,4-c]pyridine; 292 3-(4-Fiuoro-phenyl)-2-isopropy-456 ,7-tetrah ydro-2H -pyrazoio[3,4 c]pyridine; 293 2 -IsopropyI- 3 -p-tolyI-4,5,6,7tetrahydro2H-pyrazolo[3,4-cpyridine; 294 2 -Cyclopenty-3-(4-f uoro-pheny)-,,7,7tetramethy245,67,8 hexahydro-i ,2,6-triaza-azulene; 295 2 -Cyc lope ntly-5,5,7,7-teramet hyl-3-phe nyI.24567,8hexahyd ro. 1,2,6-triaza-azuiene; 296 2 -Isopropyl-55,7,7-tetramethy-3.pheny24567,8hexahydro. 1 ,2,6-triaza-azuiene; 297 3

-(

4 -Fluoro-pheny)-2-isopropyi5,5,7,7tetramethyl.24567,8 hexahydro-1 ,2 ,6-triaza-azulene; 32 298 2 -sec-B utyi-3-p he nyl-2,4,5,6,7,8.hexahyd ro- 1 ,2,6-triaza-azu lene; 299 2 -sec-ButyI-3-(4-f uoropheny)2,45,678.hexahydro- 1 ,2,6-triaza azulene; 300 2 -sec-ButyI-3-p-tolyl-2,4,5,6,7,8.hexahyd ro- 1 ,2,6-triaza-azu le ne; 301 2 -sec- ButyI-3-(4-trif I uoromethyl-phe ny).2,4,5,6,7,8.hexahyd ro- 1 ,2,6 triaza-azulene; 302 2 -Cyclopentyl- 3 -(4-f luoro-phenyI)-6-methyl-2,4,5,6,7,8..hexahydro 1 ,2,6-triaza-azulene; 303 4

-(

2 -i1sopropyi-2,4,5,6,7,8-hexahyd ro- 1 ,2,6-triaza-azu len -3-y) benzamlde; 304 2- Isop ropyl-3-[4-( 1 H-tetrazol-5-yI)-phenyl]-2,4,5,6,7,8..hexahydro 1 ,2,6-triaza-azulene; 305 6 -Benzyi-3-(4-fluoro-phenyl)-2-isopropyI8-m~thyI..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..methyi..2,4,5,6,7,8.hexahydro. 1 ,2,6-triaza-azulene; 308 2 -Cyc lope ntyl-3-(4-f luo ro-ph eny)7methylI2,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azulene; 309 2 -CyclopentyI-3-(4-fluoro-phenyl)-5-methyi..2,4,5,6,7,8..hexahydro 1 ,2,6-triaza-azulene; 310 2 -Cyclopentyi-7-methyl-3-p-tolyl-2,4,5,67,8hexahydro-1,2,6-triaza azu len e; 311 2 -1sop ropyI-7- meth yI-3-p he ny-2,4,5,6,7,8- h exahyd ro-1, 2,6-triaza azuiene; 312 2 -lsopropyI-5-methyi-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-azuiene; 314 3 -(4-Fluoro-phenyi)-2-isopropyl-5-methyl.2 ,4 ,5,6,7, 8-hexahydro 1 ,2,6-triaza-azulene; 33 315 2-i sopropyl-7-methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza azulene; 318 3 -(4-Chloro-phenyl)-2-pyridin-2-ylmethyl- 1,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 327 3

-[

3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2 yl]-propionitrile; 328 3

-(

4 -Chloro-phenyl)-2-cycloheptyl-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene; 329 3

-(

4 -Chloro-phenyl)-2-cyclooctyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene; 330 3

-(

4 -Chloro-phenyl)-2-(4-methyl-cyclohexyl)-2,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 331 2-Benzyl-3-(4-chloro-phenyl)-2,4,5,6-tetrahydro-pyrrolo[3,4 c]pyrazole; and 338 3

-(

4 -Fluoro-phenyl)-2-isopropyl-5,7-dimethyl-2,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene. In another embodiment of the present invention, preferred compounds are selected from the group consisting of: EX CHEMICAL NAME 59 1-Benzyl-3-(4-chloro-phenyl)-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; 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; 34 108 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-4H-1,2,6-triaza-azulen-1 ylmethyl]-2-fluoro-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; 214 2-Ethyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 257 2-Ethyl-3-(4-ethyl-phenyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene; and 273 1 -Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene citrate salt. In still another embodiment of the present invention, preferred compounds are selected from the group consisting of: EX -CHEMICAL NAME 131 3

-(

4 -Chloro-phenyl)-2-isobutyl-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 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; 184 2-(1-Ethyl-propyl)-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene; 35 186 2-(1 -Ethyl-propyi)-3-phenyi-2,4,5,6,7,8-hexahydro.1 ,2,6-triaza azuiene; 1 91 2-(1 -Ethyl-propyl)-3-thiophen-2-yl-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; 216 2 -tert-Butyl-3-(4-fuoropheny)2,4,5,6,7,8..hexahydro-1,2,6-triaza azu len e; 217 2 -Cyclopentyl-3-p-tolyi-2,4,5,6,7,8-hexahydro.1 ,2,6-triaza-azulene; 218 2 -Cyclopentyl-3-(4-trifluoromethyl.pheny).2456,7,8hexahydro. 1 ,2,6-triaza-azulene; 220 2 -Cyc lope ntyl-3- (4 -met hoxy-p he nyl) -2,4,5,6,7,8..hexa hyd rol 1 2,6 triaza-azuiene; 236 2 -Cyciopentyi-3-(3,4-diluoro-phe nyl)-2,4,5 ,6,7,8-hexahydro- 1,2,6 triaza-azuiene; 238 3-(4-Chloro-phenyi)-2-cyclobutyi-2,4 ,5 ,6,7,8-hexahydro-1 ,2,6-triaza azuiene; 241 3

-(

3 -Chloro- 4 -fiuoro-phenyl)-2-cyclopentyl..2,4,5,6,7,8-hexahydro. 1 ,2,6-triaza-azuiene; 242 2 -isopropyl-3-(4-methoxy-phenyg)..2,4,5,6,7,8.hexahydro-1 ,2,6 triaza-azulene, 277 2 -Cyciobutyl-3-(4-fluoro-phenyl).2 4,5,6,7,8-hexahydro- 1,2,6-triaza azulene; 278 2-Cyciobutyl-3-p-tolyl-2 ,4,5,6,7 ,8-hexahydro-1 ,2,6-triaza-azulene; 279 2 -Cyciobuty-3-(4-trifuoromethy-pheny)245678hexahydro 1 ,2,6-triaza-azuiene; 284 2 -Cycilop ropy-3-p-toyl -2,4,5,6,7,8h exa hyd rol 1,2,6-t ri aza-azuIe n e; 300 2 -sec-Butyl-3-p-toiyi-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azuiene; 302 2 -Cyciopenty-3-(4-f luoro-pheny)-6-methy[2456,7,8hexahydro 1 ,2,6-triaza-azulene; 306 3

-(

4 -Fluoro-pheny)-2-isopropyl8methyi-2,4,5,6,7,8-hexahydro 1 ,2,6-triaza-azuiene; and 36 310 2 -Cyclopentyl-7-methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. In yet another embodiment of the present invention preferred compounds are selected from the group consisting of: EX CHEMICAL NAME 47 1 -Benzyl-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 -Isopropyl-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; 211 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 -Isopropyl- 3

-(

4 -trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene; 232 2 -Cyclopentyl-3-furan-3-yl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene; 233 2 -Cyclopentyl-3-thiophen-2-yi-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; 37 300 2 -sec-Butyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1, 2 ,6-trlaza-azulene; and 315 2-1sopropyl-7-methyl-3-p-tolyl-2,4,5,6,7,8- hexahydro-1,2,6-triaza azulene. The features and advantages of the invention are apparent to one of ordinary skill in the art. Based on this disclosure, including the summary, detailed description, background, examples, and claims, one of ordinary skill in 5 the art will be able to make modifications and adaptations to various conditions and usages. Publications described herein are incorporated by reference in their entirety. The fused heterocyclic compounds of formulas (1), (11), and (Ill) may be prepared by a number of reaction schemes. Access to compounds of formula 10 (1) Is described in Scheme 1. Preparation of compounds of formula (11) Is described in Schemes 2, 3, 5, and 6. Synthesis of compounds of formula (Ill) is shown in Schemes 3 and 4. Persons skilled in the art will recognize that certain compounds are more advantageously produced by one scheme as compared to the other. 15 Scheme 1 O CYC-(ALK)q-N Ar NO 2

R

2 CYC-(ALK)q-NH 2

R

2 CYC-(ALK)g-N Ar G G N (IV) (VI) G (Vill) R 2 2 CYC-(ALK)-N ' Ar (R 1 )=O CYC-(ALK)F--N N Ar

-(X)-

)n or on ( mNH

R

1 X R (lX) (XI) (1) Referring to Scheme 1, compounds of formula (1) may be prepared from compounds of formula (IV). The amine moiety in compounds of formula (IV) can be suitably protected, shown by substituent G, as an alkyl or benzyl amine, amide, carbamate or other groups such as those described in "Protecting Groups In Organic Synthesis", 3 rd ed.; T.W. Greene and P.G.M. Wuts, John Wiley & Sons, 1999 (G is -C 1

.

6 alkyl, -COOC 1

.

6 alkyi, -(C=O)Cl.6alkyl, or benzyl 5 unsubstituted or substituted with -OC 1

.

6 alkyl or -C1.

6 alkyl). A preferred protecting group would be the t-butyl carbamate (Boc) group. The carbonyl functional group of compound (IV) can be treated with a primary amine of type (V), in a suitable solvent like THF, toluene, benzene, methanol or ethanol at temperatures between 20 and 110 OC with removal of water by either Dean 10 Stark apparatus or by the addition of a dehydrating agent such as SiO 2 , MgSO 4 , CuSO 4 , Ti(O-iPr) 4 or 4 A molecular sieves to form the corresponding Mines of type (VI). Preferred solvents are toluene and ethanol with preferred dehydrating agents being S10 2 and 4 A molecular sieves. One skilled In the art would recognize that the imInes of type (VI) might exist as more than one 15 tautomeric form. Compounds of type (VI) can then be treated with a nitro olefin of type (VII) to give pyrrole compounds of formula (VIII). One skilled in the art would recognize that Imines of formula (VI), existing as more that one enamine tautomer, would give rise to regloisomers upon treatment with a nitro olefin of type (VII) depending on the structure of the compound of formula (IV). The 20 protecting group on the nitrogen can either be removed using generally accepted methods or, depending on the type of group involved, can be converted directly to compounds of formula (1). More specifically, a group such as a t-butyl carbamate can be removed with an acid like trifluoroacetic acid or hydrochloric acid and the like in a solvent such as CH 2

CI

2 , ethanol or methanol 25 to afford compounds of formula (IX). It will be generally recognized that compounds of formula (IX) represent a subset of compounds of formula (I) wherein R' is equal to H. Compounds of formula (IX) and (1) may be converted to their corresponding salts using methods known to those skilled in the art. Compounds such as (1) can be prepared from compounds of type (IX) 30 using conventional synthetic methods such as alkylation or reductive amination. Thus, treatment of compounds of formula (IX) with a compound of formula (X) containing a carbonyl group in the presence of a reductant such as NaBH 4 , NaBH 3 CN, NaBH(OAc) 3 or hydrogen gas in the presence of a catalyst 39 in a solvent such as CH 2 Cl 2 , DCE, THF, ethanol, methanol or similar will afford compounds of formula (1). One skilled in the art will recognize that the addition of acid to decrease the pH of the reaction mixture to less than pH 7 may be required. Examples of acids may include AcOH, Ti(O-iPr) 4 , trifluoroacetic acid 5 or hydrochloric acid and the like. In addition, compounds such as (IX) can be treated with an alkylating agent of type (XI). For example, treatment with an alkyl chloride, bromide, iodide, mesylate or tosylate (wherein X is Cl, Br, I, OMs, OTs, or the like) in solvent such as DMF, DMA, THF or ethanol and in the presence of a base like NaHCO 3 , Na 2

CO

3 , K 2

CO

3 or Cs2CO3 will give 10 compounds of formula (1). Scheme 2 0 H H o OH 2 Nt HN'N O CYC-(ALK)q-X CYC-(ALK)q-N .,N 0 ( N, 'P mN 'p G G (XII) (XIII) (XV) N -OTfN CYC-(ALK)-N Ar-B(OR) 2 CYC-(ALK)-N Ar ( QM )p ~(XV) QrP30 G ( GN (XVI) 'G (XVIII) CYC-(ALK) N A( R CYC -(ALK) N Ar )p ~ or ) (mNH RIX (inN, (XIX) (XI) R1 Referring to Scheme 2, compounds of formula (II) can be prepared from 15 compounds of formula (XII). As in Scheme 1, the amine moiety in compounds of formula (XII) can be suitably protected, shown by substituent G, as an alkyl or benzyl amine, amide, carbamate or other groups such as those described in "Protecting Groups In Organic Synthesis", 3 rd ed.; T.W. Greene and P.G.M. Wuts, John Wiley & Sons, 1999. A preferred protecting group would be the t 40 butyl carbamate (Boc) group. The condensation of hydrazine with compounds of formula (XII) in a solvent like methanol, ethanol, isopropanol or t-butyl alcohol at temperatures from 20 to 80 0C will form compounds of type (XIII). One skilled it the art will recognize that compounds of formula (XIII) may exist 5 in more that one resonance form. More specifically, compounds of formula (XIII) are tautomeric with the corresponding 3-hydroxypyrazoles. Compounds such as (XIII) can be treated with an alkylating agent such as formula (XIV) to afford compounds of type (XV). For example, treatment with an alkyl or benzyl chloride, bromide, iodide, mesylate or tosylate (wherein X is CI, Br, I, OMs, 10 OTs, or the like) in DMF, DMA, THF or ethanol In the presence of a base like NaHCO 3 , Na 2

CO

3 , K 2

CO

3 , NaH, potassium tert-butoxide, or Cs2CO3 will afford compounds of formula (XV). One skilled In the art will recognize that the alkylation of compounds of formula (XIII) may give rise to regioisomers. Compounds of type (XV) can be converted into a precursor for transition metal 15 catalyzed cross-coupling reactions, such as Stille, Suzuki, Negishi or other such coupling reactions known to one skilled in the art. For example, treatment with POCl 3 , PC 3 , PCI 5 , PBr 3 or POBr 3 can afford the corresponding 3 halopyrazoles. A preferred method would involve treatment with a triflating agent such as trifluoromethanesulfonic anhydride or N 20 phenyltrifluoromethanesulfonimide in DCE, CH 2

CI

2 , THF or the like in the presence of a base like pyridine, triethylamine or diisopropylethylamine to provide pyrazole triflates of formula (XVI). Treatment of triflates of formula (XVI) with an organoboron compound of formula (XVII) in the presence of a catalyst like Pd(PPh 3

)

4 , PdCl 2 (PPh 3

)

2 , PdCl 2 (Po-tol 3

)

2 , PdCl 2 (dppe) or 25 PdCl 2 (dppf) in a solvent such as THF, 1,4-dioxane, DMA, DMF, DME, toluene, toluene/ethanol, or toluene/H 2 0 mixtures, in the presence of a base such as Na 2

CO

3 , K 2

CO

3 , Cs 2

CO

3 , K 3

PO

4 , KF, CsF, KOAc or the like will afford compounds of formula (XVIII). Preferred catalysts are Pd(PPh 3

)

4 and PdCI 2 (dppf), with or without additives such as dppf and catalytic Bu 4 NBr. 30 Preferred solvents include THF, 1,4-dioxane, toluene, and toluene/H 2 0 mixtures with preferred bases being Na 2

CO

3 , K 2

CO

3 , Cs 2

CO

3 , and KGP0 4 . The protecting group on the nitrogen of compounds of formula (XVIII) may be removed using generally accepted methods, which one skilled in the art would 41 recognize. More specifically, a group such as a t-butyl carbamate can be removed with an acid like trifluoroacetic acid or hydrochloric acid and the like in a solvent such as CH 2 Cl 2 , ethanol or methanol to afford compounds of formula (XIX). Compounds of formula (XIX) or (11) may be converted to their 5 corresponding salts using methods known to those skilled in the art. For example, amines of formula (XIX) can be treated with citric acid in a solvent such as methanol to provide the corresponding citrate salt. It will be generally recognized that compounds of formula (XIX) represent a subset of compounds of formula (II) wherein R' is equal to H. 10 Compounds such as (II) can be prepared from compounds of type (XIX) using conventional synthetic methods such as alkylation or reductive amination. Thus, treatment of compounds of formula (XIX) with a compound of formula (X) containing a carbonyl group in the presence of a reductant such as NaBH 4 , NaBH 3 CN, NaBH(OAc) 3 or hydrogen gas in the presence of a catalyst 15 in a solvent such as CH 2

CI

2 , DCE, THF, ethanol, methanol or similar will afford compounds of formula (II). One skilled in the art will recognize that the addition of acid to decrease the pH of the reaction mixture to less than pH 7 may be required. Examples of acids may include AcOH, Ti(O-iPr) 4 , trifluoroacetic acid or hydrochloric acid and the like. In addition, compounds such as (XIX) can be 20 treated with an alkylating agent of type (XI). For example, treatment with an alkyl chloride, bromide, iodide, mesylate or tosylate (wherein X is Cl, Br, I, OMs, OTs, or the like) in solvent such as DMF, DMA, THF or ethanol and in the presence of a base like NaHCO 3 , Na 2

CO

3 , K 2

CO

3 or Cs 2

CO

3 will give compounds of formula (II). 42 Scheme 3 0 )p 0 (R)-N N21-1-r Ar (XX) XXII) O N 0 Ar HN-Ar

NH

2

NH

2 CYC(ALK)-X 3 )(XIV) (R ) N

(R

3 )r j\ N o GG N ClIAr (XXIV) (XXV)

-

)p (XXII) (R3)r \N (XXI) CYC-(ALK)q N'N Ar CYC-(ALK)-N Ar CYC-(ALK)--N' Ar (R3)r mN (R3)r ) N P(3rN (XXVI) (XVIII) (XIX)

(R

1 )=O (X) or

R

1 X (X 1) CYC-(ALK)q CYC-(ALK)q N'N Ar (R1)=O N Ar CYC-(ALK)-N' Ar )n or .)

(R

3 )+NH

R

1 X (R)r N (XXVil) (XI) (1)R1 R11 Referring to Scheme 3, compounds of formula (11), (1ll), (XXVII), and 5 (XXVIII) can be prepared as described. The amine moiety in compounds of formula (XX) can be suitably protected, shown by substituent G, as an alkyl or benzyl amine, amide, carbamate or other groups such as those described in "Protecting Groups In Organic Synthesis", 3 rd ed.; T.W. Greene and P.G.M. Wuts, John Wiley & Sons, 1999. A preferred protecting group would be the t 10 butyl carbamate (Boc) group. The carbonyl functional group of compound (XX) 43 can be treated with a saturated secondary amine, such as morpholine, in a suitable solvent like toluene or benzene at temperatures between 20 and 110 C with removal of water by a Dean-Stark apparatus with or without an acid catalyst such as TsOH, will afford the corresponding enamines of type (XXI). 5 One skilled in the art would recognize that enamines of type (XXI) might exist as more that one enamine regioisomer depending on the structure of the compound of formula (XX). Treatment of enamines (XXI) with a benzoyl chloride will afford the diketone compounds of formula (XXIV). Additionally, the carbonyl functional group of compound (XX) can be treated with a diazoketone 10 in the presence of a Lewis acid, such as BF 3 , to give the diketone compounds (XXIV) directly. The condensation of hydrazine with compounds of formula (XXIV) in a solvent like methanol, ethanol, isopropanol or t-butyl alcohol at temperatures from 20 to 80 *C will form pyrazole compounds of type (XXV). Compounds such as (XXV) can be treated with an alkylating agent of formula 15 (XIV). For example, treatment with an alkyl or benzyl chloride, bromide, iodide, mesylate or tosylate (wherein X is Cl, Br, I, OMs, OTs or the like) in DMF, DMA, THF or ethanol in the presence of a base like NaHCO 3 , Na 2

CO

3 , NaH, potassium tert-butoxide, K 2

CO

3 or Cs 2

CO

3 will afford a mixture of compounds of formula (XXVI) and (XVIII). One skilled in art would recognize that a mixture 20 of compounds of formula (XXVI) and (XVIII) may be separated by chromatographic or crystallization techniques. The protecting group on the nitrogen may be removed using generally accepted methods, which one skilled in the art would recognize. More specifically, a group such as a t-butyl carbamate can be removed from compounds of formula (XXVI) and (XVIII) with 25 an acid like trifluoroacetic acid or hydrochloric acid and the like in a solvent such as CH 2 Cl 2 , ethanol or methanol to afford compounds of formula (XXVII) and (XIX) respectively. Compounds of formula (XXVII), (XIX), (1l), or (Ill) may be converted to their corresponding salts using methods known to those skilled in the art. It will be generally recognized that compounds of formula (XXVII) 30 and (XIX) represent subsets of compounds of formula (Ill) and (II) respectively, wherein R' is equal to H. Compounds such as (II) and (Ill) can be prepared from compounds of formula (XIX) and (XXVII) respectively, using conventional synthetic methods 44 such as alkylation or reductive amination. Thus, treatment of compounds of formula (XIX) with a compound of formula (X) containing a carbonyl group in the presence of a reductant such as NaBH 4 , NaBH 3 CN, NaBH(OAc) 3 or hydrogen gas in the presence of a catalyst in a solvent such as CH 2 Cl 2 , DCE, 5 THF, ethanol, methanol or similar will afford compounds of formula (11). One skilled in the art will recognize that the addition of acid to decrease the pH of the reaction mixture to less than pH 7 may be required. Examples of acids may include AcOH, Ti(O-iPr) 4 , trifluoroacetic acid or hydrochloric acid and the like. In addition, compounds such as (XIX) can be treated with an alkylating 10 agent of type (XI). For example, treatment with an alkyl chloride, bromide, iodide, mesylate or tosylate (wherein X is Cl, Br, I, OMs, OTs, or the like) in solvent such as DMF, DMA, THF or ethanol in the presence of a base like NaHCO 3 , Na 2

CO

3 , K 2

CO

3 or Cs 2

CO

3 will give compounds of formula (11). Scheme 4 0 Et CYC-(ALK)q CYC-(ALK)q R3 CYC-(ALK)q-NHNH 2 N'N N N OTf )n (XXVIII) \ ( nN * (R)r ) (R 3 )r . G (inMN. iN (XII) G G (XXIX) (XXX) CYC-(ALK)q CYC-(ALK)q CYC-(ALK)q Ar-B(OR) 2 N'N Ar N'N Ar (R 1 )=O N' Ar (XV )r) R 3 ) (R(R)r M 3 G R 1 X ( m 1 15 (XXVI) (XXVlI) (XI) (111) Referring to Scheme 4, compounds of formula (Ill) can be prepared as outlined. The amine moiety in compounds of formula (XII) can be suitably protected, shown by substituent G, as an alkyl or benzyl amine, amide, 20 carbamate or other groups such as those described in "Protecting Groups In Organic Synthesis", 3 rd ed.; T.W. Greene and P.G.M. Wuts, John Wiley & Sons, 1999. The condensation of an alkyl or aryl hydrazine of type (XXVIII), or the salt thereof, with compounds of formula (XII) in a solvent like methanol, 45 ethanol, isopropanol or t-butyl alcohol at temperatures from 20 to 80 *C with or without a base such as NaHCO 3 , Na 2

CO

3 , K 2

CO

3 , Cs 2

CO

3 , triethylamine or diisopropylethylamine will afford compounds of formula (XXIX). Preferred solvents are ethanol and t-butyl alcohol with preferred bases being 5 triethylamine and diisopropylethylamine. Compounds of formula (XXIX) can be converted into a precursor for transition metal-catalyzed cross-coupling reactions, such as Stille, Suzuki, Negishi or other such coupling reactions known to one skilled in the art. For example, treatment with POCIS, PCI 3 , PCI 5 , PBr 3 or POBr 3 can afford the corresponding 3-halopyrazoles. A preferred 10 method would involve treatment with a triflating agent such as trifluoromethanesulfonic anhydride or N-phenyltrifluoromethanesulfonimide in DCE, CH 2

CI

2 , THF or the like in the presence of a base like pyridine, triethylamine or diisopropylethylamine to provide pyrazole triflates of formula (XXX). Treatment of triflates of formula (XXX) with an organoboron compound 15 of formula (XVII).in the presence of a catalyst like Pd(PPh 3

)

4 , PdCl 2 (PPh 3

)

2 , PdCl 2 (Po-tol 3

)

2 , PdCl 2 (dppe) or PdCI 2 (dppf) in a solvent such as THF, 1,4 dioxane, DMA, DMF, DME, toluene, toluene/ethanol, or toluene/H 2 0 mixtures, in the presence of a base such as Na 2

CO

3 , K 2

CO

3 , CS 2

CO

3 , K 3

PO

4 , KF, CsF, KOAc or the like will afford compounds of formula (XXVI). Preferred catalysts 20 are Pd(PPh 3

)

4 and PdCl 2 (dppf), with or without additives such as dppf and catalytic Bu 4 NBr. Preferred solvents are THF, 1,4-dioxane, toluene, and toluene/H 2 0 mixtures with preferred bases being Na 2

CO

3 , K 2

CO

3 , Cs 2

CO

3 , and

K

3

PO

4 . The protecting group on the nitrogen of compounds of formula (XXVI) may be removed using generally accepted methods, which one skilled in the 25 art would recognize. More specifically, a group such as a t-butyl carbamate can be removed with an acid like trifluoroacetic acid or hydrochloric acid and the like in a solvent such as CH 2

CI

2 , ethanol or methanol to afford compounds of formula (XXVII). Compounds of formula (XXVII) or (ll) may be converted to their corresponding salts using methods known to those skilled in the art. It will 30 be generally recognized that compounds of formula (XXVII) represent a subset of compounds of formula (ll) wherein R' is equal to H. Compounds such as (Ill) can be prepared from compounds of type (XXVII) using conventional synthetic methods such as alkylation or reductive 46 amination. Thus, treatment of compounds of formula (XXVII) with a compound of formula (X) containing a carbonyl group in the presence of a reductant such as NaBH 4 , NaBH 3 CN, NaBH(OAc) 3 or hydrogen gas in the presence of a catalyst in a solvent such as CH 2

CI

2 , DCE, THF, ethanol, methanol or similar 5 will afford compounds of formula (ll). One skilled in the art will recognize that the addition of acid to decrease the pH of the reaction mixture to less than pH 7 may be required. Examples of acids may include AcOH, Ti(O-iPr) 4 , trifluoroacetic acid or hydrochloric acid and the like. In addition, compounds such as (XXVII) can be treated with an alkylating agent of type (XI). For 10 example, treatment with an alkyl chloride, bromide, iodide, mesylate or tosylate (wherein X is Cl, Br, I, OMs, OTs, or the like) in solvent such as DMF, DMA, THF or ethanol in the presence of a base like NaHCO 3 , Na 2

CO

3 , K 2

CO

3 or Cs 2

CO

3 will afford compounds of formula (111). Scheme 5 CYC-(ALK)q--N' Ar CYC-(ALK)-N'N Ar mm 0)P ))P (XXXI) (XXXII) (XXXI1I CYC-(ALK)g-N N Ar CYC-(ALK)g-N'N Ar CYC-(ALK)g-NN Ar )p )P )P (m\ mNH mN 15 (XXXIV) N-OH (XIX) (1)R Referring to Scheme 5, in an alternative embodiment, compounds of formula (1l) may be prepared from a ketone of formula (XXXI). A ketone of formula (XXXI) may be converted to the pyrazole of formula (XXXII) according 20 to the procedure shown in Scheme 3 for the conversion of a compound of formula (XX) to a compound of formula (XVIII). A compound of formula (XXXIII) may be prepared from a compound of formula (XXXII) upon treatment with aqueous acid. For example, treatment of a compound of formula (XXXII) with HCI in aqueous THF at elevated temperatures will afford compounds of 25 formula (XXXIII). A ketone of formula (XXXIII) may be converted to an oxime 47 of formula (XXXIV) by treatment with hydroxylamine, preferably upon treatment with hydroxylamine in pyridine. Compounds of formula (XXXIV) may exist as a single isomer or mixture of stereoisomers. Treatment of an oxime of formula (XXXIV) with a hydride reducing agent can afford compounds of formula (XIX). 5 In a preferred embodiment, the reducing agent is diisobutylaluminum hydride in

CH

2

CI

2 . Conversion of compounds of formula (XIX) to compounds of formula (II) can be effected using the methods described in Scheme 3. Scheme 6 H HN N O HN' OTf CYC-(ALK)-N' OTf PhN(SO 2

CF

3

)

2 3 CYC4ALK)q-X

(R

3 Rr3)r N )p (XIV) G G G (X111) (XXXV) (XVI) 10 Referring to Scheme 6, in an alternative embodiment, compounds of formula (XIX) may also be prepared as outlined. The amine moiety in compounds of formula (X111) can be suitably protected, shown by substituent G, as an alkyl or benzyl amine, amide, carbamate or other groups such as those described in "Protecting Groups In Organic Synthesis", 3 rd ed.; T.W. Greene 15 and P.G.M. Wuts, John Wiley & Sons, 1999. Preferably, the sequence outlined in Scheme 6 may be employed for compounds where p = 1, m = 2, and G = t-butyl carbamoyl. Treatment of pyrazolones of formula (XIII) with a triflating agent such as N-phenyltrifluoromethanesulfonimide or trifluoromethanesulfonic anhydride in pyridine or another non-nucleophilic 20 amine base gives pyrazole triflates of formula (XXXV). Compounds such as (XXXV) can be treated with an alkylating agent of formula (XIV). For example, treatment with an alkyl or benzyl chloride, bromide, iodide, mesylate or tosylate (wherein X is Cl, Br, I, OMs, OTs or the like) in DMF, DMA, THF or ethanol in the presence of a base like NaHCO 3 , Na 2

CO

3 , NaH, K 2

CO

3 , Cs 2

CO

3 , or 25 potassium tert-butoxide will afford compounds of formula (XVI). Preferably, alkylation is affected using alkylating agents such as benzyl bromide in the presence of a suitable base such as potassium tert-butoxide. Pyrazoles of formula (XVI) can be carried forward as described in Scheme 2 to provide compounds of formula (XIX) and (11). 48 The compounds of the present invention are serotonin receptor modulators, and as such, the compounds are useful in the treatment of serotonin-mediated disease states. Particularly, the compounds may be used in the treatment or prevention of CNS disorders, such as sleep disorders, 5 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 10 mediated hypertension, sleep/wake disturbances, jetlag, and circadian rhythm abnormalities. The compounds may also be used in the treatment and prevention 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 15 related to the gastrointestinal and vascular systems. In addition, compounds of the present invention may be used in the treatment or prevention of a range of ocular disorders including glaucoma, optic neuritis, diabetic retinopathy, retinal edema, and age-related macular degeneration. The compounds of the present invention are 5-HT 7 modulators and 20 many are 5-HT 7 antagonists. As such, the compounds are useful in the treatment of 5-HT 7 -mediated disease states. Where the compounds possess substantial 5-HT 7 antagonist activity, they may be particularly useful in the treatment or prevention of depression/anxiety, sleep/wake disturbances, jetlag, migraine, urinary incontinence, gastric motility, and irritable bowel disorders. 25 Many of the compounds of the present invention are 5-HT 2 modulators and many are 5-HT 2 antagonists. As such, the compounds are useful in the treatment of 5-HT 2 -mediated diseases and conditions. Where the compounds possess substantial 5-HT 2 antagonist activity, they may be particularly useful in the treatment or prevention of depression/anxiety, generalized anxiety disorder, 30 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. 49 It is anticipated that the compounds of the invention can be administered by oral or parenteral routes, including intravenous, intramuscular, intraperitoneal, subcutaneous, rectal and topical administration, and inhalation. For oral administration, the compounds of the invention will generally be 5 provided in the form of tablets or capsules or as an aqueous solution or suspension. Tablets for oral use may include the active ingredient mixed with pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives. Suitable inert diluents include 10 sodium and calcium carbonate, sodium and calcium phosphate and lactose. Cornstarch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatin. The lubricating agent, if present, will generally be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate, to 15 delay absorption in the gastrointestinal tract. Capsules for oral use include hard gelatin capsules in which the active ingredient is mixed with a solid diluent and soft gelatin capsules wherein the active ingredient is mixed with water or an oil such as peanut oil, liquid paraffin or olive oil. For intramuscular, intraperitoneal, subcutaneous and intravenous use, the compounds of the 20 invention will generally be provided in sterile aqueous solutions or suspensions, buffered to an appropriate pH and isotonicity. Suitable aqueous vehicles include Ringer's solution and isotonic sodium chloride. Aqueous suspensions according to the invention may include suspending agents such as cellulose derivatives, sodium alginate, polyvinyl-pyrrolidone and gum tragacanth, and a 25 wetting agent such as lecithin. Suitable preservatives for aqueous suspensions include ethyl and n-propyl p-hydroxybenzoate. Effective doses of the compounds of the present invention may be ascertained by conventional methods. The specific dosage level required for any particular patient will depend on a number of factors, including severity of 30 the condition being treated, the route of administration and the weight of the patient. In general, however, it is anticipated that the daily dose (whether administered as a single dose or as divided doses) will be in the range 0.01 to 1000 mg per day, more usually from 1 to 500 mg per day, and most usually 50 from 10 to 200 mg per day. Expressed as dosage per unit body weight, a typical dose will be expected to be between 0.0001 mg/kg and 15 mg/kg, especially between 0.01 mg/kg and 7 mg/kg, and most especially between 0.15 mg/kg and 2.5 mg/kg. 5 EXAMPLES In order to illustrate the invention, the following examples are included. These examples do not limit the invention. They are only meant to suggest a method of practicing the invention. Those skilled in the art may find other 10 methods of practicing the invention, which are obvious to them. However, those methods are deemed to be within the scope of this invention. Protocol for Preparative Reversed-Phase HPLC Gilson@ 15 Column: YMC-Pack ODS-A, 5 Rm, 75x30 mm Flow rate: 25 mLmin Detection: X = 220 & 254 nm Gradient (acetonitrile/water, 0.05% trifluoroacetic acid) 1) 0.0 min 15% acetonitrile/85% water 20 2) 20.0 min 99% acetonitrile/1% water Protocol for HPLC (Reversed-Phase) Method A: Hewlett Packard Series 1100 Column: Agilent ZORBAX@ Bonus RP, 5 gim, 4.6x250 mm 25 Flow rate: 1 mLmin Detection: % = 220 & 254 nm Gradient (acetonitrile/water, 0.05% trifluoroacetic acid) 1) 0.0 min 1% acetonitrile/99% water 2) 20.0 min 99% acetonitrile/1% water 30 Method B: Hewlett Packard HPLC Column: Agilent ZORBAX@ Eclipse XDB-C8, 5 pm, 4.6x150 mm Flow rate: 1 mL/min 51 Detection: X = 220 & 254 nm Gradient (acetonitrile/water, 0.05% trifluoroacetic acid) 1) 0.0 min 1% acetonitrile/99% water 2) 8.0 min 99% acetonitrile/1% water 5 3) 12.0 min 99% acetonitrile/1% water Protocol for Preparative SF0 Thar Technologies@ Column: Chiracel AD, 10 Rm, 250x20 mm Flow rate: 37gm/min 10 Detection: X = 220 & 254 nm Mobile phase: Isocratic 30% IPA/ 70% C02 Pressure: 150 Bar Temperature: 3 5 *C Protocol for Analytical SFC 15 Jasco@ Column: Chiracel AD, 10 gm, 250x4.6 mm Flow rate: 1 gm/min Detection: X = 220 & 254 nm Mobile phase: Isocratic 30% IPA/ 70% C02 20 Pressure: 150 Bar Temperature: 35 *C Mass spectra were obtained on an Agilent series 1100 MSD using electrospray ionization (ESI) in either positive or negative modes as indicated. 25 Thin-layer chromatography was performed using Merck silica gel 60 F 254 2.5 cm x 7.5 cm 250 pm or 5.0 cm x 10.0 cm 250 pm pre-coated silica gel plates. Preparative thin-layer chromatography was performed using EM Science silica gel 60 F 2 5 20 cm x 20 cm 0.5 mm pre-coated plates with a 20 cm x 4 cm concentrating zone. 30 NMR spectra were obtained on either a Bruker model DPX400 (400 MHz), DPX500 (500 MHz), or DPX600 (600 MHz) spectrometer. The format of the 'H NMR data below is: chemical shift in ppm down field of the tetramethylsilane reference (multiplicity, coupling constant Jin Hz, integration). 52 Example 1 NO2 H 1-Benzyl-3-(4-nitro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 5 Step A. 1-Benzvl-3-(4-nitro-phenvl)-1, 4 ,67-tetrahdro-pyrrolof3,2-clpvridine-5 carboxylic acid tert-butyl ester. To a stirred solution of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester (0.69 g) in toluene (5 mL) was added 378 pL of benzylamine. The mixture was stirred for 10 min and then 0.70 g of silica gel (SiO 2 ) was added. After stirring at RT for 8 h, 0.77 g of 1 -nitro-4-(2-nitro-vinyl) 10 benzene in toluene (5 mL) was added and the mixture was stirred for 14 h at RT. The mixture was then filtered through diatomaceous earth and the filtrate was concentrated in vacuo. Chromatography on SiO 2 (8 to 20% EtOAc/hexanes) afforded 0.48 g of the desired compound. MS (ESI): exact mass calculated for C 25

H

27

N

3 0 4 , 433.20; found, m/z 434.2 [M+H]*, 456.2 15 [M+Na]*. Step B. To a stirred solution of 0.20 g of the above compound in a 10:1 mixture of CH 2

CI

2 /MeOH (6 mL) was added 1.9 mL of 1.0 M HCI in Et 2 0. After stirring for 12 h at RT, a white solid had formed, which was collected by filtration to afford 0.11 g of the title compound. MS (ESI): exact mass 20 calculated for C 20

H

19

N

3 0 2 , 333.15; found, rn/z 334.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 8.26-8.21 (m, 2H), 7.59-7.55 (m, 2H), 7.42 (s, 1 H), 7.36 (t, J= 7.4 Hz, 2H), 7.30 (t, J= 7.4 Hz, 1 Hz), 7.20 (d, J= 7.4 Hz, 2H), 5.19 (s, 2H), 4.44 (s, 2H), 3.53 (t, J= 6.3 Hz, 2H), 2.89 (t, J= 6.3 Hz, 2H). 25 Examples 2-25 were prepared according to the procedure described in Example 1, with alterations as noted. 53 Example 2 F N C1 H 1-Benzyl- 3

-(

3 -chloro-4-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. 5 The title compound (0.18 g) was prepared from 0.54 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 293 pL of benzylamine, and 0.62 g of 2-chloro 1-fluoro-4-(2-nitro-vinyl)-benzene. MS (ESI): exact mass calculated for

C

20

H

8 1CIFN 2 , 340.11; found, m/z 341.1 [M+H]*, 343.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.45-7.43 (m, 1H), 7.36-7.16 (m, 8H), 5.15 (s, 2H), 4.35 (s, 10 2H), 3.50 (t, J= 6.3 Hz, 2H), 2.85 (t, J= 6.3 Hz, 2H). Example 3 OH N H 4-(1 -Benzyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridin-3-yl)-phenol. 15 The title compound (0.09 g) was prepared from 1.22 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 856 pL of benzylamine, and 1.29 g of 4-(2-nitro vinyl)-phenol, which was added in EtOH (12 mL). MS (ESI): exact mass calculated for C 20

H

20

N

2 0, 304.16; found, m/z 305.2 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.35-7.32 (m, 2H), 7.29-7.25 (m, 2H), 7.17-7.14 (m, 4H), 6.98 20 (s, 1H), 6.80-6.77 (m, 2H), 5.12 (s, 2H), 4.31 (s, 2H), 3.49 (t, J= 6.3 Hz, 2H), 2.85 (t, J= 6.3 Hz, 2H). Example 4 0 N CF 3 H 54 1-Benzyl-3-(4-trifluoromethoxy-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. The title compound (0.28 g) was prepared from 0.50 g of 4 -oxo-piperidine-1 carboxylic acid tert-butyl ester, 274 liL of benzylamine, and 0.59 g of 1 5 trifluoromethoxy-4-(2-nitro-vinyl)-benzene using CH 2

CI

2 as the solvent. MS (ESI): exact mass calculated for C 2 1

H

19

F

3

N

2 0, 372.14; found, m/z 373.2

[M+H]

4

.

1 H NMR (400 MHz, CD 3 0D): 7.44-7.41 (m, 2H), 7.37-7.26 (m, 5H), 7.19- 7.17 (m, 3H), 5.15 (s, 2H), 4.37 (s, 2H), 3.51 (t, J= 6.3 Hz, 2H), 2.87 (t, J = 6.3 Hz, 2H). 10 Example 5 "- ~ S C1 cl N H 1-Benzyl- 3 -(5-chloro-thiophen-2-yl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. 15 The title compound (82.3 mg) was prepared from 0.56 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 300 gL of benzylamine, and 0.53 g of 2-chloro 5-( 2 -nitro-vinyl)-thiophene. MS (ESI): exact mass calculated for C 1 8

H

17

CIN

2 S, 328.08; found, m/z 329.1 [M+H]*. 1H NMR (500 MHz, CD 3 0D): 7.36-7.33 (m, 2H), 7.30-7.27 (m, 1H), 7.17-7.15 (m, 2H), 7.12 (s, 1H), 6.89 (d, J= 3.8 Hz, 20 1H), 6.73 (d, J= 3.8 Hz, 1H), 5.12 (s, 2H), 4.31 (s, 2H), 3.48 (t, J= 6.3 Hz, 2H), 2.84 (t, J= 6.3 Hz, 2H). Example 6 N H 25 1-Benzyl-3-thiophen-2-yl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (136.8 mg) was prepared from 0.53 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 300 gL of benzylamine, and 0.41 g of 2-(2-nitro 55 vinyl)-thiophene. MS (ESI): exact mass calculated for C1 8

H

1

N

2 S, 294.12; found, m/z 295.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.36-7.32 (m, 2H), 7.30-7.26 (m, 1H), 7.22 (dd, J= 5.2, 1.1 Hz, 1H), 7.18-7.15 (m, 2H), 7.12 (s, 1H), 7.02 (dd, J= 5.2, 3.6 Hz, 1H), 6.94 (dd, J= 3.6, 1.1 Hz, 1H), 5.13 (s, 2H), 5 4.34 (s, 2H), 3.49 (t, J= 6.3 Hz, 2H), 2.85 (t, J= 6.3 Hz, 2H). Example 7 CI H 1-(3-Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 10 The title compound (159.0 mg) was prepared from 0.55 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 334 gL of 3-chlorobenzylamine, and 0.40 g of (2-nitro-vinyl)-benzene and without Si02. MS (ESI): exact mass calculated for

C

20

H

19

CIN

2 , 322.12; found, m/z 323.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.38-7.32 (m, 5H), 7.31-7.28 (m, 1H), 7.23-7.19 (m, 1H), 7.17-7.16 (m, 1H), 15 7.13 (s, 1 H), 7.12-7.10 (m, 1 H), 5.16 (s, 2H), 4.37 (s, 2H), 3.52 (t, J= 6.3 Hz, 2H), 2.86 (t, J= 6.3 Hz, 2H). Example 8 O N F N H 20 1 -Benzyl-3-(3-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (282.6 mg) was prepared from 0.61 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 330 gL of benzylamine, and 0.50 g of (2-nitro vinyl)-3-fluorobenzene, using EtOH as the solvent and without SiO 2 . MS (ESI): exact mass calculated for C 2 0

H

19

FN

2 , 306.15; found, m/z 307.2 [M+H]*. 'H 25 NMR (500 MHz, CD 3 OD): 7.38-7.32 (m, 3H), 7.30-7.26 (m, 1H), 7.20-7.14 (m, 4H), 7.10-7.06 (m, 1H), 6.95-6.90 (m, 1H), 5.15 (s, 2H), 4.36 (s, 2H), 3.50 (t, J = 6.3 Hz, 2H), 2.86 (t, J= 6.3 Hz, 2H). 56 Example 9 F '6 N CI N H 3-(4-Chloro-phenyl)-1 -(2-fluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 5 c]pyridine. The title compound (129.2 mg) was prepared from 0.49 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 286 gL of 2-fluorobenzylamine, and 0.46 g of

(

2 -nitro-vinyl)-4-chlorobenzene, replacing SiO 2 with crushed 4A molecular sieves. MS (ESI): exact mass calculated for C 20

H

18

CIFN

2 , 340.11; found, m/z 10 341.1 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.38-7.30 (m, 5H), 7.18-7.12 (m, 3H), 7.10-7.06 (m, 1H), 5.20 (s, 2H), 4.35-4.34 (m, 2H), 3.54 (t, J= 6.3 Hz, 2H), 2.94 (t, J = 6.3 Hz, 2H). Example 10 ci 01 N 15 H 1-( 3 -Chloro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. The title compound (212.8 mg) was prepared from 0.55 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 340 4L of 3-chlorobenzylamine, and 0.51 g of 20 ( 2 -nitro-vinyl)-4-chlorobenzene, replacing SiO 2 with crushed 4A molecular sieves. MS (ESI): exact mass calculated for C 2 0H1 8 CI2N 2 , 356.08; found, m/z 357.1 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.38-7.28 (m, 6H), 7.18-7.15 (m, 2H), 7.12-7.09 (m, 1H), 5.16 (s, 2H), 4.36 (s, 2H), 3.52 (t, J= 6.3 Hz, 2H), 2.86 (t, J= 6.3 Hz, 2H). 25 57 Example 11 Cl 61?N N H 1-( 2 -Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (113.8 mg) was prepared from 0.55 g of 4-oxo-piperidine-1 5 carboxylic acid tert-butyl ester, 334 gL of 2 -chlorobenzylamine, 0.40 g of (2 nitro-vinyl)-benzene, and without SiO 2 . MS (ESI): exact mass calculated for

C

20

H

19

CIN

2 , 322.12; found, m/z323.2 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.46 (m, 1 H), 7.37-7.26 (m, 6H), 7.22-7.19 (m, 1H), 7.07 (s, 1H), 6.85-6.82 (m, 1H), 5.25 (s, 2H), 4.39 (s, 2H), 3.54 (t, J= 6.3 Hz, 2H), 2.88 (t, J= 6.3 Hz, 2H). 10 Example 12 C I Cl N H 1-( 4 -Chloro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. 15 The title compound (260.2 mg) was prepared from 0.55 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 340 pL of 4-chlorobenzylamine, and 0.51 g of

(

2 -nitro-vinyl)-4-chlorobenzene. MS (ESI): exact mass calculated for

C

2 0

H

16 C1 2

N

2 , 356.08; found, m/z 357.1 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.37-7.31 (m, 6H), 7.17-7.13 (m, 3H), 5.15 (s, 2H), 4.35 (s, 2H), 3.51 (t, J= 6.3 20 Hz, 2H), 2.85 (t, J= 6.3 Hz, 2H). Example 13 CC 'NC N 'N N H 1-Benzyl-3-(2,4-dichloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 58 The title compound (454.6 mg) was prepared from 0.52 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 280 pL of benzylamine, and 0.57 g of 2,4 dichloro-1 -(2-nitro-vinyl)-benzene, using a 5:1 EtOH/toluene mixture as the solvent. MS (ESI): exact mass calculated for C 20 H1C1 2

N

2 , 356.08; found, m/z 5 357.1 [M+H]. 'H NMR (500 MHz, CDsOD): 7.53 (d, J= 2.2 Hz, 1H), 7.36-7.32 (m, 3H), 7.30-7.28 (m, 2H), 7.20-7.17 (m, 2H), 7.04 (s, 1H), 5.16 (s, 2H), 4.13 (s, 2H), 3.50 (t, J= 6.3 Hz, 2H), 2.88 (t, J= 6.3 Hz, 2H). Example 14 '

-

N _ N 10 H 1-(4-Methoxy-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (0.19 g) was prepared from 1.51 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 1.0 mL of 4-methoxybenzylamine, and 1.13 g of (2-nitro-vinyl)-benzene, using EtOH as the solvent and omitting SiO 2 . MS 15 (ESI): exact mass calculated for C 2 1 H22N 2 0, 318.17; found, m/z319.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.39-7.30 (m, 4H), 7.20-7.15 (m, 1H), 7.14-7.11 (m, 2H), 7.08 (s, 1H), 6.90-6.87 (m, 2H), 5.05 (s, 2H), 4.34 (s, 2H), 3.50 (t, J= 6.3 Hz, 2H), 2.88 (t, J= 6.3 Hz, 2H). 20 Example 15 C1 CI N H 1-(2-Chloro-benzyl)-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. The title compound (149.9 mg) was prepared from 0.50 g of 4-oxo-piperidine-1 25 carboxylic acid tert-butyl ester, 304 gL of 2-chlorobenzylamine, and 0.46 g of (2-nitro-vinyl)-4-chlorobenzene, replacing SiO 2 with crushed 4A molecular sieves. MS (ESI): exact mass calculated for C 2 0 H1 8 Cl 2

N

2 , 356.08; found, m/z 59 357.1 [M+H]*. 1H NMR (500 MHz, CD 3 OD): 7.58-7.56 (m, 1H), 7.47-7.45 (m, 1H), 7.37-7.26 (m, 5H), 7.10 (s, 1H), 6.85-6.82 (m, 1H), 5.25 (s, 2H), 4.38 (s, 2H), 3.53 (t, J= 6.3 Hz, 2H), 2.88 (t, J= 6.3 Hz, 2H). 5 Example 16 C1 C1 N H 1-( 2

,

4 -Dichloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (0.43 g) was prepared from 0.55 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 370 RL of 2,4-dichlorobenzylamine, and 0.41 g 10 of (2-nitro-vinyl)-benzene, using EtOH as the solvent. MS (ESI): exact mass calculated for C 20

H

1 8 Cl 2

N

2 , 356.08; found, m/z 357.1 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.55-7.50 (m, 2H), 7.37-7.29 (m, 4H), 7.22-7.18 (m, 1H), 7.07 (s, 1H), 6.77 (d, J= 8.5 Hz, 1H), 5.23 (s, 2H), 4.38 (s, 2H), 3.54 (t, J= 6.3 Hz, 2H), 2.86 (t, J= 6.3 Hz, 2H). 15 Example 17 N N. H 1 -Benzyl-2-methyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (89.4 mg) was prepared from 0.51 g of 4-oxo-piperidine-1 20 carboxylic acid tert-butyl ester, 272 laL of benzylamine, and 0.41 g of (2-nitro propenyl)-benzene. MS (ESI): exact mass calculated for C21H 22

N

2 , 302.18; found, m/z 303.2 [M+H]*. 'H NMR (400 MHz, CD 3 OD): 7.41-7.36 (m, 2H), 7.35-7.30 (m, 2H), 7.28-7.21 (m, 4H), 7.05-7.01 (m, 2H), 5.16 (s, 2H), 4.18 (s, 2H), 3.52 (t, J= 6.3 Hz, 2H), 2.89 (t, J= 6.3 Hz, 2H). 25 60 Example 18 Q?N N H 1 -Benzyl-3-p-tolyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (89.7 mg) was prepared from 0.51 g of 4-oxo-piperidine-1 5 carboxylic acid tert-butyl ester, 272 gL of benzylamine, and 0.41 g of 1-methyl 4-(2-nitro-vinyl)-benzene. MS (ESI): exact mass calculated for C21H 22

N

2 , 302.18; found, m/z 303.2 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.35-7.31 (m, 2H), 7.29-7.25 (m, 1H), 7.23-7.20 (m, 2H), 7.18-7.14 (m, 4H), 7.06 (s, 1H), 5.13 (s, 2H), 4.33 (s, 2H), 3.49 (t, J = 6.3 Hz, 2H), 2.86 (t, J = 6.3 Hz, 2H). 10 Example 19 C1 N C H 1 -Benzyl-3-(3,4-dichloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (228.2 mg) was prepared from 0.49 g of 4-oxo-piperidine-1 15 carboxylic acid tert-butyl ester, 268 gL of benzylamine, and 0.55 g of 1,2 dichloro-4-(2-nitro-vinyl)-benzene. MS (ESI): exact mass calculated for C2H 18 Cl 2

N

2 , 356.08; found, m/z 357.1 [M+H] 4

.

1 H NMR (400 MHz, CD.OD): 7.51-7.47 (m, 2H), 7.36-7.32 (m, 2H), 7.32-7.25 (m, 2H), 7.22 (s, 1H), 7.19 7.15 (m, 2H), 5.15 (s, 2H), 4.35 (s, 2H), 3.50 (t, J= 6.3 Hz, 2H), 2.85 (t, J= 6.3 20 Hz, 2H). Example 20 K N_? N0 H 3-Benzo[1,3]dioxol-5-yl-1 -benzyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 61 The title compound (306.0 mg) was prepared from 0.49 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 268 gL of benzylamine, and 0.48 g of 5-(2-nitro vinyl)-benzo[1,3]dioxole. MS (ESI): exact mass calculated for C 21

H

2 0

N

2 0 2 , 332.15; found, m/z 333.2 [M+H]*. 1H NMR (400 MHz, CDsOD): 7.36-7.30 (m, 5 2H), 7.29-7.24 (m, 1H), 7.18-7.14 (m, 2H), 7.01 (s, 1H), 6.85-6.75 (m, 3H), 5.93 (s, 2H), 5.12 (s, 2H), 4.31 (s, 2H), 3.49 (t, J= 6.3 Hz, 2H), 2.85 (t, J= 6.3 Hz, 2H). Example 21 'N F N 10 H 1 -Benzyl-3-(4-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (706.2 mg) was prepared from 1.31 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 700 gL of benzylamine, and 1.10 g of 1 -fluoro 4-(2-nitro-vinyl)-benzene. MS (ESI): exact mass calculated for C 2 0

H

19

FN

2 , 15 306.15; found, m/z 307.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.36-7.25 (m, 5H), 7.18-7.15 (n, 2H), 7.11-7.05 (m, 3H), 5.13 (s, 2H), 4.33 (s, 2H), 3.50 (t, J = 6.3 Hz, 2H), 2.86 (t, J= 6.3 Hz, 2H). Example 22 N 20 H 1 -Butyl-3-p-tolyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (292.8 mg) was prepared from 0.56 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 260 pL of butylamine, and 0.45 g of 1 -methyl-4

(

2 -nitro-vinyl)-benzene. MS (ESI): exact mass calculated for C 18

H

24

N

2 , 25 268.19; found, m/z 269.2 [M+H]*. 1 H NMR (500 MHz, CD3OD): 7.20-7.14 (m, 4H), 6.93 (s, 1H), 4.32 (s, 2H), 3.88 (t, J= 7.1 Hz, 2H), 3.56 (t, J= 6.0 Hz, 2H), 62 3.00 (t, J= 6.0 Hz, 2H), 2.32 (s, 3H), 1.77-1.70 (m, 2H), 1.41-1.33 (m, 2H), 0.97 (t, J= 7.4 Hz, 3H). Example 23 Br N 5 H 1 -Benzyl-3-(4-bromo-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (0.38 g) was prepared from 0.66 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 300 L of benzylamine, and 0.63 g of 1-bromo 4-(2-nitro-vinyl)-benzene. MS (ESI): exact mass calculated for C 2 oH 19 BrN 2 , 10 366.07; found, m/z 367.1 [M+H]*. 1H NMR (500 MHz, CD 3 0D): 7.51-7.48 (m, 2H), 7.36-7.32 (m, 2H), 7.30-7.25 (m, 3H), 7.19-7.16 (m, 2H), 5.14 (s, 2H), 4.35 (s, 2H), 3.50 (t, J= 6.3 Hz, 2H), 2.87 (t, J= 6.3 Hz, 2H). Example 24

/CF

3 N 15 H 1 -Benzyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. The title compound (0.23 g) was prepared from 0.50 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 274 RL of benzylamine, and 0.55 g of 1 20 trifluoromethyl-4-(2-nitro-vinyl)-benzene, using acetonitrile as the solvent. MS (ESI): exact mass calculated for C 2 1

H

19

F

3

N

2 , 356.16; m/z found, 357.2 [M+H]*. 1 H NMR (500 MHz, CD3OD): 7.65-7.63 (m, 2H), 7.54-7.52 (m, 2H), 7.36-7.27 (m, 4H), 7.20-7.18 (m, 2H), 5.17 (s, 2H), 4.40 (s, 2H), 3.52 (t, J= 6.3 Hz, 2H), 2.88 (t, J= 6.3 Hz, 2H). 25 63 Example 25 _C1 " N H 1 -Benzyl- 3 -(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. The title compound (1.19 g) was prepared from 1.55 g of 4-oxo-piperidine-1 5 carboxylic acid tert-butyl ester, 850 gL of benzylamine, and 1.43 g of 1 -chloro 4 -(2-nitro-vinyl)-benzene, using a 1:1 mixture of EtOH/toluene as the solvent. MS (ESI): exact mass calculated for C 20

H

20 Cl 2

N

2 , 322.12; m/z found, 323.2 [M+H]*, 325.2 [M+H]*. 1H NMR (400 MHz, CD 3 OD): 7.37-7.26 (m, 7H), 7.18 7.16 (m, 3H), 5.15 (s, 2H), 4.35 (s, 2H), 3.50 (t, J= 6.3 Hz, 2H), 2.87 (t, J= 6.3 10 Hz, 2H). Example 26 N HN 1 -Benzyl-3-phenyl-1, 4 ,5,6,7,8-hexahydro-pyrrolo[2,3-djazepine. 15 Step A. 1-Benzvl-3-phenvl-4,5,7,8-tetrahvdro-1H-pyrrolo2,3-dlazepine-6 carboxylic acid tert-butyl ester. A solution of the compound (0.53 g) from Example 59, Step B, and 272 gL of benzylamine in benzene (10 mL) was heated at reflux for 24 h using a Dean-Stark apparatus. The solvent was removed, the crude material was dissolved in toluene (10 mL), and 0.38 g of 20 (2-nitro-vinyl)-benzene was added. The mixture was stirred for 24 h at RT and concentrated in vacuo. Chromatography on Si0 2 (1 to 20% EtOAc/hexanes) afforded 108.0 mg of the desired compound. MS (ESI): exact mass calculated for C 26

H

3 oN 2 0 2 , 402.53; found, m/z 403.2 [M+H]*. Step B. To a stirred solution of the compound from Step A (108.0 mg) in 25 CH 2 Cl 2 (5 mL) was added TFA (1 mL). The mixture was stirred at RT for 12 h and then concentrated in vacuo. The residue was partitioned between CH 2 Cl 2 (10 mL) and 1 M NaOH (10 mL). The layers were separated and the aqueous layer was extracted with CH 2 Cl 2 (2 x 10 mL). The combined organic layers 64 were concentrated. Chromatography on Si02 (5% 2 M NH 3 in MeOH/CH 2

C

2 ) gave 66.5 mg of the title compound. MS (ESI): exact mass calculated for

C

2 1 H22N 2 , 302.41; found, m 1 z 303.2 [M+H]*. 1 H NMR (500 MHz, CDCI 3 ): 7.42 7.22 (m, 8H), 7.08 (m, 2H), 6.67 (s, 1H), 5.08 (s, 2H), 3.06-2.91 (m, 4H), 2.90 5 2.82 (m, 2H), 2.77-2.68 (m, 2H), 2.25 (br s, 1 H). Example 27 S N H 1 -Benzyl-3-(5-methyl-thiophen-2-yl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 10 c]pyridine. StepA. 1-Benzvl-3-(5-methyl-thiophen-2-yl)-1,4,6,7-tetrahydro-pyrrolo[3,2 clpyridine-5-carboxylic acid tert-butyl ester. A mixture of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester (0.54 g) and 300 p.L of benzylamine in toluene (10 mL) was heated at reflux for 6 h using a Dean-Stark apparatus. The 15 solution was cooled to RT and 0.47 g of 2-methyl-5-(2-nitro-vinyl)-thiophene was added. The mixture was stirred for 16 h at RT and then was concentrated in vacuo. The residue was chromatographed on Si0 2 (1 to 30% EtOAc/hexanes) to afford 281.9 mg of the desired compound. TLC (SiO 2 , 33% EtOAc/hexanes): Rf = 0.54. 20 Step B. To a stirred solution of the compound from Step A (281.9 mg) in EtOH (10 mL) was added HCI (1 M in Et 2 O, 5 mL). The resulting mixture was stirred at RT for 24 h and concentrated in vacuo. The residue was then partitioned between CH 2

CI

2 (10 mL) and 1 M NaOH (10 mL). Th'e layers were separated and the aqueous layer was extracted with CH 2

CI

2 (2 x 10 mL). The combined 25 organic layers were concentrated. Chromatography on SiO 2

(CH

2

CI

2 to 5% 2 M NH 3 in MeOH/CH 2

CI

2 ) gave 59.0 mg of the title compound. MS (ESI): exact masscalculated for Cj9H 2 0N 2 S, 308.13; found, m/z 309.2 [M+H]. 1 H NMR (500 MHz, CDCl 3 ): 7.35-7.25 (m, 3H), 7.09-7.06 (m, 2H), 6.76 (s, 1H), 6.65 6.62 (m, 2H), 4.96 (s, 2H), 4.03 (s, 2H), 3.14 (t, J= 5.8 Hz, 2H), 2.50 (t, J= 5.8 30 Hz, 2H), 2.45 (s, 3H). 65 Example 28 cl HN 1-Benzyl-3-(4-chloro-phenyl)-1, 4 ,5, 6 ,7,8-hexahydro-pyrrolo[2,3-jazepine. 5 Step A. 1 -Benzvl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-pvrrolo[2,3 dlazepine-6-carboxvlic acid tert-butyl ester. The desired compound (54.2 mg) was prepared from the compound of Example 59, Step B (0.56 g), 280 L of benzylamine, and 0.49 g of 1 -chloro-4-(2-nitro-vinyl)-benzene as in Example 1, Step A. MS (ESI): exact mass calculated for C2 6

H

29

CIN

2 0 2 , 436.19; found, 10 m/z 437.2 [M+H]*. Step B. The above compound (54.2 mg) was converted to the title compound (19.2 mg) as in Example 27, Step B. MS (ESI): exact mass calculated for C21H 21

CIN

2 , 336.14; found, m/z 337.1 [M+H]. 1 H NMR (500 MHz, CDCl 3 ): 7.34-7.24 (m, 7H), 7.04 (d, J= 7.1 Hz, 2H), 6.62 (s, 1H), 5.05 (s, 2H), 3.03 15 3.00 (m, 2H), 2.97-2.94 (m, 2H), 2.83-2.80 (m, 2H), 2.74-2.71 (m, 2H). Example 29 "- N ci HN 1 -Benzyl-3-(5-chloro-thiophen-2-yl)-1,4,5,6,7,8-hexahydro-pyrrolo[2,3 20 djazepine. StepA. 1-Benzvl-3-(5-chloro-thiophen-2-vl)-4,5,7,8-tetrahdro-1H-pvrrolof2,3 dlazepine-6-carboxylic acid tert-butvl ester. The desired compound (124.5 mg) was prepared from the compound of Example 59, Step B (0.55 g), 280 L of benzylamine, and 0.49 g of 2-chloro-5-(2-nitro-vinyl)-thiophene as in Example 25 1, Step A. MS (ESI): exact mass calculated for C 24

H

27

CIN

2 0 2 S, 442.15; found, m/z 443.2 [M+H]. Step B. The above compound (124.5 mg) was converted to the title compound (30.7 mg) as in Example 27, Step B. MS (ESI): exact mass calculated for 66

C

19

H

19

CIN

2 S, 342.10; found, m/z 343.1 [M+H]*. 'H NMR (500 MHz, CDC1 3 ): 7.35-7.31 (m, 2H), 7.29-7.25 (m, 1 H), 7.04-7.00 (m, 2H), 6.82 (d, J= 3.8 Hz, 1 H), 6.66 (s, 1 H), 6.64 (d, J = 3.8 Hz, 1 H), 5.02 (s, 2H), 3.06-3.03 (m, 2H), 2.97-2.93 (m, 2H), 2.88-2.84 (m, 2H), 2.72-2.68 (m, 2H). 5 Example 30 '~ N Ci N H 1-( 4 -Chloro-benzyl)-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. Step A. 1-(4-Chloro-benzyl)-3-phenyl-1,4,6,7-tetrahvdro-pyrrolo[3,2-clpvridine 10 5-carboxylic acid tert-butyl ester. The desired compound (405.6 mg) was prepared from 0.53 g of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester, 334 pL of 2-chlorobenzylamine, and 0.34 g of (2-nitro-vinyl)-benzene as in Example 1, Step A. MS (ESI): exact mass calculated for C2 5

H

27

CIN

2 0 2 , 422.18; found, m/z 423.2 [M+H]*. 15 Step B. The above compound (405.6 mg) was converted to the title compound (206.7 mg) as in Example 27, Step B, using MeOH as the solvent. The desired product was then treated with malic acid (75.0 mg) in EtOAc. The solids were collected by filtration to give the corresponding maleate salt. MS (ESI): exact mass calculated for C 20

H

1 9 ClN 2 , 322.12; found, n/z 323.2 [M+H]*. 1 H NMR 20 (500 MHz, CD 3 OD): 7.37-7.32 (m, 6H), 7.22-7.18 (m, 1H), 7.16-7.13 (m, 2H), 7.12 (s, 1H), 6.24 (s, 2H), 5.14 (s, 2H), 4.35 (s, 2H), 3.51 (t, J= 6.3 Hz, 2H), 2.84 (t, J = 6.3 Hz, 2H). Example 31 O' N N 25 H 1 -Benzyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 67 Step A. 1 -Benzvl-3.henyl-1,4,6,7-tetrahydro-pyrrolo3,2-clpvridine-5 carboxylic acid tert-butyl ester. The desired compound (380.7 mg) was prepared from 0.51 g of 4-ox 6 -piperidine-1-carboxylic acid tert-butyl ester, 280 pL of benzylamine, and 0.39 g of (2-nitro-vinyl)-benzene as in Example 1, Step 5 A. MS (ESI): exact mass calculated for C 25

H

2 8

N

2 0 2 , 388.22; found, m/z 389.2 [M+H]*. Step B. The above compound (0.37 g) was converted to the title compound (234.7 mg) as in Example 26, Step B. MS (ESI): .exact mass calculated for

C

20 H20N 2 , 288.16; found, m/z 289.2 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 7.27 10 7.23 (m, 6H), 7.22-7.17 (m, 1H), 7.12-7.07 (m, 1H), 7.03-6.99 (m, 2H), 6.77 (s, 1 H), 4.93 (s, 2H), 3.98 (s, 2H), 3.07 (t, J = 5.8 Hz, 2H), 2.48 (t, J = 5.8 Hz, 2H). Example 32 N- CI 15 1 -Benzyl-3-(3-chloro-phenyl)-1, 4 ,5,6,7,8-hexahydro-pyrrolo[2,3-cjazepine. To a solution of the compound from Example 59, Step B (0.51 g) in toluene (5 mL) was added 280 L of benzylamine and 0.8 mL of Ti(OiPr) 4 . The resulting mixture was stirred for 3 h at RT. 1 -Chloro-3-(2-nitro-vinyl)-benzene (0.46 g) was then added in one portion and stirring was continued for an additional 16 h 20 at RT. The mixture was poured into water and filtered through diatomaceous earth. The aqueous filtrate was extracted with EtOAc (3 x 20 mL) and the combined organic layers were concentrated in vacuo. Chromatography on Si0 2 (1 to 35% EtOAc/hexanes) afforded 106.7 mg of 1 -benzyl-3-(3-chloro phenyl)-4,5,7,8-tetrahydro-1 H-pyrrolo[2,3-jazepine-6-carboxylic acid tert-butyl 25 ester. This compound was then converted to the title compound (19.1 mg) as in Example 27, Step B, using 10:1 CH 2

CI

2 /MeOH as the solvent. MS (ESI): exact mass calculated for C21H 2 1

CIN

2 , 336.14; found, m/z 337.2 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 7.36-7.30 (m, 3H), 7.29-7.25 (m, 2H), 7.23-7.17 (m, 2H), 7.05-7.02 (m, 2H), 6.64 (s, 1 H), 5.05 (s, 2H), 3.01-2.98 (m, 2H), 2.94-2.91 30 (m, 2H), 2.82-2.97 (m, 2H), 2.71-2.68 (m, 2H). 68 Example 33 ON CI N H 1 -Benzyl-3-(3-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 5 The title compound (193.3 mg) was prepared from 0.50 g of 4-oxo-piperidine-1 carboxylic acid tert-butyl ester, 260 VL of benzylamine, and 0.45 g of 1-chloro 3-(2-nitro-vinyl)-benzene as in Example 9. MS (ESI): exact mass calculated for C 20

H

1 9

CIN

2 , 322.12; found, m/z 323.2 [M+H]*. 1 H NMR (500 MHz, CDCla): 7.36-7.20 (m, 6H), 7.14-7.07 (m, 3H), 6.81 (s, 1H), 5.01 (s, 2H), 4.04 (s, 2H), 10 3.14 (t, J= 5.8 Hz, 2H), 2.51 (t, J= 5.8 Hz, 2H). Example 34 N N H 1-Benzyl-3-( 4 -methoxy-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 15 Step A. 1-Benzvl-3-(4-methoxy-phenyl)-1,4,6,7-tetrahydro-pyrrolo[3,2 clpvridine-5-carboxylic acid tert-butyl ester. To a solution of 0.50 g of 4-oxo piperidine-1-carboxylic acid tert-butyl ester and 260 gL of benzylamine in toluene (5 mL) was added 0.48 g of MgSO 4 and 16.7 mg of Bu 2 SnCl 2 . After 1 h, 0.45 g of 1 -methoxy-4-(2-nitro-vinyl)-benzene was added and the mixture 20 was stirred for 16 h at RT. The mixture was then diluted with water (80 mL) and extracted with EtOAc (3 x 15 mL) and the combined organic layers were concentrated in vacuo. Chromatography on SiO 2 (1 to 20% EtOAc/hexanes) afforded 0.38 g of the desired compound. MS (ESI): exact mass calculated for

C

26

H

3 oN 2 0 3 , 418.23; found, m/z 419.2 [M+H]*. 25 Step B. The above compound (0.47 g) was converted to the title compound (275.2 mg) as in Example 26, Step B. MS (ESI): exact mass calculated for

C

21

H

22

N

2 0, 318.17; found, m/z319.2 [M+H]*. 'H NMR (400 MHz, CDC 3 ): 69 7.35-7.24 (m, 5H), 7.12-7.08 (m, 2H), 6.90-6.86 (m, 2H), 6.74 (s, 1H), 4.99 (s, 2H), 4.04 (s, 2H), 3.81 (s, 3H), 3.16 (t, J= 5.8 Hz, 2H), 2.53 (t, J= 5.8 Hz, 2H). Example 35 Cl N 5 ( 1 -Benzyl-3-(4-chloro-phenyl)-5-ethyl-4,5,6,7-tetrahydro-i H-pyrrolo[3,2 c]pyridine. To a solution of 1 -benzyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine (Example 25; 0.11 g) in 1,2-dichloroethane (5 mL) was added 18 RL 10 of acetic acid, 26 4L of acetaldehyde, and 0.10 g of NaBH(OAc) 3 . The mixture was stirred at RT for 15 h. The mixture was diluted with CH 2

CI

2 and washed with satd. aq. NaHCO 3 (2x). The combined organic layers were dried over Na 2

SO

4 , filtered, and concentrated in vacuo. Chromatography on SiO 2 (1% 2 M NH 3 in MeOH/CH 2 Cl 2 ) afforded 0.02 g of the title compound. The product 15 was dissolved in Et 2 O and treated with excess 1.0 M HCI in Et 2 O to afford 0.02 g of the corresponding HCI salt. MS (ESI): exact mass calculated for

C

22 H23CIN 2 , 350.15; found, m/z351.2 [M+H]*, 353.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.37-7.27 (m, 7H), 7.19-7.17 (m, 3H), 5.17-5.13 (m, 2H), 4.48 4.37 (m, 2H), 3.85-3.76 (m, 2H), 3.45-3.23 (m, 2H), 3.00-2.84 (m, 2H), 1.38 (t, 20 J= 7.1 Hz, 3H). Example 36 NN CI N 1-Benzyl-3-(4-chloro-phenyl)-5-isopropyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 25 c]pyridine. The title compound (0.1 g) was prepared from 1-benzyl-3-(4-chloro-phenyl) 4 ,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine (Example 25; 0.10 g) and 32 ltL of 70 acetone as in Example 35. MS (ESI): exact mass calculated for C 23

H

25

CIN

2 , 364.17; found, m/z 365.2 [M+H]*, 367.2 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.37-7.27 (m, 7H), 7.21-7.17 (m, 3H), 5.15 (d, J= 5.2 Hz, 2H), 4.58-4.54 (m, 1 H), 4.28-4.25 (m, 1 H), 3.78-3.65 (m, 2H), 3.45-3.35 (m, 1 H), 3.03-2.85 (m, 5 2H), 1.42 (t, J= 6.6 Hz, 6H). Example 37 DN ci N HO 3-[1 -Benzyl-3-(4-chloro-phenyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-5-yl] 10 propan-1-ol. To a solution of 1 -benzyl-3-(4-chloro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine (Example 25; 0.51 g) in DMF (14 mL) was added 1.39 g of Cs 2 CO3 and 142 LL of 3-bromo-1 -propanol. The mixture was stirred at RT for 12 h and then was diluted with water. The aqueous layer was extracted with Et 2 0 and 15 the combined organic layers were dried over Na 2

SO

4 , filtered, and concentrated in vacuo. Chromatography on SiO 2 (2% 2 M NH 3 in MeOH/CH 2 Cl 2 ) afforded 0.15 g of the title compound. The product was dissolved in Et 2 O and treated with excess 1.0 M HCI in E20 to afford 0.16 g the corresponding HCI salt. MS (ESI): exact mass calculated for C 23

H

25

CIN

2 0, 20 380.17; found, m/z 381.2 (M+H]*, 383.2 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.37-7.27 (m, 7H), 7.19-7.17 (m, 3H), 5.15 (s, 2H), 4.47 (br s, 2H), 3.93-3.25 (m, 6H), 2.94-2.93 (m, 2H), 2.01-1.96 (m, 2H). Example 38 C1 N 25 1 1-Benzyl- 3 -(4-chloro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. 71 Ste A. 1 -Benz-3-(4-chloro-h 1 ,467-tetrahydro-pyrrolor3,2-cpyridine: 5-carboxylic acid ethyl ester. To a stirred solution of 3.0 g of 4-oxo-piperidine 1 -carboxylic acid ethyl ester in benzene (35 mL) was added 1.91 mL of benzylamine. The mixture was heated at reflux for 24 h using a Dean-Stark 5 apparatus. The solvent was removed to give a pale yellow oil. A portion of the crude product (0.50 g) was dissolved in toluene (4 mL) and 0.35 g of 1-chloro 4 -(2-nitro-vinyl)-benzene was added, followed by 0.7 g of 4A molecular sieves. The resulting mixture was stirred for 12 h at RT. The mixture was then filtered through diatomaceous earth and the filtrate was washed with satd. aq. NH 4 Cl 10 (3x). The combined organic extracts were dried over Na 2

SO

4 , filtered, and concentrated in vacuo. Chromatography on Si0 2 (8% EtOAc/hexanes) afforded 0.25 g the title compound. TLC (SiO 2 , 25% EtOAc/hexanes): Rf= 0.34. MS (ESI): exact mass calculated for C23H 2 3

CIN

2 0 2 , 394.14; found, m/z 395.2 [M+H)*, 397.2 [M+H], 417.1 [M+Na]*. 15 Step B. To a stirred solution of the above compound (0.25 g) in toluene (20 mL) was added 571 gL of sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al, 1.5 M in toluene). The mixture was stirred for 48 h at RT and then was quenched by the addition of satd. aq. potassium sodium tartrate. The organic layer was separated and dried over Na 2

SO

4 , filtered, and concentrated 20 in vacuoto give 0.16 g of the title compound. TLC (Si0 2 , 10% MeOH/EtOAc): R= 0.14. MS (ESI): exact mass calculated for C 2 1

H

2 1 ClN 2 , 336.14; found, m/z 337.2 [M+H], 339.2 [M+H]*. 'H NMR (500 MHz, CDCIa): 7.31-7.24 (m, 7H), 7.07-7.06 (m, 2H), 6.76 (s, 1H), 4.98 (s, 2H), 3.56 (s, 2H), 2.72 (t, J= 6.3 Hz, 2H), 2.60 (t, J= 6.3 Hz, 2H). 25 Example 39 S N Cl N 1 -Benzyl-3-(3-chloro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2 c]pyridine. 72 The title compound (0.34 g) was prepared from 3.0 g of 4-oxo-piperidine-1 carboxylic acid ethyl ester, 1.91 mL of benzylamine, and 1.2 g of 1 -chloro-3-(2 nitro-vinyl)-benzene as in Example 38. TLC (Si02, 2% NH 3 in MeOH/EtOAc): Rf = 0.25. MS (ESI): exact mass calculated for C21H 2 1

CIN

2 , 336.14; found, m/z 5 337.2 [M+H]*, 339.2 [M+H]. 'H NMR (500 MHz, CD 3 OD): 7.36-7.32 (m, 4H), 7.30-7.25 (m, 2H), 7.21-7.16 (m, 4H), 5.15 (s, 2H), 4.41 (s, 2H), 3.53 (t, J= 6.3 Hz, 2H), 2.98 (s, 3H), 2.91 (t, J= 6.3 Hz, 2H), 2.82-2.70 (m, 4H). Example 40 "N _ N C 10 I 1 -Benzyl-3-(3-chloro-4-fluoro-phenyl)-5-methyl-4,5,6,7-tetrahydro-1

H

pyrrolo[3,2- c]pyridine. The title compound (0.03 g) was prepared from 1-benzyl-3-(3-chloro-4-fluorophenyl)-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine (Example 2) and 15 paraformaldehyde as in Example 35. The product was then dissolved in 1/1 EtOAc/CH 2 Cl 2 and treated with 0.03 g (0.15 mmol) of citric acid to afford 0.05 g of the corresponding citrate salt. MS (ESI): exact mass calculated for

C

21

H

20 ClFN 2 , 354.13; found, m/z355.1 [M+H]*, 357.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.44-7.22 (m, 1H), 7.34 (t, J= 7.7 Hz, 2H), 7.30-7.26 (m, 2H), 20 7.22 (t, J= 9.1 Hz, 1H), 7.19-7.13 (m, 3H), 5.14 (s, 2H), 4.36 (s, 2H), 3.50 (t, J = 5.8 Hz, 2H), 2.96 (s, 3H), 2.89 (t, J= 5.8, 2H), 2.82-2.71 (m, 4H). Example 41 NN N 25 1,5-Dibenzyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 73 To a stirred solution of 0.46 mL of 1-benzyl-piperidin-4-one in absolute EtOH (5 mL) was added 0.27 mL of benzylamine. After 3 h, the solvent was removed in vacuo. The residue was diluted with absolute EtOH (5 mL) and 0.37 g of (2 nitro-vinyl)-benzene was added in one portion. The mixture was stirred at RT 5 for 16 h, filtered through diatomaceous earth, and the filtrate was concentrated. Chromatography on SiO 2 (1 to 20% EtOAc/hexanes) afforded 0.48 g of the title compound. MS (ESI): exact mass calculated for C 27

H

2 eN 2 , 378.21; found, m/z 379.2 [M+H)*. 'H NMR (500 MHz, CDCl 3 ): 7.40-7.22 (m, 12H), 7.18-7.10 (m, 3H), 6.80 (s, 1H), 4.99 (s, 2H), 3.78 (br m, 2H), 3.75 (s, 2H), 2.79-2.74 (m, 2H), 10 2.59-2.55 (m, 2H). Example 42 ON N 1 -Benzyl-5-isopropyl-3-phenyl-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridine. 15 The title compound (111.0 mg) was prepared from 372 4L of 1 -isopropyl piperidin-4-one, 270 pL of benzylamine, and 0.38 g of (2-nitro-vinyl)-benzene as in Example 41. The product was diluted with EtOAc and malic acid (39.0 mg) was added. The solids that formed were collected by filtration to give the title compound as a maleate salt. MS (ESI): exact mass calculated for 20 C 23

H

2 6

N

2 , 330.21; found, m/z 331.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.38-7.33 (m, 6H), 7.30-7.27 (m, 1H), 7.23-7.19 (m, 3H), 7.14 (s, 1H), 6.25 (s, 2H), 5.15 (s, 2H), 3.74-3.66 (m, 1 H), 2.96-2.91 (br m, 2H), 1.41 (d, J = 6.6 Hz, 6H). 25 Example 43

CF

3 HN 1 -Benzyl-3-(4-trifluoromethyl-phenyl)-1,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene. 74 Step A. 3-Oxo-2,3,4,5,7,8-hexahvdro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. To a solution of 5-oxo-azepane-1,4-dicarboxylic acid 1 tert-butyl ester 4-ethyl ester (Example 59, Step A; 8.29 g) in 80 mL of EtOH was added 1.5 mL of hydrazine hydrate. The solution was heated at reflux for 5 2 days and then was cooled to RT. The solvent volume was reduced to ca. 20 mL and the resulting solution was stored at -15 *C for 16 h. Water was added and the solids were collected by filtration, washed with water, and dried to give 4.99 g of the desired compound as a white crystalline solid. MS (ESI): exact mass calculated for C 12

H

19

N

3 0 3 , 253.14; found, m/z 254.1 [M+HJ*. 10 Step B. 1-Benzvl-3-oxo-2,3,4,5,7,8-hexahvdro-1H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester. To a stirred solution of 1.16 g the compound from step A in 15 mL of DMF was added 1.80 g of Cs 2

CO

3 . The suspension was stirred at RT for 20 min. Benzyl bromide (0.6 mL) was added and the mixture was stirred at RT for an additional 12 h. The mixture was diluted with 15 water and extracted with Et 2 0. The combinedorganic layers were washed with water, brine, dried over Na 2

SO

4 , and concentrated to afford 1.77 g of a colorless semi-solid. Chromatography on Si0 2 (15 to 50% EtOAc/hexanes) over 1 h gave 1.21 g of the desired compound as a mixture of mono benzylated isomers. TLC (Si0 2 , 50% EtOAc/hexanes): Rf = 0.34. MS (ESI): 20 exact mass calculated for C 19

H

25

N

3 0 3 , 343.19; found, m/z 344.2 [M+H], 366.2 [M+Na]*. Step C. 1-Benzvl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester. To a stirred solution of the above mixture of regioisomers (1.21 g) in 35 mL of CH 2

CI

2 was added 1.93 mL 25 of i-Pr 2 NEt and 1.58 g of N-phenyltrifluoromethane-sulfonimide. The mixture was heated at reflux for 12 h and then was cooled and concentrated in vacuo. Chromatography on SiO 2 (5 to 20% EtOAc/hexanes) afforded 0.63 g of the desired compound. TLC (SiO 2 , 25% EtOAc/hexanes): Rf = 0.37. MS (ESI): exact mass calculated for C 20

H

24

F

3

N

3 0 5 S, 475.14; found, m/z 476.2 [M+H]*. 30 Also, 0.68 g of the undesired mono-benzylated 3-benzyloxy-4,5,7,8-tetrahydro 1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester was obtained. Step D. 1 -Benzvl-3-(4-trifluromethl-henl),5,7,8-tetrahvdro-1 H-1,2,6 triaza-azulene-6-carboxVlic acid tert-butyl ester. To a solution of the compound 75 from step C (0.17 g) in 5 mL of THF was added 0.12 g of K 3 P0 4 , 0.08 g of 4 trifluoromethylphenylboronic acid and 0.03 g of PdCl 2 dppf. The mixture was heated at reflux for 12 h. The mixture was cooled, filtered through diatomaceous earth, and concentrated in vacuo. Chromatography on SiO 2 (5 5 to 40% EtOAc/hexanes) afforded 0.05 g of the desired compound. TLC (SiO 2 , 25% EtOAc/hexanes): Rf = 0.49. Ste _ E. 1-Benzvl-3-(4-trifluoromethyl-henvl)-1.4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. To a stirred solution of the compound from step D (0.05 g) in 2 mL of CH 2

CI

2 was added 2.0 mL of TFA. The mixture was stirred at RT for 2 h 10 and concentrated in vacuo. The crude product was re-dissolved in CH 2 Cl 2 and treated with Dowex* 550A resin. After stirring for 2 h, the mixture was filtered and concentrated in vacuo to afford 0.04 g of the title compound. The product was dissolved in Et 2 0 and treated with excess 1.0 M HCI in Et 2 0 for 30 min. The solvent was removed in vacuo to afford 0.05 g of the corresponding HCI 15 salt. MS (ESI): exact mass calculated for C 2 1

H

20

F

3

N

3 , 371.16; found, m/z 372.2 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.78-7.74 (m, 4H), 7.37-7.28 (m, 3H), 7.20 (t, J= 6.9 Hz, 2H), 5.46 (br s, 2H), 4.65 (br s, 1H), 3.40- 3.37 (m, 3H), 3.17- 3.10 (m, 4H). 20 The title compounds of Examples 44 - 53 were prepared according to the general procedure indicated by Example 43, Steps D and E, unless otherwise noted. Example 44 25 HN 1-Benzyl-3-phenyl-1, 4 ,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.07 g) was prepared from the compound of Example 43, Step C (0.16 g), and 0.05 g of phenylboronic acid. MS (ESI): exact mass calculated for C2 0

H

21

N

3 , 303.17; found, m/z304.2 [M+H]*. 'H NMR (500 MHz, 30 CD 3 0D): 7.56-7.54 (m, 2H), 7.51-7.43 (m, 3H), 7.39-7.36 (m, 2H), 7.33-7.29 76 (m, 1 H), 7.21 (d, J= 6.9 Hz, 2H), 5.50 (s, 2H), 3.43-3.38 (m, 4H), 3.22-3.20 (m, 2H), 3.12-3.10 (m, 2H). Example 45 jN N - N F 5 HN 1 -Benzyl-3-(2-fluoro-phenyl)- 1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.06 g) was prepared from the compound of Example 43, Step C (0.31 g), and 0.10 g of 2-fluorophenylboronic acid, using 1,4-dioxane as the solvent. MS (ESI): exact mass calculated for C 20

H

20

FN

3 , 321.16; found, 10 m/z322.2 [M+H]. 1 H NMR (500 MHz, CDaOD): 7.52-7.46 (m, 2H), 7.38-7.18 (m, 7H), 5.46 (s, 2H), 3.38-3.33 (m, 4H), 3.17-3.15 (m, 2H), 2.91-2.89 (m, 2H). Example 46 N-N F HN 15 1 -Benzyl-3-(3-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.07 g) was prepared from the compound of Example 43, Step C (0.30 g), and 0.10 g of 3-fluorophenylboronic acid, using 1,4-dioxane as the solvent. MS (ESI): exact mass calculated for C 20

H

20

FN

3 , 321.16; found, m/z 322.2 [M+H]). 1 H NMR (400 MHz, CD 3 OD): 7.52-7.47 (m, 1H), 7.38-7.27 20 (m, 5H), 7.20-7.13 (m, 3H), 5.47 (s, 2H), 3.43-3.34 (m, 4H), 3.23-3.06 (m, 4H). Example 47 S N-N F 1 -Benzyl-3-(4-fluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 25 The title compound (0.07 g) was prepared from the compound of Example 43, Step C (0.22 g), and 0.20 g of 4-fluorophenylboronic acid, adding 9.1mg of 77 dppf and using 1,4-dioxane as the solvent. MS (ESI): exact mass calculated for C 20

H

20

FN

3 , 321.16; found, m/z 322.2 [M+H]. 'H NMR (500 MHz, CDCI 3 ): 7.54-7.51 (m, 2H), 7.33-7.30 (m, 2H), 7.28-7.24 (m, 1 H), 7.12-7.07 (m, 4H), 5.35 (s, 2H), 2.98-2.95 (m, 2H), 2.94-2.92 (m, 2H), 2.80-2.77 (m, 2H), 2.76 5 2.74 (m, 2H). Example 48 F "- N-N FF HN 1 -Benzyl-3-(2,3-difluoro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 10 The title compound (0.05 g) was prepared from the compound of Example 43, Step C (0.30 g), and 0.11 g of 3,4-difluorophenylboronic acid, using 1,4 dioxane as the solvent. MS (ESI): exact mass calculated for C20H1 9

F

2

N

3 , 339.15; found, m/z 340.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.37-7.26 (m, 6H), 7.21-7.18 (m, 2H), 5.46 (s, 2H), 3.38-3.34 (m, 4H), 3.18-3.16 (m, 2H), 15 2.92-2.90 (m, 2H). Example 49 0 14 N-N HN ci 1 -Benzyl-3-(3,4-dichloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 20 The title compound (0.02 g) was prepared from the compound of Example 43, Step C (0.17 g), and 0.08 g of 3,4-dichlorophenylboronic acid. MS (ESI): exact mass calculated for C 20

H

19 Cl 2

N

3 , 371.10; found, m/z 372.1 [M+H]*, 374.1 [M+H]*, 376.1 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.78-7.74 (m, 4H), 7.37 7.28 (m, 3H), 7.21 -7.18 (m, 2H), 5.46-5.45 (m, 2H), 3.40-3.30 (m, 4H), 3.17 25 3.10 (m, 4H). 78 Example 50 'N N-N 1-[4-(1 -Benzyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)-phenyl] ethanone. 5 The title compound (0.02 g) was prepared from the compound of Example 43, Step C (0.20 g), and 0.08 g of 4-acetylphenylboronic acid, using 1,4-dioxane as the solvent. MS (ESI): exact mass calculated for C 22

H

23

N

3 0, 345.18; found, m/z 346.2 [M+H]). 1 H NMR (500 MHz, CD 3 0D): 8.10-8.09 (m, 2H), 7.71-7.70 (m, 2H), 7.38-7.19 (m, 5H), 5.48 (s, 2H), 3.40 (br s, 4H), 3.28-3.10 (m, 4H), 10 2.64 (s, 3H). Example 51 'N N-N CF HN F 3 1 -Benzyl-3-(4-trifluoromethoxy-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza 15 azulene. The title compound (0.03 g) was prepared from the compound of Example 43, Step C (0.26 g), and 0.13 g of 4 -trifluoromethoxyphenylboronic acid, using 1,4 dioxane as the solvent. MS (ESI): exact mass calculated for C 2 1

H

2 0

F

3

N

3 0, 387.16; found, m/z 388.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.67-7.63 (m, 20 2H), 7.39-7.28 (m, 5H), 7.20-7.17 (m, 2H), 5.44 (s, 2H), 3.39-3.36 (m, 2H), 3.32-3.30 (m, 2H), 3.15-3.06 (m, 4H). Example 52 'N N-N CI HN 25 1 -Benzyl-3-(3-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 79 The title compound (0.04 g) was prepared from the compound of Example 43, Step C (0.20 g), and 0.07 g of 3-chlorophenylboronic acid, using 1,4-dioxane as the solvent. MS (ESI): exact mass calculated for C 2 0

H

20

CIN

3 , 337.13; found, m/z 338.1 [M+H]*, 340.1 [M+H] 4

.

1 H NMR (400 MHz, CD 3 0D): 7.56 (br 5 s, 1H), 7.47-7.29 (m, 6H), 7.29-7.19 (m, 2H), 5.44 (s, 2H), 3.38-3.36 (m, 2H), 3.32-3.30 (m, 2H), 3.19-3.06 (m, 4H). Example 53 N-N CN HN 10 3-(1-Benzyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)-benzonitrile. The title compound (0.04 g) was prepared from the compound of Example 43, Step C (0.30 g), and 0.10 g of 3-cyanophenylboronic acid, using 1,4-dioxane as the solvent. MS (ESI): exact mass calculated for C 21 H20N 4 , 328.17; found, m/z 329.2 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.91-7.86 (m, 2H), 7.76-7.75 15 (m, 1 H), 7.65 (t, J = 7.7 Hz, 1 H), 7.37-7.20 (m, 3H), 7.19-7.18 (m, 2H), 5.45 (s, 2H), 3.39-3.37 (m, 4H), 3.17-3.08 (m, 4H). Example 54 CN-N 20 4-(1 -Benzyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)-benzonitrile. To a solution of 1 -benzyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1

H

1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 43, Step C; 0.30 g) in 9 mL of 1,4-dioxane was added 0.20 g of K 3 P0 4 , 0.10 g of 4 cyanophenylboronic acid, and 0.05 g of PdCl 2 dppf. The mixture was heated at 25 reflux for 72 h. The mixture was filtered through diatomaceous earth and concentrated in vacuo to give 0.33 g of an orange solid. Chromatography on SiO 2 (5 to 30% EtOAc/hexanes) afforded 0.21 g of a 7:1 mixture of 1-benzyl-3 (4-cyano-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid 80 tert-butyl ester and a side product, 1 -benzyl-4,5,7,8-tetrahydro-1 H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester. The mixture of compounds (0.21 g) was dissolved in 7 mL CH 2 Cl 2 and 7 mL of TFA was added. The mixture was stirred at RT for 1 h and concentrated in vacuo. The crude product was 5 dissolved in CH 2

CI

2 and treated with Dowex* 550A resin. After stirring for 2 h, the mixture was filtered and concentrated in vacuo. Chromatography using a C18 reverse phase column afforded 0.14 g of the title compound as its TFA salt. MS (ESI): exact mass calculated for C21H 2 0

N

4 , 328.17; found, m/z 329.1 [M+H]*, 351.1 [M+Na]*. 1 H NMR (500 MHz, CD 3 OD): 7.83-7.81 (m, 2H), 7.76 10 7.74 (m, 2H), 7.36-7.28 (m, 3H), 7.19-7.17 (m, 2H), 5.46 (s, 2H), 3.39-3.37 (m, 4H), 3.15-3.09 (m, 4H). Example 55 '-~N-N CI 15 1-(4-Chloro-benzyl)-3-phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. 1-( 4 -Chloro-benzl)-3-phenyl-4,5,7.8-tetrahydro-1H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester. To a solution of 0.13 g of 1-(4 chloro-benzyl)-3-trifluoromethanesulfonyl-4,5,7,8-tetrahydro-1 H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester, prepared as in Example 43, Steps A 20 through C, in 3 mL of THF was added 300 gL of water, 0.11 g of K 2

CO

3 , 44.9 mg of phenylboronic acid, and 20.0 mg of PdCl 2 dppf. The mixture was heated at 100 0C for 18 h. The mixture was filtered through diatomaceous earth and concentrated in vacuo. Chromatography on SiO 2 (hexanes to 45% EtOAc/hexanes) afforded 16.1 mg of the desired compound. MS (ESI): exact 25 mass calculated for C 25

H

28 ClN 3 0 2 , 437.19; found, m/z 438.2 [M+H]*. Step B. The above compound (16.1 mg) was converted to the title compound (7.1 mg) as in Example 26, Step B. MS (ESI): exact mass calculated for

C

20

H

20 ClN 3 , 337.13; found, m/z 338.1 [M+H]*. 1 H NMR (500 MHz, CDCl 3 ): 7.57-7.54 (m, 2H), 7.44-7.40 (m, 2H), 7.35-7.31 (m, 1 H), 7.30-7.26 (m, 3H), 30 7.04 (d, J= 8.5 Hz, 2H), 5.32 (s, 2H), 2.99-2.93 (m, 4H), 2.85-2.82 (m, 2H), 2.77-2.73 (m, 2H), 1.97 (br s, 1 H). 81 Example 56 "' N-N CI 1-( 4 -Chloro-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza 5 azulene. StepA. 1 4-Ch loro-be nzl)-3-(4-ch loro-phe nyl)-4,5,7,8 -tetrahdr-1 H-1.2,6 triaza-azulene-6-carboxylic acid tert-butyl ester. To a solution of 142.7 mg of 1-( 4 -chloro-benzyl)-3-trifluoromethanesulfonyl-4,5,7,8-tetrahydro-1 H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester, prepared as in Example 43, 10 Steps A through C, in 3 mL of THF was added 0.17 g of K 3 P0 4 , 54.9 mg of 4 chlorophenylboronic acid, and 22.1 mg of PdCl 2 dppf. The mixture was heated at reflux for 48 h. The mixture was filtered through diatomaceous earth, rinsing with toluene, and the filtrate was concentrated in vacuo. Chromatography on SiO 2 (hexanes to 75% EtOAc/hexanes) afforded 6.7 mg of the desired 15 compound. MS (ESI): exact mass calculated for C 25

H

27 Cl 2

N

3 0 2 , 471.15; found, m/z 472.1 [M+H]*. Step B. The above compound (6.7 mg) was converted to the title compound (5.0 mg) as in Example 26, Step B. MS (ESI): exact mass calculated for

C

20

H

19 C1 2

N

3 , 371.10; found, m/z372.1 [M+H)*. 1 H NMR (500 MHz, CDCl 3 ): 20 7.48 (d, J = 8.5 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H), 7.29 (d, J= 8.5 Hz, 2H), 7.03 (d, J= 8.5 Hz, 2H), 5.30 (s, 2H), 3.02-2.96 (m, 4H), 2.84-2.80 (m, 2H), 2.79 2.76 (m, 2H). Example 57 S N-N 25 1 -Benzyl-3-phenyl-6-propyl-1, 4 ,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.05 g) was prepared from 1 -benzyl-3-phenyl-1,4,5,6,7,8 hexahydro-1, 2 ,6-triaza-azulene (Example 44, 0.09 g) and 23 gL of 82 propionaldehyde as in Example 35. MS (ESI): exact mass calculated for

C

23

H

27

N

3 , 345.22; found, m/z 346.3 [M+H]*. 'H NMR (400 MHz, CD 3 0D); 7.56-7.54 (m, 2H), 7.47-7.28 (m, 6H), 7.21-7.19 (m, 2H), 5.44 (s, 2H), 3.70 3.66 (m, 2H), 3.41-3.07 (m, 8H), 1.86-1.76 (m, 2H), 1.03 (t, J= 7.3 Hz, 3H). 5 Example 58 N-N N 1 -Benzyl-6-isopropyl-3-phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.03 g) was prepared from 1-benzyl-3-phenyl-1,4,5,6,7,8 10 hexahydro-1,2,6-triaza-azulene (Example 44, 0.07 g) and 22 RL of acetone as in Example 35. MS (ESI): exact mass calculated for C 23

H

27

N

3 , 345.22; found, m/z 346.3 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.57-7.52 (m, 2H), 7.50-7.27 (m, 6H), 7.22-7.20 (m, 2H), 5.47 (s, 2H), 3.77-3.61 (m, 3H), 3.29-3.28 (m, 3H), 3.24-3.08 (m, 3H), 1.40 (d, J= 6.0 Hz, 6H). 15 Example 59 HN r C1 1 -Benzyl-3-(4-chloro-phenyl)-1, 4 ,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulene. Step A. 5-Oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester. 20 A solution of 4-oxo-piperidine-1 -carboxylic acid tert-butyl ester (35 mmol, 7.0 g) in anhydrous Et 2 O (50 mL) was stirred in a 200 mL 3-neck flask equipped with two addition funnels. The solution was cooled to -25 OC. Ethyl diazoacetate (46.5 mmol, 4..89 mL) in anhydrous Et 2 0 (10 mL) and BF 3 -OEt 2 (36.7 mmol, 4.65 mL) in anhydrous Et 2 O (10 mL) were simultaneously but independently 25 added to the solution over 90 min. The mixture was stirred for an additional 1 h and-was slowly warmed to RT. Then, 30% aq. K2CO3 was added dropwise to the mixture until gas evolution ceased. The organic layer was separated, 83 dried over Na 2

SO

4 , and concentrated. The residue was purified via chromatography (Si02, 5 to 20% EtOAc/hexanes) to yield the desired compound (7.5 g). Step B. 4-Oxo-azepane-1 -carboxylic acid tert-butyl ester. To a solution of the 5 product of Step A in 1,4-dioxane (50 mL) was added 1 N NaOH (40.83 mmol, 40.83 mL). The mixture was allowed to stir at rt overnight. The solution was then acidified to pH 4-5 with 3 N HCl. The mixture was extracted with Et 2 0 followed by CH202 until TLC showed no product remaining in the aqueous layer. The combined organic layers were dried over Na 2

SO

4 and concentrated 10 in vacuo to yield the desired compound (7.46 g). MS (ESI): exact mass calculated for C,1 H 19

NO

3 , 213.14; found, m/z 236.2 [M+Na]*. Step, C. 3-(4-Ch loro-rhen)-4,5.7,8-tetrahvdro-1 H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester. p-Toluenesulfonic acid (0.033 mg, 0.18 mmol) and morpholine (3.4 mL, 38 mmol) were added to a solution of the product of 15 step B (7.46 g, 35.0 mmol) in benzene (15 mL). The reaction mixture was heated at reflux for 20 h using a Dean-Stark trap. The reaction mixture was cooled to RT and concentrated in vacuo to afford the intermediate enamine, which was used without further purification. To a 0 *C solution of the enamine in CH 2 Cl 2 (30 mL) was added triethylamine (27.5 mmol, 3.80 mL) followed by a 20 solution of 4-chlorobenzoyl chloride (27.5 mmol, 3.50 mL) in CH 2 Cl 2 (10 mL). The reaction mixture was allowed to warm to RT and was stirred for 16 h. The mixture was poured over water and the layers were separated. The organic layer was dried over Na 2

SO

4 and concentrated. The resulting oil was diluted with EtOH (120 mL), cooled to 0 0C, and treated with hydrazine (75 mmol, 2.4 25 mL). The reaction mixture was allowed to warm to RT and was stirred for 16 h. The mixture was concentrated and the residue was purified by SFC purification to yield the desired compound (1.2 g). MS (ESI): exact mass calculated for C1 8

H

22 ClN 3 0 2 , 347.14; found, m/z 346.0 [M-H]~. 1 H NMR (500 MHz, CD 3 0D): 7.40-7.35 (m, 4H), 3.62-3.59 (m, 2H), 3.54-3.51 (m, 2H), 2.96-2.93 (m, 2H), 30 2.81-2.77 (m, 2H), 1.20 (s, 9H). The reaction sequence also yielded 3-(4 chloro-phenyl)-4,6,7,8-tetrahydro-1H-1, 2 ,5-triaza-azulene-5-carboxylic acid tert butyl ester (1.5 g). MS (ESI): exact mass calculated for C 18 H22CIN 3 0 2 , 347.14; found, m/z346.0 [M-H]~. 1H NMR (500 MHz, CD 3 0D): 7.65. (d, J=8.2 Hz, 84 1H), 7.47-7.41 (m, 3H), 4.67-4.45 (m, 2H), 3.71-3.65 (m, 2H), 2.90-2.89 (m, 2H), 1.90-1.87 (m, 2H), 1.18 (s, 9H). Step D. 1-Benzvl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester. To a 0 "C solution of the product 5 from Step C (0.10 g, 0.29 mmol) in DMF (2 mL) was added NaH (60% dispersion in oil, 92 mg, 2.3 mmol). The solution was allowed to warm to RT over 1 h, and, benzyl chloride (2.3 mmol) was then added. The reaction mixture was stirred for 16 h and then concentrated. The residue was diluted with water and extracted with CH 2

CI

2 . The organic layer was washed with 10 brine, dried over Na 2

SO

4 , and concentrated. The crude product was purified via SiO 2 chromatography to give the desired ester, which was carried directly into the next step. Also obtained was 2-benzyl-3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-2H- 1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester. MS (ESI): exact mass calculated for C2 5

H

28

CIN

3 0 2 , 437.19; found, m/z 438.4 [M+H]*. 1 H 15 NMR (500 MHz, CDCl 3 ): 7.50-7.48 (m, 2H), 7.40-7.38, (m, 2H), 7.33-7.26 (m, 3H), 7.13-7.11 (m, 2H), 5.33 (s, 2H), 3.55-3.51 (m, 4H), 2.86-2.77 (m, 4H), 1.47 (s, 9H). Step E. The product from Step D was dissolved in 9:1 CH 2

CI

2 /MeOH (4 mL). An excess of 1 N HCI In Et 2 O was added and the resulting mixture was stirred 20 for 2 h. The progress of the reaction was monitored by MS until no more starting material was evident. The reaction mixture was concentrated to obtain the desired product (51 mg). MS (ESI): exact mass calculated for C 20

H

2 0

CIN

3 , 337.13; found, m/z 338.2 [M+H]*. 'H NMR (500 MHz, CD30D): 7.56-7.53 (m, 2H), 7.51-7.48 (m, 2H), 7.38-7.29 (m, 3H), 7.20-7.19 (m, 2H), 5.48 (s, 2H), 25 3.42-3.37 (m, 4H), 3.20-3.18 (m, 2H), 3.10-3.08 (m, 2H). An alternative method as outlined in Scheme 5 is shown below: Step F. 3-(4-Chloro-phenvl)-1,4,6,7-tetrahvdro-indazol-5-rl,31dioxolane. The 30 desired compound (5.0 g) was prepared from 5.0 g of 1,4-dioxa spiro[4.5]decan-8-one, 4.5 mL of 4-chloro-benzoyl chloride and 3.0 mL of hydrazine according to the procedure outlined in Step C above. 1 H NMR (500 85 MHz, CDC 3 ): 7.53-7.50 (m, 2H), 7.36-7.33 (m, 2H), 4.02 (s, 4H), 2.91 (s, 2H), 2.89 (t, J= 6.6 Hz, 2H), 2.01 (t, J= 6.6 Hz, 2H). Step G. 1-Benzvl-3-(4-chloro-phenyl)-1,4,6,7-tetrahydro-indazol-5 [1,3ldioxolane. The desired compound (3.93 g) was prepared from 4.0 g of the 5 compound from step F as outlined in Step D, using benzyl bromide (1.9 mL) in place of benzyl chloride and K 2

CO

3 (6.1 g) in place of NaH. 1H NMR (500 MHz, CDCla): 7.67-7.64 (m, 2H), 7.39-7.27 (m, 5H), 7.21-7.18 (m, 2H), 5.29 (s, 2H), 4.05-3.98 (m, 4H), 2.95 (s, 2H), 2.71 (t, J= 6.6 Hz, 2H), 1.98 (t, J= 6.6 Hz, 2H). 10 Step H. 1-Benzyl-3-(4-chloro-phenvl)-1,46,7-tetrahydro-indazol-5-one oxime. A solution of 3.87 g of the compound from step G in 80 mL of THF with 5 mL of 1 M HCI was heated at reflux for 16 h. The volatiles were removed in vacuo and water was added (300 mL). The mixture was adjusted to pH 9 by the addition of 1 M NaOH and then was extracted with CH 2 Cl 2 . The combined 15 extracts were washed with brine and the solvent was removed in vacuo to provide 1-benzyl-3-(4-chloro-phenyl)-1,4,6,7-tetrahydro-indazol-5-one. This product (3.13 g) was treated with hydroxylamine hydrochloride (3.0 g) in 20 mL of pyridine. The reaction mixture was stirred at RT for 14 h then was diluted with water (300 mL), and stirred an additional hour. The mixture was filtered 20 on paper and the solids were washed with EtOAc and dried in vacuo to afford 2.48 g of the desired compound. 1H NMR (500 MHz, acetone-d 6 ): 10.24 (s, 1 H), 7.30-7.26 (m, 2H), 7.06-7.02 (m, 2H), 6.91-9.87 (m, 2H), 6.85-6.81 (m, 1 H), 6.77-6.73 (m, 2H), 4.87 (s, 2H), 3.21 (s, 2H), 2.31 (t, J= 6.6 Hz, 2H), 2.09 (t, J = 6.6 Hz, 2H). 25 Step 1. 1-Benzvl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahvdro-1,2,6-triaza azulene. A solution of the compound from step H (78.2 mg) in 15 mL of

CH

2 C1 2 was cooled to 0 *C and diisobutylaluminum hydride (1.5 M in toluene, 0.75 mL) was added. The mixture was allowed to warm to RT and was stirred for 12 h. Water (0.2 mL) and NaF (0.40 g) were added and the mixture was 30 stirred for 1 h. The mixture was filtered through diatomaceous earth and the filtrate was concentrated to afford 66.7 mg of a mixture of the title compound and 1-benzyl-3-(4-chloro-phenyl)-1, 4 ,5,6,7,8-hexahydro-1,2,5-triaza-azulene. 86 MS (ESI): exact mass calculated for C 2 0

H

2 0

CIN

3 , 337.13; found, m/z 338.0 [M+H]*. Example 60 through 102 were prepared using the procedures described in 5 Example 59, Steps D and E, unless otherwise noted. Example 60 N N-N N H 1 -Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,5-triaza-azulene. 10 The title compound (0.068 g) was prepared as in Example 59, Steps D and E, starting with 3

-(

4 -chloro-phenyl)-4,6,7,8-tetrahydro-1H-1,2,5-triaza-azulene-5 carboxylic acid tert-butyl ester (0.1 g), the isomer from Example 59, Step C. The reaction sequence also yielded 2-benzyl-3-(4-chloro-phenyl)-2,6,7,8 tetrahydro-4H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester. MS (ESI): 15 exact mass calculated for C 2 0

H

20

CIN

3 , 337.13; found, m/z 338.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.51-7.30 (m, 4H), 7.37-7.29 (m, 3H), 7.29-7.21 (m, 3H), 5.45 (s, 2H), 4.32 (s, 2H), 3.53-3.50 (m, 2H), 3.06-3.03 (m, 2H), 2.04-1.99 (m, 2H). 20 Example 61 N-N H 6N 3-(4-Chloro-phenyl)-1 -methyl- 1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.028 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 25 59, Step C; 0.1 g) using methyl iodide (0.21 mL) in place of benzyl chloride. The reaction sequence also yielded 3-(4-chloro-phenyl)-2-methyl-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azu lene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 1 4

H

1 ClN 3 , 261.10; 87 found, m/z 262.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.69-7.65 (m, 4H), 4.07 (s, 3H), 3.69-3.67 (m, 2H), 3.58-3.56 (m, 2H), 3.44-3.42 (m, 2H), 3.05 3.04 (m, 2H). 5 Example 62 N-N H Cl H6N 3

-(

4 -Chloro-phenyl)-2-methyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.011 g) was prepared from 3-(4-chloro-phenyl)-2-methyl 4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester 10 (Example 61) according to Example 59, Step E. MS (ESI): exact mass calculated for C 14

H

16

CIN

3 , 261.10; found, m/z 262.1 [M+H)*. 1 H NMR (500 MHz, CD 3 0D): 7.48-7.45 (m, 2H), 7.28-7.26 (m, 2H), 3.60 (s, 3H), 3.31-3.29 (m, 2H), 3.21 (m, 2H), 3.04-3.02 (m, 2H), 2.72-2.70 (m, 2H). 15 Example 63 N- N / CI HNY 3-(4-Chloro-phenyl)-1 -ethyl- 1, 4 ,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulene. The title compound (0.035 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2, 6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 20 59, Step C; 0.1 g) using ethyl iodide (0.27 mL) in place of benzyl chloride. The reaction sequence also yielded 3

-(

4 -chloro-phenyl)-2-ethyl-4,5,7,8-tetrahyd ro 2H-1,2, 6 -triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 15

H

1 8 ClN 3 , 275.12; found, m/z 276.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.39-7.34 (m, 4H), 7.11 (q, J= 7.3 Hz, 25 2H), 3.38-3.36 (m, 2H), 3.27-3.24 (m, 2H), 3.15-3.13 (m, 2H), 2.94-2.92 (m, 2H), 1.30 (t, J = 7.3 Hz, 3H). 88 Example 64 N--N H Cl HN 3-(4-Chloro-phe nyl)- 2 -ethyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene. The title compound (0.021 g) was prepared from 3-(4-chloro-phenyl)-2-ethyl 5 4,5,7,8-tetrahydro-2H-1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 63) according to Example 59, Step E. MS (ESI): exact mass calculated for C 15

H

1 8 ClN 3 , 275.12; found, m/z 276.2 [M+H]*. H NMR (500 MHz, CD 3 OD): 7.46 (d, J = 8.6 Hz, 2H), 7.24 (d, J = 8.6 Hz, 2H), 3.90 (q, J= 7.2 Hz, 2H), 3.31-3.29 (m, 2H), 3.20-3.19 (m, 2H), 3.06-3.04 (m, 2H), 2.69-2.67 10 (m, 2H), 1.17 (t, J= 7.2 Hz, 3H). Example 65 '- N-N H Cl HN 3-(4-Chloro-phenyl)-1-propyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 15 The title compound (0.031 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 1-iodopropane (0.33 mL) in place of benzyl chloride. The reaction sequence also yielded 3-(4-chloro-phenyl)-2-propyl-4,5,7,8 tetrahydro-2H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester in the 20 alkylation step. MS (ESI): exact mass calculated for C1 6

H

20

CIN

3 , 289.13; found, m/z 290.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.39-7.35 (m, 4H), 4.03 (t, J= 7.2 Hz, 2H), 3.37-3.35 (m, 2H), 3.27-3.24 (m, 2H), 3.15-3.13 (m, 2H), 2.95-2.93 (m, 2H), 1.76-1.69 (m, 2H), 0.84 (t, J = 7.4 Hz, 3H). 89 Example 66 N-N / CI HN 3 -(4-Chloro-phenyl)-2-propyl-2,4,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulene. The title compound (0.016 g) was prepared from 3 -(4-chloro-phenyl)-2-propyl 5 4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 65) according to Example 59, Step E. MS (ESI): exact mass calculated for C 16

H

20

CIN

3 , 289.13; found, m/z 290.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.45 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 3.83 (d, J= 7.2 Hz, 2H), 3.30-3.28 (m, 2H), 3.20-3.19 (m, 2H), 3.05-3.03 (m, 2H), 2.68-2.66 10 (m, 2H), 1.62-1.18 (m, 2H), 0.65 (t, J=7.4 Hz, 3H). Example 67 N -N / C I HNY 1 -Butyl-3-(4-chloro-phenyl)-1, 4 ,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 15 The title compound (0.033 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 1-iodobutane (0.038 mL) In place of benzyl chloride. The reaction sequence also yielded 2-butyl-3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-2H-1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester in the 20 alkylation step. MS (ESI): exact mass calculated for C 17

H

22 ClN 3 , 303.15; found, m/z 304.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.39-7.34 (m, 4H), 4.07 (t, J= 7.2 Hz, 2H), 3.37-3.35 (m, 2H), 3.27-3.25 (m, 2H), 3.14-3.12 (m, 2H), 2.95-2.92 (m, 2H), 1.69-1.66 (m, 2H), 1.22-1.20 (m, 2H), 0.86 (t, J = 7.4 Hz, 3H). 25 90 Example 68 N-N HNC 2- utyl-3-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.018 g) was prepared from 2-butyl-3-(4-chloro-phenyl) 5 4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 67) according to Example 59, Step E. MS (ESI): exact mass calculated for C 17 H22CIN 3 303.15; found, m/z 304.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.46 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 3.91-3.88 (m, 2H), 3.32-3.30 (m, 2H), 3.21-3.19 (m, 2H), 3.07-3.05 (m, 2H), 2.70-2.68 (m, 10 2H), 1.58-1.52 (m, 2H), 1.06-1.03 (m, 2H), 0.68 (t, J = 7.4 Hz, 3H). Example 69 N-N HN C 3-(4-Chloro-phenyl)-1 -(2-cyclohexyl-ethyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza 15 azulene. The title compound (0.056 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 1-bromo-2-cyclohexylethane (0. 053 mL) in place of benzyl chloride. The reaction sequence also yielded 3-(4-chloro-phenyl)-2-(2 20 cyclohexyl-ethyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ES!): exact mass calculated for

C

21

H

2 8

CIN

3 , 357.20; found, m/z 358.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.46-7.34 (m, 4H), 4.08 (t, J = 7.6 Hz, 2H), 3.37-3.35 (m, 2H), 3.27-3.25 (m, 2H), 3.13-3.11 (m, 2H), 2.94-2.92 (m, 2H), 1.68-1.20 (m, 7H), 1.18-1.05 (m, 25 4H), 0.93-0.86 (m, 2H). 91 Example 70 N-N H CI HN 3

-(

4 -Chloro-phenyl)-2-(2-cyclohexyl-ethyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.026 g) was prepared from 3-(4-chloro-phenyl)-2-(2 cyclohexyl-ethyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 69) according to Example 59, Step E. MS (ESI): exact mass calculated for C21 H 28

CIN

3 , 357.20; found, m/z 358.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.46 (d, J= 8.5 Hz, 2H), 7.23 (d, J= 8:5 Hz, 2H), 10 3.90 (t, J= 7.3 Hz, 2H), 3.30-3.28 (m, 2H), 3.20-3.19 (m, 2H), 3.05-3.03 (m, 2H), 2.69-2.67 (m, 2H), 1.48-1.41 (m, 5H), 1.36-1.33 (m, 2H), 1.03-1.00 (m, 3H), 0.95-0.89 (m, 1 H), 0.81-0.67 (m, 2H). Example 71 N-N 15 HNC 3-(4-Chloro-phenyl)-1 -phenethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.048 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using (2-chloroethyl)benzene (0.045 mL) in place of benzyl 20 chloride. The reaction sequence also yielded 3-(4-chloro-phenyl)-2-phenethyl 4,5,7,8-tetrahydro-2H-1.,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C21H 2 2 ClN 3 , 351.15; found, m/z 352.2 [M+H]*. 1H NMR (500 MHz, CD 3 0D): 7.52-7.47 (m, 4H), 7.28-7.21 (m, 3H), 7.03-7.01 (m, 2H), 4.39 (t, J= 6.4 Hz, 2H), 3.20-3.18 (m, 25 2H), 3.13-3.10 (m, 2H), 2.95-2.93 (m, 2H), 2.91-2.89 (m, 2H), 2.69-2.67 (m, 2H). 92 Example 72 N-N H CI H N 3 -(4-Chloro-phenyl)-2-phenethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 5 The title compound (0.020 g) was prepared from 3-(4-chloro-phenyl)-2 phenethyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert butyl ester (Example 71) according to Example 59, Step E. MS (ESI): exact mass calculated for C21 H 22 ClN 3 , 351.15; found, m/z 352.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.38-7.36 (m, 2H), 7.19-7.14 (m, 3H), 6.83-6.79 (m, 4H), 10 4.14 (t, J = 6.7 Hz, 2H), 3.41-3.39 (m, 2H), 3.26-3.24 (m, 2H), 3.19-3.17 (m, 2H), 3.01-2.98 (m, 2H), 2.69-2.67 (m, 2H). Example 73 '- N-N F Cl/ 15 3-(4-Chloro-phenyl)-1 -(4-fluoro-3-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.002 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of 20 benzyl chloride. MS (ESI): exact mass calculated for C21 H 21

CIFN

3 , 369.14; found, m/z 370.1 [M+H]. 'H NMR (500 MHz, CD 3 0D): 7.49-7.47 (m, 2H), 7.45-7.42 (m, 2H), 7.07-7.01 (m, 1 H), 7.00-6.95 (m, 1 H), 6.95-6.90 (m, 1 H), 5.31 (s, 2H), 2.97-2.91 (m, 4H), 2.89-2.84 (m, 2H), 2.82-2.77 (m, 2H), 2.22 (s, 3H). 25 93 Example 74 N N-N Cl 3-(4-Chloro-phenyl)-1 -(3-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.004 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 3-methylbenzyl chloride (0.6 mL) in place of benzyl chloride. MS (ESI): exact mass calculated for C21H22ClN 3 , 351.15; found, m/z 352.2 [M+H]*. 1H NMR (500 MHz, CD 3 OD): 7.31-7.26 (m, 2H), 7.26-7.21 (m, 10 2H), 6.99 (t, J= 7.5 Hz, 1 H), 6.88 (d, J= 7.1 Hz, 1H), 6.76 (s, 1H), 6.67 (d, J= 7.1 Hz, 1H), 5.13 (s, 2H), 2.79-2.73 (m, 4H), 2.69-2.65 (m, 2H), 2.63-2.60 (m, 2H), 2.09 (s, 3H). Example 75 '~N-N 15 H N 3-(4-Chloro-phenyl)-1 -(4-f luoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.003 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 20 59, Step C; 0.1 g) using 4-fluorobenzyl chloride (0.5 mL) in place of benzyl chloride. MS (ESI): exact mass calculated for C 20

H

19 ClFN 3 , 355.13; found, m/z 356.2 [M+H], 1 H NMR (500 MHz, CD 3 OD): 7.40-7.37 (m, 2H), 7.35-7.32 (m, 2H), 7.08-7.04 (m, 2H), 6.98-6.94 (m, 2H), 5.26 (s, 2H), 2.89-2.86 (m, 4H), 2.80-2.78 (m, 2H), 2.73-2.70 (m, 2H). 25 94 Example 76 F ~ N-N F C1 H N 3-(4-Chloro-phenyl)-1 -(3-fluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.01 g) was prepared from,3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 3-fluorobenzyl chloride (0.5 mL) in place of benzyl chloride. MS (ESI): exact mass calculated for C 20

H

1

CIFN

3 , 355.13; found, m/z 356.1 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.42-7.37 (m, 2H), 7.35-7.32 10 (m, 2H), 7.28-7.21 (m, 1 H), 6.93-6.88 (m, 1 H), 6.84 (d, J = 7.7 Hz, 1 H), 6.75 6.71 (m, 1 H), 5.29 (s, 2H), 2.89-2.85 (m, 4H), 2.79-2.76 (m, 2H), 2.74-2.70 (m, 2H). Example 77 ~- N-N 15 C1 15 H6N 3-(4-Chloro-phenyl)-1 -(4-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.013 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 20 59, Step C; 0.74 g) using 4-methylbenzyl chloride (0.45 g) in place of benzyl chloride. The reaction sequence also yielded 3-,(4-chloro-phenyl)-2-(4-methyl benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C211H 22

CIN

3 , 351.15; found, m/z352.2 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.39-7.36 (m, 25 2H), 7.34-7.31 (m, 2H), 7.03 (d, J= 8.0 Hz, 2H), 6.90 (d, J= 8.0 Hz, 2H), 5.21 (s, 2H), 2.83-2.67 (m, 4H), 2.75-2.72 (m, 2H), 2.69-2.67 (m, 2H), 2.20 (s, 3H). 95 Example 78 F N-N FC 3-(4-Chloro-phenyl)-i -(3,4-difluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.002 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2 ,6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.07 g) using 3,4-difluorobenzyl bromide (0.4 mL) in place of benzyl chloride. The reaction sequence also yielded 3-(4-chloro-phenyl)-2 (3,4-difl uoro-benzyl)-4,5,7,8-tetrahydro-2H- 1,2,6-triaza-azu lene-6-carboxylic 10 acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for

C

2 aH 18 ClF 2

N

3 , 373.12; found, m/z 374.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.41-7.38 (m, 2H), 7.36-7.33 (m, 2H), 7.22-7.20 (m, 1H), 7.07-7.02 (m, 1H), 6.96-6.92 (m, 1 H), 5.26 (s, 2H), 3.06-3.02 (m, 4H), 2.94-2.91 (m, 2H), 2.87 2.84 (m, 2H). 15 Example 79 0 2 N C HN 3-(4-Chloro-phenyl)-1 -(3-nitro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 20 The title compound (0.005 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2, 6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 3-nitrobenzyl bromide (0.09 g) in place of benzyl chloride and Cs 2

CO

3 (0.2 g) in place of NaH. MS (ESI): exact mass calculated for C 20 H1 9 ClN 4 0 2 , 382.12; found, m/z 383.1 [M+H]*. 'H NMR (500 MHz, 25 CD 3 0D): 8.07-8.05 (m, 1H), 7.91-7.87 (m, 1H), 7.50 (t, J= 7.9 Hz, 1H), 7.44 7.38 (m, 3H), 7.36-7.33 (m, 2H), 5.41 (s, 2H), 2.88-2.85 (m, 4H), 2.82-2.79 (m, 2H), 2.73-2.71 (m, 2H). 96 Example 80 F N N-N F C 1 HN 3-(4-Chloro-phenyl)-1 -(3-fluoro-4-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. 5 The title compound (0.003 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 3-fluoro-4-methylbenzyl bromide (0.9 g) in place of benzyl chloride. MS (ESI): exact mass calculated for C21H 21

CIFN

3 , 369.14; found, m/z 370.1 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.50-7.47 (m, 2H), 10 7.44-7.42 (m, 2H), 7.19 (t, J = 7.6 Hz, 1 H), 6.84-6.81 (m, 1 H), 6.78-6.75 (m, 1H), 5.33 (s, 2H), 2.95-2.92 (m, 4H), 2.87-2.84 (m, 2H), 2.81-2.78 (m, 2H), 2.22 (s, 3H). Example 81 N N-N 15 HN 3-(4-Chloro-phenyl)-1 -(3,4-dimethyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.003 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 20 59, Step C; 0.1 g) using 3,4-dimethylbenzyl chloride (0.6 mL) in place of benzyl chloride. MS (ESI): exact mass calculated for C 22

H

2 4

CIN

3 , 365.17; found, m/z 366.2 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.40-7.38 (m, 2H), 7.35-7.32 (m, 2H), 6.98-6.96 (m, 1 H), 6.90-6.86 (m, 1 H), 6.72-6.69 (m, 1 H), 5.30 (s, 1 H), 5.19 (s, 1 H), 2.90-2.87 (m, 2H), 2.86-2.82 (m, 2H), 2.77-2.73 (m, 2H), 2.72-2.68 (m, 25 2H), 2.21 (s, 3H), 2.17 (s, 3H). 97 Example 82 o / N-N / C1 H6N 5-[ 3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentanoic acid methyl ester. 5 The title compound (0.0042 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.15 g) using methyl 5-chlorovalerate (0.90 mL) in place of benzyl chloride. The reaction sequence also yielded 3-(4-chloro-phenyl)-1 -(4 methoxycarbonyl-butyl)-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic 10 acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C1 9

H

24

CIN

3 0 2 , 361.16; found, m/z362.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.54-7.51 (m, 2H), 7.31-7.29 (m, 2H), 3.95 (t, J= 7.0 Hz, 2H), 3.60 (s, 3H), 3.03-3.01 (m, 2H), 2.93-2.91 (m, 4H), 2.56-2.53 (m, 2H), 2.16 (t, J= 7.4 Hz, 2H), 1.67-1.62 (m, 2H), 1.41-1.38 (m, 2H). 15 Example 83 0 OH N-N H CI HNY 5-[ 3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentanoic acid. 20 5-[ 3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1, 2 ,6-triaza-azulen-2-yl]-pentanoic acid methyl ester (Example 82, 0.009 g) was dissolved in 1 mL of 9:1 THF/MeOH and treated with 2 mL of 1 M NaOH. After stirring at RT for 5 h, the solvent was removed in vacuo. The aqueous residue was acidified with 1 mL of 1 N HCl and the mixture was extracted with EtOAc (3x). The combined 98 organic layers were dried over Na 2

SO

4 , concentrated, and dried on a vacuum line. The residue was then dissolved in 1 mL of 9:1 CH 2 Cl2/MeOH and treated with 3 mL of 1 N HCl in Et 2 0. After 4 h, the volatiles were removed in vacuo. The crude oil was purified by preparative TLC (9:1 CH 2

CI

2 /2 M NH 3 in MeOH) 5 to afford 0.002 g of the title compound. MS (ESI): exact mass calculated for

C

18 H22ClN 3 0 2 , 347.14; found, m/z 348.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.55-7.53 (m, 4H), 7.35-7.32 (m, 2H), 3.98 (t, J= 7.0 Hz, 2H), 3.38-3.35 (m, 2H), 3.28-3.26 (m, 2H), 3.13-3.10 (m, 2H), 2.77-2.74 (m, 2H), 2.09-2.06 (m, 2H), 1.71-1.66 (m, 2H), 1.41-1.37 (m, 2H). 10 Example 84 OH N--N H C 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentan-1 ol. 15 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentanoic acid methyl ester (Example 82, 0.009 g) was dissolved in 9:1 Et 2 0/CH 2

CI

2 (3 mL) and the solution was added slowly to a stirred suspension of lithium aluminum hydride (2 mg) in 5 mL of anhydrous Et20. After stirring at RT for 6 h, the reaction was quenched with 2 mL of water. The mixture was treated with 20 2 mL of 1 N NaOH, followed by another 2 mL of water. The mixture was then filtered through diatomaceous earth. The organic layer was separated, dried over MgSO 4 , and concentrated. After further drying via vacuum line, the resulting oil was dissolved in 2 mL of 9:1 CH 2 Cl 2 /MeOH and treated with 3 mL of 1 N HCl in Et 2 0. After 4 h, the volatiles were removed in vacuo. The crude 25 oil was purified by preparative TLC (9:1 CH 2 Cl 2 /2 M NH 3 in MeOH) to afford 0.001 g of the title compound as a colorless oil. MS (ESI): exact mass calculated for C 18

H

24

CIN

3 0, 333.16; found, m/z 334.2 [M+H)*. 1H NMR (500 MHz, CD 3 0D): 7.54-7.52 (m, 2H), 7.32-7.30 (m, 2H), 3.95 (t, J= 7.1 Hz, 2H), 3.44 (t, J= 6.6 Hz, 2H), 3.13-3.09 (m, 2H), 3.03-3.00 (m, 2H), 2.98-2.95 (m, 99 2H), 2.61-2.58 (m, 2H), 1.70-1.64 (m, 2H), 1.40-1.35 (m, 2H), 1.20-1.16 (m, 2H). Example 85 0 O N-N /Ci 5 HN C 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1-yl]-pentanoic acid methyl ester. The title compound (0.0051 g) was prepared from 3-(4-chloro-phenyl)-1 -(4 methoxycarbonyl-butyl)-4,5,7,8-tetrahydro- 1 H-1,2,6-triaza-azulene-6-carboxylic 10 acid tert-butyl ester (Example 82) according to Example 59, Step E. MS (ESI): exact mass calculated for C 19

H

2 4

CIN

3 0 2 , 361.16; found, m/z 362.2 [M+H]*. 1 H NMR (500 MHz, CDsOD): 7.45-7.40 (m, 4H), 4.13 (t, J= 7.0 Hz, 2H), 3.63 (s, 3H), 3.04-3.03 (m, 2H), 2.97-2.95 (m, 4H), 2.79-2.76 (m, 2H), 2.34 (t, J= 7.4 Hz, 2H), 1.81-1.77 (m, 2H), 1.61-1.58 (m, 2H). 15 Example 86 0 HO N-N H N 5-[ 3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-pentanoic acid. 20 5-[ 3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-pentanoic acid methyl ester (Example 85, 0.014 g) was hydrolyzed and de-protected as in Example 83 to afford the title compound (0.0014 g). MS (ESI): exact mass calculated for C 18

H

2 2

CIN

3 0 2 , 347.14; found, m/z 348.0 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.49-7.43 (m, 4H), 4.18 (t, J= 7.0 Hz, 2H), 3.45-3.43 (m, 2H), 25 3.25-3.22 (m, 2H), 3.17-3.16 (m, 2H), 3.04-3.01 (m, 2H), 2.28-2.24 (m, 2H), 1.84-1.82 (m, 2H), 1.60-1.57 (m, 2H). 100 Example 87 HO _- 'N-N H CI 5-[ 3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-pentan-1 ol. 5 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-pentanoic acid methyl ester (Example 85, 0.015 g) was reduced as in Example 84 to afford the title compound (0.0063 g) as a colorless oil. MS (ESI): exact mass calculated for C1 8

H

24

CIN

3 0, 333.16; found, m/z 334.1 [M+H]*. 1H NMR (500 MHz, CDsOD): 7.45-7.40 (m, 4H), 4.13 (t, J= 7.2 Hz, 2H), 3.53 (t, J= 6.4 Hz, 10 2H), 3.04-3.01 (m, 2H), 2.97-2.92 (m, 4H), 2.78-2.75 (m, 2H), 1.82-1.75 (m, 2H), 1.57-1.51 (m, 2H), 1.41-1.34 (m, 2H). Example 88 N-N HN CI 15 4-[3-(4-Chloro-phenyl)-5,6,7,8 -tetrahydro-4H- 1,2,6-triaza-azulen-1 -yl]-butyric acid methyl ester. The title compound (0.003 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using methyl 4-chlorobutyrate (0.8 mL) in place of benzyl 20 chloride. The reaction sequence also yielded 3-(4-chloro-phenyl)-2-(3 methoxycarbony-propyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 18

H

22

CIN

3 0 2 , 347.14; found, m/z 348.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.37-7.31 (m, 4H), 4.07 (t, J= 6.6 Hz, 2H), 3.52 (s, 3H), 2.97 25 2.94 (m, 2H), 2.88-2.84 (m, 4H), 2.70-2.66 (m, 2H), 2.25 (t, J= 6.6 Hz, 2H), 1.98-1.95 (m, 2H). 101 Example 89 0 N-N H/ CI

HN

4-[3-(4-Ch loro-phenyl)-5,6,7,8-tetrahydro-4H- 1,2,6-triaza-azulen-2-yl]-butyric acid methyl ester. 5 The title compound (0.003 g) was prepared from 3-(4-chloro-phenyl)-2-(3 methoxycarbonyl-propyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid terl-butyl ester (Example 88) according to Example 59, Step E. MS (ESI): exact mass calculated for C 18 H22ClN 3

O

2 , 347.14; found, m/z 348.2 [M+H]*. 1 H NMR (400 MHz, CD 3 OD): 7.45-7.42 (m, 2H), 7.23-7.20 (m, 2H), 10 3.91 (t, J= 6.9 Hz, 2H), 3.44 (s, 3H), 3.04-3.00 (m, 2H), 2.93-2.86 (m, 4H), 2.52-2.49 (m, 2H), 2.07 (t, J= 7.0 Hz, 2H), 1.88-1.80 (m, 2H). Example 90 OH 0 N-N H C1 HNy 15 4 -[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-y]-butyric acid. 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-butyric acid methyl ester (Example 89, 0.006 g) was hydrolyzed as in Example 83 to afford the title compound (0.005 g). MS (ESI): exact mass calculated for 20 C 17

H

20 ClN 3 0 2 , 333.12; found, m/z 334.1 [M+H]*. 1 H NMR (400 MHz, CD 3 OD): 7.55-7.52 (m, 2H), 7.35-7.33 (m, 2H), 3.98 (t, J= 6.8 Hz, 2H), 3.12-3.09 (m, 2H), 3.03-2.96 (m, 4H), 2.62-2.59 (m, 2H), 2.03-1.97 (m, 4H). 102 Example 91 HO N-N OH CI 4 -[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-butyric acid. 5 4

-[

3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-butyric acid methyl ester (Example 88, 0.009 g) was hydrolyzed as in Example 83 to afford the title compound (0.003 g). MS (ESI): exact mass calculated for

C

17

H

20

CIN

3 0 2 , 333.12; found, m/z 334.1 [M+H]*, m/z 332.0 (M-H]~. 1 H NMR (400 MHz, CDOD): 7.46-7.44 (m, 4H), 4.17 (t, J= 7.1 Hz, 2H), 3.11-3.08 (m, 10 2H), 3.05-2.98 (m, 4H), 2.83-2.79 (m, 2H), 2.18-2.15 (m, 2H), 2.07-2.03 (m, 2H). Example 92 OH N-N H &N 15 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-butan- 1 ol. 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-butyric acid methyl ester (Example 89, 0.006 g) was reduced as in Example 84 to afford the title compound as a white solid (0.001 g). MS (ESI): exact mass 20 calculated for C 17 H22ClN 3 0, 319.15; found, m/z 320.2 [M+H]*. 'H NMR (400 MHz, CD 3 0D): 7.45-7.41 (m, 2H), 7.22-7.20 (m, 2H), 3.89-3.84 (m, 2H), 3.32 3.29 (m, 2H), 2.94-2.91 (m, 2H), 2.85-2.81 (m, 4H), 2.47-2.43 (m, 2H), 1.63 1.58 (m, 2H), 1.24-1.17 (m, 2H). 103 Example 93 HO,,--,,, ,N-N H CI N 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-butan-1 ol. 5 4

-[

3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-butyric acid methyl ester (Example 88, 0.02g) was reduced and de-protected as in Example 84 to afford the title compound as a white solid (0.007 g). MS (ESI): exact mass calculated for C 17

H

22

CIN

3 0, 319.15; found, m/z 320.2 [M+H)*. 'H NMR (400 MHz, CD 3 0D): 7.36-7.31 (m, 4H), 4.05 (t, J= 7.2 Hz, 2H), 3.45 (t, J 10 = 6.4 Hz, 2H), 2.96-2.94 (m, 2H), 2.89-2.84 (m, 4H), 2.70-2.66 (m, 2H), 1.77 1.68 (m, 2H), 1.46-1.39 (m, 2H). Example 94 F N-N F H CI HN 15 3

-(

4 -Chloro-phenyl)-2-(3,4-difluoro-benzyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.001 g) was prepared from 3-(4-chloro-phenyl)-2-(3,4 difluoro-benzyl)-4,5,7,8-tetrahydro-2H- 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 78) according to Example 59, Step E. MS (ESI): 20 exact mass calculated for C 20

H

1 8 ClF 2

N

3 , 373.12; found, m/z374.1 [M+H]. 'H NMR (500 MHz, CD 3 OD): 7.41-7.36 (m, 2H), 7.15-7.10 (m, 2H), 7.07-7.01 (m, 1H), 6.77-6.72 (m, 1H), 6.65-6.62 (m, 1H), 5.06 (s, 2H), 3.17-3.15 (m, 2H), 09 3.05 (m, 2H), 2.99-2.97 (m, 2H), 2.62-2.59 (m, 2H). 104 Example 95 N-N H C1 HN 3

-(

4 -Chloro-phenyl)-2-(4-methyl-benzyl)-2,4,5,6,7,8-hexa hydro-1 ,2,6-triaza azulene. 5 The title compound (0.005 g) was prepared from 3-(4-chloro-phenyl)-2-(4 methyl-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 77) according to Example 59, Step E. MS (ESI): exact mass calculated for C21 H22CIN 3 , 351.15; found, m/z 352.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.36-7.33 (m, 2H), 7.10-7.01 (m, 2H), 6.95 (d, J= 10 7.8 Hz, 2H), 6.69 (d, J= 8.0 Hz, 2H), 5.01 (s, 2H), 2.92-2.90 (m, 2H), 2.83-2.80 (m, 4H), 2.46-2.43 (m, 2H), 2.16 (s, 3H). Example 96 F )C- N-N 15 3-(4-Chloro-phenyl)-1-(3-fluoro-4-methoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.021 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.35 g) using 3-fluoro-4-methoxybenzyl bromide (0.25 g) in place of 20 benzyl chloride. The reaction sequence also provided 3-(4-chloro-phenyl)-2-(3 fluoro-4-methoxy-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 21

H

21

CIFN

3 0, 385.14; found, m/z 386.1 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.50-7.47 (m, 2H), 7.47-7.42 (m, 2H), 7.06-7.02 (m, 1 H), 6.90 25 6.86 (m, 2H), 5.29 (s, 2H), 3.84 (s, 3H), 3.35-3.29 (m, 2H), 2.94-2.92 (m, 4H), 2.88-2.85 (m, 2H), 2.80-2.77 (m, 2H). "C NMR (125 MHz, CD 3 0D): 154.2, 105 152.2, 149.1, 148.1, 143.5, 134.2,132.9,131.1, 131.0,130.5, 129.1, 123.3, 118.7, 115.0, 114.8, 114.4, 56.2, 52.4, 49.9, 28.8, 27.3. Example 97 F N-N / /71 5 HN 3

-(

4 -Chloro-phenyl)-2-(3-fluoro-4-methoxy-benzyl)-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.017 g) was prepared from 3-(4-chloro-phenyl)-2-(3 fluo ro-4-methoxy-benzyl)-4,5,7,8-tetrahyd ro-2 H-1 ,2,6-triaza-azulene-6 10 carboxylic acid tert-butyl ester (Example 96) according to Example 59, Step E. MS (ESI): exact mass calculated for C21H 21

CIFN

3 0, 385.14; found, m/z 386.0 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.48-7.45 (m, 2H), 7.21-7.18 (m, 2H), 6.95-6.92 (m, 1H), 6.67-6.63 (m, 2H), 5.08 (s, 2H), 3.81 (s, 3H), 3.31-3.30 (m, 2H), 3.01-2.98 (m, 2H), 2.94-2.88 (m, 4H), 2.55-2.52 (m, 2H). 13C NMR (125 15 MHz, CD 3 OD): 154.9, 153.8, 153.0, 148,9, 142.5, 136.6, 133.0,132.1, 130.5, 130.0, 129.4,124.3, 120.7, 116.0, 115.8, 115.1, 57.1, 53.3, 51.3, 32.7, 28.0. Example 98 N-N 0 2 N C 20 3-(4-Chloro-phenyl)-1 -(4-nitro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.004 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.3 g) using 4-nitrobenzyl bromide (0.3 g) in place of benzyl 25 chloride. MS (ESI): exact mass calculated for C 20

H

19 ClN 4 0 2 , 382.12; found, m/z 383.1 [M+H]*. 1 H NMR (400 MHz, CD 3 0D): 8.23-8.19 (m, 2H), 7.51-7.47 106 (m, 2H), 7.45-7.47 (m, 2H), 7.32 (d, J= 8.6 Hz, 2H), 5.52 (s, 2H), 2.98-2.95 (m, 4H), 2.89-2.85 (m, 2H), 2.83-2.79 (m, 2H). Example 99

H

2 N 5 H&N 4-(3-Phenyl-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl)-phenylamine. 3-(4-Chloro-phenyl)-1

-(

4 -nitro-benzyl)-4,5,7,8-tetrahydro-1 H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester (Example 98, 70 mg) was dissolved in 25 mL of anhydrous EtOH and treated with 10% palladium on carbon (20 mg). 10 The mixture was subjected to hydrogen for 4 h at 30 psi. The mixture was filtered through diatomaceous earth. The filtrate was concentrated and dried via vacuum line to afford 55 mg of 1-(4-amino-benzyl)-3-phenyl-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The intermediate aniline was then dissolved in 1 mL of MeOH and treated with 5 15 mL of 1 N HCI in Et 2 O. After 6 h, the volatiles were removed in vacuo. The resulting yellow semi-solid was purified by preparative TLC (9:1 CH 2 Cl 2 /2 M

NH

3 in MeOH) to afford 0.007 g of the title compound as a light yellow solid. MS (ESI): exact mass calculated for C 20 H22N 4 , 318.18; found, m/z 319.2 [M+H]. 'H NMR (500 MHz, CD 3 OD): 7.50-7.47 (m, 2H), 7.44-7.41 (m, 2H), 20 7.37-7.34 (m, 1 H), 6.94-6.90 (m, 2H), 6.68-6.65 (m, 2H), 5.23 (s, 2H), 3.11 3.06 (m, 4H), 2.99-2.96 (m, 2H), 2.91-2.88 (m, 2H). Example 100 0 0 N-N HN 25 N-[4-(3-Phenyl-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl)-phenyl] methanesulfonamide. To a solution of 0.022 g of 1-( 4 -amino-benzyl)-3-phenyl-4,5,7,8-tetrahydro-1

H

1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 99) in DMF (1 107 mL) was added 1 equivalent of triethylamine. After 5 min, 1 equivalent of methanesulfonyl chloride was added and the mixture was stirred overnight. The reaction was quenched with water and extracted with EtOAc (3x). The combined organic layers were dried over Na 2

SO

4 and concentrated. The 5 resulting oil was purified by preparative TLC (50% EtOAc/hexanes) to give 1

(

4 -methanesulfonylamino-benzyl)-3-phenyl-4,5,7,8-tetrahydro-.1 H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester. This mono-mesylate was then dissolved in 9:1 CH 2 Cl 2 /MeOH (2 mL) and treated with 3 mL of 1 N HCI in Et 2 0. After 6 h, the volatiles were removed in vacuo. The resulting oil was 10 purified by preparative TLC (9:1 CH 2 Cl 2 /2 M NH 3 in MeOH) to afford 0.004 g of the title compound as a white solid. MS (ESI): exact mass calculated for

C

2 1 1H 2 4

N

4 0 2 S, 396.16; found, m/z 397.1 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.50-7.47 (m, 2H), 7.42 (t, J= 7.7 Hz, 2H), 7.37-7.34 (m, 1 H), 7.22-7.20 (m, 2H), 7.13-7.10 (m, 2H), 5.34 (s, 2H), 2.97-2.93 (m, 4H), 2.92 (s, 3H), 2.90-2.87 15 (m, 2H), 2.82-2.78 (m, 2H). Example 101 0 0 N-N II HN 0 N,N-[4-(3-phenyl-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl)-phenyl] 20 dimethanesulfonanide. 1-( 4 -Amino-benzyl)-3-pheryl-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 99, 0.05 mmol) was dissolved in 1 mL of DMF and treated with 1 equivalent of triethylamine. After 5 min, 1.5 equivalents of methanesulfonyl chloride were added and the mixture was 25 stirred overnight. The reaction was quenched with water and extracted with EtOAc (3x). The combined organic layers were dried over Na 2

SO

4 and concentrated. The resulting oil was purified by preparative TLC (50% EtOAc/hexanes) to provide 1-(4-dimethanesulfonylamino-benzyl)-3-phenyl 4,5,7,8-tetrahydro- 1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. 30 The intermediate was then dissolved in 2 mL of 9:1 CH 2

CI

2 /MeOH and treated 108 with 3 mL of 1 N HCI in Et 2 O. After 6 h, the volatiles were removed in vacuo. The crude oil was purified by preparative TLC (9:1 CH 2

CI

2 /2 M NH 3 in MeOH) to afford 0.006 g of the title compound as an off-white solid. MS (ESI): exact mass calculated for C 22

H

26

N

4 0 4

S

2 , 474.14; found, m/z 475.1 [M+H]*. 'H NMR 5 (500 MHz, CD 3 OD): 7.50-7.47 (m, 2H), 7.44-7.40 (m, 2H), 7.37-7.35 (m, 1 H), 7.22-7.20 (m, 2H), 7.13-7.11 (m, 2H), 5.34 (s, 2H), 2.97-2.94 (m, 4H), 2.92 (s, 6H), 2.89-2.87 (m, 2H), 2.82-2.80 (m, 2H). Example 102 ~- N-N 10 HN 1 -Benzyl-3-p-tolyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.2 g) was prepared from 4-oxo-azepane-1 -carboxylic acid tert-butyl ester (Example 59, Step B; 10 mmol) as in Example 59, Steps C through E, using 4-methyl-benzoyl chloride (11 mmol) in place of 4-chloro 15 benzoyl chloride. MS (ESI): exact mass calculated for C 21

H

23

N

3 , 317.19; found, m/z 318.2 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.34-7.33 (m, 2H), 7.29-7.26 (m, 2H), 7.24-7.21 (m, 3H), 7.10-7.09 (m, 2H), 5.40 (s, 2H), 3.33 3.27 (m, 4H), 3.11-3.09 (m, 2H), 3.00-2.98 (m, 2H), 2.30 (s, 3H). 20 Example 103 N N

HN

3-(4-Chloro-phenyl)-1 -thiophen-2-ylmethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. Step A. 1 -(4-Chlorophenvl)-2-diazo-ethanone. To a solution of diazomethane 25 (33.2 mmmol) in Et 2 0 (70 mL) was added triethylamine (33. 2 mmol). The mixture was cooled to 0 0C, and 4-chlorobenzoyl chloride (30 mmol) in Et 2 0 (30 mL) was added slowly. The mixture was then warmed to RT and stirred for 109 1 h. After filtration of the mixture, the clear filtrate was concentrated to provide the crude desired compound (5.4 g). Step B. 3-(4-Chloro-phenyl)-4,5,7,8-tetrahVdro-1 H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester. To a 0 DC mixture of 4-oxo-piperidine 1 5 carboxylic acid tert-butyl ester (20 mmol) in Et 2 0 (150 mL) was added a solution of BF 3 -Et 2 O (30 mmol) in Et 2 O (150 mL) followed by a solution of the product from Step A (21 mmol) in Et 2 0 (150 mL). After the addition was complete, the mixture was warmed to 25 *C and stirred for 1 h. Satd. aq. NaHCO 3 (200 mL) was added, and the layers were separated. The organic 10 layer was concentrated, and the resulting residue was diluted with MeOH (100 mL). Hydrazine (3 mL) was added and the mixture was stirred at 25 *C for 16 h. Purification by flash chromatography (EtOAc/CH 2 Cl 2 ) provided the desired compound (1.8 g). Step C. The product from Step B (0.2 mmol) was mixed with 2-chloromethyl 15 thiophene (0.3 mmol) in DMF (2 mL), and Cs2CO3 (0.3 mmol) was then added. The mixture was stirred at 25 0C for 16 h. After concentration and purification by SiO 2 chromatography (EtOAc/hexanes), 3-(4-chloro-phenyl)-1 -thiophen-2 ylmethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene was obtained. The intermediate was treated with TFA (1 mL) in CH 2 0 2 (10 mL) for 4 h. After 20 concentration of the reaction mixture, the title compound was obtained (0.029 g). The reaction sequence also provided 3-(4-chloro-phenyl)-2-thiophen-2 ylmethyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C1 8 H1 8 ClN 3 0, 343.09; found, m/z 344.1 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.46-7.44 (m, 25 2H), 7.41-7.39 (m, 2H), 7.29 (dd, J=5.1, 1.1 Hz, 1 H), 7.00 (dd, J = 3.5. 1.1 Hz, 1H), 6.91 (dd, J= 5.1, 3.5 Hz, 1H), 5.52 (s, 2H), 3.36-3.34 (m, 2H), 3.30-3.28 (m, 2H), 3.24-3.18 (m, 2H), 2.99-2.97 (m, 2H). Example 104 through 155 were prepared using the procedure described in 30 Example 103 unless otherwise noted. 110 Example 104 N' N-N \S 1 -Benzyl-3-thiophen-2-y-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (28 mg) was prepared from 3-thiophen-2-yl-4,5,7,8 5 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester as described in Example 103, using thiophene-2-carbonyl chloride (5 mmol) in place of 4-chlorobenzoyl chloride, and benzyl chloride (0.3 mmol) in place of 2 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 18

H

19

N

3 S, 309.13; found, m/z 310.1 [M+H]*.

'

H NMR (500 MHz, CD 3 OD): 7.27-7.01 (m, 10 8H), 5.28 (s, 2H), 3.26-3.24 (br m, 2H), 3.18-3.16 (br m, 2H), 3.11-3.09 (br m, 2H), 2.96-2.94 (br m, 2H). Example 105 1.10 N-N C 15 3-(4-Chloro-phenyl)-1 -(3-methoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.095 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 1 mmol) using 3-methoxy-benzyl chloride (1.5 mmol) in place of 2 20 chloromethyl-thiophene. MS (ESI): exact mass calculated for C21 H 2 2

CIN

3 0, 367.15; found, m/z 368.1 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.60 (d, J= 8.5 Hz, 2H), 7.56 (d, J= 8.5 Hz, 2H), 7.32 (d, J= 7.9 Hz, 1H), 6.92 (dd, J= 8.2, 2.1 Hz, 1H), 6.84 (s, 1H), 6.80 (d, J= 8.2 Hz, 1H), 5.57 (s, 2H), 3.79 (s, 3H), 3.48-3.46 (br m, 2H), 3.44-3.42 (br m, 2H), 3.33-3.31 (br m, 2H), 3.16-3.14 (br 25 m, 2H). 111 Example 106 F N-N H CI HNy 3-(4-Chloro-phenyl)-1-(2-fluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.042 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 2-fluorobenzyl chloride (0.3 mmol) in place of 2 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 2 oHl 9

CIFN

3 , 355.13; found, m/z 356.2 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.55-7.48 (br 10 m, 4H), 7.39-3.37 (br m, 1 H), 7.20-7.14 (m, 3H), 5.54 (s, 2H), 3.48-3.46 (br m, 2H), 3.40-3.38 (br m, 2H), 3.31-3.29 (br m, 2H), 3.13-3.11 (br m, 2H). Example 107 N N-N H CI HNy 15 3-(4-Chloro-phenyl)-1 -(2-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.03 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 2-methylbenzyl chloride (0.3 mmol) in place of 2 20 chloromethyl-thiophene. The reaction sequence also yielded 3-(4-chloro phenyl)- 2 -(2-methyl-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 2 1H 22

CIN

3 , 351.15; found, m/z 352.2 [M+H]*. 'H NMR (400 MHz, CD 3 0D): 7.56 (d,. J= 8.5 Hz, 2H), 7.49 (d, J= 8.5 Hz, 2H), 7.23-7.15 (m, 25 3H), 6.58 (d, J= 7.5, 1 H), 5.50 (s, 2H), 3.42-3.39 (br m, 4H), 3.15-3.12 (br m, 4H), 2.40 (s, 3H). 112 Example 108 F ~ N-N F H Cl HN 3-(4-Chloro-phenyl)-1 -(2,4-difluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.030g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 2,4-difluorobenzyl bromide (0.3 mmol) in place of 2-chloromethyl-thiophene. The reaction sequence also yielded 3-(4-chloro phenyl)-2-(2,4-difluoro-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 10 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 2 aH 1 aCIF 2

N

3 , 373.12; found, m/z 374.1 [M+H]*. 'H NMR (400 MHz, CD 3 0D): 7.52-7.49 (br m, 4H), 7.27-7.24 (br m, 1 H), 7.01-6.99 (br m, 2H), 5.52 (s, 2H), 3.51-3.49 (br m, 2H), 3.43-3.40 (br m, 2H), 3.34-3.31 (br m, 2H), 3.11-3.09 (br m, 2H). 15 Example 109

N

0 N-N H C1 HN 3-(4-Chloro-phenyl)-1 -(2-methoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 20 The title compound (0.06 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.3 mmol) using 2-methoxybenzyl chloride (0.3 mmol) in place of 2-chloromethyl-thiophene. The reaction sequence also yielded 3-(4-chloro phenyl)-2-(2-methoxy-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 25 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 21

H

22

CIN

3 0, 367.15; found, m/z368.1 (M+H]*. 1 H NMR (500 MHz, CDCl 3 ): 7.45-7.43 (m, 2H), 7.30-7.27 (m, 2H), 7.18-7.17 (m, 1H), 6.80 113 6.77 (m, 2H), 6.61-6.59 (m, 1 H), 5.26 (s, 2H), 3.80 (s, 3H), 2.92-2.86 (m, 4H), 2.74-2.69 (m, 4H). Example 110 CI N-N 5 HNCI 1-(2-Chloro-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.01 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 10 103, Step B; 0.2 mmol) using 2-chlorobenzyl chloride (0.3 mmol) in place of 2 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 1 7

H

22

CIN

3 0, 371.10; found, rn/z 372.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.43-7.41 (m, 2H), 7.32-7.30 (m, 2H), 7.32 (d, J= 8.6 Hz, 2H), 6.76 (d, J= 8.6 Hz, 2H), 5.23 (s, 2H), 2.94-2.91 (br m, 4H), 2.79-7.77 (br m, 2H), 2.73-7.71 (br m, 2H). 15 Example 111 N-N H _C1 HN 1-But-3-enyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.028 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 20 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 1 -but-3-enyl chloride (0.3 mmol) in place of 2 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 17

H

2 2

CIN

3 0, 301.13; found, m/z 302.1 [M+H]. 'H NMR (500 MHz, CDCI 3 ): 7.40-7.37 (m, 2H), 7.31-7.28 (m, 2H), 6.75-6.67 (m, 1H), 5.02-5.00 (br m, 2H), 4.07 (t, J= 7.3 25 Hz, 2H), 2.99-2.97 (br m, 2H), 2.91-2.89 (br m, 2H), 2.80-2.78 (br m, 2H), 2.71 2.69 (br m, 2H), 2.48 (q, J= 7.3 Hz, 2H). 114 Example 112 Br N-N H C1 HN 1 -(2-Bromo-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.035 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 2-bromobenzyl bromide (0.3 mmol) in place of 2 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 20

H

1 gBrCIN 3 , 415.05; found, m/z 418.0 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.69 (d, J= 10 7.8 Hz, 1H), 7.53-7.27 (m, 6H), 6.78 (d, J= 7.8 Hz, 1H), 5.58 (s, 2H), 3.50-3.48 (br m, 4H), 3.19-3.17 (br m, 4H). Example 113 'N N-N Br \ Ci 15 1 -(4-Bromo-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.032 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.3 mmol) using 4-bromobenzyl bromide (0.3 mmol) in place of 2 20 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 2 0H 1 gBrCIN 3 , 415.05; found, m/z 418.0 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.48-7.40 (m, 6H), 6.92 (d, J = 8.4 Hz, 2H), 5.28 (s, 2H), 3.32-3.30 (br m, 4H), 3.03-3.01 (br m, 4H). 115 Example 114 N-N Cl HN 3-(4-Chloro-phenyl)-1 -(2-ethyl-butyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.010 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 1-bromo-2-ethyl-butane (0.3 mmol) in place of 2 chloromethyl-thiophene. The reaction sequence also yielded 3-(4-chloro phenyl)-2-(2-ethyl-butyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 10 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 1 9

H

26

CIN

3 , 331.18; found, m/z 332.3 [M+H]*. 1H NMR (400 MHz, CD30D): 7.50-7.48 (br m, 4H), 4.11-4.09 (br m, 2H), 3.71-3.69 (br m, 2H), 3.33-3.31 (br m, 2H), 3.26-3.24 (br m, 2H), 3.06-3.04 (br m, 2H), 1.91-1.89 (m, 1H), 1.36-1.34 (m, 4H), 0.93 (t, J= 7.3 Hz, 6H). 15 Example 115 N-N HN 3-(4-Chloro-phenyl)-1 -(5-chloro-thiophen-2-ylmethyl)-1,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene. 20 The title compound (0.029 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 5-chloro-thiophen-2-ylmethyl chloride (0.3 mmol) in place of 2-chloromethyl-thiophene. The reaction sequence also yielded 3-(4 chloro-phenyl)-2-(5-chloro-thiophen-2-ylmethyl)-4,5,7,8-tetrahydro-2H- 1,2,6 25 triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 1 8

H

17 Cl 2

N

3 S, 377.05; found, m/z 378.0 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.54-7.51 (m, 2H), 7.49-7.46 (m, 2H), 116 3.91 (d, J= 3.8 Hz, 1H), 6.86 (d, J= 3.8 Hz, 1H), 5.51 (s, 2H), 3.45-3.44 (m, 2H), 3.38-3.61 (m, 2H), 3.27-3.25 (m, 2H), 3.07-3.05 (m, 2H). Example 116 Br C 1-(3-Bromo-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.04 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 10 103, Step B; 0.2 mmol) using 3-bromobenzyl chloride (0.3 mmol) in place of 2 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 2 aH 1 gBrCIN 3 , 415.05; found, m/z416.0 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.50-6.86 (m, 8H), 5.36 (s, 2H), 3.30-3.27 (br m, 4H), 3.06-3.04 (m, 4H). 15 Example 117 ?N

-

/ N HN 3-(4-Chloro-phenyl)-1 -cyclohexylmethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.09 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 20 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 170 mg) using cyclohexylmethyl bromide (2 mmol) in place of 2 chloromethyl-thiophene. The reaction sequence also yielded 3-(4-chloro phenyl)-2-cyclohexylmethyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass 25 calculated for C 2 oH 26

CIN

3 , 343.18; found, m/z 344.3 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.37 (d, J = 6.6 Hz, 2H), 7.32 (d, J = 6.6 Hz, 2H), 3.94 (d, J = 7.3 Hz, 2H), 3.44-3.40 (br m, 2H), 3.35-3.32 (br m, 2H), 3.17-3.14 (br m, 2H), 117 3.01-2.99 (br m, 2H), 1.74-1.53 (m, 4 H), 1.52 (d, J= 11.2 Hz, 2H), 1.17-1.10 (m, 3H), 0.94-0.90 (m, 2H). Example 118 N-N 5 HNC 3-(4-Chloro-phenyl)-1-isobutyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.031 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 --1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using isobutyl bromide (0.3 mmol) in place of 2 10 chloromethyl-thiophene. The reaction sequence also yielded 3-(4-chloro phe nyl)-2-isobutyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-ca rboxylic acid tert-butyl ester from the alkylation step. MS (ESI): exact mass calculated for

C

17

H

2 2 ClN 3 , 303.15; found, m/z 304.1 [M+H]*. 'H NMR (500 MHz, CDaOD): 7.64 (d, J= 6.6 Hz, 2H), 7.56 (d, J= 6.6 Hz, 2H), 4.20 (d, J=7.4 Hz, 2H), 3.72 15 3.69 (br m, 2H), 3.62-3.60 (br m, 2H), 3.44-3.42 (br m, 2H), 3.29-3.27 (br m, 2H), 2.35 (m, 1H), 1.14 (d, J= 6.7 Hz, 6H). Example 119 o0 N-N HN 20 1 -Benzo[1,3]dioxol-5-ylmethyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.035 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using benzo[1,3]dioxol-5-ylmethyl chloride (0.3 mmol) 25 in place of 2-chloromethyl-thiophene. The reaction sequence also yielded 2 benzo[1, 3 ]dioxol-5-ylmethyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C21H 2 0

CIN

3 0 2 , 381.12; found, m/z 382.1 118 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.39-7.32 (m, 4H), 6.67-6.65 (m 1H), 6.54-6.61 (m, 2H), 5.81 (s, 2H), 5.16 (s, 2H), 2.81-2.79 (m, 4H), 2.76-2.74 (m, 2H), 2.68-2.66 (m, 2H). 5 Example 120 N-N 0 CHN 3-(4-Chloro-phenyl)-1 -(tetrahydro-pyran-4-ylmethyl)-1 ,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene. The title compound was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro 10 1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using toluene-4-sulfonic acid tetrahydro-pyran-4-ylmethyl ester (0.3 mmol) in place of 2-chloromethyl-thiophene. The title compound was obtained as a 2:1 mixture (25 mg) with 3-(4-chloro-phenyl)-2-(tetrahydro-pyran 4-ylmethyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Data for the mixture: 15 MS (ESI): exact mass calculated for C 19

H

24

CIN

3 0, 345.16; found, m/z 346.1 [M+H]*. 1 H NMR (500 MHz, CDaOD): 7.47-7.23 (m, 4H), 4.10-3.78 (m, 4H), 3.37-3.14 (m, 8H), 3.06-2.67 (m, 2H), 2.02-1.93 (m, 1H), 1.42-0.97 (m, 4H). Example 121 F F N-N C/ CI 20 HN 3-(4-Chloro-phenyl)-1-(2,6-difluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.07 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 25 103, Step B; 1 mmol) using 2,6-difluorobenzyl chloride (1.5 mmol) in place of 2 chloromethyl-thiophene. The reaction sequence also yielded 3-(4-chloro 119 phenyl)-2-(2,6-difluoro-benzyl)-4,5,7,8-tetrahydro-2H- 1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 20

H

18

CIF

2

N

3 , 373.12; found, m/z 374.1 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.34-7.30 (m, 5H), 6.93-6.90 (m, 2H), 5.34 (s, 2H), 3.59-3.57 5 (m, 2H), 3.39-3.37 (m, 4H), 2.94-2.92 (m, 2H). Example 122 N-N H C1

HN

3-(4-Chloro-phenyl)-2-cyclohexylmethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza 10 azulene. The title compound (0.06 g) was prepared from 3-(4-chloro-phenyl)-2 cyclohexylmethyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 117) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 20

H

2

CIN

3 , 15 343.18; found, m/z 344.2 [M+H]*. 'H NMR (500 MHz, CD3OD): 7.39 (d, J= 8.5 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 4.10 (d, J = 7.3 Hz, 2H), 3.49-3.47 (br m, 2H), 3.37-3.35 (br m, 2H), 3.21-3.19 (br m, 2H), 3.03-3.01 (br m, 2H), 1.88-1.61 (m, 4 H), 1.52-1.49 (m, 2H), 1.17-1.10 (m, 3H), 0.94-0.90 (m, 2H). 20 Example 123 1 N -~ N C1 3-(4-Chloro-phenyl)-1 -(4-methoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.1 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 25 tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 1 mmol) using 4-methoxybenzyl chloride (1.5 mmol) in place of 2 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 2 1

H

2 2 ClN 3 0, 120 367.15; found, m/z 368.1 [M+H]*. 1H NMR (400 MHz, CDsOD): 7.41-7.39 (m, 2H), 7.31 (d, J = 7.7 Hz, 2H), 6.70 (d, J = 7.7 Hz, 2H), 5.36 (s, 2H), 3.60 (s, 3H), 3.33-3.31 (br m, 2H), 3.21-3.19 (br m, 2H), 3.18-3.16 (br m, 2H), 2.96-2.94 (br m, 2H). 5 Example 124 N-N H C I HN: 3-(4-Chloro-phenyl)-1 -(3-methyl-butyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 10 The title compound (0.030 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 1-bromo-3-methyl-butane (0.3 mmol) in place of 2-chloromethyl-thiophene. MS (ESI): exact mass calculated for C 18

H

24

CIN

3 , 317.17; found, m/z 318.3 [M+H]*. 'H NMR (400 MHz, CD 3 0D): 7.56-7.54 (m, 15 4H), 4.34 (s, 2H), 3.57-3.55 (br m, 2H), 3.44-3.42 (br m, 2H), 3.40-3.38 (br m, 2H), 3.29-3.27 (br m, 2H), 1.79-1.77 (br m, 1 H), 1.02 (d, J = 4.5 Hz, 6H)., Example 125

CF

3 N-N H Cl HN: 20 3-(4-Chloro-phenyl)-1 -(2-trifluoromethyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.04 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 2-trifluoromethylbenzyl bromide (0.3 mmol) in 25 place of 2-chloromethyl-thiophene. The reaction sequence also yielded 3-(4 chloro-phenyl)-2-(2-trifluoromethyl-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): 121 exact mass calculated for C 2 1

H

1 9

CIF

3

N

3 , 405.12; found, m/z406.1 [M+H]*. 1 H NMR (400 MHz, CDaOD): 7.45 (d, J= 7.7 Hz, 2H), 7.25-7.24 (br m, 3H), 7.18 7.16 (br m, 3H), 6.46-6.44 (br m, 1H), 5.43-5.41 (s, 2H), 3.14-3.11 (br m, 4H), 2.89-2.87 (br m, 4H). 5 Example 126 N-N / CI HNy 3-(4-Chloro-phenyl)-2-(2-methyl-benzyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 10 The title compound (0.020 g) was prepared from 3-(4-chloro-phenyl)-2-(2 methyl-benzyl)-4,5,7,8-tetrahydro-2H- 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 107) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 2 1

H

22

CIN

3 , 351.15; found, m/z 352.2 [M+H]*. 'H NMR (400 MHz, CD3OD): 7.47 (d, J= 15 8.4 Hz, 2H), 7.24 (d, J= 8.4 Hz, 2H), 7.15 (m, 3H), 6.60 (d, J= 7.6 Hz, 1H), 5.23 (s, 2H), 3.46-3.44 (m, 2H), 3.36-3.34 (m, 2H), 3.21-3.19 (m , 2H), 2.89 2.87 (m, 2H), 2.13 (s, 3H). Example 127 N-N/--/ / Ci 20 HN 2 -Benzyl-3-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.018 g) was prepared from 2-benzyl-3-(4-chloro-phenyl) 4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 59, Step D) according to the deprotection method in Example 103, 25 Step C. MS (ESI): exact mass calculated for C 20

H

20

CIN

3 , 337.13; found, m/z 338.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.30-7.28 (m, 2H), 7.20-7.15 (m, 122 3H), 7.03-7.01 (m, 2H), 6.91-6.89 (m, 2H), 5.06 (s, 2H), 3.03-3.01 (m, 2H), 2.94-2.90 (m, 4H), 2.51-2.49 (m, 2H). Example 128 N-N 5 HN 3-(4-Chloro-phenyl)-1 -(4-methoxy-2-methyl-benzyl)-1,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene. To a solution of 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene 6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.4 mmol) in toluene (3 10 mL) was added 4-methoxy-2-methyl-benzyl chloride (0.9 mmol) and cyanomethylene-tri-n-butylphosphorane (1 mmol). The mixture was heated at 110 0C for 16 h. After concentration and purification (SiO 2 , EtOAc/hexanes), 3 (4-chloro-phenyl)-1 -(4-methoxy-2-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester was obtained (54 mg). The 15 other regioisomer, 3-(4-chloro-phenyl)-2-(4-methoxy-2-methyl-benzyl) 1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester, was also obtained (86 mg). 3-(4-Chloro-phenyl)-1-(4-methoxy-2-methyl benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (20 mg) was treated with TFA (1 mL) in CH 2 02 (10 mL) for 4 h. After 20 concentration of the reaction mixture, the title compound was obtained (0.02 g). MS (ESI): exact mass calculated for C22H 24

CIN

3 0, 381.16; found, m/z 382.1 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.39-7.37 (m, 2H), 7.34-7.32 (m, 2H), 6.68-6.66 (br m, 1 H), 6.54-6.52 (br m, 1 H), 6.37 (d, J= 8.3 Hz, 1 H), 5.21 (s, 2H), 2.81-2.79 (m, 4H), 2.71-2.69 (m, 4H). 25 123 Example 129 F F N--N H / CI HN 3-(4-Chloro-phenyl)-2-(2,4-difluoro-benzyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.016 g) was prepared from 3-(4-chloro-phenyl)-2-(2,4 difluoro-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 108; 0.2 mmol) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 20

H

18

CIF

2

N

3 , 373.12; found, m/z 374.1 [M+H]*. 1H NMR (400 MHz, CD 3 0D): 7.54 (d, J= 10 8.0 Hz, 2H), 7.49 (d, J= 8.0 Hz, 2H), 6.96-6.88 (m, 3H), 5.27 (s, 2H), 3.46-3.44 (br m, 2H), 3.34-3.32 (br m, 2H), 3.23-3.21 (br m, 2H), 2.86-2.84 (br m, 2H). Example 130 0 0 0 N-N / CI HN 15 5-[ 3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-ylmethyl] furan-2-carboxylic acid ethyl ester. The title compound (0.008 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 5-chloro-furan-2-carboxylic acid ethyl ester (0.3 20 mmol) in place of 2-chloromethyl-thiophene. The reaction sequence also provided 3-(4-chloro-phenyl)-1-(5-ethoxycarbonyl-furan-2-ylmethyl)-4,5,7,8 tetrahydro-1 H-1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 2 1

H

22

CIN

3 0 3 , 399.13; found, m/z 400.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.44 (d, J= 8.4 Hz, 25 2H), 7.30 (d, J= 8.4 Hz, 2H), 7.00 (d, J= 3.5 Hz, 1H), 6.21 (d, J= 3.5 Hz, 1H), 124 5.09 (s, 2H), 4.21 (q, J = 7.1 Hz, 2H), 3.21-3.19 (m, 2H), 3.11-3.09 (m, 2H), 2.96-2.94 (m, 2H), 2.61-2.59 (m, 2H), 1.24 (t, J= 7.1 Hz, 2H). Example 131 N-N 5 HN C 3-(4-Chloro-phenyl)-2-isobutyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azu lene. The title compound (0.010 g) was prepared from 3-(4-chloro-phenyl)-2-isobutyl 4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 118, Step C) according to the deprotection method from Example 10 103, Step C. MS (ESI): exact mass calculated for C 17

H

22

CIN

3 , 303.15; found, m/z 304.1 [M+H]*. 'H NMR (400 MHz, CD 3 OD): 7.58-7.56 (m, 2H), 7.37-7.34 (m, 2H), 3.81 (d, J=7.5 Hz, 2H), 3.42-3.40 (m, 2H), 3.34-3.30 (m, 2H), 3.18 3.15 (m, 2H), 2.81-2.78 (m, 2H), 2.02-2.00 (m, 1H), 0.74 (d, J= 6.7 Hz, 6H). 15 Example 132 -0 N-N/- / H &N 3-( 4 -Chloro-phenyl)-2-(2-methoxy-benzyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.040 g) was prepared from 3-(4-chloro-phenyl)-2-(2 20 methoxy-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 109) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C21H 22

CIN

3 0 3 , 399.13; found, m/z 368.2 [M+H]*. 1 H NMR (500 MHz, CDCI 3 ): 7.26 (d, J= 6.5 Hz, 2H), 7.12 (t, J= 7.6 Hz, 1 H), 7.03 (d, J= 6.5 Hz, 2H), 6.80 (t, J= 7.6 Hz, 25 1H), 6.71 (d, J= 7.6 Hz, 1H), 6.62 (d, J= 7.6 Hz, 1H), 5.08 (s, 2H), 2.99-2.97 (m, 2H), 2.89-2.87 (m, 4H), 2.49-2.47 (m, 2H). 125 Example 133 N-N HN 2 -Benzyl-3-phenyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene. 5 To a solution of 2-benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (0.1 mmol) (Example 59, Step D) in THF (25 mL) was added lithium aluminum hydride (100 mg). The mixture was heated at reflux for 4 h. Water (1 mL) was added, the mixture was filtered, and the filtrate was concentrated. After purification (SiO 2 , EtOAc/hexanes), 2 10 benzyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester was obtained. The intermediate was diluted with CH 2

CI

2 (5 mL) and TFA (1 mL) was added. The reaction mixture was stirred at RT for 4 h. The reaction mixture was concentrated to obtain the title compound (0.018 g). MS (ESI): exact mass calculated for C 20

H

2 1 1N 3 , 303.17; found, m/z 304.3 15 [M+H]*. 'H NMR (400 MHz, CD 3 0D): 7.38-7.35 (m, 3H), 7.19-7.18 (m, 3H), 7.12-7.10 (m, 2H), 5.13 (s, 2H), 3.35-3.21 (br m, 6H), 3.34-3.30 (br m, 2H), 2.81-2.79 (br m, 2H). Example 134 >N--N / CI 20 HN 3-(4-Chloro-phenyl)-1 -prop-2-ynyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.014 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 2-propynyl chloride (0.3 mmol) in place of 2 25 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 16

H

16

CIN

3 , 285.10; found, m/z 286.2 [M+H]*. 1H NMR (500 MHz, CD 3 0D): 7.38-7.32 (m, 126 4H), 7.13 (t, J = 6.4 Hz, 1 H), 5.48 (d, J= 6.4 Hz, 2H), 2.93-2.91 (m, 4H), 2.84 2.81 (m, 2H), 2.68-2.65 (m, 2H). Example 135 F F F F F N-N 5 HN C 3-(4-Chloro-phenyl)-1 -pentafluorophenylmethyl-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.02 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 10 103, Step B; 0.2 mmol) using pentafluorophenylmethyl chloride (0.3 mmol) in place of 2-chloromethyl-thiophene. The reaction sequence also yielded 3-(4 chloro-phenyl)-2-pentafluorophenylmethyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 20

H

15

CIF

5

N

3 , 427.09; found, m/z428.1 [M+H]*. 1 H 15 NMR (500 MHz, CD 3 0D): 7.30 (br s, 4H), 5.34 (s, 2H), 3.01 (br s, 4H), 2.90 2.88 (m, 2H), 2.71-2.69 (m, 2H). Example 136 S N-N HNC 20 3-(4-Chloro-phenyl)-2-thiophen-2-ylmethyl-2,4,5,6,7,8-hexahydro-1, 2,6-triaza azulene. The title compound (0.010 g) was prepared from 3-(4-chloro-phenyl)-2 thiophen-2-ylmethyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester according to the method in Example 103. MS (ESI): exact 127 mass calculated for C1 8

H

1 8 01N 3 S, 343.09; found, m/z 344.1 [M+H]*. 1H NMR (500 MHz, CD 3 OD): 7.60-7.58 (m, 2H), 7.38-7.35 (m, 2H), 7.32 (dd, J=5.1, 1.1 Hz, 1H), 6.92 (dd, J= 5.1, 3.5 Hz, 1H), 6.78 (dd, J= 3.5, 1.1 Hz, 1H), 5.41 (s, 2H), 3.47-3.45 (m, 2H), 3.37-3.35 (m, 2H), 3.23-3.21 (m, 2H), 2.85-2.83 (m, 5 2H). Example 137 F F F N-N HNY 3-(4-Chloro-phenyl)-1-(2,4,6-trifluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6 10 triaza-azulene. The title compound (0.027 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using 2,4,6-trifluorobenzyl chloride (0.3 mmol) in place of 2-chloromethyl-thiophene. MS (ESI): exact mass calculated for 15 C 20 Hl 7

CIF

3

N

3 , 391.11; found, m/z 392.1 [M+H]*. 1 H NMR (500 MHz, CD3OD): 7.30-7.26 (m, 4H), 6.80-6.78 (br m, 2H), 5.25 (s, 2H), 2.94-2.92 (m, 4H), 2.82 2.80 (m, 2H), 2.66-2.62 (m, 2H). Example 138 CN / C 20 HN 2

-[

3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl] benzonitrile. The title compound (0.032 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2, 6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 25 103, Step B; 0.2 mmol) using 2-chloro-benzonitrile (0.3 mmol) in place of 2 128 chloromethyl-thiophene. MS (ESI): exact mass calculated for C 21

H

19

CIN

4 , 362.13; found, m/z 363.2 [M+H]*. 'H NMR (400 MHz, CDaOD): 7.81 (d, J= 7.6 Hz, 1 H), 7.68-7.66 (br m, 1 H), 7.54-7.51 (m, 3H), 7.46 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 7.6 Hz, 1 H), 5.64 (s, 2H), 3.51-3.49 (br m, 2H), 3.43-3.41 (br m, 5 2H), 3.31-3.29 (br m, 2H), 3.13-3.11 (br m, 2H). Example 139 S C N-N H Cl HN 3-( 4 -Chloro-phenyl)-2-(5-chloro-thiophen-2-ylmethyl)-2,4,5,6,7,8-hexahydro 10 1,2,6-triaza-azulene. The title compound (0.009 g) was prepared from 3-(4-chloro-phenyl)-2-(5 chloro-thiophen-2-ylmethyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 115) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for 15 C18H 17 Cl 2 NsS, 377.05; found, m/z 378.0 [M+H]*. 1 H NMR (500 MHz, CDsOD): 7.47-7.44 (m, 2H), 7.22-7.20 (m, 2H), 6.65 (d, J = 3.8 Hz, 1H), 6.44 (d, J= 3.8 Hz, 1H), 5.17 (s, 2H), 3.32-3.30 (m, 2H), 3.21-3.19 (m, 2H), 3.07-3.05 (m, 2H), 2.70-2.68 (m, 2H). 20 Example 140 FF F N-N 1/1 H/ Ci 3

-(

4 -Chloro-phenyl)-2-(2,6-difluoro-benzyl)-2,4,5,6,7,8- hexahydro-1,2,6-triaza azulene. The title compound (0.036 g) was prepared from 3-(4-chloro-phenyl)-2-(2,6 25 difluoro-benzyl)-4,5,7,8-tetrahydro-2H-1, 2 ,6-triaza-azulene-6-carboxylic acid 129 tert-butyl ester (Example 121, Step C) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 20

H

18 C1F 2

N

3 , 373.12; found, m/z374.2 [M+H]*. 1H NMR (500 MHz, CD30D): 7.44-7.42 (m, 2H), 7.27-7.23 (m, 3H), 6.79 (m, 2H), 5.14 (s, 2H), 3.27-3.25 (m, 2H), 3.21-3.18 5 (m, 2H), 3.02-3.00 (m, 2H), 2.69-2.67 (m, 2H). Example 141

F

3 C N-N H N 3-(4-Chloro-phenyl)-2-(2-trifluoromethyl-benzyl)-2,4,5,6,7,8-hexahydro-1,2,6 10 triaza-azulene. The title compound (0.021 g) was prepared from 3-(4-chloro-phenyl)-2-(2 trifluoromethyl-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 125) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 2 1

H

19

CIF

3

N

3 , 15 405.12; found, m/z 406.1 [M+H]*. 'H NMR (400 MHz, CD 3 OD): 7.69 (d, J= 7.8 Hz, 1H), 7.59 (t, J= 7.2 Hz, 1H), 7.53-7.46 (m, 3H), 7.27 (d, J= 8.1, 2H), 6.83 (d, J= 7.2 Hz, 1H), 5.47 (s, 2H), 3.51-3.49 (br m, 2H), 3.42-3.40 (br m, 2H), 3.31-3.29 (br m, 2H), 2.94-2.92 (br m, 2H). 20 Example 142 ~K N-N C1 3-(4-Chloro-phenyl)-1 -naphthalen-2-ylmethyl-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.043 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 25 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.2 mmol) using naphthalen-2-ylmethyl chloride (0.3 mmol) in place of 2-chloromethyl-thiophene. MS (ESI): exact mass calculated for 130

C

2 4

H

2 2

CIN

3 , 387.15; found, m/z 388.1 [M+H]-. 1 H NMR (500 MHz, CDCl 3 ): 7.74-7.69 (m, 3H), 7.45-7.38 (m, 5H), 7.34-7.32 (m, 1H), 7.18-7.16 (m, 2H), 5.43 (s, 2H), 3.04 (m, 2H), 2.99-2.97 (m, 2H), 2.87-2.85 (m, 4H). 5 Example 143 N-N H C& 3-(4-Chloro-phenyl)-2-(2-ethyl-butyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.012 g) was prepared from 3-(4-chloro-phenyl)-2-(2-ethyl 10 butyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 114) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 19

H

26

CIN

3 , 331.18; found, m/z 332.2 [M+H]*. 'H NMR (400 MHz, CD 3 OD): 7.50-7.25 (br m, 4H), 3.76-3.74 (m, 2H), 3.33-3.31 (br m, 2H), 3.22-3.20 (br m, 2H), 3.09-3.07 (br m, 2H), 2.73 15 2.71 (br m, 2H), 1.56-1.54 (m, 1H), 1.16-1.14 (m, 4H), 0.82-0.55 (m, 6H). Example 144 0 N-N HN 5-[ 3

-(

4 -Chloro-phenyl)-5,6,7,8-tetrahydro-4 H-1,2,6-triaza-azulen- 1 -ylimethyl] 20 furan-2-carboxylic acid ethyl ester. The title compound (0.017 g) was prepared from 3-(4-chloro-phenyl)-1 -(5 ethoxyca rbonyl-fu ran-2-ylimethyl)-4,5,7,8-tetrahydro- 1 H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 130) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for 25 C 2 1

H

22

CIN

3 0 3 , 399.13; found, m/z 400.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.37-7.32 (m, 4H), 7.06 (d, J = 3.5 Hz, 1 H), 6.41 (d, J = 3.5 Hz, 1 H), 5.34 (s, 131 2H), 4.21 (q, J= 7.1 Hz, 2H), 3.26-3.24 (m, 2H), 3.19-3.17 (m, 2H), 3.13-3.11 (m, 2H), 2.86-2.84 (m, 2H), 1.24 (t, J= 7.1 Hz, 2H). Example 145 N N-N 5 HNC 3-(4-Chloro-phenyl)-1 -naphthalen-1 -ylmethyl-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.015 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 10 103, Step B; 0.2 mmol) using 1-naphthalen-methyl chloride (0.3 mmol) in place of 2-chloromethyl-thiophene. The reaction sequence also provided 3-(4-chloro phenyl)-2-naphthalen-1 -ylmethyl-4,5,7,8-tetrahydro-2H- 1,2,6-triaza-azu lene-6 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 24 H22CIN 3 , 387.15; found, m/z 388.1 [M+H]*. 1 H NMR (500 15 MHz, CD 3 OD): 7.79-7.18 (m, 11H), 5.74 (d, J= 7.3 Hz, 2H), 3.42 (s, 2H), 3.21 3.19 (br m, 2H), 3.10-3.08 (br m, 2H), 2.92-2.90 (br m, 2H), 2.84-2.82 (br m, 2H). Example 146 N-N / / CI 20 HN 2-Benzo[1, 3 ]dioxol-5-ylmethyl-3-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.021 g) was prepared from 2-benzo[1,3]dioxol-5-ylmethyl 3

-(

4 -chloro-phenyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic 25 acid tert-butyl ester (Example 119) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 21

H

20

CIN

3 0 2 , 132 381.12; found, m/z382.0 [M+H)*. 'H NMR (500 MHz, CD 3 0D): 7.37-7.34 (m, 2H), 7.11-7.10 (m, 2H), 6.57 (d, J= 7.9 Hz, 1H), 6.31-6.29 (r,, 2H), 5.79 (s, 2H), 4.95 (s, 2H), 3.55-3.40 (m, 1H), 2.82-2.80 (m, 5H), 2.42-2.41 (m, 2H). 5 Example 147 0N-N OH Cl HN [3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1-yl]-acetic acid methyl ester. The title compound (0.09 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 10 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyi ester (Example 103, Step B; 1 mmol) using 2-bromoacetic acid methyl ester (1.5 mmol) in place of 2-chloromethyl-thiophene. MS (ESI): exact mass calculated for

C

16

H

18

CIN

3 0 2 , 319.11; found, m/z 320.2 [M+H]*. 'H NMR (500 MHz, CD:OD): 7.31 (d, J= 8.1 Hz, 2H), 7.26 (d, J= 8.1 Hz, 2H), 4.93 (s, 2H), 3.56 (s, 3H), 15 3.27-3.25 (br m, 2H), 3.19-3.17 (br m, 2H), 3.04-3.03 (br m, 2H), 2.90-2.88 (br m, 2H). Example 148 H HNC 20 2-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl]-N-methyl acetamide. To a solution of 3-(4-chloro-phenyl)-1 -imethylcarbamoylmethyl-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (44 mg) (Example 147) in THF (0.5 mL) was added 8% aq. NaOH (0.3 mL). The 25 mixture was stirred at RT for 16 h, and then was acidified with 1 N HCI (0.5 mL). The mixture was extracted with CH 2

CI

2 (2x2 mL). The combined organic layers were washed with brine, dried over Na 2

SO

4 , and concentrated. The residue was diluted with CH 3 CN (0.5 mL) and treated with DCC (26 mg) and 133 HOBt (18 mg). After 2 h at RT, a solution of methylamine hydrochloride (70 mg) in H 2 0 (0.3 mL) was added. The mixture was stirred at RT for 16 h. Concentration of the reaction mixture and purification of the residue by SiO 2 chromatography (EtOAc/hexanes) gave 3-(4-chloro-phenyl)-1 5 methylcarbamoylmethyl-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The intermediate was treated with TFA (1 mL) in CH 2 Cl 2 (10 mL) for 4 h, and the solution was concentrated to obtain the title compound (0.015 g). MS (ESI): exact mass calculated for C 1 6 H1 9

CIN

4 0, 318.12; found, m/z 319.1 [M+H]*. 1 H NMR (500 MHz, CD30D): 7.41-7.32 (m, 4H), 5.94 (br s, 10 1 H), 4.70 (s, 2H), 2.98-2.90 (m, 4H), 2.77-2.71 (m, 7H). Example 149 F F F F F N-N / CI HN 3

-(

4 -Chloro-phenyl)-2-pentafluorophenylmethyl-2,4,5,6,7,8-hexahydro-1,2,6 15 triaza-azulene. The title compound (0.016 g) was prepared from 3-(4-chloro-phenyl)-2 pentafluorophenylmethyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 135) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for 20 C 2 0H 1 5 ClF 5

N

3 , 427.09; found, m/z 428.1 [M+H]*.'H NMR (500 MHz, CD 3 OD): 7.45-7.43 (m, 2H), 7.26-7.23 (m, 2H), 5.15 (s, 2H), 2.91-2.89 (m, 2H), 2.83 2.81 (m, 2H), 2.79-2.77 (m, 2H), 2.46-2.44(m, 2H). Example 150 1-0 N-N 25 HN 134 3-(4-Chloro-phenyl)-1 -(3,4,5-trimethoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.006 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 5 103, Step B; 0.2 mmol) using 3,4,5-trimethoxybenzyl chloride (0.3 mmol) in place of 2-chloromethyl-thiophene. The reaction sequence also yielded 3-(4 chloro-phenyl)-2-(3,4,5-trimethoxy-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C23H 26

CIN

3 0 3 , 427.17; found, n/z 428.1 [M+H]*. 'H 10 NMR (500 MHz, CD 3 OD): 7.51-7.49 (m, 2H), 7.46-7.44 (m, 2H), 6.44 (s, 2H), 5.32 (s, 2H), 3.78 (s, 6H), 3.74 (s, 3H), 2.95-2.89 (m, 6H), 2.81-2.79 (m, 2H). Example 151 N-N / / Ci 15 3 -(4-Chloro-phenyl)-2-naphthalen-1 -ylmethyl-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (0.015 g) was prepared from 3-(4-chloro-phenyl)-2 naphthalen-1 -ylmethyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 145) according to the deprotection method in 20 Example 103, Step C. MS (ESI): exact mass calculated for C 24 H22CIN 3 , 387.15; found, m/z 388.2 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 7.78-7.75 (m, 2H), 7.67 (d, J= 8.3 Hz, 1H), 7.41-7.39 (m, 2H), 7.00 (td, J= 8.0, 1.0 Hz, 1H), 7.21-7.19 (m, 2H), 7.02-7.01 (m, 2H), 6.69-6.67 (dd, J= 7.1, 1.0 Hz, 1H), 5.56 (s, 2H), 3.31-3.29 (m, 2H), 2.90-2.88 (m, 4H), 2.49-2.47 (m, 2H). 25 135 Example 152 N-N HNCI 3-(4-Chloro-phenyl)-1 -(2,6-dimethyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (0.018 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, step B; 0.2 mmol) using 2,6-dimethylbenzyl chloride (0.3 mmol) in place of 2-chloromethyl-thiophene. MS (ESI): exact mass calculated for C22H 24

CIN

3 , 365.17; found, m/z 366.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.48-7.45 (m, 10 4H), 7.17-7.15 (br m, 1 H), 7.11-7.09 (m, 2H), 5.51 (s, 2H), 3.43-3.41 (br m, 2H), 3.39-3.37 (br m, 2H), 3.31-3.29 (br m, 2H), 3.10-3.08 (br m, 2H), 2.31 (s, 3H). Example 153 \0 / N-N 1/1 15 H N 3

-(

4 -Chloro-phenyl)-2-(3,4,5-trimethoxy-benzyl)-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (25 mg) was prepared from 3-(4-chloro-phenyl)-2-(3,4,5 trimethoxy-benzyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid 20 tert-butyl ester (Example 150) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C23H 2 6 ClN 3 0 3 , 427.17; found, m/z 428.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.39-7.36 (m, 136 2H), 7.13-7.11 (m, 2H), 6.07 (s, 2H), 5.00 (s, 2H), 3.59 (s, 9H), 2.90-2.70 (m, 6H), 2.46-2.44 (m, 2H). Example 154 a ~ N-N 0 C 5 1HN 1-( 3

,

4 -Bis-benzyloxy-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (22 mg) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 10 103, Step B; 0.2 mmol) using 3 ,4-bis(benzyloxy)benzyl chloride (0.3 mmol) in place of 2 -chloromethyl-thiophene. The reaction sequence also provided 2 (3,4-bis-benzyloxy-benzyl)-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C34H 32

CIN

3 0 2 , 549.22; found, m/z550.1 15 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.36-7.16 (m, 14H), 6.86 (d, J= 8.3 Hz, 1H), 6.65 (d, J= 1.9 Hz, 1H), 6.56 (dd, J= 8.3, 1.9 Hz, 1H), 5.13 (s, 2H), 4.99 (s, 2H), 4.97 (s, 2H), 2.78-2.76 (m, 2H), 2.73-2.71 (m, 2H), 2.65 (m, 4H). Example 155 0a 0 N-N / CI 20 HN 2-(3,4-Bis-benzyloxy-benzyl)-3-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (20 mg) was prepared from 2-(3,4-bis-benzyloxy-benzyl)-3 (4-chloro-phenyl)-4,5,7,8-tetrahydro-2H-1,2 , 6-triaza-azulene-6-carboxylic acid 137 tedt-butyl ester (Example 154) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C34H 3 2

CIN

3

O

2 , 549.22; found, m/z550.1 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.43-7.30 (m, 12H), 7.07-7.05 (m, 2H), 6.89-6.87 (m, 1H), 6.47-6.46 (m, 2H), 5.09 (s, 2H), 5 5.04 (s, 2H), 5.01 (s, 2H), 2.99-2.97 (m, 2H), 2.93-2.91 (m, 2H), 2.88-2.86 (m, 2H), 2.52-2.50 (m, 2H). Example 156 HO Ho C1 10 3-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl) phenol. A solution of 3-(4-chloro-phenyl)-1 -(3-methoxy-benzyl)-1,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene (Example 105, 0.1 mmol) in CH 2

CI

2 (5 mL) was cooled to 0 *C, and 1 M BBr 3 in CH 2

CI

2 (0.5 mL) was added. The mixture was allowed to 15 warm to 25 *C. After 2 h, satd. aq. NaHCO 3 (5 mL) was added. The layers were separated, and the aqueous layer was extracted with EtOAc (2x5 mL). The combined organic layers were dried over Na 2

SO

4 and concentrated. Purification by flash chromatography (2 M NH 3 in MeOH/CH 2 Cl 2 ) provided the title compound (10 mg). MS (ESI): exact mass calculated for C 2 0

H

2 0

CIN

3 0, 20 353.13; found, m/z354.1 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.40-7.38 (m, 2H), 7.35-7.32 (m, 2H), 7.03 (t, J= 7.9 Hz, 1 H), 6.57 (dd, J= 8.1, 2.0 Hz, 1 H), 6.49 (d, J= 8.1 Hz, 1H), 6.39-6.37 (br m, 1H), 5.20 (s, 2H), 2.81-2.78 (br m, 4H), 2.74-2.72 (br m, 2H), 2.70-2.68 (br m, 2H). 25 Example 157 HO C1 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl] phenol. 138 The title compound (10 mg) was prepared from (4-chloro-phenyl)-1-(4 methoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 123, 0.1 mmol) as in Example 156. MS (ES I): exact mass calculated for C 2 0

H

2 0

CIN

3 0, 353.13; found, m/z 354.1 [M+H]*. 'H NMR 5 (500 MHz, CD 3 OD): 7.39-7.37 (m, 2H), 7.34-7.31 (m, 2H), 6.89-6.86 (m, 2H), 6.64-6.61 (m, 2H), 5.16 (s, 2H), 2.77-2.75 (br m, 6H), 2.67-2.65 (br m, 2H). Example 158 j6 N-N HO H C1 HN 10 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl]-3 methyl-phenol. The title compound (8 mg) was prepared from (4-chloro-phenyl)-1 -(4-methoxy 2-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 128, 34 mg) as in Example 156. MS (ESI): exact 15 mass calculated for C 21

H

2 2

CIN

3 0, 367.15; found, m/z 368.0 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.39-7.37 (m, 2H), 7.33-7.32 (m, 2H), 6.54-6.52 (br m, 1H), 6.41-6.39 (br m, 1H), 6.28 (d, J= 8.3 Hz, 1H), 5.17 (s, 2H), 2.83-2.78 (m, 4H), 2.71-2.67 (m, 2H). 20 Example 159 HO1 HO 4Cc1 HN 4 -[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1-ylmethyl] benzene-1,2-diol. A solution of 1-(3,4-bis-benzyloxy-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8 25 hexahydro-1,2,6-triaza-azulene-carboxylic acid tert-butyl ester (Example 154, 0.1 mmol) in CH 2

CI

2 (5 mL) was cooled to 0 C, and 1 M BBr 3 in CH 2

CI

2 (0.5 mL) was added. The mixture was allowed to warm to RT and was stirred at RT for 1 h. The precipitate that had formed was collected by filtration, washed with 139 water, and dried under vacuum to provide the title compound (25 mg). MS (ESI): exact mass calculated for C 20

H

20

CIN

3 0 2 , 369.12; found, n/z 370.0 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.44-7.42 (m, 4H), 7.39-7.37 (m, 2H), 6.63 (d, J= 8.1 Hz, 1H), 6.50 (d, J= 2.1 Hz, 1H), 6.45 (dd, J= 8.1, 2.1 Hz, 1H), 5 5.18 (s, 2H), 3.29-3.25 (m, 4H), 3.06-3.04 (m, 2H), 2.97-2.95 (m, 2H). Example 160 F N-N HO cl 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1-ylmethyl]-2 10 fluoro-phenol. BBr 3 (0.13 mL) was added slowly to a 0 0C solution of 0.022 g of 3-(4-chloro phenyl)-1 -(3-fluoro-4-methoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene (Example 96) in CH 2 Cl 2 (20 mL). After 1 h, the mixture was warmed to RT and stirred for 18 h. The reaction was then cooled back to 0 0C and 15 quenched by the addition of 5 mL of satd. aq. NaHCO 3 . The aqueous layer was extracted with methanolic CH 2 Cl 2 (2x). The combined organic layers were dried over Na 2

SO

4 and concentrated. The crude oil was purified by preparative TLC (9:1 CH 2

CI

2 /2 M NH 3 in MeOH) to afford the title compound (0.016 g) as a tan solid. MS (ESI): exact mass calculated for C 2 aH 19

CIFN

3 O, 371.12; found, 20 m/z 372.1 [M+H]*. 'H NMR (400 MHz, CD 3 OD): 7.50-7.42 (m, 4H), 6.86-6.79 (m, 3H), 5.26 (s, 2H), 3.31-3.26 (m, 2H), 2.96-2.95 (m, 4H), 2.90-2.87 (m, 2H), 2.81-2.79 (m, 2H). 13C NMR (100 MHz, CD 3 0D): 154.2,151.8,149.6,146.1, 146.0,143.8, 134.8, 133.4, 131.1, 130.3, 130.2, 129.7, 124.0, 119.1, 115.6, 115.4, 53.1, 50.4, 29.0, 27.5. 25 Example 161 F N-N \ OH H CI 140 4-[3-(4-Chloro-phe nyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-ylmethyl]-2 fluoro-phenol. 3-(4-Ch loro-phenyl)-2-(3-fluoro-4-methoxy-benzyl)-2,4,5,6,7,8-hexahydro- 1,2,6 triaza-azulene (Example 97, 0.12 g) was de-methylated as in Example 160 to 5 afford the title compound (0.027 g) as an off-white solid. MS (ESI): exact mass calculated for C 2 0H 19

CIFN

3 O, 371.12; found, m/z 372.0 [M+H)*. 'H NMR (500 MHz, CD 3 OD): 7.48-7.44 (m, 2H), 7.21-7.18 (m, 2H), 6.75 (t, J= 8.6 Hz, 1 H), 6.61-6.58 (m, 1 H), 6.53-6.50 (m 1 H), 5.04 (s, 2H), 3.31-3.30 (m, 2H), 3.01-2.99 (m, 2H), 2.94-2.88 (m, 4H), 2.55-2.52 (m, 2H). 13C NMR (125 MHz, 10 CD 3 OD): 154.2, 153.7, 152.3, 146.5, 146.4, 142.4, 136.6, 133.1, 130.6, 130.5, 130.1, 124.5, 120.7, 119.2, 116.0, 115.9, 53.4, 51.2, 32.6, 28.0. Example 162 OH N-N H N 15 2 -[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl] phenol. The title compound (13 mg) was prepared from 3-(4-chloro-phenyl)-1-(2 methoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 109, 0.1 mmol) as in Example 156. MS (ESI): exact 20 mass calculated for C 2 oH 2 0CIN 3 O, 353.13; found, m/z 354.2 [M+H]*. 'H NMR (500 MHz, CDC 3 ): 7.37 (d, J= 6.5 Hz, 2H), 7.33 (d, J= 6.5 Hz, 2H), 7.19 (t, J = 7.6 Hz, 1 H), 7.10 (d, J= 7.6 Hz, 1 H), 6.91 (d, J= 7.6 Hz, 1 H), 6.62 (t, J= 7.6 Hz, 1H), 5.12 (s, 2H), 2.91-2.80 (br m, 6H), 2.68-2.66 (m, 2H). 25 Example 163 NN/- / OH H C1 H14N 141 4-[3-(4-Ch loro-phenyl)-5,6,7,8-tetrahyd ro-4H-1,2,6-triaza-azu len-2-ylmethyl]-3 methyl-phenol. The title compound (14 mg) was prepared from (4-chloro-phenyl)-2-(4 methoxy-2-methyl-benzyl)- 1,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene-6 5 carboxylic acid tert-butyl ester (Example 128, 42 mg) as in Example 156. MS (ESI): exact mass calculated for C21H22CIN 3 O, 367.15; found, m/z 368.1 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.33-7.30 (m, 2H), 7.07-7.06 (m, 2H), 6.43 (d, J= 2.3 Hz, 1H), 6.36 (dd, J= 8.4, 2.3 Hz, 1H), 6.30 (d, J= 8.4 Hz, 1H), 4.96 (s, 2H), 2.89-2.86 (m, 2H), 2.82-2.77 (m, 4H), 2.44 (m, 2H), 1.89 (s, 3H). 10 Example 164 HO N-Nr7 H/ Ci HNY 2-[3-(4-Chloro-phenyl)-5,6,7, 8-tetrahydro-4H- 1,2,6-triaza-azu len-2-ylmethyl] phenol. 15 The title compound (8 mg) was prepared from 3-(4-chloro-phenyl)-2-(2 methoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 132, 30 mg) as in Example 156. MS (ESI): exact mass calculated for C 20

H

20

CIN

3 0, 353.13; found, n/z354.1 [M+H]*. 1 H NMR (500 MHz, CDCla): 7.62 (d, J= 6.5 Hz, 2H), 7.36-7.34 (m, 3H), 7.13 (d, J= 8.0 20 Hz, 1H), 7.00 (d, J= 8.0 Hz, 1H), 6.82 (t, J= 8.0 Hz, 1H), 5.08 (s, 2H), 3.11 3.00 (br m, 6H), 2.60-2.58 (m, 2H). Example 165 D N-N / Ci / N 25 1-Benzyl-3-(4-chloro-phenyl)-6-methyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 142 To a solution of 1-benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene (Example 59, Step E; 0.1 mmol) in 1,2-dichloroethane (5 mL) was added acetic acid (0.2 mmol), formaldehyde (37% water solution, 0.037 mL), and NaBH(OAc) 3 (0.2 mmol). The mixture was stirred at RT for 15 h. 5 The mixture was diluted with CH 2 Cl 2 and washed with satd. aq. NaHCO 3 (2x). The combined organic layers were dried over Na 2

SO

4 , filtered, and concentrated in vacuo. Chromatography on SiO 2 (2 M NH 3 in MeOH/CH 2 Cl 2 ) afforded 0.015 g of the title compound. MS (ESI): exact mass calculated for C21H 22

CIN

3 , 351.15; found, m/z 352.2 [M+H]*. 'H NMR (400 MHz, CDC13): 10 7.45-7.42 (m, 2H), 7.32-7.29 (m, 2H), 7.26-7.19 (m, 3H), 7.03-7.01 (br m, 2H), 5.27 (s, 2H), 2.75-2.68 (m, 4H), 2.64-2.58 (m, 4H), 2.36 (s, 3H). Examples 166 through 169 were synthesized using the procedure described in Example 165 unless otherwise noted. 15 Example 166 N-N \/ c CI 1 -Benzyl-3-(4-chloro-phenyl)-6-ethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 20 The title compound (18 mg) was prepared using acetaldehyde (0.2 mmol) in place of formaldehyde. MS (ESI): exact mass calculated for C 22

H

24

CIN

3 , 365.17; found, m/z 366.2 [M+H]*. 'H NMR (400 MHz, CDCI3): 7.45-7.43 (m, 2H), 7.31-7.29 (m, 2H), 7.26-7.19 (m, 3H), 7.03-7.01 (br m, 2H), 5.26 (s, 2H), 2.74-2.71 (m, 1OH), 1.01 (t, J= 7.1 Hz, 3H). 25 Example 167 HN-N - - CI /O 143 3-(4-Chloro-phenyl)-6-(3,4-dimethoxy-benzyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. To a solution of 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene 6-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 mmol) in CH 2

CI

2 (5 5 mL) was added TFA (1 mL). The mixture was stirred at RT for 16 h. After concentration, the intermediate 3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene was obtained. The intermediate (0.1 mmol) was converted to the title compound (16 mg) according to the procedure described in Example 165 using 3,4-dimethoxy-benzaldehyde (0.2 mmol) in place of 10 formaldehyde. MS (ESI): exact mass calculated for C22H 24

CIN

3 0 2 , 397.16; found, m/z 398.2 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.38-7.35 (br m, 4H), 7.91 (d, J= 1.8 Hz, 1H), 6.82-6.80 (dd, J= 8.1, 1.8 Hz, 1H), 6.76-6.74 (d, J= 8.1 Hz, 1H), 3.83-3.80 (s, 6H), 2.84-2.82 (m, 4H), 2.71-2.69 (m, 4H). 15 Example 168 N-N N / 1 -Butyl-3-(4-chloro-phenyl)-6-(3,4-dimethoxy-benzyl)-1,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene. The title compound (8 mg) was prepared from 1 -butyl-3-(4-chloro-phenyl) 20 1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (Example 67, 14 mg) using 3,4 dimethoxy-benzaldehyde (0.2 mmol) in place of formaldehyde. MS (ESI): exact mass calculated for C 26 H32CIN 3

O

2 , 453.22; found, m/z 454.2 [M+H]*. 1 H NMR (400 MHz, CDCl 3 ): 7.38 (d, J= 8.4 Hz, 2H), 7.28 (d, J= 8.4 Hz, 2H), 7.20 (s, 1 H), 6.91 -6.90 (br m, 1 H), 6.81 (d, J = 8.2 Hz, 1 H), 6.75 (d, J = 8.2 Hz, 1 H), 25 3.98 (t, J= 7.3 Hz, 2H), 3.82 (d, J= 7.0 Hz, 6H), 3.66 (s, 2H), 2.78-2.72 (br m, -8H), 1.67 (m, 2H), 1.27 (m, 2H), 0.86 (t, J= 7.3 Hz, 6H). 144 Example 169 -o -0 __ I Cl o ~ N / -b N 1 -Benzyl-3-(4-chloro-phenyl)-6-(3,4-dimethoxy-benzyl)-1,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene. 5 The title compound was prepared (12 mg) from 1 -benzyl-3-(4-chloro-phenyl) 1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (Example 59, Step E; 0.1 mmol) using 3,4-dimethoxy-benzaldehyde (0.2 mmol) in place of formaldehyde. MS (ESI): exact mass calculated for C29HaoClN 3 0 2 , 487.20; found, m/z488.2 [M+H]*. 1 H NMR (500 MHz, CDCl 3 ): 7.44-7.43 (m, 2H), 7.30-7.29 (m, 2H), 10 7.25-7.22 (m, 2H), 7.20-7.18 (m, 1H), 7.03-7.02 (m, 2H), 6.86 (d, J= 1.7 Hz, 1 H), 6.76-6.71 (m, 2H), 5.25 (s, 2H), 3.79 (s, 6H), 3.63 (s, 2H), 2.72 (s, 4H), 2.68-2.66 (m, 4H). Example 170 IIZ N-N - ~ ' \ / CI 0 N 15 -0 [1-Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-lH-1,2,6-triaza-azulen-6-y] acetic acid methyl ester. To a solution of 1 -benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene (Example 59, Step E; 1 mmol) in acetone (3 mL) was added 20 Na 2 COs (2 mmol) and bromoacetic methyl ester (2 mmol). The mixture was stirred at RT for 1 h. After concentration and purification (SiO 2 , 2 M NH 3 in MeOH/CH 2

CI

2 ), the title compound was obtained (60 mg). MS (ESI): exact mass calculated for C 2 3

H

24

CIN

3 0 2 , 409.16; found, m/z410.1 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 7.44-7.42 (m, 2H), 7.31-7.29 (m, 2H), 7.25-7.23 (br m, 2H), 25 7.20-7.18 (br m, 1 H), 7.02-6.99 (br m, 2H), 5.26 (s, 2H), 3.64 (s, 2H), 3.41 (s, 2H), 2.81-2.79 (br m, 4H), 2.75-2.73 (br m, 2H), 2.70-2.68 (br m, 2H). 145 Example 171 ci N 1 HO 2-[1 -Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulen-6-yl] 5 ethanol. To a solution of [1 -benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1 H-1,2,6 triaza-azulen-6-yl]-acetic acid methyl ester (Example 170, 16 mg) in THF (1 mL) was added lithium aluminum hydride (100 mg). The mixture was stirred at RT for 16 h. The reaction was quenched by the addition of H 2 0 (0.1 mL). 10 Concentration and purification (SiO 2 , 2 M NH 3 in MeOH/CH 2 Cl 2 ) provided the title compound (5 mg). MS (ESI): exact mass calculated for C 22

H

24

CIN

3 0, 381.16; found, m/z382.1 [M+H]*. 1 H NMR (500 MHz, CDC 3 ): 7.50 -7.20 (m, 7H), 7.04 (d, J = 7.2 Hz, 1 H), 5.29 (s, 2H), 3.07-3.04 (m, 2H), 2.89-2.77 (m, 1OH). 15 Example 172 SN-N N - /NC H CI HNY 3-(4-Chloro-phenyl)-1 -phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. A solution of 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6 20 carboxylic acid tert-butyl ester (Example 59, Step C; 0.3 mmol) in CH 2

CI

2 (5 mL) was treated with phenylboronic acid (0.6 mmol), pyridine (0.6 mmol), and copper(II) acetate (4.5 mmol). The mixture was stirred at RT for 16 h. After concentration and purification (SiO 2 , EtOAc/hexanes), 3-(4-chloro-phenyl)- 1 phenyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl 25 ester was obtained. This intermediate was then diluted with CH 2 Cl 2 (10 mL), and TFA (1 mL) was added. The mixture was stirred at RT for 4 h. The 146 mixture was concentrated and the residue was purified (SiO 2 , 2 M NH 3 in MeOH/CH 2 Cl 2 ) to provide the title compound (40 mg). MS (ESI): exact mass calculated for C1 9

H

1 8

CIN

3 , 323.12; found, m/z 324.1 [M+H]. 'H NMR (500 MHz, CDCl 3 ): 7.46-7.40 (m, 4H), 7.36-7.32 (m, 5H), 3.09-3.07 (br m, 4H), 5 3.00-2.98 (br m, 2H), 3.92-2.90 (br m, 2H). Example 173 N-N CI N H 3-(4-Chloro-phenyl)-1 -(2-methyl-benzyl)-4,5,6,7,8,9-hexahydro-1 H-1,2,6-triaza 10 cyclopentacyclooctene. Step A. 3-(4-Chloro-phenyl)-1,4,5,7,8,9-hexahvdro-1,2,6-triaza cyclopentacyclooctene-6-carboxylic acid tert-butyl ester. To a 0 0C solution of 4-oxo-azepane-1-carboxylic acid tert-butyl ester (Example 59, Step B; 0.915 g) in Et 2 0 (30 mL) was added BF 3 *Et 2 O (0.733 mL) followed by a solution of 1-(4 15 chlorophenyl)-2-diazo-ethanone (Example 103, Step A; 4.5 mmol) in Et 2 0 (30 mL). The mixture was warmed to 25 0C and stirred for 1 h. Satd. aq. NaHCO 3 (40 mL) was added, and the organic layer was separated and concentrated. The resulting residue was diluted with MeOH (50 mL) and treated with hydrazine (1.5 mL). The reaction mixture was stirred at 25 0C for 16 h. 20 Concentration and purification by flash chromatography (SiO 2 , EtOAc/CH 2 Cl 2 ) provided the desired ester. Step B. 3-(4-Chloro-phenyl)-1 -(2-methyl-benzvl)-1,4,5,7,8,9-hexahydro-1,2,6 triaza-cyclopentacyclooctene-6-carboxylic acid tert-butyl ester. A solution of the product from Step A (0.2 mmol) in DMF (2 mL) was treated with 2 25 methylbenzyl chloride (0.3 mmol) followed by Cs 2

CO

3 (0.3 mmol). The mixture was stirred at 25 0C for 16 h. Concentration and purification by chromatography (Si0 2 , EtOAc/hexanes) provided the target intermediate. Step C. A solution of the product from Step B in MeOH (20 mL) was treated with HCI (2 M in Et 2 0, 1 mL) for 16 h. After concentration and purification by 147 chromatography (Si0 2 , 2 M NH 3 in MeOH/CH 2

CI

2 ), the title compound was obtained (24 mg). The reaction sequence also yielded 3-(4-chloro-phenyl)-1 (2-methyl-benzyl)-4,5,6,7,8,9-hexahydro-1 H-1,2,7-triaza-cyclopentacyclooctene (20 mg). MS (ESI): exact mass calculated for C 2 2

H

2 4

CIN

3 , 365.17; found, m/z 5 366.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.51-7.50 (m, 2H), 7.42-7.40 (m, 2H), 7.14-7.05 (m, 3H), 6.58 (d, J= 7.6 Hz, 1 H), 5.42 (s, 2H), 3.25 (t, J= 5.6 Hz, 2H), 3.13 (t, J= 5.6 Hz, 2H), 3.01 (t, J= 5.6 Hz, 2H), 2.89 (t, J= 5.6 Hz, 2H), 2.30 (s, 3H), 1.78-1.76 (m, 2H). 10 Example 174 N-N H~ CI H N 3-(4-Chloro-phenyl)-1 -(2-methyl-benzyl)-4,5,6,7,8,9-hexahydro-1 H-1,2,7-triaza cyclopentacyclooctene. The title compound (20 mg) was obtained as in Example 173. MS (ESI): exact 15 mass calculated for C22H 24

CIN

3 , 365.17; found, m/z 366.2 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.48-7.46 (m, 2H), 7.39-7.36 (m, 2H), 7.14-7.05 (m, 3H), 6.55-6.54 (m, 1 H), 5.39 (s, 2H), 3.02-3.00 (m, 2H), 2.98-2.96 (m, 4H), 2.80 2.78 (m, 2H), 2.30-2.28 (s, 3H), 1.99-1.97 (m, 2H). 20 Example 175 N-N HN 3-(4-Chloro-phenyl)-1 -(2- methyl-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[3,4 c]pyridine. The title compound (22 mg) was prepared from 3 -oxo-pyrrolidine-1-carboxylic 25 acid tert-butyl ester (0.858 g) and 1-(4-chlorophenyl)-2-diazo-ethanone (Example 103, Step A; 5.79 mmol) as in Example 173. MS (ESI): exact mass calculated for C1 7

H

22

CIN

3 0, 337.13; found, m/z 338.2 [M+H)*. 1H NMR (500 148 MHz, CD3OD): 7.62-7.60 (m, 2H), 7.36-7.34 (m, 2H), 7.14-7.06 (m, 3H), 6.76 (d, J= 7.5 Hz, 1H), 5.33 (s, 2H), 4.09 (s, 2H), 3.38 (t, J= 6.1 Hz, 2H), 3.10 (t, J = 6.1 Hz, 2H), 2.25 (s, 3H). 5 Example 176 N-N HN 2 ,3-Diphenyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene. Step A. 3-Oxo-2-phenV-2,3,4,5,7,8-hexahydro-lH-1,2,6-triaza-azulene-6 carboxylic acid ter-butyl ester. To a solution of the compound (3.13 g) from 10 Example 59, Step A in 80 mL of EtOH was added 1.2 mL of phenylhydrazine. The resulting solution was heated at reflux for 3 days and then was cooled to RT and the solvent was removed in vacuo. The residue was chromatographed on Si02 (0 to 80% EtOAc/hexanes) to afford 3.13 g of the desired compound. MS (ESI): exact mass calculated for C 1 8

H

23

N

3 0 3 , 329.17; found, m/z330.2 15 [M+H]*. Step B. 2 -Phenl-3-trifluoromethanesulfonyloxv-4,5,7,8-tetrahvdro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester. To a stirred solution of the above compound (1.79 g) in 35 mL of CH 2 Cl 2 was added 3.0 mL of i-Pr 2 NEt and 3.05 g of N-phenyltrifluoromethanesulfonimide. The mixture was heated at 20 reflux for 24 h and then was concentrated in vacuo. Chromatography on Si0 2 (0 to 75% EtOAc/hexanes) afforded 1.88 g of the desired compound. MS (ESI): exact mass calculated for C 9

H

2 2

F

3

N

3 0 5 S, 461.12; found, m/z 407.1 [M+H]*. Step 0. 2 ,3-Dihenl-4,57,8-tetrahvdro-2H-1,2,6-triaza-azulene-6-carboxylic 25 acid tert-butyl ester. To a solution of the above compound (0.28 g) in 5 mL of 1,4-dioxane was added 0.29 g of K 3

PO

4 , 104.3 mg of phenylboronic acid and 43.0 mg of PdCl 2 dppf. The mixture was heated at 80 0C for 3 h. More phenylboronic acid (0.10 g) and PdCl 2 dppf (26 mg) were added and the temperature was increased to 100 *C. After an additional 12 h, the mixture 149 was poured into water (100 mL) and extracted with CH 2

CI

2 (3 x 20 mL). The combined organic layers were filtered through diatomaceous earth and the filtrate was concentrated in vacuo. Chromatography on SiO 2 (0 to 20% EtOAc/hexanes) afforded 158.8 mg of the desired compound. MS (ESI): 5 exact mass calculated for C 2 4

H

27

N

3 0 2 , 389.21; found, m/z 390.2 [M+H]*. Step D. To a stirred solution of the above compound (158.8 mg) in 5 mL of EtOH was added 2 mL of 1.0 M HCI in Et 2 0. The mixture was stirred at RT for 12 h and concentrated in vacuo to give 75.6 mg of the title compound. MS (ESI): exact mass calculated for C 19

H

19

N

3 , 289.16; found, m/z 290.2 [M+H]*. 10 'H NMR (500 MHz, CD 3 0D): 7.41-7.38 (m, 3H), 7.36-7.32 (m, 3H), 7.23-7.18 (m, 4H), 3.49-3.45 (m, 2H), 3.38-3.34 (m, 2H), 3.26-3.23 (m, 2H), 2.96-2.93 (m, 2H). Example 177 Q N-N 15 HN 2 -Cyclohexyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. Cyclohexyl-hydrazine hydrochloride. To a solution of cyclohexanone (1.25 mL) in hexanes (8 mL) was added 1.59 g of tert-butyl carbazate. The mixture was heated at reflux for 10 min and then allowed to cool to RT. The 20 white precipitate that had formed was removed by filtration and washed with cold hexanes. The white solid was then treated with BH 3 (1.0 M in THF, 12 mL). After stirring at RT for 20 min, the mixture was treated with 16 mL of 6 N HCL. The mixture was heated at 110 C for 20 min and then was concentrated in vacuo. The residue was treated with 30 mL of THF. The title compound 25 (1.82 g), a white solid, was collected from this mixture by filtration. MS (ESI): exact mass calculated for C 6

H

14

N

2 , 114.12; found, m/z 115.1 [M+H)*. 1 H NMR (500 MHz, CDCI 3 ): 3.05-2.99 (m, 1H), 2.11-2.09 (m, 2H), 1.88-1.86 (m, 2H), 1.72-1.69 (m, 1 H), 1.37-1.19 (m, 5H). 150 Step B. 2 -Cyclohexvl-3-trifluoromethanesulfonlox-4,5,7,8-tetrahvdro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The desired compound was made as in Steps A and B of Example 176, with cyclohexylhydrazine hydrochloride from Step A in place of phenylhydrazine. The hydrazine salt was 5 neutralized with Dowex 550 resin prior to use. Step C. 2 -Cyclohexyl-3-phenyl-4,5,7,8-tetrahdro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester. To a solution of 126 mg of the compound from Step A in 3 mL of 1,4-dioxane were added 229 mg of K 3 P0 4 , 131 mg of phenylboronic acid, and 7.5 mg of dppf. PdCl 2 dppf (22 mg) was then added 10 and the mixture was heated at reflux overnight. The mixture was concentrated in vacuo and the residue was dissolved in toluene. The solution was filtered through diatomaceous earth and the filtrate was concentrated to afford 202 mg of an oil. Chromatography on SiO 2 (5 to 25% EtOAc/hexanes) provided 98.7 mg of the desired compound. MS (ESI): exact mass calculated for 15 C 24 H33N 3 0 2 , 395.26; found, m/z 396.2 [M+H]*. Step D. The above compound (98.7 mg) was converted to the title compound (71.0 mg) as in Example 43, Step E, and the crude product was chromatographed on SiO 2 (2 to 8% 2 M NH 3 in MeOH/EtOAc). MS (ESI): exact mass calculated for C 19

H

25

N

3 , 295.20; found, m/z296.2 [M+H]*. 1 H NMR 20 (500 MHz, CDCl 3 ): 7.59-7.49 (m, 3H), 7.35-7.29 (m, 2H), 3.97-3.88 (m, 1 H), 3.44-3.38 (m, 2H), 3.34-3.27 (m, 2H), 3.20-3.14 (m, 2H), 2.81-2.73 (m, 2H), 1.99-1.76 (m, 6H), 1.65 (br s, 1 H), 1.28-1.17 (m, 3H). Example 178 N-N /CI 25 H N 3

-(

4 -Chloro-phenyl)-2-cyclohexyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (48 mg) was prepared as in Example 177, Steps C and D, using 129 mg of 2 -cyclohexyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 177, Step 151 B) and 173 mg of 4-chlorophenylboronic acid. MS (ESI): exact mass calculated for C 19

H

2 4

CIN

3 , 329.17; found, m/z 330.1 [M+H]*. 1 H NMR (500 MHz, CDCI 3 ): 7.60-7.53 (m, 2H), 7.36-7.27 (m, 2H), 3.94-3.83 (m, 1 H), 3.43 3.36 (m, 2H), 3.34-3.26 (m, 2H), 3.2-3.12 (m, 2H), 2.80-2.72 (m, 2H), 1.98-1.76 5 (m, 6H), 1.67 (br s, 1 H), 1.32-1.17 (m, 3H). Example 179 N-N

CF

3 HNf 2 -Cyclohexyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza 10 azulene. The title compound (68 mg) was prepared as in Example 177, Steps C and D, using 130 mg of 2 -cyclohexyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2H-1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 177, Step B) and 132 mg of 4-trifluoromethylphenylboronic acid. MS (ESI): exact mass 15 calculated for C 20

H

24

F

3 N, 363.19; found, m/z 364.2 [M+H]*. 1 H NMR (500 MHz, CDCIa): 7.90-7.84 (m, 2H), 7.57-7.50 (m, 2H), 4.64 (br s, 2H), 3.94-3.85 (m, 1 H), 3.33-3.05 (m, 4H), 2.93-2.72 (m, 2H), 2.00-1.76 (m, 6H), 1.67 (br s, 1H), 1.38-1.17 (m, 3H). 20 Example 180 p N-N HN 2 -Cyclopentyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. 2-Cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1.

2 6-triza-azulene-6-arboxVlic acid tert-butyl ester. The desired triflate was 25 prepared as in Steps A and B of Example 176, using cyclopentylhydrazine 152 hydrochloride (made according to the procedure of Example 177, Step A using cyclopentanone in place of cyclohexanone) in place of phenylhydrazine, t butanol in place of EtOH, with the addition of 3 equiv. of triethylamine. Step B. The title compound (52 mg) was prepared from the product of Step A 5 (101 mg) according to the procedure of Example 177, Steps C and D, using 109 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 1 8

H

23

N

3 , 281.19; found, mr/z282.1 [M+H]*. 1H NMR (500 MHz, CDCl 3 ): 7.58-7.48 (m, 3H), 7.36-7.30 (m, 2H), 4.50 (m, 1 H), 3.44-3.38 (m, 2H), 3.34-3.27 (m, 2H), 3.22-3.16 (m, 2H), 2.81-2.75 (m, 2H), 2.06-1.84 (m, 6H), 1.65-1.54 (m, 2H). 10 Example 181 2 N-N H' C I HNY 3

-(

4 -Chloro-phenyl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (74 mg) was prepared as in Example 177, Steps C and D, 15 using 215 mg of 2 -cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 296 mg of 4-chlorophenylboronic acid. MS (ESI): exact mass calculated for C 18 H22CIN 3 , 315.15; found, m/z 316.1 [M+H]*. 1 H NMR (500 MHz, CDCI 3 ): 7.59-7.53 (m, 2H), 7.36-7.30 (m, 2H), 4.48 (m, 1H), 3.44 20 3.37 (m, 2H), 3.34-3.27 (m, 2H), 3.22-3.15 (m, 2H), 2.81-2.74 (m, 2H), 2.06 1.84 (m, 6H), 1.65-155 (m, 2H). Example 182 p N-N H N 25 2 -Cyclopentyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 153 The title compound (113 mg) was prepared as in Example 177, Steps C and D, using 200 mg of 2-cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 185 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass 5 calculated for C 18

H

22

FN

3 , 299.18; found, m/z 300.5 [M+H]*. 1 H NMR (500 MHz, CDCI 3 ): 7.45-7.39 (m, 2H), 7.35-7.29 (m, 2H), 4.53 (m, 1 H), 3.48-3.42 (m, 2H), 3.36-3.28 (m, 2H), 3.28-3.23 (m, 2H), 2.84-2.78 (m, 2H), 2.08-1.85 (m, 6H), 1.67-1.56 (m, 2H). 10 Example 183 N-N F HN 2-(1 -Ethyl-propyl)-3-(3-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. Step A. 2-( 1 -Ethyl-propvl)-3-trif luoromethanesulfonylox-4,5,7,8-tetrahydro-2H 15 1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The desired triflate was prepared as in Steps A and B of Example 176, using (1-ethyl-propyl)-hydrazine hydrochloride (made from 3-pentanone as described in Example 177, Step A) in place of phenylhydrazine. The hydrazine was neutralized with NaH in DMF prior to use. 20 Step B. The title compound (82 mg) was prepared as in Example 177, Steps C and D, using 150 mg of the triflate from Step A and 138 mg of 3 fluorophenylboronic acid. MS (ESI): exact mass calculated for C 18

H

24

FN

3 , 301.20; found, m/z302.4 [M+H]*. 1 H NMR (500 MHz, CDCIs): 7.61-7.55 (m, 1H), 7.31 -7.25 (m, 1H), 7.16-7.12 (m, 1H), 7.10-7.05 (m, 1 H), 3.85-3.77 (m, 25 1 H), 3.45-3.40 (m, 2H), 3.35-3.29 (m, 2H), 3.23-3.18 (m, 2H), 2.82-2.76 (m, 2H), 1.97-1.80 (m, 2H), 1.79-1.70 (m, 2H), 0.71 (t, J = 7.4 Hz, 3H). 154 Example 184 N-N HN 2-(1-Ethyl-propyl)-3-(4-fluoro-phe nyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene. 5 The title compound (93 mg) was prepared as in Example 177, Steps C and D, using 150 mg of 2-(1 -ethyl-propyl)-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 183, Step A) and 138 mg of 3-fluorophenylboronic acid. MS (ESI): exact mass calculated for C 1 8

H

24 FN3, 301.20; found, m/z 302.5 [M+H]*. 1 H NMR (500 10 MHz, CDCla): 7.44-7.30 (m, 4H), 3.92-3.85 (m, 1H), 3.51-3.43 (m, 2H), 3.38 3.33 (m, 2H), 3.30-3.24 (m, 2H), 2.86-2.78 (m, 2H), 1.98-1.85 (m, 2H), 1.84 1.73 (m, 2H), 0.73 (t, J= 7.4 Hz, 3H). Example 185 N-N S /_0 15 HN 2-(1 -Ethyl-propyl)-3-thiophen- 3-yl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene. The title compound (95 mg) was prepared as in Example 177, Steps C and D, using 150 mg of 2-(1 -ethyl-propyl)-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H- 1, 2

,

6 -triaza-azulene-6-carboxyl ic acid tert-butyl ester (Example 20 183, Step A) and 126 mg of 3-thiopheneboronic acid. MS (ESI): 'exact mass calculated for C 16

H

23

N

3 S, 289.16; found, m/z 290.4 [M+H]. 1 H NMR (500 MHz, CDC 3 ): 7.68-7.64 (m, 1H), 7.52-7.48 (m, 1H), 7.12-7.07 (m, 1H), 3.93 3.86 (m, 1H), 3.44-3.39 (m, 2H), 3.34-3.28 (m, 2H), 3.22-3.17 (m, 2H), 2.85 2.79 (m, 2H), 1.95-1.84 (m, 2H), 1.79-1.69 (m, 2H), 0.71 (t, J= 7.4 Hz, 3H). 25 155 Example 186 N-N HN 2-(1-Ethyl-propyl)-3-phenyl-2,4,5,6,7,8-hexahydro.-1,2,6-triaza-azulene. The title compound (40 mg) was prepared as in Example 177, Steps C and D, 5 using 150 mg of 2-(1 -ethyl-propyl)-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 183, Step A) and 120 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 1 8

H

25

N

3 , 283.20; found, m/z 284.4 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 7.48-7.38 (m, 3H), 7.24-7.19 (m, 2H), 3.77-3.70 (m, 1H), 3.36-3.31 (m, 10 2H), 3.24-3.19 (m, 2H), 3.14-3.09 (m, 2H), 2.71-2.65 (m, 2H), 1.85-1.75 (m, 2H), 1.68-1.58 (m, 2H), 0.61 (t, J= 7.4 Hz, 3H). Example 187 /-CF3 N-N H Cl HN 15 3

-(

4 -Chloro-phenyl)-2-(2,2,2-trifluoro-ethyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. Step A. 2

-(

2

,

2

,

2 -Trifluoro-ethvl)-3-trifluoromethanesulfonvloxy-4,5,7,8 tetrahVdro-2H- 1,2,6-triaza-azu lene-6-carboxylic acid tert-butyl ester. The desired triflate was prepared as in Steps A and B of Example 176, using 2,2,2 20 trifluoroethylhydrazine in place of phenylhydrazine. Step B. The title compound (40 mg) was prepared as in Example 177, Steps C and D, using 304 mg of the triflate from Step A and 407 mg of 4 chlorophenylboronic acid. MS (ESI): exact mass calculated for C1 5

H

1 5

CF

3

N

3 , 329.09; found, m/z 330.0 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 7.62-7.52 (m, 25 2H), 7.40-7.29 (m, 2H), 4.70 (q, J= 8.6 Hz, 2H), 3.44-3.37 (m, 2H), 3.36-3.25 (m, 2H), 3.22-3.13 (m, 2H), 2.83-2.73 (m, 2H). 156 Example 188

/-CF

3 N-N /

CF

3 HNf 2-(2,2, 2 -Trifluoro-ethyl)-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8 -hexahydro 5 1,2,6-triaza-azulene. The title compound (128 mg) was prepared as in Example 177, Steps C and D, using 288 mg of 2-(2,2,2-trifluoro-ethyl)-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 187, Step A) and 468 mg of 4-trifluoromethylphenylboronic acid. MS (ESI): 10 exact mass calculated for C 16

H

15

F

6

N

3 , 363.12; found, m/z 364.0 [M+H]*. 1 H NMR (500 MHz, CDCI 3 ): 7.93-7.83 (m, 2H), 7.62-7.54 (m, 2H), 4.75 (q, J= 8.6 Hz, 2H), 3.47-3.39 (m, 2H), 3.38-3.27 (m, 2H), 3.24-3.15 (m, 2H), 2.87-2.76 (m, 2H). 15 Example 189 N-N HN 2 -1sopropyl-3-phenyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene. Step A. 2-Isopropyl-3-trifluoromethanesulfonvloxv-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester. The desired triflate was 20 prepared as in Steps A and B of Example 176, using isopropylhydrazine hydrochloride in place of phenylhydrazine, t-butanol in place of EtOH, with the addition of 3 equiv. of triethylamine. Step B. The title compound (93 mg) was prepared as in Example 177, Steps C and D, using 172 mg of the triflate from Step A and 147 mg of phenylboronic 25 acid. MS (ESI): exact mass calculated for C 1 6

H

2 1

N

3 , 255.17; found, m/z 256.5 [M+H]*. 1 H NMR (500 MHz, CDCl 3 ): 7.58-7.49 (m, 3H), 7.36-7.30 (m, 2H), 157 4.40 (m, 1H), 3.45-3.40 (m, 2H), 3.34-3.28 (m, 2H), 3.23-3.18 (m, 2H), 2.82 2.75 (m, 2H), 1.40 (d, J = 6.9 Hz, 6H). Example 190 N-N F 5 HN 3

-(

4 -Fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (92 mg) was prepared as in Example 177, Steps C and D, using 159 mg of 2 -isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step 10 A) and 156 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for C 1 6

H

20

FN

3 , 273.16; found, m/z 274.4 [M+H]*. 1 H NMR (500 MHz, CDCI 3 ): 7.42-7.35 (m, 2H), 7.33-7.27 (m, 2H), 4.37 (m, 1H), 3.46-3.39 (m, 2H), 3.34-3.28 (m, 2H), 3.23-3.18 (m, 2H), 2.81-2.74 (m, 2H), 1.41 (d, J= 6.9 Hz, 6H). 15 Example 191 N--N HN 2-(1 -Ethyl-propyl)-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (35 mg) was prepared as in Example 177, Steps C and D, 20 using 148 mg of 2 -(1-ethyl-propyl)-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahyd ro-2H- 1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 183, Step A) and 122 mg of 2-thiopheneboronic acid. MS (ESI): -exact mass calculated for C 1 6 H2aN 3 S, 289.16; found, nVz 290.5 [M+H]*. 'H NMR (500 MHz, CDCI 3 ): 7.72-7.67 (m, 1H), 7.25-7.21 (m, 1H), 7.13-7.09 (m, 1H), 4.01 25 3.94 (m, 1 H), 3.43-3.38 (m, 2H), 3.34-3.28 (m, 2H), 3.20-3.14 (m, 2H), 2.86 2.80 (m, 2H), 1.95-1.85 (m, 2H), 1.79-1.69 (m, 2H), 0.71 (t, J = 7.4 Hz, 3H). 158 Example 192 N-N H 2 -Cyclopentyl-3-thiophen-3-yl-2,4,5,6,7,8-hexahydro--1,2,6-triaza-azulene. 5 The title compound (114 mg) was prepared as in Example 177, Steps C and D, using 200 mg of 2 -cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2 H- 1,2,6-triaza-azu lene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 169 mg of 3-thiopheneboronic acid. MS (ESI): exact mass calculated for C 16

H

21

N

3 S, 287.15; found, m/z 288.4 [M+H]). 'H NMR (500 10 MHz, CDCI 3 ): 7.68-7.63 (m, 1H), 7.56-7.51 (m, 1H), 7.17-7.12 (m, 1H), 4.58 (m, 1H), 3.43-3.37 (m, 2H), 3.34-3.28 (m, 2H), 3.19-3.14 (m, 2H), 2.86-2.80 (m, 2H), 2.04-1.85 (m, 6H), 1.67-1.57 (m, 2H). Example 193 N-N 15 HN 2 -Ethyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. 2 -Ethyl- 3 -trifluoromethanesulfonlox-4,5,7,8-tetrahdro-2H-1,2,6 triaza-azulene-6-carboxvlic acid tert-butyl ester. The desired triflate was prepared as in Steps A and B of Example 176, using ethyihydrazine oxalate in 20 place of phenylhydrazine, t-butanol in place of EtOH, with the addition of 3 equiv. of triethylamine. Step B. The title compound (106 mg) was prepared as in Example 177, Steps C and D, using 198 mg of the triflate from Step A and 122 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 1 5

H

19

N

3 , 241.16; found, m/z 242.4 25 [M+H]*. .H NMR (500 MHz, CDCI 3 ): 7.61-7.54 (m, 3H), 7.43-7.39 (m, 2H), 4.11 (q, J= 7.1 Hz, 2H), 3.49-3.44 (m, 2H), 3.37-3.32 (m, 2H), 3.28-3.22 (m, 2H), 2.89-2.82 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H). 159 Example 194 N-N F I-I 2 -Ethyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 5 The title compound (114 mg) was prepared as in Example 177, Steps C and D, using 208 mg of 2 -ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 211 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for C 1 5

H

18

FN

3 , 259.15; found, m/z 260.4 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 10 7.41-7.35 (m, 2H), 7.32-7.26 (m, 2H), 3.99 (q, J= 7.1 Hz, 2H), 3.43-3.38 (m, 2H), 3.33-3.28 (m, 2H), 3.18-3.12 (m, 2H), 2.80-2.75 (m, 2H), 1.27 (t, J= 7.1 Hz, 3H). Example 195 N-N S 15 HN 2 -Ethyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (101 mg) was prepared as in Example 177, Steps C and D, using 148 mg of 2-ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) 20 and 306 mg of 2-thiopheneboronic acid. MS (ESI): exact mass calculated for

C

13

H

17

N

3 S, 247.11; found, m/z 248.4 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 7.62-7.57 (m, 1H), 7.16-7.11 (m, 1H), 7.10-7.05 (m, 1H), 3.98 (q, J= 7.1 Hz, 2H), 3.33-3.27 (m, 2H), 3.24-3.18 (m, 2H), 3.07-3.01 (m, 2H), 2.80-2.73 (m, 2H), 1.22 (t, J= 7.1 Hz, 3H). 25 160 Example 196 / \Cl N-N HN 2-(3-Chloro-phenyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. 2-(3-Chloro-phenyl)-3-phenyl-4,5,7,8-tetrahvdro-2H-1,2,6-triaza 5 azulene-6-carboxylic acid tert-butyl ester. The desired compound (53.9 mg) was prepared from 142.7 mg of 2-(3-chloro-phenyl)-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (made as in Example 176, Steps A and B) replacing phenylhydrazine with (3-chloro-phenyl)-hydrazine, as described in 10 Example 43, Step D, using 102.1 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 2 4

H

26

CIN

3 0 2 , 423.17; found, m/z 424.1 [M+H]*. Step B. The above compound (53.9 mg) was converted to the title compound (37.6 mg) as in Example 26, Step B. MS (ESI): exact mass calculated for C1 9 H1 8

CIN

3 , 323.12; found, m/z 324.1 [M+H]*. 'H NMR (500 MHz, CDCI 3 ): 15 7.38-7.32 (m, 4H), 7.16-7.09 (m, 4H), 6.96-6.93 (m, 1 H), 3.09-3.05 (m, 2H), 3.02-2.98 (m, 2H), 2.97-2.94 (m, 2H), 2.65-2.62 (m, 2H), 2.07 (br s, 1 H). Example 197 F N-N HN 20 2

-(

3 -Fluoro-phenyl)-3-phenyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene. The title compound (37.6 mg) was prepared from 339.2 mg of 2-(3-fluoro phenyl)-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester (made as in Example 176, Steps A and B from (3-fluoro-phenyl)-hydrazine) as described in Example 196, using 25 1,4-dioxane as the solvent. MS (ESI): exact mass calculated for C1 9

H

1 8

FN

3 , 161 307.15; found, m/z 308.1 [M+H]*. 1 H NMR (400 MHz, CDCI 3 ): 7.39-7.35 (m, 3H), 7.20-7.14 (m, 3H), 7.00-6.96 (m, 1 H), 6.94-6.86 (m, 2H), 3.13-3.09 (m, 2H), 3.06-3.02 (m, 2H), 3.01-2.96 (m, 2H), 2.69-2.66 (m, 2H). 5 Example 198 N-N HN 2 -(2-Chloro-phenyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (17.2 mg) was prepared from 199.8 mg of 2-(2-chloro phenyl)-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza 10 azulene-6-carboxylic acid tert-butyl ester (made from (2-chloro-phenyl) hydrazine as in Example 176, Steps A and B) , as described in Example 196 using 1,4-dioxane as the solvent. MS (ESI): exact mass calculated for

C

19

H

1 8

CIN

3 , 323.12; found, m/z 324.1 [M+H]. 1 H NMR (500 MHz, CDCI 3 ): 7.37-7.34 (m, 2H), 7.29-7.24 (m, 5H), 7.14-7.10 (m, 2H), 3.12-3.09 (m, 2H), 15 3.04-2.99 (m, 4H), 2.74-2.71 (m, 2H), 2.13 (br s, 1H). Example 199 N-N HN 2 -Phenyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 20 Step A. 2-Phenyl-3-thiophen-2-vl-4,5,7,8-tetrahvdro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester. To a solution of 199.8 mg of 2-phenyl-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 176, Step B) in 3.5 mL of DMF were added 0.6 mL of 2 M aq. Na 2

CO

3 and 75.6 mg of thiophene-2-boronic acid. 25 PdCl 2 dppf (20.2 mg) was added and the mixture was heated at 80 0 C for 16 h. 162 The mixture was poured into water (50 mL) and extracted with CH 2

CI

2 (3 x 15 mL) and the combined organic layers were concentrated in vacuo. Chromatography on Si02 (0 to 50% EtOAc/hexanes) afforded 58.9 mg of the desired compound as a white solid. MS (ESI): exact mass calculated for 5 C 22

H

2 5

N

3 0 2 S, 395.17; found, m/z 396.1 [M+H]*. Step B. The above compound (58.9 mg) was converted to the title compound (28.1 mg) as in Example 26, Step B. MS (ESI): exact mass calculated for

C

17

H

17

N

3 S, 295.11; found, m/z 296.1 [M+H]*. 1 H NMR (500 MHz, CDCl3): 7.36 (dd, J = 5.2,1.3 Hz, 1 H), 7.32-7.23 (m, 5H), 7.01 (dd, J = 5.2, 3.3 Hz, 1 H), 10 6.85 (dd, J = 3.3,1.3 Hz, 1H), 3.11-3.08 (m, 2H), 3.03-2.99 (m, 4H), 2.76-2.73 (m, 2H), 2.12 (br s, 1H). Example 200 N-N HNF 15 3

-(

4 -Fluoro-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (70.0 mg) was prepared from 207.0 mg of 2-phenyl-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 176, Step B) and 98.5 mg of 4 fluorophenylboronic acid as in Example 199. MS (ESI): exact mass calculated 20 for CjqH 1 8

FN

3 , 307.15; found, m/z 308.2 [M+H]*. 1 H NMR (500 MHz, CDCl 3 ): 7.28-7.24 (m, 2H), 7.22-7.16 (m, 3H), 7.13-7.10 (m, 2H), 7.05-7.01 (m, 2H), 3.12-3.08 (m, 2H), 3.05-3.02 (m, 2H), 3.01-2.98 (m, 2H), 2.68-2.64 (m, 2H). Example 201 N-N 25 H N 163 3

-(

4 -Chloro-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (9.3 mg) was prepared from 164.0 mg of 2-phenyl-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 176, Step B) and 63.8 mg of 4 5 chlorophenylboronic acid as in Example 196. MS (ESI): exact mass calculated for C 19

H

18

CIN

3 , 323.12; found, m/z 324.1 [M+H]*. 1 H NMR (500 MHz, CDCl 3 ): 7.33-7.25 (m, 4H), 7.23-7.16 (m, 3H), 7.09-7.06 (m, 2H), 3.10 3.07 (m, 2H), 3.03-3.00 (m, 2H), 2.99-2.96 (m, 2H), 2.66-2.63 (m, 2H). 10 Example 202 N-N CI HN 3

-(

3 -Chloro-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (37.5 mg) was prepared from 192.3 mg of 2-phenyl-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 15 carboxylic acid tert-butyl ester (Example 176, Step B) and 84.7 mg of 3 chlorophenylboronic acid as in Example 199. MS (ESI): exact mass calculated for C 1 9

H

1 8

CIN

3 , 323.12; found, m/z 324.1 [M+H]*. 1 H NMR (500 MHz, CDCla): 7.32-7.16 (m, 8H), 7.01-6.98 (m, 1H), 3.12-3.08 (m, 2H), 3.05 3.02 (m, 2H), 3.01-2.98 (m, 2H), 2.69-2.66 (m, 2H). 20 Example 203 N-N HN 2 -Phenyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2 ,6-triaza-azulene. The title compound (17.5 mg) was prepared from 188.9 mg of 2-phenyl-3 25 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro- 2 H-1, 2 ,6-triaza-azulene-6 164 carboxylic acid tert-butyl ester (Example 176, Step B) and 93.3 mg of p tolylboronic acid as in Example 199, using DME as the solvent. MS (ESI): exact mass calculated for C 2 oH 2 1

N

3 , 303.17; found, m/z 304.2 [M+H]. 1 H NMR (500 MHz, CDC1s): 7.26-7.23 (m, 2H), 7.21-7.16 (m, 3H), 7.15-7.12 (m, 2H), 5 7.04-7.01 (m, 2H), 3.11-3.07 (m, 2H), 3.04-3.00 (m, 2H), 2.98-2.96 (m, 2H), 2.68-2.65 (m, 2H), 2.35 (s, 3H). Example 204 N-N (N H 10 2,3-Diphenyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine. Step A. 2

,

3 -Diphenyl-2,4,6,7-tetrahydro-pyrazolo4,3-cpyridine-5-carboxylic acid tert-butyl ester. To a solution of 156.6 mg of 2-phenyl-3 trifluoromethanesulfonyloxy-2,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5 carboxylic acid tert-butyl ester (made from 4-oxo-piperidine-1,3-dicarboxylic 15 acid 1-tert-butyl ester 3-methyl ester as in Example 176, Steps A and B) in

THF/H

2 0 (10:1, 4 mL) were added 148.4 mg of K 2

CO

3 and 56.2 mg of phenylboronic acid. PdCl 2 dppf (23.4 mg) was added and the mixture was heated at reflux for 16 h. The mixture was concentrated in vacuo. The residue was chromatographed on Si02 (0 to 75% EtOAc/hexanes) to afford 45.6 mg of 20 the desired ester as an off-white solid. MS (ESI): exact mass calculated for

C

23

H

25

N

3 0 2 , 375.19; found, m/z 376.2 [M+H]*. Step B. The above compound (45.6 mg) was converted to the title compound (24.5 mg) as in Example 26, Step B. MS (ESI): exact mass calculated for

C

18

H

17

N

3 , 275.14; found, m/z 276.2 [M+H]*. 1 H NMR (500 MHz, CDCI 3 ): 7.34 25 7.22 (m, 8H), 7.16-7.12 (m, 2H), 3.96 (s, 2H), 3.23 (t, J= 6.0 Hz, 2H), 2.88 (t, J = 6.0 Hz, 2H). 165 Example 205

CF

3 N-N HN 3-Phenyl-2-(3-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 Step A. 3 -PhenVl-2-(3-trifluoromethyl-phenyl)-4,5,7,8-tetrahVdro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester. The desired compound (172.0 mg) was prepared from 279.1 of mg of 3-trifluoromethanesulfonyloxy-2-(3 trifluoromethyl-phenyl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (made from (3-trifluoromethyl-phenyl)-hydrazine as in 10 Example 176, Steps A and B) and 0.21 g of phenylboronic acid, as described in Example 177, Step C. MS (ESI): exact mass calculated for C 2 5

H

26

F

3

N

3 0 2 , 457.20; found, m/z 458.1 [M+H]*. Step B. The above compound (172.0 mg) was converted to the title compound (106.4 mg) as in Example 26, Step B. MS (ESI): exact mass calculated for 15 C 20

H

18

F

3

N

3 , 357.15; found, m/z 358.1 [M+H]*. 1 H NMR (500 MHz, CDC 3 ): 7.53 (s, 1H), 7.44-7.41 (m, 1 H), 7.39-7.29 (m, 5H), 7.17-7.13 (m, 2H), 3.12 3.09 (m, 2H), 3.06-3.02 (m, 2H), 3.00-2.97 (m, 2H), 2.69-2.66 (m, 2H). Example 206 N-N 20 HN 3 -(4-Methoxy-phenyl)-2-phenyl-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene. The title compound (43.6 mg) was prepared from 198.3 mg of 2-phenyl-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1 ,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 176, Step B) and 94.7 mg of 4 25 methoxyphenylboronic acid as described in Example 199. MS (ESI): exact 166 mass calculated for C 20

H

21

N

3 0, 319.17; found, m/z320.2 [M+H]*. 1 H NMR (500 MHz, CDCIa): 7.28-7.24 (m, 2H), 7.21-7.17 (m, 3H), 7.07 (d, J= 8.8 Hz, 2H), 6.87 (d, J= 8.8 Hz, 2H), 3.81 (s, 3H), 3.11-3.08 (m, 2H), 3.04-3.01 (m, 2H), 3.00-2.97 (m, 2H), 2.68-2.65 (m, 2H). 5 Example 207 CI N-N HN 2 -(4-Chloro-phenyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (50.4 mg) was prepared from 201.1 mg of 2-(4-chloro 10 phenyl)-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester (made from (4-chloro-phenyl) hydrazine as in Example 176, Steps A and B), and 65.1 mg of phenylboronic acid as described in Example 204. MS (ESI): exact mass calculated for

C

1 9

H

1 8

CIN

3 , 323.12; found, m/z 324.1 [M+H]*. 'H NMR (500 MHz, CDCI 3 ): 15 7.39-7.34 (m, 3H), 7.22-7.19 (m, 2H), 7.15-7.11 (m, 4H), 3.11-3.07 (m, 2H), 3.04-3.00 (m, 2H), 2.99-2.96 (m, 2H), 2.67-2.64 (m, 2H). Example 208 N-N N 20 6-Methyl-2,3-diphenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. To a solution of 33.5 mg of 2,3-diphenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene (Example 176, Step D) in 5 mL of CH 2

CI

2 were added 0.15 g of paraformaldehyde and 0.15 g of NaBH(OAc) 3 . The mixture was stirred at RT for 12 h and was diluted with 20 mL of 1 M NaOH. After stirring for 3 h, the 167 mixture was extracted with CH 2 Cl 2 (2 x 10 mL) and the combined organic layers were concentrated. Chromatography on Si02 (0 to 5% 2 M NH 3 in MeOH/CH 2 Cl 2 ) gave 22.3 mg of the title compound as a white solid. MS (ESI): exact mass calculated for C 2 oH 2 1 Na, 303.17; found, m/z 304.2 [M+H]*. 'H NMR 5 (500 MHz, CDCI 3 ): 7.35-7.30 (m, 3H), 7.27-7.21 (m, 2H), 7.20-7.16 (m, 3H), 7.15-7.12 (m, 2H), 3.06-3.02 (m, 2H), 2.83-2.79 (m, 2H), 2.72-2.67 (m, 4H), 2.50 (s, 3H). Example 209 N-N C/

OH

3 10 HN 2 -Isopropyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (129 mg) was prepared as in Example 177, Steps C and D, using 204 mg of 2-isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step 15 A) and 194 mg of 4-methylphenylboronic acid. MS (ESI): exact mass calculated for C 17

H

23

N

3 , 269.19; found, m/z 270.5 [M+H]*. 'H NMR (500 MHz,

CD

3 OD): 7.28 (d, J= 7.7 Hz, 2H), 7.12 (d, J= 7.7 Hz, 2H), 4.32 (m, 1H), 3.34 3.33 (m, 2H), 3.12-3.10 (m, 2H), 2.70-2.68 (m, 2H), 2.33 (s, 3H), 1.30 (d, J= 6.6 Hz, 6H). 20 Example 210 N-N HN CH 3 3

-(

4 -Ethyl-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (134 mg) was prepared as in Example 177, Steps C and D, 25 using 202 mg of 2 -isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 212 mg of 4-ethylphenylboronic acid. MS (ESI): exact mass calculated 168 for C1 8

H

25

N

3 , 283.20; found, m/z 284.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.44 (d, J = 7.7 Hz, 2H), 7.31 (d, J = 7.7 Hz, 2H), 4.52 (m, 1 H), 3.50-3.48 (m, 2H), 3.36-3.34 (m, 2H), 2.85-2.83 (m, 2H), 2.75 (q, J= 7.7 Hz, 2H), 1.47 (d, J= 6.6 Hz, 6H), 1.29 (t, J = 7.7 Hz, 3H). 5 Example 211 N-N 1/1 H N 3

-(

4 -Chloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (82 mg) was prepared as in Example 177, Steps C and D, 10 using 205 mg of 2-isopropyl- 3 -trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 332 mg of 2

-(

4 -chloro-phenyl)-benzo[1,3,2]dioxaborole. MS (ESI): exact mass calculated for C1 6

H

20

CIN

3 , 289.13; found, m/z 290.4 [M+H]*, 292.4 [M+H]. 'H NMR (500 MHz, CD30D): 7.57 (d, J= 8.5 Hz,'2H), 7.33 (d, J = 8.5 15 Hz, 2H), 4.36 (m, 1H), 3.44-3.40 (m, 2H), 3.20-3.18 (m, 2H), 2.81-2.76 (m, 2H), 1.40 (d, J= 6.6 Hz, 6H). Example 212 N-N HCN 20 4

-(

2 -Isopropyl-2,4,5,6,7,8-hexahydro- 1, 2

,

6 -triaza-azulen-3-yl)-benzonitrile. The title compound (95 mg) was prepared as in Example 177, Steps C and D, using 205 mg of 2 -isopropyl- 3 -trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 211 mg of 4-cyanophenylboronic acid. MS (ESI): exact mass 25 calculated for C1 7

H

20

N

4 , 280.17; found, m/z 281.4 [M+H]*. 'H NMR (500 MHz,

CD

3 OD): 7.57 (d, J= 8.5 Hz, 2H), 7.33 (d, J= 8.5 Hz, 2H), 4.36 (m, 1H), 3.42 3.40 (m, 2H), 3.19-3.17 (m, 2H), 2.79-2.77 (m, 2H), 1.40 (d, J= 6.6 Hz, 6H). 169 Example 213 N-N H/ CF 3 HN 2-Isopropyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza 5 azulene. The title compound (103 mg) was prepared as in Example 177, Steps C and D, using 199 mg of 2-isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 265 mg of 4-trifluoromethylphenylboronic acid. MS (ESI): exact mass 10 calculated for C 17

H

20

F

3

N

3 , 323.16; found, m/z 324.4 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.86 (d, J= 8.0 Hz, 2H), 7.55 (d, J= 8.0 Hz, 2H), 4.34 (m, 1 H), 3.43-3.40 (m, 2H), 3.20-3.18 (m, 2H), 2.80-2.78 (m, 2H), 1.40 (d, J= 6.6 Hz, 6H). 15 Example 214

/

N-N H C H 3 HN 2-Ethyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (136 mg) was prepared as in Example 177, Steps C and D, using 201 mg of 2-ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 20 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 198 mg of 4-methylphenylboronic acid. MS (ESI): exact mass calculated for C 16

H

21

N

3 , 255.17; found, m/z256.5 [M+HJ*. 1 H NMR (500 MHz, CD 3 0D): 7.38 (d, J = 8.0 Hz, 2H), 7.25 (d, J= 8.0 Hz, 2H), 4.67 (br s,.1 H), 4.05 (q, J = 7.1 Hz, 2H), 3.92-3.41 (m, 2H), 3.28-3.18 (m, 3H), 2.89-2.80 (m, 2H), 2.43 (s, 25 3H), 1.29 (t, J= 7.1 Hz, 3H). 170 Example 215 N-N HN 2-tert-Butyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. 2-(tert-Butyl)-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 5 1_,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The desired triflate was prepared as in Steps A and B of Example 176, using tert-butyl hydrazine hydrochloride in place of phenylhydrazine, t-butanol in place of EtOH, with the addition of 3 equiv. of triethylamine. Step B. The title compound (53 mg) was prepared as in Example 177, Steps C 10 and D, using 200 mg of the triflate from Step A and 166 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 17

H

23

N

3 , 269.19; found, m/z 270.5 (M+H]*, 214.4 [M-'Bu]+. 'H NMR (500 MHz, CD30D): 7.49-7.47 (m, 3H), 7.32 7.30 (m, 2H), 3.41-3.39 (m, 2H), 3.25-3.23 (m, 2H), 3.18-3.15 (m, 2H), 2.52 2.520 (m, 2H), 1.41 (s, 9H). 15 Example 216 N-N HNF 2 -tert-Butyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (88 mg) was prepared as in Example 177, Steps C and D, 20 using 204 mg of 2-(tert-butyl)-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro 2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 215 Step A) and 194 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for C 17

H

22

FN

3 , 287.18; found, m/z 288.4 [M+H]*, 232.4 [M-'Bu]+. 1 H NMR (500 MHz, CD 3 OD): 7.37-7.33 (m, 2H), 7.26-7.22 (m, 2H), 3.41-3.38 (m, 2H), 3.26 25 3.24 (m, 2H), 3.18-3.15 (m, 2H), 2.53-2.51 (m, 2H), 1.42 (s, 9H). 171 Example 217 2 N-N H/ CH 3 2-Cyclopentyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (70.4 mg) was prepared as in Example 177, Steps C and 5 D, using 204.3 mg of 2-cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2- 1, 2,6-triaza-azulene-6-ca rboxylic acid tert-butyl ester (Example 180, Step A) and 204.1 mg of 4-methylphenylboronic acid. MS (ESI): exact mass calculated for C 19

H

25

N

3 , 295.42; found, m/z296.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.37 (d, J= 7.9 Hz, 2H), 7.21 (d, J= 7.9 Hz, 2H), 4.50 (m, 1H), 10 3.43-3.40 (m, 2H), 3.32-3.28 (m, 2H), 3.20-3.17 (m, 2H), 2.80-2.77 (m, 2H), 2.43 (s, 3H), 2.04-1.86 (m, 6H), 1.64-1.55 (m, 2H). Example 218 2 N-N /

CF

3 HN 15 2-Cyclopentyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (45.2 mg) was prepared as in Example 177, Steps C and D, using 269.2 mg of 2-cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2 H-1,2,6-triaza-azu lene-6-carboxyl ic acid tert-butyl ester (Example 20 180, Step A) and 359.2 mg of 4-trifluoromethylphenylboronic acid. MS (ESI): exact mass calculated for C1 9

H

22

F

3

N

3 , 349.49; found, m/z 350.3 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.87 (d, J = 7.9 Hz, 2H), 7.55 (d, J = 7.9 Hz, 2H), 4.48 (m, 1H), 3.43-3.40 (m, 2H), 3.21-3.17 (m, 2H), 2.81-2.77 (m, 2H), 2.07 1.86 (m, 6H), 1.66-1.57 (m, 2H). 25 172 Example 219 N-N CI HN 3-(3-Chloro-phenyl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (34.9 mg) was prepared as in Example 177, Steps C and 5 D, using 204.4 mg of 2-cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 234.5 mg of 3-chlorophenylboronic acid. MS (ESI): exact mass calculated for C 18 H22CIN 3 , 315.84; found, m/z 316.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.57-7.52 (m, 2H), 7.37-7.35 (m, 1 H), 7.29-7.26 (m, 1 H), 10 4.46 (m, 1 H), 3.43-3.39 (m, 2H), 3.20-3.16 (m, 2H), 2.80-2.76 (m, 2H), 2.06 1.86 (m, 6H), 1.66-1.57 (m, 2H). Example 220 N-N HN 15 2-Cyclopentyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (34.9 mg) was prepared as in Example 177, Steps C and D, using 299.2 mg of 2-cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 20 180, Step A) and 329.2 mg of 4-methoxyphenylboronic acid. MS (ESI): exact mass calculated for C, 9

H

25

N

3 0, 311.42; found, m/z 312.3 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.26-7.23 (m, 2H), 7.11-7.08 (m, 2H), 4.51 (m, 1H), 3.87 (s, 3H), 3.43-3.40 (m, 2H), 3.20-3.16 (m, 2H), 2.80-2.76 (m, 2H), 2.02-1.86 (m, 6H), 1.64-1.55 (m, 2H). 25 173 Example 221 N-N HN 2

-(

3

,

3 -Dimethyl-cyclopentyl)-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 Step A. 2-(3,3-Dimethyl-cyclope ntvl)-3-trifluoromethanesulfonyloxy-45,7,8 tetrahydro-2H-1.2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The desired triflate was prepared as in Steps A and B of Example 176, using (3,3 dimethyl-cyclopentyl)-hydrazine hydrochloride in place of phenylhydrazine, t butanol in place of EtOH, with the addition of 3 equiv. of triethylamine. 10 Step B. The title compound (92.8 mg) was prepared as in Example 177, Steps C and D, using 197.5 mg of the triflate from Step A and 150 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 20

H

27

N

3 , 309.45; found, m/z 310.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.58-7.50 (m, 3H), 7.34-7.31 (m, 2H), 4.66-4.58 (m, 1 H), 3.44-3.40 (m, 2H), 3.32-3.28 (m, 2H), 15 3.21-3.17 (m, 2H), 2.81-2.77 (m, 2H), 2.21-2.03 (m, 2H), 2.01-1.95 (m, 1 H), 1.80-1.73 (m, 2H), 1.48-1.39 (m, 1H), 1.16 (s, 3H), 0.92 (s, 3H). Example 222 N-N HNF 20 2

-(

3

,

3 -Dimethyl-cyclopentyl)-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (52.6 mg) was prepared as in Example 177, Steps C and D, using 201.7 mg of 2-(3,3-dimethyl-cyclopentyl)-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 25 carboxylic acid tert-butyl ester (Example 221, Step A) and 180 mg of 4 fluorophenylboronic acid. MS (ESI): exact mass calculated for C 20

H

26

FN

3 , 174 327.44; found, m/z 328.5 [M+H]*.

'

H NMR (500 MHz, CD 3 0D): 7.39-7.34 (m, 2H), 7.33-7.28 (m, 2H), 4.62-4.53 (m, 1 H), 3.44-3.39 (m, 2H), 3.31 -3.29 (m, 2H), 3.21-3.17 (m, 2H), 2.80-2.75 (m, 2H), 2.20-2.03 (m, 2H), 2.00-1.94 (m, 1 H), 1.80-1.73 (m, 2H), 1.49-1.41 (m, 1 H), 1.16 (s, 3H), 0.93 (s, 3H). 5 Example 223 N-N H CI 3

-(

4 -Chloro-phenyl)-2-(3,3-dimethyl-cycIopentyl)-2,4,5,6,7,8-hexahydro- 1,2,6 triaza-azulene. 10 The title compound (25.6 mg) was prepared as in Example 177, Steps C and D, using 203.3 mg of 2-(3,3-dimethyl-cyclopentyl)-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (Example 221 Step A) and 204.1 mg of 4 chlorophenylboronic acid. MS (ESI): exact mass calculated for C 20

H

2 6

CIN

3 , 15 343.89; found, mlz 344.5 [M+H]*. 1 H NMR (500 MHz, CD30D): 7.57 (d, J= 8.5 Hz, 2H), 7.32 (d, J= 8.5 Hz, 2H), 4.62-4.54 (m, 1 H), 3.43-3.39 (m, 2H), 3.32-3.28 (m, 2H), 3.20-3.16 (m, 2H), 2.79-2.75 (m, 2H), 2.19-2.03 (m, 2H), 1.99-1.94 (m, 1 H), 1.80-1.73 (m, 2H), 1.49-1.40 (m, 1 H), 1.16 (s, 3H), 0.94 (s, 3H). 20 Example 224 N-N HN 2 -Cyclohexyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (17.2 mg) was prepared as in Example 177, Steps C and 25 D, using 206.5 mg of 2 -cyclohexyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2 H-1, 2

,

6 -triaza-azulene-6-carboxyl ic acid tert-butyl ester (Example 175 177, Step B) and 193.2 mg of 4 -fluorophenylboronic acid. MS (ESI): exact mass calculated for Cj 9

H

24

FN

3 , 313.41; found, m/z314.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.37-7.28 (m, 4H), 3.91-3.84 (m, 1H), 3.43-3.38 (m, 2H), 3.32-3.27 (m, 2H), 3.18-3.14 (m, 2H), 2.78-2.74 (m, 2H), 1.96-1.79 (m, 6H), 5 1.69-1.63 (m, 1H), 1.30-1.19 (m, 3H). Example 225 N-N F H F 2 -Cyclohexyl-3-(3,4-difluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza 10 azulene. The title compound (42.7 mg) was prepared as in Example 177, Steps C and D, using 205.2 mg of 2 -cyclohexyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 177, Step B) and 224.9 mg of 3 ,4-difluorophenylboronic acid. MS (ESI): exact 15 mass calculated for C, 9

H

23

F

2

N

3 , 331.40; found, m/z 332.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7 .51-7.44 (m, 1H), 7.34-7.28 (m, 1H), 7.17-7.13 (m, 1H), 3.91-3.84 (m, 1H), 3.42-3.38 (m, 2H), 3.18-3.14 (m, 2H), 2.78-2.74 (m, 2H), '1.96-1.78 (m, 6H), 1.70-1.64 (m, 1H), 1.32-1.19 (m, 3H). 20 Example 226 N-N HN 2 -Cyclohexyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (60.2 mg) was prepared as in Example 177, Steps C and D, using 203.8 mg of 2 -cyclohexyl-3-trifluoromethanesulfonyloxy-4,5,7,8 25 tetrahydro-2H-1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 177, Step B) and 181.6 mg of 4-methylphenylboronic acid. MS (ESI): exact 176 mass calculated for C 2 0

H

27

N

3 , 309.45; found, m/z 310.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.37 (d, J= 7.7 Hz, 2H), 7.19 (d, J= 7.7 Hz, 2H), 3.97-3.89 (m, 1 H), 3.44-3.39 (m, 2H), 3.31-3.26 (m, 2H), 3.20-3.15 (m, 2H), 2.80-2.75 (m, 2H), 1.96-1.78 (m, 6H), 1.70-1.62 (m, 1 H), 1.28-1.18 (m, 3H). 5 Example 227 Q N-N / -/

-

0 HN 2 -Cyclohexyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (96.8 mg) was prepared as in Example 177, Steps C and 10 D, using 207 mg of 2-cyclohexyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 177, Step B) and 224.1 mg of 4-methoxyphenylboronic acid. MS (ESI): exact mass calculated for C 2 0

H

2 7

N

3 0, 325.45; found, m/z 326.5 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.25 (d, J= 8.7 Hz, 2H), 7.11 (d, J= 8.7 Hz, 2H), 4.00 15 3.92 (m, 1H), 3.87 (s, 3H), 3.45-3.40 (m, 2H), 3.22-3.17 (m, 2H), 2.81-2.75 (m, 2H), 1.96-1.65 (m, 7H), 1.29-1.19 (m, 3H). Example 228 N-N H CN HN 20 4-(2-Cyclohexyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)-benzonitrile. The title compound (135.4 mg) was prepared as in Example 177, Steps C and D, using 203.8 mg of 2 -cyclohexyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 177, Step B) and 198 mg of 4-cyanophenylboronic acid. MS (ESI): exact 25 mass calculated for C 20

H

24

N

4 , 320.43; found, m/z 321.5 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.93 (d, J= 8.5 Hz, 2H), 7.53 (d, J= 8.5 Hz, 2H), 3.92-3.84 177 (m, 1 H), 3.43-3.38 (m, 2H), 3.19-3.15 (m, 2H), 2.80-2.75 (m, 2H), 1.98-1.80 (m, 6H), 1.71-1.64 (m, 1 H), 1.32-1.20 (m, 3H). Example 229 N-N CI 5 HN 3

-(

3 -Chloro-phenyl)-2-cyclohexyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (14.4 mg) was prepared as in Example 177, Steps C and D, using 199.3 mg of 2-cyclohexyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1 ,2,6-triaza-azulene-6-ca rboxylic acid tert-butyl ester (Example 10 177, Step B) and 216.2 mg of 3-chlorophenylboronic acid. MS (ESI): exact mass calculated for C 1 9

H

24 C1N 3 , 329.87; found, m/z 330.5 [M+H]*. 1 H NMR (500 MHz, CDaOD): 7.57-7.54 (m, 2H), 7.35 (s, 1 H), 7.28-7.25 (m, 1 H), 3.91 3.84 (m, 1H), 3.43-3.38 (m, 2H), 3.19-3.14 (m, 2H), 2.79-2.74 (m, 2H), 1.97 1.80 (m, 6H), 1.71-1.64 (m, 1H), 1.28-1.19 (m, 3H). 15 Example 230 N ci H 4I H N

{

4 -[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -ylmethyl] phenyl)-methyl-amine. 20 A mixture of 1-( 4 -bromo-benzyl)-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1

H

1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 113; 0.04 mmol), tert-butyl carbamate (0.05 mmol), sodium phenoxide trihydrate (0.05 mmol), tris(dibenzylideneacetone)dipalladium(O) (0.001 mmol), and tri-tert butylphosphine (0.05 mmol) in anhydrous toluene (3 mL) was heated under N 2 25 at 100 *C for 6 h, 70 *C for 15 h and 100 0C for 2.5 h. After cooling to RT, the reaction mixture was purified directly by preparative TLC (2:1 hexanes/EtOAc) to yield 0.008 g of 1-( 4 -tert-butoxycarbonylamino-benzyl)-3-(4-chloro-phenyl) 178 4,5,7,8-tetrahydro-1 H-1,2, 6 -triaza-azulene-6-carboxylic acid tert-butyl ester, which was then diluted with DMF (1 mL) and treated with NaH (60%, 1.5 equiv.). After 15 min, methyl iodide (1.5 equiv.) was added. After 1 h, the reaction was quenched with H 2 0 and the mixture was extracted with EtOAc 5 (2x). The combined organic layers were dried over Na 2

SO

4 and concentrated. The resulting semi-solid was then dissolved in CH 2

CI

2 /MeOH (9:1, 1 mL) and treated with HCI (1 N in Et 2 0, 4 mL). The mixture was stirred at RT for 3 h, then was concentrated. The resulting oil was purified by preparative TLC (10% 2 M NH 3 in MeOH/CH 2 Cl 2 ) to yield 0.002 mg of the title compound as a white 10 solid. MS (ESI): exact mass calculated for C 2 1

H

23

CIN

4 , 366.16; found, m/z 367.1 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.39-7.32 (m, 4H), 6.84 (d, J= 8.6 Hz, 1H), 6.48-6.45 (m, 2H), 5.12 (s, 2H), 2.84-2.81 (m, 4H), 2.79-2.77 (m, 2H), 2.69-2.66 (m, 2H), 2.63 (s, 3H). 15 Example 231 N-N F N H 3

-(

4 -Fluoro-phenyl)-2-isopropyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine. Step A. 2-Isopropyl-3-trifluoromethanesulfonvloxy-2,4,6,7-tetrahvdro Pyrazolor4,3-clpvridine-5-carboxylic acid tert-butyl ester. The desired triflate 20 was prepared according to Example 189, Step A, starting with 4-oxo-piperidine 1,3-dicarboxylic acid 1 -tert-butyl ester 3-methyl ester. Step B. The title compound (26 mg) was prepared as in Example 177, Steps C and D, using 221 mg of the triflate from Step A and 140 mg of 4 fluorophenylboronic acid. MS (ESI): exact mass calculated for C 1 5

H

18

FN

3 , 25 259.32; found, m/z 260.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.44-7.39 (m, 2H), 7.33-7.28 (m, 2H), 4.48 (m, 1H), 4.15 (s, 2H), 3.58 (t, J= 6.3 Hz, 2H), 3.08 (t, J= 6.3 Hz, 2H), 1.42 (d, J= 6.6 Hz, 6H). 179 Example 232 p N-N HN 2-Cyclopentyl-3-furan-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (101 mg) was prepared according to Example 180 using 5 202 mg of 2-cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 149 mg of 3-furanboronic acid. MS (ESI): exact mass calculated for

C

16

H

21

N

3 0, 271.17; found, m/z 272.5 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.73-7.72 (m, 2H), 6.57-6.56 (m, 1H), 4.64 (m, 1H), 3.40-3.38 (m, 2H), 3.16 10 3.14 (m, 2H), 2.86-2.84 (m, 2H), 2.03-1.91 (m, 6H), 1.66-1.64 (m, 2H). Example 233 P N-N /7 S HN 2-Cyclopentyl-3-thiophen-2-yl-2,4,5,6,7,8 -hexahydro-1,2,6-triaza-azulene. 15 The title compound (83 mg) was prepared according to Example 180 using 200 mg of 2-cyclopentyl-3-trifuoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1 ,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 282 mg of 2-thiopheneboronic acid. MS (ESI): exact mass calculated for C1 6

H

21

N

3 S, 287.15; found, m/z 288.4 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 20 7.70-7.68 (m, 1H), 7.24-7.22 (m, 1H), 7.15-7.14 (m, 1H), 4.64 (m, 1H), 3.41 3.39 (m, 2H), 3.16-3.15 (m, 2H), 2.85-2.83 (m, 2H), 2.01-1.88 (m, 6H), 1.64 1.60 (m, 2H). 180 Example 234 N-N 1/ "S HN 2-tert-Butyl-3-thiophen-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (83 mg) was prepared according to Example 215 using 204 5 mg of 2-(tert-butyl)-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 215, Step A) and 177 mg of 3-thiopheneboronic acid. MS (ESI): exact mass calculated for

C

15

H

21

N

3 S, 275.15; found, m/z 276.4 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.59-7.57 (m, 1H), 7.43-7.42 (m, 1H), 7.08-7.06 (m, 1H), 3.38-3.36 (m, 2H), 10 3.25-3.23 (m, 2H), 3.13-3.11 (m, 2H), 2.56-2.54 (m, 2H), 1.43 (s, 9H). Example 235 N-N H O 6 2-tert-Butyl-3-furan-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 15 The title compound (60 mg) was prepared according to Example 215 using 203 mg of 2 -(tert-butyl)-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 215, Step A) and 154 mg of 3-furanboronic acid. MS (ESI): exact mass calculated for C 15

H

2 1

N

3 0, 259.17; found, m/z 260.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.69-7.68 (m, 20 1 H), 7.61 (br s, 1 H), 6.50-6.49 (m, 1 H), 3.38-3.36 (m, 2H), 3.27-3.25 (m, 2H), 3.13-3.11 (m, 2H), 2.63-2.61 (m, 2H), 1.50 (s, 9H). 181 Example 236 N-N F HNF 2 -Cyclopentyl-3-(3,4-difl uoro-phenyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene. 5 The title compound (70 mg) was prepared according to Example 180 using 209 mg of 2 -cyclopentyl-3-trifluoromethanesu Ifonyloxy-4,5,7,8-tetrahydro-2H- 1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 218 mg of 3, 4 -difluorophenylboronic acid. MS (ESI): exact mass calculated for

C

1 8

H

21

F

2

N

3 , 317.17; found, m/z318.4 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 10 7.50-7.45 (m, 1H), 7.36-7.32 (m, 1H), 7.18-7.17 (m, 1H), 4.49 (m, 1H), 3.43 3.41 (m, 2H), 3.21-3.19 (m, 2H), 2.80-2.78 (m, 2H), 2.15-1.87 (m, 6H), 1.66 1.61 (m, 2H). Example 237 9 N-N 15 HN Cl 3-(4-Chloro-phenyl)-1 -cyclobutyl-1, 4 ,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulene. The title compound (0.01 g) was prepared from 3-(4-chloro-phenyl)-1 cyclobutyl-1,4,5,6,7,8-hexahydro-1,2, 6 -triaza-azulene-6-carboxylic acid tert butyl ester (Example 238) according to Example 103, Step C. (MS (ESI): 20 exact mass calculated for C 17 H20CIN 3 , 301.13; found, m/z302.4 [M+H)*. 'H NMR (500 MHz, CD 3 0D): 7.54-7.48 (m, 4H), 5.15-5.05 (m, 1H), 3.47-3.46 (m, 2H), 3.35-3.30 (m, 4H), 3.22-3.21 (m, 2H), 2.70-2.60 (m, 2H), 2.50-2.40 (m, 2H),,1.90-1.80 (m, 2H). 182 Example 238 P N-N / C1 HN4I 3

-(

4 -Chloro-phenyl)-2-cyclobutyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. To a solution of 3 -(4-chloro-phenyl)-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene 5 6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.40 mmol) in DMF (2 mL) was added NaH (60% dispersion in oil, 60 mg) at 25 *C . After 10 min, the mixture was heated to 80 *C, and chloro-cyclobutane (1.5 mmol) was. added. The mixture was heated at this temperature for 16 h. The mixture was concentrated and purified by chromatography (Si02, EtOAc/hexanes) to 10 provide 3-(4-chloro-phenyl)-2-cyclobutyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester. The title compound (0.030 mg) was obtained from this ester according to the deprotection method in Example 103, Step C. The reaction sequence also yielded 3-(4-chloro-phenyl)-1 -cyclobutyl 2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester in 15 the alkylation step. MS (ESI): exact mass calculated for C 17

H

2 0 ClN 3 , 301.13; found, m/z 302.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.52-7.51 (m, 2H), 7.30-7.29 (m, 2H), 4.70-4.60 (m, 1 H), 3.40-3.89 (m, 2H), 3.27-3.21 (m, 4H), 2.79-2.76 (m, 2H), 2.60-2.50 (m, 2H), 2.30-2.20 (m, 2H), 1.81-1.65 (m, 2H). 20 Example 239 N--N HN C 3-(4-Chloro-phenyl)-1 -cyclohexyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (15 mg) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 25 103, Step B; 0.40 mmol) using bromo-cyclohexane (1.5 mmol) in place of chloro-cyclobutane according to Example 238. MS (ESI): exact mass 183 calculated for C 19

H

24

CIN

3 , 329.17; found, m/z 330.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.45-7.41 (m, 4H), 4.30-4.27 (m, 1 H), 3.44-3.42 (m, 2H), 3.31 3.26 (m, 4H), 2.98-2.96 (m, 2H), 1.93-1.84 (m, 5H), 1.70-1.65 (m, 1 H), 1.46 1.40 (m, 2H), 1.24-1.89 (m, 2H). 5 Example 240 N-N IS HN 2-tert-Butyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (83 mg) was prepared according to Example 215 using 203 10 mg of 2 -(tert-butyl)-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 215, Step A) and 176 mg of 2-thiopheneboronic acid. MS (ESI): exact mass calculated for

C

1 5

H

21

N

3 S, 275.15; found, m/z 276.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.57-7.56 (m, 1H), 7.08-7.06 (m, 1H), 7.01-7.00 (m, 1H), 3.29-3.27 (m, 2H), 15 3.17-3.14 (m, 2H), 2.51-2.48 (m, 2H), 1.37 (s, 9H). Example 241 P N-N F HCI 3-(4-Chloro-3-fluoro-phenyl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza 20 azulene. The title compound (31 mg) was prepared according to Example 180 using 146 mg of 2 -cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1, 2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 168 mg of 3-chloro-4-fluorophenylboronic acid. MS (ESI): exact mass calculated 25 for C 1 8

H

21

CIFN

3 , 333.14; found, m/z 334.4 [M+H]*, 336.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.39-7.31 (m, 2H), 7.22-7.18 (m, 1H), 4.37 (m, 1H), 3.31 184 3.28 (m, 2H), 3.07-3.03 (m, 2H), 2.67-2.64 (m, 2H), 2.11-1.78 (m, 6H),' 1.56 1.47 (m, 2H). Example 242 N-N 5 HN 2-1sopropyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (148 mg) was prepared according to Example 189 using 206 mg of 2-isopropyl-3-trifluoromethanesu If onyloxy-4,5,7,8-tetrahydro-2 H-. 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) 10 and 219 mg of 4-methoxyphenylboronic acid. MS (ESI): exact mass calculated for C 17

H

23

N

3 0, 285.18; found, m/z286.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.30-7.28 (m, 2H), 7.13-7.11 (m, 2H), 4.68 (m, 1H), 4.47 (m, 1 H), 3.87 (s, 3H), 3.47-3.44 (m, 1 H), 3.25-3.23 (m, 1 H), 2.89-2.81 (m, 2H), 1.43 (d, J= 6.6 Hz, 6H). 15 Example 243 N-N / OCF 3 HN 2 -Isopropyl-3-(4-trifluoromethoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 20 The title compound (196 mg) was prepared according to Example 189 using 278 mg of 2 -isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 402 mg of 4-trifluoromethoxyphenylboronic acid. MS (ESI): exact mass calculated for C 17

H

20

F

3

N

3 0, 339.36; found, m/z 340.5 [M+H)*. 'H NMR (500 25 MHz, CD 3 0D): 7.53-7.45 (m, 4H), 4.66 (br s, 1H), 4.40 (J= 6.68 Hz, 1H), 3.45 3.43 (m, 1H), 3.23-3.21 (m, 1H), 2.88-2.79 (m, 2H), 1.42 (d, J= 6.7 Hz, 6H). 185 Example 244 N-N HN 2-Isopropyl-3-(4-isopropyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (177 mg) was prepared according to Example 189 using 5 270 mg of 2 -isopropyl- 3 -trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 311 mg of 4-isopropylphenylboronic acid. MS (ESI): exact mass calculated for C 19

H

27

N

3 , 297.44; found, m/z 298.5 [M+H]*. 1 H NMR (500 MHz,

CD

3 OD): 7.35-7.34 (m, 2H), 7.19-7.17 (m, 2H), 4.57 (br s, 1H), 4.38-4.32 (m, 10 1H), 3.36-3.34 (m, 1H), 3.15-3.13 (m, 1H), 2.90 (m, 1H), 2.79-2.70 (m, 2H), 1.31 (d, J= 13.3 Hz, 6H), 1.20 (d, J= 6.9 Hz, 6H). Example 245 N-N HN 15 3

-(

4 -tert-Butyl-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (28 mg) was prepared according to Example 189 using 215 mg of 2 -isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 268 mg of 4-tert-butylphenylboronfc acid. MS (ESI): exact mass calculated for 20 C 20

H

29

N

3 , 311.24; found, m/z 312.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.61-7.59 (m, 2H), 7.27-7.25 (m, 2H), 4.40 (m, 1H), 3.43-3.40 (m, 2H), 3.19 3.17 (m, 2H), 2.79-2.77 (m, 2H), 1.50-1.25 (m, 15H). 186 Example 246 N-N

CH

3 HN 2 -1sopropyl-3-m-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (24 mg) was prepared according to Example 189 using 219 5 mg of 2 -isopropyl- 3 -trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 209 mg of 3-methylphenylboronic acid. MS (ESI): exact mass calculated for

C

17

H

23

N

3 , 269.19; found, m/z 270.5 [M+H)*. 'H NMR (500 MHz, CD 3 0D): 7.44-7.41 (m, 1H), 7.34-7.33 (m, 1H), 7.13-7.10 (m, 2H), 4.37 (m, 1H), 3.42 10 3.40 (m, 2H), 3.19-3.17 (m, 2H), 2.78-2.76 (m, 2H), 2.42 (s, 3H), 1.38 (d, J= 6.7 Hz, 6H). Example 247 N-N .HN H 3 C 15 2 -IsopropyI-3-o-tolyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene. The title compound (80 mg) was prepared according to Example 189 using 207 mg of 2 -isopropyl- 3 -trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 198 mg of 2-methylphenylboronic acid. MS (ESI): exact mass calculated for 20 C 17

H

23

N

3 , 269.19; found, m/z 270.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.45-7.40 (m, 2H), 7.36-7.33 (m, 1H), 7.19-7.18 (m, 1H), 4.66 (br s, 2H), 4.10 (m, 1H), 4.00-3.66 (m, 2H), 2.76-2.61 (m, 2H), 2.13 (s, 3H), 1.45-1.29 (m, 6H). 187 Example 248 N-N CI 1/1 H CI HN 3

-(

3

,

4 -Dichloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulene. The title compound (60 mg) was prepared according to Example 189 using 200 5 mg of 2 -isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 268 mg of 3 ,4-dichlorophenylboronic acid. MS (ESI): exact mass calculated for

C

1 6

H

1 Cl 2

N

3 , 323.10; found, m/z 324.4 [M+H]*, 326.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.72-7.71 (m, 1 H), 7.53-7.52 (m, 1 H), 7.29-7.27 (m, 1 H), 4.64 10 (br s, 2H), 4.32 (m, 1H), 3.86-3.57 (m, 2H), 3.31-3.08 (m, 2H), 2.84-2.75 (m, 2H), 1.39 (d, J= 6.6 Hz, 6H). Example 249 N-N HN 15 2 -Benzyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulene. Step A. 2 -Benzvl- 3 -trifluoromethanesulfonloxy-4,5,7,8-tetrahvdro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester. The desired triflate was prepared according to Example 189, Step A, using benzylhydrazine hydrochloride in place of isopropylhydrazine hydrochloride. 20 Step B. The title compound (29 mg) was prepared as in Example 177, Steps C and D, using 230 mg of the trif late from Step A and 23'4 mg of 4 fluorophenylboronic acid. MS (ESI): exact mass calculated for C 2 0

H

2 0

FN

3 , 321.39; found, m/z322.4 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.31-7.19 (m, 7H), 6.97-6.93 (m, 2H), 5.20 (s, 2H), 3.45-3.40 (m, 2H), 3.35-3.30, (m, 2H), 25 3.20-3.15 (m, 2H), 2.83-2.78 (m, 2H). 188 Example 250 N-N IS HN 2 -Isopropyl-3-thiophen-2-yl-2,4,5,6,7,8-hexahydro-1, 2,6-triaza-azulene. The title compound (46 mg) was prepared according to Example 189 using 208 5 mg of 2 -isopropyl- 3 -trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 187 mg of 2-thiopheneboronic acid. MS (ESI): exact mass calculated for

C

14 HjqN 3 S, 261,13; found, m/z 262.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.70-7.69 (m, 1H), 7.25-7.23 (m, 1H), 7.15-7.14 (m, 1H), 4.65 (br s, 2H), 4.55 10 4.49 (m, 1H), 3.8-3.6 (m, 2H), 3.23-3.10 (m, 2H), 2.93-2.83 (m, 2H), 1.44-1.36 (m, 6H). Example 251 N-N HN CI 15 3

-(

2 -Chloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (90 mg) was prepared according to Example 189 using 266 mg of 2 -isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 292 mg of 2-chlorophenylboronic acid. MS (ESI): exact mass calculated for 20 C 16 H2oCIN 3 , 289.13; found, m/z 290.4 [M+H]*, 292.4 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.65-7.63 (m, 1H), 7.58-7.49 (m, 2H), 7.41-7.39 (m, 1H), 4.66 (br s, 2H), 4.16 (m, 1H), 4.00-3.44 (m, 2H), 3.0-2.6 (m, 2H), 1.47-1.38 (m, 6H). 189 Example 252 N-N H 1-[ 4

-(

2 -Isopropyl-2,4,5,6,7,8-hexahydro-1,2 ,6-triaza-azulen-3-yl)-phenyl] ethanone. 5 The title compound (168 mg) was prepared according to Example 189 using 255 mg of 2-isoprop'yl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2

,

6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 341 mg of 4 -acetylphenylboronic acid. MS (ESI): exact mass calculated for C 18

H

23

N

3 0, 297.18; found, m/z298.5 [M+H}*. 1 H NMR (500 MHz, CD 3 0D): 10 8.17-8.15 (m, 1H), 7.69-7.67 (m, 1H), 7.51-7.49 (m, 1H), 7.37-7.35 (m, 1H), 4.65 (br s, 1H), 4.46-4.38 (m, 1H), 4.00-3.50 (m, 2H), 3.48-3.42 (m, 1H), 3.25 3.17 (m, 1H), 3.13-2.81 (m, 2H), 2.67 (s, 1.5H), 1.55 (s, 1.5H), 1.44-1.40 (m, 6H). 15 Example 253 N-N H NO 2 2 -Isopropyl-3-(4-nitro-phenyl)-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene. The title compound (34 mg) was prepared according to Example 189 using 274 mg of 2 -isopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 20 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 321 mg of 4-nitrophenylboronic acid. MS (ESI): exact mass calculated for C1 6

H

2 0

N

4 0 2 , 300.16; found, m/z 301.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 8.42-8.40 (m, 2H), 7.62-7.60 (m, 2H), 4.37 (m, 1 H), 3.43-3.41 (m, 2H), 3.21 3.18 (m, 2H), 2.82-2.79 (m, 2H), 1.41 (d, J= 8.2 Hz, 6H). 25 190 Example 254 N'N HN C 3-(4-Chloro-phenyl)-1 -cycloheptyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (22 mg) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 5 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.30 mmol) using chloro-cycloheptane (1.0 mmol) in place of chloro-cyclobutane according to Example 238. The reaction sequence also yielded 3-(4-chloro-phenyl)-2-cycloheptyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): 10 exact mass calculated for C 20

H

26

CIN

3 , 343.18; found, m/z 344.4 [M+H)*. 1 H NMR (500 MHz, CD 3 0D): 7.40-7.34 (m, 4H), 4.31-4.27 (m, 1H), 3.39-3.37 (m, 2H), 3.28-3.26 (m, 2H), 3.17-3.16 (m, 2H), 2.95-2.92 (m, 2H), 2.04-2.01 (m, 2H), 1.92-1.90 (m, 2H), 1.77-1.75 (m, 2H), 1.63-1.53 (m, 6H). 15 Example 255 NN HIC HN C 3-(4-Chloro-phenyl)-1-cyclooctyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (47 mg) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 20 103, Step B; 0.30 mmol) using chloro-cyclooctane (1.0 mmol) in place of chloro-cyclobutane according to Example 238. The reaction sequence also yielded 3-(4-chloro-phenyl)-2- cyclooctyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 21

H

28

CIN

3 , 357.20; found, m/z 358.5 [M+H]*. 1H 25 NMR (500 MHz, CD 3 0D): 7.50-7.44 (m, 4H), 4.49-4.45 (m, 1H), 3.51-3.48 (m, 191 2H), 3.38-3.36 (in, 2H), 3.33-3.32 (m, 2H), 3.05-3.04 (m, 2H), 2.21-2.18 (m, 2H), 1.97-1.88 (m, 4H), 1.72-1.64 (m, 8H), Example 256 N-N C CN 5 H 2 -Benzyl-3-(4-chloro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,5-triaza-azulene. The title compound (0.023 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8 tetrahydro-1 H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g), as described in Example 60. MS (ESI): exact mass 10 calculated for C20H 20

CIN

3 , 337.13; found, m/z338.4 [M+H]*. 1H NMR (500 MHz, CD 3 0D): 7.47-7.44 (m, 2H), 7.25-7.19 (m, 5H), 6.94-6.92 (m, 2H), 5.17 (s, 2H), 3.66 (s, 2H), 3.21-3.19 (m, 2H), 2.93-2.90 (m, 2H), 1.93-1.84 (s, 2H). Example 257 N-N 15 HN 2-Ethyl-3-(4-ethyl-phenyl)-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene. The title compound (140 mg) was prepared according to Example 193 using 213 mg of 2 -ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8 -tetrahydro-2H-1 ,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 232 20 mg of 4-ethylphenylboronic acid. MS (ESI): exact mass calculated for

C

17

H

23

N

3 , 269.19; found, m/z 270.5 [M+H]*, 1 H NMR (500 MHz, CD 3 0D): 7.40-7.39 (m, 2H), 7.27-7.26 (m, 2H), 4.65 (br s, 2H), 4.05-4.00 (m, 2H), 3.8 3.6 (m, 2H), 3.18-3.00 (m, 2H), 2.88-2.81 (m, 2H), 2.76-2.71 (m, 2H), 1.32-1.24 (m, 6H). 25 192 Example 258 N-N HN 4-(2-Ethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)-benzonitrile. The title compound (47 mg) was prepared according to Example 193 using 205 5 mg of 2-ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 218 mg of 4-cyanophenylboronic acid. MS (ESI): exact mass calculated for C 1 6

H

18

N

4 , 266.15; found, m/z267.5 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.93-7.91 (m, 2H), 7.58-7.56 (m, 2H), 4.03 (q, J= 7.2 Hz, 2H), 3.43-3.40 (m, 2H), 3.18-3.16 10 (m, 2H), 2.82-2.80 (m, 2H), 1.29 (t, J= 7.2 Hz, 3H). Example 259 N-N F N

H

3 C 3-(4-Fluoro-phenyl)-2-isopropyl-6-methyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza 15 azulene. The title compound (113 mg) was prepared from 3-(4-fluoro-phenyl)-2 isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (Example 190) and paraformaldehyde as in Example 35. MS (ESI): exact mass calculated for

C

17 H22FN 3 , 287.18; found, m/z 288.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 20 7.42-7.40 (m, 2H), 7.34-7.30 (m, 2H), 4.42 (m, 1H), 3.77-3.74 (m, 1H), 3.67 3.62 (m, 2H), 3.36-3.34 (m, 1 H), 3.27-3.21 (m, 3H), 3.03 (s, 3H), 2.92-2.89 (m, 1H), 2.80-2.76 (m, 1 H), 1.49-1.29 (m, 6H). 193 Example 260 N-N F N 3

-(

4 -Fluoro-phenyl)-2,6-diisopropyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza-azulene. The title compound (92 mg) was prepared from 3-(4-fluoro-phenyl)-2-isopropyl 5 2

,

4 ,5,6, 7

,

8 -hexahydro-1,2,6-triaza-azulene (Example 190) and acetone as in Example 35. MS (ESI): exact mass calculated for C 19

H

26

FN

3 , 315.21; found, m/z 316.5 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.42-7.39 (m, 2H), 7.33-7.30 (m, 2H), 4.40 (m, 1 H), 3.78-3.74 (m, 2H), 3.68-3.63 (m, 1 H), 3.36-3.21 (m, 4H), 2.99-2.94 (m, 1H), 2.80-2.76 (m, 1H), 1.54-1.37 (m, 12H). 10 Example 261 N-N HN 2 -Ethyl-3-(4-isopropyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (131 mg) was prepared according to Example 193 using 15 205 mg of 2 -ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 245 mg of 4-isopropylphenylboronic acid. MS (ESI): exact mass calculated for

C

18

H

25

N

3 , 283.20; found, m/z284.5 [M+H]*. 'H NMR (500 MHz, CD3OD): 7.48-7.46 (m, 2H), 7.34-7.33 (m, 2H), 4.12 (q, J= 7.3 Hz, 2H), 3.50-3.45 (m, 20 2H), 3.36-3.33 (m, 2H), 3.27-3.25 (m, 2H), 3.01 (m, 1H), 2.87-2.85 (m, 2H), 1.34 (t, J= 7.3 Hz, 3H), 1.31 (d, J= 6.9 Hz, 6H). Example 262 /~ N-N HN 194 2-Ethyl-3-(4-methoxy-phe nyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azu le ne. The title compound (134 mg) was prepared according to Example 193 using 219 mg of 2-ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 241 5 mg of 4-methoxyphenylboronic acid. MS (ESI): exact mass calculated for C1 6

H

21

N

3 0, 271.17; found, m/z272.5 [M+H]. 1 H NMR (500 MHz, CD 3 0D): 7.36-7.33 (m, 2H), 7.15-7.12 (m, 2H), 4.12 (q, J= 7.3 Hz, 2H), 3.88 (s, 3H), 3.49-3.47 (m, 2H), 3.36-3.34 (m, 2H), 3.28-3.25 (m, 2H), 2.88-2.85 (m, 2H), 1.35 (t, J= 7.3 Hz, 3H). 10 Example 263 N-N /

CF

3 N 2-Ethyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. 2-Ethyl-3-(4-trifluoromethvl-phenyl)-4,5,7,8-tetrahvdro-2H-1,2,6-triaza 15 azulene-6-carboxylic acid tert-butyl ester. To a 25 mL round bottom flask was added 216 mg of 2-ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A), 139 mg of 4-trifluoromethylphenylboronic acid, 17 mg of Bu 4 N*Br~, 6 mg of dppf and 17 mg of PdC 2 (dppf). Toluene (5 mL) was added, followed by 0.8 mL of 2 20 M aq. Na 2

CO

3 , and the mixture was heated at 120 *C for 12 h under N 2 . The mixture was filtered through diatomaceous earth and the filtrate was concentrated in vacuo to afford 294 mg of dark brown viscous oil. Chromatography on SiO 2 (0 to 25% EtOAc/hexanes) provided 177 mg of the desired product. MS (ESI): exact mass calculated for C21H 26

F

3

N

3 0 2 , 409.20; 25 found, m/z 410.5 [M+H]*. Step B. The title compound (149 mg) was prepared according to Example 43, Step E. MS (ESI): exact mass calculated for C 16

H,

8

F

3

N

3 , 309.15; found, m/z 310.5 [M+H]*. 'H NMR (500 MHz, CD30D): 7.90-7.89 (m, 2H), 7.65-7.63 (m, 2H), 4.67 (br s, 2H), 4.10 (q, J= 7.2 Hz, 2H), 4.00-3.56 (m, 2H), 3.36-3.24 (m, 30 2H), 2.95-2.85 (m, 2H), 1.33 (t, J= 7.2 Hz, 3H). 195 Example 264 N-N H HN H 3 C 2-Ethyl-3-o-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 5 The title compound (138 mg) was prepared according to Example 263 using 206 mg of 2 -ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 95 mg of 2-methylphenylboronic acid. MS (ESI): exact mass calculated for

C

1 6

H

21 1N 3 , 255.17; found, m/z 256.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 10 7.49-7.42 (m, 2H), 7.38-7.35 (m, 1 H), 7.25-7.24 (m, 1 H), 4.69 (br s, 2H), 4.03 3.17 (m, 5H), 2.76-2.68 (m, 2H), 2.15 (s, 3H), 1.28 (t, J= 7.2 Hz, 3H). Example 265 N-N HN C' 15 3-(2-Chloro-phenyl)-2-ethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (73 mg) was prepared according to Example 263 using 227 mg of 2-ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 120 mg of 2-chlorophenylboronic acid. MS (ESI): exact mass calculated for C1 5

H

1 8

CIN

3 , 20 275.12; found, m/z 276.4 [M+H]*, 278.4 [M+H]. 'H NMR (500 MHz, CD 3 OD): 7.64-7.62 (m, 1 H), 7.58-7.48 (m, 2H), 7.41-7.39 (m, 1 H), 3.97-3.86 (m, 2H), 3.44-3.42 (m, 2H), 3.20-3.17 (m, 2H), 2.70-2.63 (m, 2H), 1.26 (t, J= 7.2 Hz, 3H). 196 Example 266 /~ N-N HN 2-Ethyl-3-(2-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (121 mg) was prepared according to Example 263 using 5 205 mg of 2-ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 97 mg of 2-fluorophenylboronic acid. MS (ESI): exact mass calculated for

C,

5

H

1 8

FN

3 , 259.15; found, m/z 260.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.61-7.55 (m, 1H), 7.39-7.30 (m, 3H), 4.01-3.91 (m, 2H), 3.43-3.41 (m, 2H), 10 3.18-3.16 (m, 2H), 2.79-2.73 (m, 2H), 1.28 (t, J= 9.0 Hz, 3H). Example 267 N-N 1/1 H/CI HN C 3

-(

2 ,4-Dichloro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 15 The title compound (37 mg) was prepared according to Example 189 using 230 mg of 2-isopropyl-3-trifluoromethanesu lfonyloxy-4,5,7,8-tetrahydro-2H- 1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 189, Step A) and 308 mg of 2,4-dichlorophenylboronic acid. MS (ESI): exact mass calculated for C1 6

H

1 9 C1 2

N

3 , 323.10; found, m/z 324.4 [M+H)*, 326.4 [M+H]*. 'H NMR (500 20 MHz, CD 3 0D): 7.73-7.72 (m, 1 H), 7.54-7.51 (m, 1 H), 7.37-7.35 (m, 1 H), 4.65 (br s, 1H), 4.11-4.05 (m, 1H), 3.43-3.40 (m, 2H), 3.29-3.16 (m, 3H), 2.70-2.63 (m, 2H), 1.39-1.32 (m, 6H). Example 268 /~ N-N 41/ 25 HN 197 [4-(2-Ethyl-2,4,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulen-3-yl)-phenyl]-dimethyl amine. The title compound (57 mg) was prepared according to Example 263 using 205 mg of 2 -ethyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza 5 azulene-6-carboxylic acid tert-butyl ester (Example 193, Step A) and 115 mg of 4-dimethylaminophenylboronic acid. MS (ESI): exact mass calculated for

C

17

H

24

N

4 , 284.20; found, m/z 285.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.87-7.85 (m, 2H), 7.65-7.63 (m, 2H), 4.67 (br s, 2H), 4.06 (q, J = 9.0 Hz, 2H), 4.00-3.62 (m, 2H), 3.36 (s, 6H), 3.32-3.29 (m, 2H), 3.18-2.81 (m, 2H), 1.31 (t, J 10 = 9.0 Hz, 3H). Example 269 N-N "F 6 -Benzyl- 3 -(4-fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza 15 azulene. The title compound (115 mg) was prepared from 3-(4-fluoro-phenyl)-2 isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (Example 190) and benzaldehyde as in Example 35. MS (ESI): exact mass calculated for

C

23

H

26

FN

3 , 363.21; found, m/z 364.5 [M+H]*. 1 H NMR (500 MHz, CDaOD): 20 7.58-7.55 (m, 2H), 7.53-7.51 (m, 3H), 7.37-7.33 (m, 2H), 7.31-7.27 (m, 2H), 4.52 (s, 2H), 4.34 (m, 1H), 3.80-3.75 (m, 1H), 3.68-3.64 (m, 1H), 3.35-3.16 (m, 4H), 2.83-2.80 (m, 2H), 1.38 (t, J= 6.7 Hz, 6H). 198 Example 270 N-N F N 3 -(4-Fluoro-phenyl)-2-isopropyl-6-(3-phenyl-propyl)-2,4,5,6,7,8-hexahydro 1,2,6-triaza-azulene. 5 The title compound (142 mg) was prepared from 3-(4-fluoro-phenyl)-2 isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (Example 190) and 3 phenyl-propionaldehyde as in Example 35. MS (ESI): exact mass calculated for C 25

H

30

FN

3 , 391.24; found, m/z 392.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.45-7.41 (m, 2H), 7.35-7.26 (m, 6H), 7.22-7.19 (m, 1H), 4.46 (m, 1H), 3.79 10 3.76 (m, 1 H), 3.67-3.63 (m, 1 H), 3.46-3.43 (m, 1 H), 3.35-3.29 (m, 5H), 2.90 2.87 (m, 1H), 2.83-2.73 (m, 3H), 2.19-2.12 (m, 2H), 1.44 (t, J= 6.7 Hz, 6H). Example 271 N-N 1 F N 15 3

-(

4 -Fluoro-phenyl)-2-isopropyl-6-phenethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (104 mg) was prepared from 3-(4-fluoro-phenyl)-2 isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (Example 190) and phenylacetaldehyde as in Example 35. MS (ESI): exact mass calculated for 20 C 24

H

28

FN

3 , 377.23; found, m/z 378.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.41-7.27 (m, 9H), 4.39 (m, 1H), 3.88-3.84 (m, 1H), 3.73-3.71 (m, 1H), 3.56 3.52 (m, 3H), 3.45-3.20 (m, 3H), 3.17-3.14 (m, 2H), 2.89-2.84 (m, 2H), 1.41 (t, J= 6.6 Hz, 6H). 199 Example 272 N-N F 0 3

-(

4 -Fluoro-phenyl)-2-isopropyl-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 5 carboxylic acid tert-butyl ester. This compound was obtained as an intermediate in the sequence described for Example 190. MS (ESI): exact mass calculated for C21 H 28

FN

3 0 2 , 373.46; found, m/z 374.5 [M+H]*. 1 H NMR (500 MHz, CDCi): 7.24-7.13 (m, 4H), 4.24 (m, 1H), 3.62-3.55 (m, 2H), 3.49-3.42 (m, 2H), 3.01-2.93 (m, 2H), 2.52-2.44 (m, 10 2H),1.50-1.45 (m, 9H), 1.39 (d. J = 6.9 Hz, 6H). Example 273 N-N / 010 H 4HO HN o OH O 0 1-Benzyl-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene citrate 15 salt. Step A. 5-Oxo-aze Pane- 1,4-dicarboxylic acid 1 -tert-butyl ester 4-ethyl ester. A dried, N2-flushed, 500-mL, three-necked, round-bottomed flask equipped with a magnetic stir bar, was charged with 4 -oxo-piperidine-1-carboxylic acid tert-butyl ester (20 g, 0.10 mol) and BF 3 -Et 2 0 (14 mL, 0.11 mol) in Et 2 0 (200 mL) and 20 the mixture was chilled to -5 0C. Slowly, ethyl diazoacetate (13.7 mL, 0.13 mol) was added over a period of 1 h causing vigorous gas evolution. The internal temperature was maintained between 0 "C and -5 0C during the addition. The reaction was stirred for 1 h at 0 0C, then slowly quenched with 30% aq. Na 2

CO

3 at 0 C. The pH was adjusted to between 7 and 8 and then 200

H

2 0 (30 mL) was added to the mixture. The organic layer was extracted with EtOAc (2 x 75 mL), dried with Na 2

SO

4 , filtered, and concentrated to an orange oil. The crude oil was purified by filtration chromatography (SiO 2 : 14 cm OD, 8 cm in height; 10 to 30% EtOAc/hexanes) to recover the title compound as light 5 yellow oil (85%). MS (ESI): exact mass calculated for C 14

H

23

NO

5 ; found, m/z none, unstable. HPLC (Method B): R 1 = 8.53 min. 1H NMR (400 MHz, CDC13): 4.25-2.03 (m, 11 H), 1.47-1.45 (d, J = 7.8 Hz, 9H), 1.31-1.24 (m, 3H). Step B. 3-Oxo-2,3,4,5,7,8-hexahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. In a 1-L, one-necked, round-bottomed flask equipped with 10 a magnetic stir bar was combined 5-oxo-azepane-1 ,4-dicarboxylic acid 1 -tert butyl ester 4-ethyl ester (24.42 g, 85.0 mmol) and hydrazine (3.0 mL, 0.095 mol) in EtOH (250 mL). The resulting reaction mixture was heated at reflux for 4 h, then was concentrated to provide the desired pyrazole as a white solid in 95% crude yield. The crude pyrazole was used in the next step without further 15 purification. MS (ESI): exact mass calculated for C 12

H

1

N

3 0 3 , 253.14; found, m/z254.1 [M+H]*. HPLC (Method B): Ri = 6.48 min. 'H NMR (400 MHz, CDC13): 3.64-3.54 (m, 4H), 2.91-2.86 (m, 2H), 2.70-2.65 (m, 2H), 1.49 (s, 9H). Step C. 3 -Trifluoromethanesulfonvloxv-4,5,7,8-tetrahdro-1H-1,2,6-triaza azulene-6-carboxylic acid tert-butyl ester. In a 250-mL, one-necked, round 20 bottomed flask equipped with a magnetic stirring bar, N phenyltrifluoromethanesulfonimide (50 g, 0.14 mol) was suspended in 100 mL pyridine and then 3 -oxo-2,3,4,5,7,8-hexahydro-1 H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (35.4 g, 0.14 mol) was added as a solid at rt. The reaction mixture formed a homogeneous solution after 1 h and stirring was 25 continued at rt overnight (15 h). The solvent was evaporated under vacuum and then the residue was partitioned between Et 2 0 (500 mL) and 1 M aq.

K

2

CO

3 (300 mL). The organic layer was separated and washed with aq. K 2 CO3 (1 mol/L, 300 mL) three times and then with brine (200 mL) once, dried over MgSO 4 , and evaporated to afford the product as a white solid (50.2 g, 0. 13 30 mol, 93%), which was used on next reaction without further purification. MS (ESI): exact mass calculated for C 13

H

18

F

3

N

3 0 5 S, 385.09; m/z found, 384.0 [M H]~. HPLC (Method B): Ri = 9.55 min. 'H NMR (500 MHz, CDC13): 9.52 (s, 1 H), 3.70-3.50 (m, 4H), 3.00-2.85 (m, 2H), 2.70-2.60 (m, 2H), 1.49 (s, 9H). 201 Step D. 1-BenzVl- 3 -trifluoromethanesulfonvloxy4578tetrahdro-1H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester. In a 1-L, three-necked, round bottomed flask containing a magnetic stirring bar, 3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene-6 5 carboxylic acid tert-butyl-ester (48 g, 0.125 mol) was dissolved in 500 mL of dry THF under N 2 . The solution was cooled to 0 *C and potassium t-butoxide (15.4 g, 0.137 mol) was added portion-wise as solid. The reaction mixture was stirred for 10 min to form a clear, homogeneous solution. Benzyl bromide (23.4 g, 0.137 mol) was added through an addition funnel over 10 min. The 10 resulting mixture was stirred at rt overnight (15 h). The solvent was evaporated and the residue was re-dissolved in EtOAc (300 mL). The organic layer was washed with H 2 0 (2x200 mL) and then with brine (200 mL), dried over MgSO 4 , filtered, and concentrated. The crude product was purified by pad-filtration through a plug of SiO 2 to afford the pure product as a white solid (44.5 g, 94 15 mmol, 75%). MS (ESI): exact mass calculated for C2 0

H

24

F

3

N

3 0 5 S, 475.14; found, m/z476.2 [M+H]*. HPLC (Method B): Rt = 10.90 min. 1H NMR (500 MHz, CDCI 3 ): 7.40-7.25 (m, 5H), 7.10-7.05 (m, 2H), 5.22-5.15 (m, 2H), 3.60 3.50 (m, 4H), 2.80-2.60 (m, 4H), 1.47-1.42 (m, 9H). Step E. 2 -(4-Chloro-phenl)-benzo[1 ,3,21dioxaborole. In a 250-mL, one 20 necked, round-bottomed flask equipped with a Dean-Stark trap and a condenser, the reaction solution of 4-chlorophenylboronic acid (17.5 g, 0.112 mol) and catechol (12.3 g, 0.112 mol) in toluene (150 mL) was heated at reflux for 4 h. The solution was cooled to rt and a white solid precipitated. The solvent was evaporated and the crude product (25.8 g, 0.112 mol, 100%) was 25 used as such in the next reaction without further purification. HPLC (Method B): Rt = 6.00 and 7.50 min. 1H NMR (500 MHz, CDCI 3 ): 8.01 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.1 Hz, 2H), 7.34-7.29 (m, 2H), 7.15-7.11 (m, 2H). Step F. 1-Benzvl- 3 -(4-chloro-phenvl)-4,5,7,8-tetrahvdro-1 H-1.2,6-triaza azulene-6-carboxylic acid tert-butyl ester. To a 1-L, three-necked, round 30 bottomed flask was added Pd(dppf)C1 2 (2.8 g, 3.4 mmol), 1,1' bis(diphenylphosphino)ferrocene (0.96 g, 1.73 mmol), Bu 4 N*Br~ (2.78 g, 8.6 mmol), Na 2

CO

3 (36.5 g, 344 mmol) and 2-(4-chloro-phenyl) benzo[1,3,2]dioxaborole (23.8 g, 103 mmol), under N 2 . A solution of 1 -benzyl 202 3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester (41 g, 86 mmol) in toluene (250 mL) was added, followed by the addition of H 2 0 (250 mL) via syringe. The reaction mixture was stirred at reflux for 3 h and then was cooled to rt. The organic layer was diluted 5 with EtOAc (200 mL) and then was washed with 1 M aq. K 2

CO

3 until the color of the aqueous layer stabilized. The organic layer was washed with brine (200 mL), dried over MgSO 4 , filtered, and concentrated. The crude product thus obtained was pad-filtered through a short plug of SiO 2 to afford the title compound (34.5, 79 mmol, 92%) as a white solid. MS (ESI): exact mass 10 calculated for C2 5

H

28

CIN

3 0 2 , 437.19; found, m/z438.1, [M+H]*. HPLC (Method B): Rt = 10.89 min. 'H NMR (400 MHz, CDC1 3 ): 7.50-7.45 (m, 2H), 7.40-7.36 (m, 2H), 7.36-7.25 (m, 3H), 7.13-7.10 (m, 2H), 5.35-5.33 (m, 2H), 3.56-3.50 (m, 4H), 2.83-2.75 (m, 4H), 1.28-1.25 (m, 9H). Step G. 1-Benzvl-3-(4-chloro-phenvl)-1,4,5,6,7,8-hexahvdro-1,2,6-triaza 15 azulene. In a 500-mL, one-necked, round-bottomed flask, 1-benzyl-3-(4 chloro-phenyl)-4,5,7,8-tetrahydro-1H-1, 2 ,6-triaza-azulene-6-carboxylic acid tert butyl ester (34 g, 77 mmol) was dissolved in CH 2

C

2 (100 mL). Trifluoroacetic acid (70 mL) was added carefully. The reaction mixture was stirred at rt for 2 h. The solvent was evaporated and the residue was re-dissolved in CH 2 C1 2 20 (200 mL). Sat. aq. NaHCO 3 solution was added slowly until C02 evolution ceased. The aqueous layer was extracted with CH 2 Cl 2 (2x200 mL). The organic layers were combined, dried over MgSO 4 , filtered, and concentrated. The crude product was recrystallized from hot EtOAc to afford the pure product as a white solid (24 g, 71 mmol, 91%). MS (ESI): exact mass calculated for 25 C 20

H

2 0

CIN

3 , 337.13; found, m/z 338.3 [M+H. HPLC (Method B): Ri = 7.53 min. 1H NMR (400 MHz, CDCI 3 ): 7.48-7.44 (m, 2H), 7.44-7.38 (m, 3H), 7.38 7.27 (m, 3H), 7.14-7.06 (m, 2H), 5.36 (s, 2H), 3.30-3.16 (m, 4H), 3.10-2.98 (m, 4H). Step H. 1-Benzvl-3-(4-chloro-phenvl)-1,4,5,6,7,8-hexahvdro-1,2,6-triaza 30 azulene citrate salt. In a 500-mL, one-necked, round-bottomed flask, 1-benzyl 3-(4-chloro-phenyl)-1, 4 ,5,6,7,8-hexahydro-1,2,6-triaza-azulene 7 (10 g, 30 mmol) was suspended in MeOH (70 mL), and the mixture was heated until a homogeneous solution formed. A solution of citric acid monohydrate (7.5 g, 36 203 mmol) in MeOH (10 mL) was added dropwise. The resulting homogeneous solution was heated at reflux for 20 min and then was cooled to rt. The solvent was evaporated to form an oil. The oil was diluted with EtOAc (200 mL) and the mixture was heated to ref lux. To this hot solution MeOH was slowly added 5 to form a slurry. The slurry was cooled to rt and the precipitated solids were collected by filtration, washed with EtOAc, and dried under vacuum to afford the citrate salt (1:1 ratio based on 'HNMR analysis, 9.1 g). The filtrate was concentrated and the above procedure to form the citrate salt was repeated by adding another 0.5 equivalents of citric acid to afford another 2 g of product. 10 The combined yield was 71%. 'H NMR (500 MHz, D 2 0): 7.35-7.22 (rp, 4H), 7.22-7.15 (m, 3H), 7.0-6.92 (m, 2H), 5.22 (s, 2H), 3.22-3.14 (m, 4H), 3.0-2.92 (m, 2H), 2.88-2.80 (m, 2H), 2.69 (d, J = 15 Hz, 2H), 2.57 (d, J = 15 Hz, 2H). Example 274 N-

CF

3 N-N I/' 15 HN 3-(4'-C hloro-biphe nyl-4-yl)-2-(2,2,2-triflIuoro-ethyl) -2,4,5,6,7,8- hexahyd ro- 1,2,6 triaza-azulene. The title compound (18 mg) was also obtained from Example 187, Step B. MS (ESI): exact mass calculated for C 2 1

H

19 0lF 3

N

3 , 405.12; found, m/z 406.1 20 [M+H]*, 408.0 [M+H]*. H NMR (500 MHz, CD 3 0D): 7.74-7.72 (m, 2H), 7.61 7.59 (m, 2H), 7.41-7.35 (m, 4H), 4.70-4.55 (m, 3H), 3.85-3.30 (m, 3H), 3.25 3.05 (m, 2H), 2.82-2.74 (m, 2H). Example 275 P N-N 25 HN 3-(4'-Chloro-biphenyl-4-yl)-2-cyclopentyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 204 The title compound (33 mg) was also obtained from Example 181. MS (ESI): exact mass calculated for C 24

H

26

CIN

3 , 391.18; found, m/z 392.1 [M+H]*, 394.1 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.81-7.80 (m, 2H), 7.70-7.68 (m, 2H), 7.50-7.41 (m, 4H), 4.65-4.53 (m, 3H), 3.85-3.67 (m, 2H), 3.30-3.10 (m, 2H), 5 2.88 (br s, 2H), 2.01-1.91 (m, 6H), 1.63-1.60 (m, 2H). Example 276 P N-N HN 2 -Cyclobutyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 10 Step A. 2 -Cvclobutvl-3-trifluoromethanesulfonloxy-4,5,7,8-tetrahydro-2H 1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The desired triflate was prepared as in Steps A and B of Example 176, using cyclobutylhydrazine hydrochloride (made from cyclobutanone as shown in Example 177, Step A) in place of phenylhydrazine and t-butanol in place of EtOH, with the addition of 3 15 equiv of triethylamine. Step B. The title compound (118 mg) was prepared according to Example 263 using 189 mg of the product from Step A and 73 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 17

H

21

N

3 , 267.17; found, m/z 268.5 [M+H]*. H NMR (500 MHz, CDGOD): 7.60-7.50 (m, 3H), 7.34-7.30 (m, 2H), 4.71-4.63 20 (m, 2H), 4.00-3.40 (m, 2H), 3.24-3.22 (m, 3H), 3.00-2.80 (m, 2H), 2.68-2.59 (m, 2H), 2.30-2.24 (m, 2H), 2.30-2.24 (m, 2H), 1.84-1.71 (m, 2H). Example 277 N-N HNF 25 2 -Cyclobutyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 205 The title compound (122 mg) was prepared according to Example 263 using 198 mg of 2 -cyclobutyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2, 6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 276, Step A) and 88 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for 5 C 17

H

2 0

FN

3 , 285.16; found, m/z286.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.35-7.27 (m, 4H), 4.65-4.59 (m, 2H), 3.95-3.3.40 (m, 2H), 3.32-3.05 (m, 3H), 3.00-2.75 (m, 2H), 2.67-2.59 (m, 2H), 2.29-2.23 (m, 2H), 1.84-1.73 (m, 2H). Example 278 N-N

/CH

3 10 HN CH 2 -Cyclobutyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (117 mg) was prepared according to Example 263 using 192 mg of 2 -cyclobutyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 276, Step A) 15 and 83 mg of 4 -methylphenylboronic acid. MS (ESI): exact mass calculated for C1 8

H

23

N

3 , 281.19; found, ni/z282.5 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.41-7.32 (m, 2H), 7.23-7.13 (m, 2H), 4.71-4.65 (m, 2H), 4.00-3.41 (m, 2H), 3.32-3.05 (m, 3H), 2.95-2.79 (m, 2H), 2.67-2.58 (m, 2H), 2.43 (s, 3H), 2.28 2.23 (m, 2H), 1.84-1.71 (m, 2H). 20 Example 279 N-N /

CF

3 HN 2 -Cyclobutyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 25 The title compound (73 mg) was prepared according to Example 263 using 201 mg of 2 -cyclobutyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 206 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 276, Step A) and 122 mg of 4 -trifluoromethylphenylboronic acid. MS (ESI): exact mass calculated for C 18

H

20

F

3

N

3 , 335.16; found, m/z 336.4 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.86-7.85 (m, 2H), 7.52-7.50 (m, 2H), 4.65-4.58 (m, 1 H), 3.45-3.41 (m, 2H), 5 3.22-3.20 (m, 2H), 2.81-2.79 (m, 2H), 2.67-2.62 (m, 2H), 2.30-2.24 (m, 2H), 1.84-1.74 (n, 2H). Example 280 P N-N H C N HN 10 4

-(

2 -Cyclobutyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl)-benzonitrile The title compound (28 mg) was prepared according to Example 263 using 172 mg of 2-cyclobutyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 276, Step A) and 172 mg of 4-cyanophenylboronic acid. MS (ESI): exact mass calculated for 15 C1 8

H

20

N

4 , 292.17; found, m/z 293.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.92-7.90 (m, 2H), 7.50-7.48 (m, 2H), 4.65-4.58 (m, 1 H), 3.42-3.40 (m, 2H), 3.21-3.19 (m, 2H), 2.81-2.78 (m, 2H), 2.66-2.62 (m, 2H), 2.30-2.25 (m, 2H), 1.85-1.74 (m, 2H). 20 Example 281 N-N HN 2 -Cyclopropyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. N-cyclopropyl-hydrazinecarboxylic acid tert-butvl ester. To a solution of 1.37 g of 3

-(

4 -cyano-phenyl)-oxaziridine-2-carboxylic acid tert-butyl ester in 25 Et 2 O (8 mL) was added 1.2 mL of cyclopropylamine. The mixture was aged for 2 h and then concentrated in vacuo. Chromatography on Si0 2 (0 to 25% EtOAc/hexanes) provided an impure pale yellow solid that was sublimed under 207 high vacuum in a 5 0 C oil bath to afford 641 mg of the desired compound. 1 H NMR (500 MHz, CDCl): 6.31 (br s, 1 H), 3.49 (br s, 1 H), 2.74 (br s, 1 H), 1.48 (s, 9H), 0.52-0.48 (m, 4H). Step B. Cyclopropyl-hydrazine hydrochloride. To a solution of the product 5 from Step A (636 mg) in CH 2 Cl 2 (10 mL) was added 9 mL of 4.0 M HCI in 1,4 dioxane. The mixture was aged for 12 h and then concentrated in vacuo to provide 507 mg of the title compound. 'H NMR (500 MHz, CD 3 0D): 2.61-2.57 (m, 1H), 0.71 -0.59 (m, 4H). Step C. 2 -Cvclopropvl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahvdro-2H 10 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The desired triflate was prepared as in Steps A and B of Example 176, using cyclopropyl-hydrazine hydrochloride in place of phenylhydrazine and t-butanol in place of EtOH, with the addition of 3 equiv. of triethylamine. Step D. The title compound (128 mg) was prepared according to Example 263 15 using 208 mg of 2 -cyclopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1

,

2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester and 84 mg of phenylboronic acid. MS (ESI): exact mass calculated for C1 6

H

1

N

3 , 253.16; found, m/z 254.4 [M+H]*. 1 H NMR (500 MHz, CD 3 0D): 7.57-7.44 (m, 5H), 3.57-3.54 (m, 1H), 3.42-3.40 (m, 2H), 3.17-3.14 (m, 2H), 2.93-2.84 (m, 2H), 20 0.91-0.85 (m, 4H). Example 282 N-N KF H N 2 -Cyclopropyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 25 The title compound (134 mg) was prepared according to Example 281 using 200 mg of 2 -cyclopropyl-3-trifluoromethanesu lfonyloxy-4,5,7,8-tetrahyd ro-2H 1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 281, Step C) and 92 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for

C

1 6

H

1 8

FN

3 , 271.15; found, m/z 272.5 [M+H]*. 'H NMR (500 MHz, CD30D): 208 7.51-7.47 (m, 2H), 7.31-7.27 (m, 2H), 3.55-3.51 (m, 1 H), 3.41-3.39 (m, 2H), 3.23-3.14 (m, 2H), 3.00-2.83 (m, 2H), 0.93-.084 (m, 4H). Example 283 N-N

CH

3 5 HNF 2-(1 -Ethyl-propyl)-3-(4-fluoro-3-methyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. The title compound (34 mg) was prepared according to Example 183 using 59 mg of 2-(1 -ethyl-propyl)-3-trifl uorometha nesu lfonyloxy-4,5,7,8-tetrahydro-2H 10 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 183, Step A) and 19 mg of 4-fluoro-3-methylphenylboronic acid. MS (ESI): exact mass calculated for C 1

H

2 6

FN

3 , 315.21; found, m/z316.5 [M+H]*. 'H NMR (500 MHz, CD3OD): 7.27-7.18 (m, 3H), 4.69-4.65 (m, 1H), 3.93-3.89 (m, 1H), 3.50 3.27 (m, 5H), 3.00-2.80 (m, 2H), 2.35 (s, 3H), 1.95-1.87 (m, 2H), 1.83-1.76 (m, 15 2H), 0.81-0.68 (m, 6H). Example 284 N-N

H\/CH

3 2 -Cyclopropyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 20 The title compound (1 33 mg) was prepared according to Example 281 using 200 mg of 2-cyclopropyl-3-trifl uoromethanesufonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 281, Step C) and 90 mg of 4-methylphenylboronic acid. MS (ESI): exact mass calculated for C 17

H

21

N

3 , 267.17; found, m/z 268.5 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 25 7.42-7.34 (m, 4H), 4.68-4.65 (m, 2H), 3.80-3.30 (m, 6H), 2.97 (br s, 2H), 2.44 (s, 3H), 0.94-0.91 (m, 4H). 209 Example 285 N-N HN 2 -Cyclopropyl-3-thiophen-3-yl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. 5 The title compound (134 mg) was prepared according to Example 281 using 200 mg of 2 -cyclopropyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1, 2

,

6 -triaza-azulene-6-carboxylic acid tert-butyl ester (Example 281, Step C) and 84 mg of 3-thiopheneboronic acid. MS (ESI): exact mass calculated for

C

14

H

17

N

3 S, 259.11; found, m/z260.4 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 10 7.64-7.63 (m, 2H), 7.31-7.29 (m, 1 H), 4.65 (br s, 1 H), 3.70-3.60 (br s, 1 H), 3.57-3.52 (m, 1H), 3.40-3.38 (m, 1H), 3.19 (br s, 1H), 3.13-3.11 (m, 1H), 2.99 2.96 (m, 1H), 2.91-2.89 (m, 1H), 0.93-0.88 (m, 4H). Example 286 N-N / N 15 HN 4

-(

2 -Cyclopropyl-2,4,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulen-3-yl)-benzonitrile. The title compound (91 mg) was prepared according to Example 281 using 200 mg of 2 -cyclopropyl- 3 -trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester (Example 281, Step C) and 97 20 mg of 4-cyanophenylboronic acid. MS (ESI): exact mass calculated for

C

17

H

1

N

4 , 278.15; found, m/z 279.4 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.94-7.92 (m, 2H), 7.71-7.70 (m, 2H), 4.66 (br s, 1 H), 3.71-3.68 (m, 1 H), 3.47 (br s, 1H), 3.39-3.19 (m, 4H), 3.01-2.88 (m, 2H), 0.96-0.90 (m, 4H). 210 Example 287 N-N N 6 -Benzyl- 2 -isopropyl- 3 -phenyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-cpyridine. Step A. Trifluoro-methanesulfonic acid 6-benzvl-2-isopropyl-4,5,6,7-tetrahydro 5 2H-pyrazolo3,4-cIpyridin-3-yl ester. The desired triflate was prepared as in Step A of Example 189, using 1-benzyl-3-oxo-piperidine-4-carboxylic acid ethyl ester in place of the product from Example 59, Step A. Step B. The title compound (54 mg) was prepared as in Example 263 using 200 mg of trifluoro-methanesulfonic acid 6-benzyl-2-isopropyl-4,5,6,7 10 tetrahydro-2H-pyrazolo[3,4-c]pyridin-3-yl ester and 85 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 22

H

25

N

3 , 331.20; found, m/z 332.5 [M+H]*. 1 H NMR (500 MHz, CD30D): 7.60-7.48 (m, 7H), 7.39-7.37 (m, 2H), 4.59-4.48 (m, 3H), 4.44-4.34 (m, 2H), 3.81-3.79 (m, 1 H), 3.46-3.40 (m, 1 H), 2.94-2.84 (m, 2H), 1.46-1.29 (m, 6H). 15 Example 288 N-N HN 2-Isopropyl-3-phenyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine. To a solution of the compound (98 mg) from Example 287, Step B in 5 mL of 20 EtOH was added 98 mg of 10% Pd/C followed by 0.14 mL of 1,4 cyclohexadiene. The mixture was placed under N 2 and heated in an 80 *C oil bath for 5h. The mixture was filtered and the filtrate was concentrated in vacuo to provide 67 mg of viscous colorless oil. Chromatography on SiC 2 (0 to 8% 2 M NH 3 in MeOH/EtOAc) afforded 59 mg of the title compound. The product 25 (59 mg) was dissolved in Et 2 O and treated with excess 1.0 M HCI in Et 2 0 for 30 min. The solvent was removed in vacuo to afford 68 mg of the corresponding HCI salt. MS (ESI): exact mass calculated for C 1 5

H

1 9

N

3 , 211 241.16; found, m/z 242.4 [M+H]. 1 H NMR (500 MHz, CD 3 0D): 7.57-7.48 (m, 3H), 7.38-7.36 (m, 2H), 4.53 (m, 1H), 4.40-4.32 (m, 2H), 3.47 (t, J= 6.2 Hz, 2H), 2.82 (t, J = 6.2 Hz, 2H), 1.41 (d, J = 6.7 Hz, 6H). 5 Example 289 N-N N 6 -Benzyl-2-isopropyl-3-thiophen-3-yl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4 c]pyridine. The title compound (69 mg) was prepared according to Example 287 using 300 10 mg of trifluoro-methanesulfonic acid 6 -benzyl-2-isopropyl-4,5,6,7-tetrahydro 2 H-pyrazolo[3,4-c]pyridin-3-yl ester and 133 mg of 3-thiopheneboronic acid. MS (ESI): exact mass calculated for C 2 0

H

23

N

3 S, 337.16; found, m/z 338.5 [M+H)*. 1 H NMR (500 MHz, CD 3 0D): 7.66-7.65 (m, 1 H), 7.60-7.57 (m, 3H), 7.55-7.53 (m, 3H), 7.21-7.20 (m, 1H), 4.65-4.52 (m, 3H), 4.42-4.33 (m, 2H), 15 3.82-3.79 (m, 1H), 3.44-3.40 (m, 1H), 2.94-2.91 (m, 2H), 1.46-1.35 (m, 6H). Example 290 N-N NCH3 . N 6-Benzyl-2-isopropyl-3-p-tolyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine. 20 The title compound (67 mg) was prepared according to Example 287 using 300 mg of trifluoro-methanesulfonic acid 6-be nzyl-2-isopropyl-4,5,6,7-tetra hydro 2 H-pyrazolo[3,4-c]pyridin-3-yl ester and 141 mg of 4-methylphenylboronic acid. MS (ESI): exact mass calculated for C 23

H

2 7

N

3 , 345.22; found, m/z346.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.60-7.58 (m, 2H), 7.54-7.53 (m, 3H), 25 7.37-7.35 (m, 2H), 7.28-7.24 (m, 2H), 4.58-4.49 (m, 3H), 4.42-4.33 (m, 2H), 3.81-3.78 (m, 1 H), 3.45-3.41 (m, 1 H), 2.90-2.82 (m, 2H), 2.41 (s, 3H), 1.42 1.29 (m, 6H). 212 Example 291 N-N N F 6-Benzyl-3-(4-fluoro-phenyl)-2-isopropyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4 5 c]pyridine. The title compound (72 mg) was prepared according to Example 287 using 300 mg of trifluoro-methanesulfonic acid 6-benzyl-2-isopropyl-4,5,6,7-tetrahydro 2 H-pyrazolo[3,4-c]pyridin-3-yl ester and 146 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for C22H 24

FN

3 , 349.20; found, m/z 350.5 10 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.60-7.57 (m, 2H), 7.55-7.53 (m, 3H), 7.43-7.40 (m, 2H), 7.32-7.27 (m, 2H), 4.59-4.34 (m, 5H), 3.81 -3.79 (m, 1 H), 3.46-3.40 (m, 1 H), 2.90-2.85 (m, 2H), 1.43-1.36 (m, 6H). Example 292 N--N 15 HN 3

-(

4 -Fluoro-phenyl)-2-isopropyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine. The title compound (101 mg) was prepared according to Example 288 using 153 mg of 6 -benzyl- 3 -(4-fluoro-phenyl)-2-isopropyl-4,5,6,7-tetrahydro-2H pyrazolo[3,4-c]pyridine in place of the product of Example 287, Step B. MS 20 (ESI): exact mass calculated for C 15

H

18

FN

3 , 259.15; found, m/z 260.4 [M+H]*. H NMR (500 MHz, CD 3 OD): 7.42-7.28 (m, 4H), 4.50-4.47 (m, 1 H), 4.35 (br s, 2H), 3.49-3.46 (m, 2H), 2.81-2.79 (m, 2H), 1.42-1.36 (m, 6H). Example 293 N-N 25 HN CH3 213 2- Isopropyl-3-p-tolyl-4,5,6,7 -tetrahydro-2H-pyrazolo[3,4-clpyridine. The title compound.(114 mg) was prepared according to Example 288 using 163 mg of 6 -benzyl-2-isopropyl-3-p-tolyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4 cipyridine in place of the product of Example 287, Step B. MS (ESI): exact 5 mass calculated for C1 6

H

21 1N 3 , 255.17; found, m/z 256.4 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.43-7.32 (m, 2H), 7.30-7.20 (m, 2H), 4.52 (m, 1 H), 4.39-4.31 (m, 2H), 3.47 (t, J= 6.2 Hz, 2H), 2.80 (t, J= 6.2 Hz, 2H), 1.42 (d, J= 6.6 Hz, 6H. 10 Example 294 2 N-N /F HN 2-Cyclopentyl-3-(4-fluoro-phenyl)-5,5,7,7-tetramethyl-2,4,5,6,7,8-hexahydro 1, 2 ,6-triaza-azulene. Step A. Trifluoro-methanesulfonic aid 2 -cclopentl-5,5,7,7-tetramethyl 15 2 4 5,6,7,8-hexahydro-1 ,2,6-triaza-azulen-3-vl ester. The desired triflate was prepared as in Step A of Example 180 using 2

,

2 ,7,7-tetramethyl-5-oxo azepane-4-carboxylic acid ethyl ester (made from 2

,

2 ,6,6-tetramethyl-piperidin 4-one as shown in Step A of Example 59) in place of 5-oxo-azepane-1,4 dicarboxylic acid tert-butyl ester 4-ethyl ester. 20 Step B. The title compound was prepared as in Step A of Example 263, using 216 mg of trifluoro-methanesulfonic acid 2 -cyclopentyl-5,5,7,7-tetramethyl 2

,

4 ,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulen-3-y ester and 103 mg of 4 fluorophenylboronic acid. The product (134 mg) was dissolved in Et 2 0 and treated with excess 1.0 M HCI in Et20 for 30 min. The solvent was removed in 25 vacuo to afford 146 mg of the corresponding HCI salt. MS (ESI): exact mass calculated for C 22

H

30

FN

3 , 355.24; found, m/z 356.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.36-7.26 (m, 4H), 4.47-4.41 (m, 1H), 3.15 (s, 2H), 2.71 (s, 2H), 2.03-1.88 (m, 6H), 1.61-1.57 (m, 2H), 1.44 (s, 6H), 1.35 (s, 6H). 214 Example 295 2 N-N HN 2 -Cyclopentyl-5,5,7,7-tetramethyl-3-phenyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene. 5 The title compound (129 mg) was prepared as in Example 294, using 263 mg of trifluoro-methanesulfonic acid 2-cyclopentyl-5,5,7,7-tetramethyl-2,4,5,6,7,8 hexahydro-1,2,6-triaza-azulen-3-y ester and 110 mg of phenylboronic acid. MS (ESI): exact mass calculated for C22H 3 1

N

3 , 337.25; found, m/z 338.5 [M+H]*. 1 H NMR (500 MHz, CDsOD): 7.56-7.49 (m, 3H), 7.32-7.30 (m, 2H), 10 4.51-4.44 (m, 1H), 3.12 (s, 2H), 2.72 (s, 2H), 2.03-1.88 (m, 6H), 1.61-1.57 (m, 2H), 1.45 (s, 6H), 1.35 (s, 6H). Example 296 N-N HN 15 2 -Isopropyl-5,5,7,7-tetramethyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. Steip A. Trifluoro-methanesulfonic acid 2-isoprovl-5,5,7,7-tetram ethyl 2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl ester. The desired triflate was prepared as in Step A of Example 294 using isopropylhydrazine in place of 20 cyclopentylhydrazine. Step B. The title compound (98 mg) was prepared as in Step B of Example 294 using 196 mg trifluoro-methanesulfonic acid 2-isopropyl-5,5,7,7 tetramethyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl ester and 87 mg of phenylboronic acid. MS (ESI): exact mass calculated for C 20

H

29

N

3 , 311.24; 215 found, m/z 312.5 [M+H]*. 1 H NMR (500 MHz, CD30D): 7.57-7.52 (m, 3H), 7.32-7.31 (m, 2H), 4.34 (m, 1 H), 3.11 (s, 2H), 2.71 (s, 2H), 1.49-1.34 (m, 18H). Example 297 N-N / F/ F HN 5 3

-(

4 -Fluoro-phenyl)-2-isopropyl-5,5,7,7-tetramethyl-2,4,5,6,7,8-hexahydro 1, 2 ,6-triaza-azulene. The title compound (100 mg) was prepared as in Example 296 using 196 mg of trifluoro-methanesulfonic acid 2 -isopropyl-5,5,7,7-tetram ethyl-2,4,5,6,7,8 10 hexahydro-1,2,6-triaza-azulen-3-y ester and 100 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for C 2 0

H

28

FN

3 , 329.23; found, m/z 330.5 [M+H]. H NMR (500 MHz, CD 3 0D): 7.36-7.27 (m, 4H), 4.31 (m, 1 H), 3.10 (s, 2H), 2.70 (s, 2H), 1.47-1.34 (m, 18H). 15 Example 298 N-N HN 2 -sec-Butyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. Step A. 2 -sec-Butl- 3 -trifluoromethanesulfonvloxy-4,5,7,8-tetrahydro-2H -1, 2,6 triaza-azulene-6-carboxylic acid terl-butyl ester. The desired triflate was 20 prepared according to Example 189, Step A, using sec-butylhydrazine hydrochloride (made from 2-butanone as shown in Example 177, Step A) in place of isopropylhydrazine hydrochloride. Step B. The title compound (97 mg) was prepared as in Example 263 using 216 mg of the triflate from Step A and 106 mg of phenylboronic acid. MS 25 (ESI): exact mass calculated for C 17

H

23

N

3 , 269.38; found, m/z270.5 [M+H]*. H NMR (500 MHz, CD 3 OD): 7.58-7.50 (m, 3H), 7.35-7.31 (m, 2H), 4.15-4.07 216 (m, 1H), 3.50-3.18 (m, 6H), 2.88-2.73 (m, 2H), 1.97-1.86 (m, 1H), 1.74-1.65 (m, 1H), 1.43 (d, J= 6.8 Hz, 3H), 0.64 (t, J= 7.4 Hz, 3H). Example 299 N-N 5 HN 2 -sec-Butyl-3-(4-fluoro-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (71 mg) was prepared as in Example 263 using 245 mg of the triflate from Example 298, Step A, and 153 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for C 17

H

22

FN

3 , 287.38; found, m/z 10 288.5 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.41-7.35 (m, 2H), 7.34-7.28 (m, 2H), 4.12-4.03 (m, 1H), 3.51-3.20 (m, 6H), 2.90-2.73 (m, 2H), 1.97-1.87 (m, 1 H), 1.75-1.65 (m, 1 H), 1.44 (d, J = 6.6 Hz, 3H), 0.66 (t, J = 7.4 Hz, 3H). Example 300 N-N 4C 15 HN 2 -sec-Butyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (116 mg) was prepared as in Example 263 using 249 mg of the triflate from Example 298, Step A, and 129 mg of 4-methylphenylboronic acid. MS (ESI): exact mass calculated for C 1 8

H

25

N

3 , 283.41; found, m/z 284.5 20 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.42-7.37 (m, 2H), 7.27-7.21 (m, 2H), 4.23-4.12 (m, 1H), 3.55-3.23 (m, 6H), 2.92-2.75 (m, 2H), 2.43 (s, 3H), 1.98 1.88 (m, 1H), 1.77-1.68 (m, 1H), 1.46 (d, J= 6.6 Hz, 3H), 0.67 (t, J= 7.4 Hz, 3H). 217 Example 301 N-N H CF 3 HN 2 -sec-Butyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 5 The title compound (71 mg) was prepared as in Example 263 using 257 mg of the triflate from Example 298, Step A, and 175 mg of 4 trifluoromethylphenylboronic acid. MS (ESI): exact mass calculated for

C

18 H22F 3

N

3 , 337.38; found, m/z 338.5 [M+H]*. 1 H NMR (500 MHz, CD30D): 7.91-7.85 (m, 2H), 7.61-7.54 (m, 2H), 4.11-4.03 (m, 1H), 3.52-3.20 (m, 6H), 10 2.93-2.75 (m, 2H), 1.99-1.88 (m, 1H), 1.75-1.65 (m, 1H), 1.45 (d, J= 6.6 Hz, 3H), 0.65 (t, J= 7.4 Hz, 3H). Example 302 N-N F N 15 2 -Cyclopentyl-3-(4-fluoro-phenyl)-6-methyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (186 mg) was prepared from 216 mg of the product of Example 182 according to Example 208. The product was dissolved in Et 2 0 and treated with excess 1.0 M HCl in Et 2 0 to afford the corresponding HCI salt. 20 MS (ESI): exact mass calculated for C 1

H

24

FN

3 , 313.41; found, m/z314.4 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.38-7.34 (m, 2H), 7.31-7.26 (m, 2H), 4.47 (m, 1H), 3.75-3.69 (m, 1H), 3.64-3.57 (m, 1H), 3.33-3.15 (m, 4H), 3.02 (s, 3H), 2.91-2.83 (m, 1 H), 2.78-2.71 (m, 1 H), 2.04-1.84 (m, 6H), 1.65-1.54 (m, 2H). 25 218 Example 303 N-N H NH 2 H NY 0 4

-(

2 -Isopropyl-2,4,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulen-3-yl)-benzamide. The title compound (26 mg) was prepared as in Example 263 using 206 mg of 5 the triflate from Example 189, Step A, and 135 mg of 4-benzamide boronic acid. MS (ESI): exact mass calculated for C1 7 H22N 4 0, 298.38; found, m/z 299.5 [M+H]*. H NMR (500 MHz, CDC1 3 ): 7.93-7.89 (m, 2H), 7.37-7.34 (m, 2H), 6.16 (br s, 1H), 5.81 (br s, 1H), 4.27 (m, 1H), 3.05-3.00 (m, 2H), 2.97-2.88 (m, 4H), 2.51-2.46 (m, 2H), 1.41 (d, J= 6.6 Hz, 6H). 10 Example 304 N-N H / H / NN HNN-N 2-Isopropy-3-[4-(1 H-tetrazol-5-yl)-phenyl]-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. 15 Step A. 2-1sopropyl-3-f4-(1 H-tetrazol-5-v)-henll-4,5,7.8-tetrahdro-2H-1..,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester. A toluene solution of 3-(4 cyano-phenyl)-2-isopropyl-4,5,7,8-tetrahydro-2H-1, 2 ,6-triaza-azulene-6 carboxylic acid tert-butyl ester (intermediate in Example 212) and tributyltin azide was heated at reflux for 48 h. The mixture was concentrated and the 20 residue was purified on Si0 2 (0 to 75% EtOAc/hexanes) to afford 89 mg of desired tetrazole as a glass. Step B. The product from Step A was dissolved in dioxane and treated with HCI (4 M in dioxane, 1 mL) and mixture was stirred at RT. After 48 h, the liqiud was decanted and the solids washed with dioxane and dried under vacuum to 25 afford 60 mg of the title compound. MS (ESI): exact mass calculated for

C

17

H

21

N

7 , 323.40; found, m/z 324.4 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 219 8.24-8.20 (m, 2H), 7.58-7.55 (m, 2H), 4.42 (m, 1 H), 3.44-3.40 (m, 2H), 3.34 3.30 (m, 2H), 3.21-3.17 (m, 2H), 2.84-2.80 (m, 2H), 1.42 (d, J= 6.8, 6H). Example 305 N-N F N 5 b 6 -Benzyl- 3 -(4-fluoro-phenyl)-2-isopropyl-8-methyl-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. Step A. Trifluoro-methanesulfonic acid 6-benzvl-2-isopropyl-8-methyl 2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-vl ester. The desired triflate was 10 prepared as in Step A of Example 189 using 1 -benzyl-6-methyl-5-oxo-azepane 4-carboxylic acid ethyl ester (made from 1 -benzyl-3-methyl-piperidin-4-one as shown in Step A of Example 59) in place of 5-oxo-azepane-1,4-dicarboxylic acid tert-butyl ester 4-ethyl ester. Step B. The title compound (29 mg) was prepared as in Example 287, Step B, 15 from 151 mg of the triflate from Step A and 110 mg of 4-fluorophenylboronic acid. MS (ESI): exact mass calculated for C 24

H

2 8

FN

3 , 377.50; found, m/z 378.5 [M+H]*. 1H NMR (500 MHz, CDCl): 7.41-7.37 (m, 2H), 7.33-7.29 (m, 2H), 7.27-7.18 (m, 3H), 7.16-7.10 (m, 2H), 4.24 (m, 1H), 3.78 (d, J= 13.4 Hz, 1H), 3.70 (d, J= 13.4 Hz, 1H), 3.19-3.12 (m, 1H), 2.78-2.68 (m, 3H), 2.55-2.43 20 (m, 3H), 1.40 (d, J= 6.6, 3H), 1.37 (d, J= 6.6, 3H), 1.33 (d, J= 7.1, 3H). Example 306 N-N F HN 3

-(

4 -Fluoro-phenyl)-2-isopropyl-8-methyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza 25 azulene. 220 Step A. 3-Methyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester. To a -78 0 C solution of of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester in THF (100 mL) was added LDA (50 mL, 1.8 M in THF) with stirring over 1 h. Methyl iodide was then added (5 mL) and the mixture was allowed to warm slowly to RT and 5 was stirred for 24 h. The reaction was quenched by the addition of satd. aq.

NH

4 CI (20 mL). The mixture was poured Into H 2 0 (800 mL), extracted with EtOAc, and concentrated. Purification on Si0 2 (120 g, 0 to 10% EtOAc/hexanes) gave 3.83 g of the desired product as an off-white solid. 'H NMR (500 MHz, CDCl 3 ): 4.23-4.14 (m, 2H), 3.31-3.21 (m, 1H), 2.61-2.37 (m, 10 4H), 1.50 (s, 9H), 1.05 (d, J= 6.6 Hz, 3H). Step B. 2-Isopropyl-8-methyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahvdro 2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The product from Step A (2.01 g) was treated with ethyl diazoacetate (1.5 mL) as in Step A of Example 59. The resulting material (2.90 g) was then transformed to the 15 desired triflate (2.68g) as shown in Step A of Example 189. The reaction sequence also produced 0.60 g of 2-isopropyl-4-methyl-3 trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester. Step C. The title compound (1.62 g) was prepared as in Step A of Example 20 263 from 2.68 g of the triflate of Step B and 1.36 g of 4-fluorophenylboronic acid. The coupling product was treated with TFA (20 mL) in 50 mL of CH 2 0 2 for 16 h. The mixture was concentrated and the residue was diluted with 1 M NaOH (50 mL) and extracted with CH 2

CI

2 (50 mL, 3x). The combined organic layers were dried over Na 2

SO

4 and concentrated to provide the desired 25 material. MS (ESI): exact mass calculated for C 17 H22FN 3 , 287.18; found, m/z 288.4 [M+H]*. 1H NMR (500 MHz, CDCl 3 ): 7.18-7.05 (m, 4H), 4.16 (m, 1H), 3.08-2.97 (m, 2H), 2.96-2.83 (m, 2H), 2.78-2.71 (m, 1 H), 2.49-2.31 (m, 2H), 1.34 (d, J = 6.6 Hz, 3H), 1.31 (d, J = 6.6 Hz, 3H), 1.29 (d, J = 7.3 Hz, 3H). 221 Example 307 N-N HN 3

-(

4 -Fluoro-phenyl)-2-isopropyI-4-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene. 5 The title compound (154 mg) was prepared as in Example 177, Steps C and D, from 0.60 g of the triflate of Example 306, Step B, and 0.57 g of 4 fluorophenylboronic acid. MS (ESI): exact mass calculated for C 7

H

22

FN

3 , 287.18; found, m/z 288.4 [M+H]*. 1 H NMR (500 MHz, CDCl 3 ): 7.25-7.20 (m, 2H), 7.17-7.12 (m, 2H), 4.15 (m, 1H), 3.35-3.30 (m, 1H), 3.08-3.03 (m, 1H), 10 3.00-2.85 (m, 3H), 2.77-2.71 (m, 1H), 2.57-2.51 (m, 1H), 1.39 (d, J= 6.6 Hz, 3H), 1.36 (d, J= 6.6 Hz, 3H), 1.15 (d, J= 7.3 Hz, 3H). Example 308 N-N 15 2 -Cyclopentyl-3-(4-fluoro-phenyl)-7-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene. Step A. 2 -Methyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester. A solution of 1, 4 -dioxa-8-aza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (2.97 g) in TMEDA (2.2 mL) was cooled to -78 0C and sec-BuLi (1.8 M in THF, 13 mL) 20 was added dropwise. The resulting yellow solution was aged at -78 0C for 1 h. Methyl iodide (1.5 mL) was added and the mixture was warmed from -78 0C to RT over 16 h. The reaction mixture was poured into water (800 mL) and extracted with EtOAc. The combined organic extracts were washed with H 2 0, brine, and dried over Na 2

SO

4 . Purification on SiO 2 (330 g, 5 to 20% 25 EtOAc/hexanes) provided 1.65 g of 7-methyl-1,4-dioxa-8-aza-spiro[4.5]decane 8-carboxylic acid tert-butyl ester. Multiple aliquots of this ester were combined 222 (2.29 g), treated with 5 mL of conc. HCI in 10 mL of dioxane, and heated at 65 0C for 6 h. The solvent was removed and the residue was dissolved in CH 2 Cl 2 and treated with di-tert-butyldicarbonate (1.0 g). After 5 d, the mixture was diluted with satd. aq. NaHCOs and H 2 0, and extracted with CH 2

CI

2 . 5 Purification on Si0 2 (120 g, 5 to 15% EtOAc/hexanes) provided 1.40 g of the desired product as a white solid. 1 H NMR (500 MHz, CDCl 3 ): 4.69-4.59 (m, 1H), 4.21-4.12 (m, 1H), 3.30-3.20 (m, 1H), 2.66-2.57 (m, 1H), 2.47-2.36 (m, 1H), 2.32-2.23 (m, 1H), 2.22-2.15 (m, 1H), 1.42 (s, 9H), 1.11 (d, J= 7.1 Hz, 3H). 10 Step B. 2 -Cyclopentyl-7-methyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1

,

2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester. The product from Step A (1.40 g) was treated with ethyl diazoacetate as in Step A of Example 59. The resulting material (1.0 g) was transformed to the desired triflate (0.78 g) as outlined in Step A of Example 180. The reaction sequence 15 also produced 2 -cyclopentyl-5-methyl-3-trifluoromethanesulfonyloxy-4,5,7,8 tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. Step C. The title compound (160.4 mg) was prepared as in Example 263 from 301 mg of the triflate from Step B and 185 mg of 4-fluorophenylboronic acid. The sequence also produced 2 -cyclopentyl-3-(4-fluoro-phenyl)-5-methyl 20 2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The isomers were separated by SFC chromotagraphy. MS (ESI): exact mass calculated for C 19

H

24

FN

3 , 313.41; found, m/z314.4 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.25-7.21 (m, 2H), 7.18-7.12 (m, 2H), 4.22 (m, 1H), 3.24-3.18 (m, 1H), 3.03-2.92 (m, 2H), 2.76-2.67 (m, 2H), 2.60-2.52 (m, 1 H), 2.45-2.39 (m, 1 H), 2.16-1.82 (m 6H), 25 1.59-1.47 (m, 2H), 1.25 (d, J = 6.3 Hz, 3H). Example 309 p N-N / F2 HN 223 2 -Cyclopentyl- 3

-(

4 -fluoro-phenyl)-5-methyl-2,4,5,6,7,8-hexahydro- 1,2,6-triaza azulene. The title compound (3.8 mg) was prepared as outlined in Example 308. MS (ESI): exact mass calculated for Cj 9

H

2 4

FN

3 , 313.41; found, m/z 314.4 [M+H]*. 5 'H NMR (500 MHz, CDCl 3 ): 7.24-7.19 (m, 2H), 7.18-7.13 (m, 2H), 4.31 (m, 1 H), 3.42-3.35 (m, 1 H), 3.09-2.90 (m, 4H), 2.57-2.45 (m, 2H), 2.14-1.80 (m 6H), 1.58-1.48 (m, 2H), 1.22 (d, J= 6.3 Hz, 3H). Example 310 N-N 10 HN 2 -Cyclopentyl-7-methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (64 mg) was prepared from 193 mg of the triflate from Example 308, Step B, and 117 mg of 4-methylphenylboronic acid. MS (ESI): exact mass calculated for C20H 27

N

3 , 309.45; found, m/z 310.4 [M+H]*. 1H NMR 15 (500 MHz, CDCI 3 ): 7.28-7.25 (m, 2H), 7.17-7.13 (m, 2H), 4.39 (m, 1H), 3.21 3.16 (m, 1 H), 3.03-2~.92 (m, 2H), 2.74-2.67 (m, 2H), 2.59-2.52 (m, 1 H), 2.49 2.43 (m, 1 H), 2.40 (s, 3H), 2.17-1.82 (m, 6H), 1.59-1.47 (m, 2H), 1.24 (d, J= 6.3 Hz, 3H). 20 Example 311 N-N HN 2 -Isopropyl-7-methyl-3-phenyl-2,4,5,6,7,8-hexahydro-1, 2 ,6-triaza-azulene. The title compound (102 mg) was prepared as in Example 263 using 260 mg of 2- isopropyl-7-methyl-3-trifluoromethanesu lfonyloxy-4,5,7,8-tetrahyd ro-2H 25 1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (as outlined in Example 308 replacing cyclopentyl hydrazine with isopropyl hydrazine) and 101 mg of 224 phenylboronic acid. The reaction sequence also yielded 2-isopropyl-5-methyl 3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. MS (ESI): exact mass calculated for C 17

H

23

N

3 , 269.19; found, m/z 270.5 [M+H]*. 1 H NMR (600 MHz,

CD

3 OD): 7.58-7.52 (m, 3H), 7.36-7.35 (m, 2H), 4.43 (m, 1 H), 3.65-3.57 (m, 5 1 H), 3.51-3.48 (m, 1 H), 3.23-3.11 (m, 3H), 2.87-2.82 (m, 2H), 2.76-2.73 (m, 1H), 1.48 (d, J= 6.4 Hz, 3H), 1.43-1.40 (m, 6H). Example 312 N-N HN 10 2 -Isopropyl-5-methyl-3-phenyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (28 mg) was prepared as in Example 311 and purified by SFC chromatography. MS (ESI): exact mass calculated for C 17

H

23

N

3 , 269.19; found, m/z 270.4 [M+H]*. 1H NMR (600 MHz, CD 3 OD): 7.58-7.52 (m, 3H), 7.35-7.33 (m, 2H), 4.40 (m, 1H), 3.63-3.59 (m, 1H), 3.5-3.47 (m, 1H), 3.31-3.19 15 (m, 3H), 2.80-2.68 (m, 2H), 1.43-1.39 (m, 6H), 1.34 (d, J= 6.6 Hz, 3H). Example 313 N-N I/ F HN 3

-(

4 -Fluoro-phenyl)-2-isopropyl-7-methyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza 20 azulene. The title compound (127 mg) was prepared as in Example 311 using 260 mg of 2 -isopropyl-7-methyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester and 115 of 4 fluorophenylboronic acid. The reaction sequence also yielded 3-(4-fluoro 25 phenyl)-2-isopropyl-5-methyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. MS (ESI): exact mass calculated for C 17

H

22

FN

3 , 287.18; found, m/z 288.5 [M+H]*. 225 1 H NMR (600 MHz, CD 3 OD): 7.39-7.37 (m, 2H), 7.32-7.28 (m, 2H), 4.36 (m, 1 H), 3.61-3.56 (m, 1 H), 3.50-3.47 (m, 1 H), 3.20-3.08 (m, 3H), 2.85-2.80 (m, 1H), 2.73-2.69 (m, 1H), 1.46 (d, J= 6.6 Hz, 3H), 1.41-1.38 (m, 6H). 5 Example 314 N-N F HN 3

-(

4 -Fluoro-phenyl)-2-isopropyl-5-methyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (36 mg) was prepared as in Example 311 and purified by 10 chromatography on SFC. MS (ESI): exact mass calculated for C 17

H

2 2

FN

3 , 287.18; found, m/z288.5 [M+H]*. 'H NMR (600 MHz, CD 3 0D): 7.37-7.35 (m, 2H), 7.31-7.28 (m, 2H), 4.33 (m, 1H), 3.61-3.58 (m, 1H), 3.48-3.45 (m, 1H), 3.27-3.13 (m, 3H), 2.77-2.65 (m, 2H), 1.41-1.37 (m, 6H), 1.34 (d, J= 6.6 Hz, 3H). 15 Example 315 N-N HN 2 -Isopropyl-7-methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (127 mg) was prepared as in Example 311 using 260 mg of 20 2 -isopropyl- 7 -methyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H 1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester and 112 mg of 4 methylphenylboronic acid. The reaction sequence also yielded 2-isopropyl-5 methyl-3-p-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. MS (ESI): exact mass calculated for C 1 8

H

25

N

3 , 283.20; found, m/z 284.5 [M+H]*. 'H NMR (600 25 MHz, CD 3 OD): 7.38-7.36 (m, 2H), 7.22-7.20 (m, 2H), 4.41 (m, 1H), 3.60-3.56 226 (m, 1H), 3.50-3.45 (m, 1H), 3.21-3.06 (m, 3H), 2.84-2.70 (m, 2H), 1-.46 (d, J= 6.6 Hz, 3H), 1.42-1.37 (m, 6H). Examples 316 through 323 were prepared as described in Example 238, with 5 adjustments as noted. Example 316 PN N-N HN 3-(4-Chloro-phenyl)-1 -pyridin-4-ylmethyl-1 ,4,5,6,7,8-hexahyd ro-1,2,6-triaza 10 azulene. The title compound (0.02 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.3 mmol) using 4-chloromethyl-pyridine hydrogen chloride (0.5 mmol) in place of 2-chloromethyl-thiophene. MS (ESI): exact mass calculated 15 for C 19

H

1

CIN

4 , 338.13; found, m/z 339.3 [M+H)*. 1 H NMR (500 MHz, CDCl 3 ): 8.49-8.48 (m, 2H), 7.43-7.41 (m, 2H), 7.33-7.31 (m, 2H), 6.90-6.89 (m, 2H), 5.28 (s, 2H), 2.92-2.87 (m, 2H), 2.75-2.73 (m, 1 H), 2.66-2.64 (m, 1 H). Example 317 HNN N'N 20 H Cl 3-(4-Chloro-phenyl)-1 -pyridin-2-ylmethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.01 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 227 103, Step B; 0.4 mmol) using 2-chloromethyl-pyridine hydrogen chloride (0.5 mmol) in place of 2-chloromethyl-thiophene. The reaction sequence also yielded 3-(4-chloro-phenyl)-2-pyridin-2-ylmethy -4,5,7,8-tetrahydro-2H-1,2,6 triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS 5 (ESI): exact mass calculated for C 19

H

19 C1N 4 , 338.13; found, m/z339.3 [M+H]*. H NMR (500 MHz, CDCIs): 8.49-8.48 (m, 1 H), 7.56-7.54 (m, 1 H), 7.44-7.42 (m, 2H), 7.32-7.30 (m, 2H), 7.19-7.11 (m, 1 H), 6.84-6.82 (m, 1 H), 5.39 (s, 2H), 2.93-2.87 (m, 4H), 2.76-2.74 (m, 4H). 10 Example 318 N N-N HN C1 3

-(

4 -Chloro-phenyl)-2-pyridin-2-ylmethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.011 g) was prepared from 3-(4-chloro-phenyl)-2-pyridin 15 2-ylmethyl -4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert butyl ester (Example 317) according to Example 103, Step C. MS (ESI): exact mass calculated for C 19

H

19

CIN

4 , 338.13; found, m/z 339.3 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 8.44-8.43 (m, 1 H), 7.56-7.55 (m, 1 H), 7.32-7.27 (m, 2H), 7.11-7.07 (m, 3H), 6.81-6.77 (m, 1H), 5.20 (s, 2H), 2.98-2.96 (m, 2H), 2.89 20 2.86 (m, 4H), 2.48-2.46 (m, 2H). Example 319 N N-N HN Ci 228 3-(4-Chloro-phenyl)-1 -pyridin-3-ylmethyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro 1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step 5 B; 0.3 mmol) using 3-chloromethyl-pyridine hydrogen chloride (0.5 mmol) in place of 2-chloromethyl-thiophene. The title compound was obtained as a 2:1 mixture (25 mg) with 3-(4-chloro-phenyl)-2-pyridin-3-ylmethyl-2,4,5,6,7,8 hexahydro-1,2,6-triaza-azulene. Data for the mixture: MS (ESI): exact mass calculated for C, 9

H

1 9

CIN

4 , 338.13; found, m/z 339.4 [M+H]*. 'H NMR (500 10 MHz, CDCI 3 ): 8.47-8.14 (m, 2H), 7.42-7.03 (m, 6H), 5.39-5.07 (two s, 2H), 2.97-2.84 (m, 2H), 2.72-2.43 (m, 2H). Example 320 o / 0 C N-N HN C 15 4-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1-ylmethyl] benzoic acid methyl ester. The title compound (0.03 g) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.3 mmol) using 4-bromomethyl-benzoic acid methyl ester (0.5 20 mmol) in place of 2-chloromethyl-thiophene. MS (ESI): exact mass calculated for C22H 22

CIN

3

O

2 , 395.14; found, m/z 396.4 [M+H]*. 1H NMR (500 MHz,

CDCI

3 ): 7.63-7.19 (m, 7H), 7.03-7.02 (m, 2H), 5.27 (s, 2H), 3.15 (s, 2H), 2.79 2.67 (m, 8H). 229 Example 321 Q N-N HN C 3-(4-Chloro-phenyl)-1 -(tetrahydro-pyran-4-yl)-1,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. 5 The title compound was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro 1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.40 mmol) using 4-chloro-tetrahydro-pyran (1.5 mmol) in place of chloro cyclobutane. The title compound was obtained as a 2:1 mixture (10 mg) with 3 -(4-chloro-phenyl)-2-(tetrahydro-pyran-4-yl)-1,4,5,6,7,8-hexahydro-1,2,6 10 triaza-azulene. Data for the mixture: MS (ESI): exact mass calculated for CBHzCIN30, 331.15; found, m/z332.4 [M+H]. 'H NMR (500 MHz, CD 3 0D): 7.44-7.42 (m, 1 H), 7.36-7.30 (m, 4H), 7.20-7.18 (m, 1 H), 4.36-4.33 (m, 1 H), 3.97-3.94 (m, 3H), 3.87-3.86 (m, 1 H), 3.51-3.49 (m, 3H), 3.28-3.25 (m, 1 H), 2.90-2.75 (m, 8H), 2.66-2.64 (m, 2H), 2.39-2.37 (m, 1 H), 2.19-2.10 (m, 3H), 15 1.74-1.71 (m, 2H), 1.65-1.62 (m, 1 H). Example 322 N-N HC HN C 3-(4-Chloro-phenyl)-1 -(4-methyl-cyclohexyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza 20 azulene. The title compound (11 mg) was prepared from 3-(4-chloro-phenyl)-4,5,7,8 tetrahydro-1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.30 mmol) using 1-bromo-4-methyl-cyclohexane (1.0 mmol) in place of chloro-cyclobutane. The reaction sequence also yielded 3-(4-chloro 230 phenyl)-2-(4-methyl-cyclohexyl)-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6 carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C 20

H

2 6 C1N 3 , 343.18; found, m/z 344.4 [M+H)*. 1H NMR (500 MHz, CD 3 0D): 7.40-7.34 (m, 4H), 4.10-4.06 (m, 1H), 3.39-3.37 (m, 2H), 3.28 5 3.26 (m, 2H), 3.17-3.15 (m, 2H), 2.94-2.91 (m, 2H), 1.96-1.89 (m, 2H), 1.83 1.76 (m, 4H), 1.52-1.10 (m, 2H), 0.91-0.87 (m, 4H). Example 323 N-N HN C1 10 {2-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1-yl]-ethyl) dimethyl-amine. The title compound was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro 1 H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.33 mmol) using (2-chloro-ethyl)-dimethyl-amine hydrogen chloride (0.66 15 mmol) in place of chloro-cyclobutane. The title compound was obtained as a 2:1 mixture (10 mg) with {2-[3-(4-chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6 triaza-azulen-2-yl]-ethyl}-dimethyl-amine. Data for the mixture: MS (ESI): exact mass calculated for C 17

H

23

CIN

4 , 318.16; found, m/z 319.4 [M+H]. 1 H NMR (500 MHz, CD 3 0D): 7.50-7.45 (m, 2H), 7.37-7.33 (m, 2H), 4.51-4.49 (m, 20 1.3H), 4.27-4.26 (m, 0.7H), 3.63-3.61 (m, 1.3H), 3.48-3.42 (m, 2H), 3.33-3.29 (m, 2H), 3.24-3.23 (m, 2H), 3.14-3.12 (m, 0.7H), 3.00-2.98 (m, 1.3H), 2.91 (s, 4H), 2.84 (s, 2H), 2.75-2.73 (m, 0.7H). 231 Example 324 N-N HN 'N Cl 3-(4-Chloro-phenyl)-1 -(1 -oxy-pyridin-2-ylmethyl)-1,4,5,6,7,8-hexahydro-1,2,6 triaia-azulene. 5 A mixture of 3-(4-chloro-phenyl)-2-pyridin-2-ylmethyl-1,4,5,6,7,8-hexahydro 1, 2 ,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 317; 0.1 mmol) and mCPBA (0.1 g) in dichloroethane (10 mL) was heated at 80 0C for 1 h. Satd. aq. NaHCO 3 (20 mL) was added, and the layers were separated. The organic layer was concentrated, and the residue was diluted with MeOH (5 10 mL). Hydrogen chloride (1 M, 2 mL) was added and the mixture was stirred at 25 0C for 16 h. After concentration, purification by flash chromatography (2 M

NH

3 /MeOH in CH 2 Cl 2 ) provided the desired compound (34 mg). MS (ESI): exact mass calculated for C 19

H

19 ClN 4 0, 354.12; found, m/z 355.2 [M+H]. 1 H NMR (500 MHz, CDCl 3 ): 8.20-8.19 (m, 1H), 7.41-7.39 (m, 2H), 7.33-7.31 (m, 15 2H), 7.18-7.15 (m, 2H), 6.69-6.67 (m, 1H), 5.50 (s, 2H), 3.10-3.03 (m, 2H), 2.93-2.86 (m, 2H). Example 325 N-N

H

2 N NC 0 Ci 20 2-[1 -Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulen-6-y] acetamide. A mixture of 1-benzyl-3-(4-chloro-phenyl)-1-pyridin-3-ylmethyl-1,4,5,6,7,8 hexahydro-1,2,6-triaza-azulene (Example 59, Step E; 0.05 mmol), 2-bromo acetamide (8 mg), and Na 2

CO

3 (15 mg) in acetone (2 mL) was stirred at 25 0C 232 for 16 h. After concentration, purification by flash chromatography (2 M NHs/MeOH in CH 2

CI

2 ) provided the desired compound (6 mg). MS (ESI): exact mass calculated for C22H 23

CIN

4 0, 394.16; found, m/z 395.3 [M+H]*. 'H NMR (500 MHz, CDCl 3 ): 8.49-8.48 (m, 1H), 7.56-7.54 (m, 1H), 7.44-7.42 (m, 5 2H), 7.32-7.30 (m, 2H), 7.19-7.11 (m, 1 H), 6.84-6.82 (m, 1 H), 5.39 (s, 2H), 2.93-2.87 (m, 2H), 2.76-2.74 (m, 2H). Example 326 -N N-N HIC HN c1 10 3

-[

3 -(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1 -yl] propionitrile. To a mixture of 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1 H-1,2,6-triaza-azulene 6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.05 mmol), NaOH (50% aq., 0.2 mL), and Bu 4

NHSO

4 (0.005 mmol) in dichloroethane (5 mL) was 15 added 3-bromo-propionitrile (0.1 mmol). The mixture was stirred at 25 0 C for 16 h and then was heated at 80 *C for 1 h. After concentration, purification by flash chromatography (EtOAc/hexanes) provided 3-[3-(4-chloro-phenyl) 5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-1-yl]-propionitrile-6-carboxylic acid tert-butyl ester. Deprotection of this ester according to the deprotection 20 method in Example 103, Step C, gave the title compound (9 mg). The reaction sequence also yielded 3-[3-(4-chloro-phenyl)-5,6,7,8-tetrahydro-4H--1,2,6 triaza-azulen-2-yl]-propionitrile-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C16H1 7

CIN

4 , 300.11; found, m/z 301.4 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.44-7.37 (m, 4H), 4.39-4.37 (t, J 25 = 6.1 Hz, 2H), 3.41-3.39 (m, 2H), 3.29-3.27 (m, 2H), 3.24-3.22 (m, 2H), 2.99 2.96 (m, 2H), 2.95-2.92 (t, J= 6.1 H z, 2H). 233 Example 327 N N-N H/ CI

HN

3-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl] propionitrile. 5 The title compound (0.004 g) was prepared from 3-[3-(4-chloro-phenyl)-5,6,7,8 tetrahydro-4H- 1, 2 ,6-triaza-azulen-2-yl]-propionitri le-6-carboxylic acid tert-butyl ester (Example 326) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 16

H

17

CIN

4 , 300.11; found, m/z 301.4 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.50-7.48 (m, 2H), 7.31-7.30 (m, 10 2H), 4.14-4.11 (t, J= 6.1 Hz, 2H), 3.32-3.31 (m, 2H), 3.23-3.21 (m, 2H), 3.09 3.07 (m, 2H), 2.86-2.84 (t, J= 6.1 Hz, 2H), 2.72-2.70 (m, 2H). Example 328 N-N / CI HN: 15 3

-(

4 -Chloro-phenyl)-2-cycloheptyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.010 g) was prepared from 3-(4-chloro-phenyl)-2 cycloheptyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert butyl ester (Example 254, Step C) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 20

H

2 6

CIN

3 , 20 343.18; found, m/z 344.5 [M+H]*.

'

H NMR (500 MHz, CD 3 0D): 7.60-7.58 (m, 2H), 7.33-7.31 (m, 2H), 4.10-4.06 (m, 1H), 3.41-3.39 (m, 2H), 3.31-3.29 (m, 2H), 3.18-3.16 (m, 2H), 2.78-2.75 (m, 2H), 2.10-2.05 (m, 2H), 1.91-1.87 (m, 2H), 1.80-1.76 (m, 2H), 1.60-1.58 (m, 4H), 1.40-1.39 (m, 2H). 234 Example 329 N-N H \ Cl HN 3

-(

4 -Chloro-phenyl)-2-cyclooctyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene. The title compound (0.017 g) was prepared from 3-(4-chloro-phenyl)-2 5 cyclooctyl -2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert butyl ester (Example 255, Step C) according to the deprotection method in Example 103, Step C. MS (ESI): exact mass calculated for C 2 1

H

28

CIN

3 , 357.20; found, m/z 358.5 [M+H]. 1 H NMR (500 MHz, CDOD): 7.61-7.58 (m, 2H), 7.34-7.32 (m, 2H), 4.24-4.21 (m, 1H), 3.41-3.39 (m, 2H), 3.31-3.29 (m, 10 2H), 3.18-3.16 (m, 2H), 2.78-2.76 (m, 2H), 2.15-2.11 (m, 2H), 1.81-1.77 (m, 4H), 1.57-1.46 (m, 6H), 1.31-1.29 (m, 2H). Example 330 N-N N H 15 3

-(

4 -Chloro-phenyl)-2-(4-methyl-cyclohexyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza azulene. The title compound (0.007 g) was prepared from 3-(4-chloro-phenyl)-2-(4 methyl-cyclohexyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tet-butyl ester (Example 322, Step C) according to the deprotection 20 method in Example 103, Step C. MS (ESI): exact mass calculated for

C

2 0

H

26 ClN 3 , 343.18; found, m/z 344.4 [M+H]*. 'H NMR (500 MHz, CD 3 OD): 7.59-7.57 (m, 2H), 7.33-7.31 (m, 2H), 3.95-3.92 (m, 1 H), 3.37-3.35 (m, 2H), 235 3.31-3.29 (m, 2H), 3.18-3.16 (m, 2H), 2.78-2.75 (m, 2H), 2.10-1.95 (m, 2H), 1.90-1,77 (m, 4H), 1.05-0.91 (m, 6H), Example 331 N-N N 5 H 2 -Benzyl-3-(4-chloro-phenyl)-2,4,5,6-tetrahydro-pyrrolo[3,4-c]pyrazole. To a solution of LDA (1.80 M in THF, 20 mmol) in THF (100 mL) at -78 *C, was added a solution of 3-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (10 mmol) in THF (10 mL) dropwise. After 20 min, a solution of 4-chlorobenzyl 10 chloride (15 mmol) in THF (10 mL) was added. Then the mixture was warmed to 25 0C and stirred for 16 h. Satd. aq. NaHCO 3 (100 mL) was added, and the organic layer was separated and concentrated to give 3-(4-chloro-benzyl)-4 oxo-pyrrolidine-1-carboxylic acid tert-butyl ester. This residue (1/8 portion, approx. 1.25 mmol) was diluted with EtOH (10 mL) and treated with benzyl 15 hydrazine hydrogen chloride (1.5 mmol) and K 2

CO

3 (5 mmol). The mixture was stirred at 25 0C for 16 h. Concentration and purification by flash chromatography (EtOAc/CH 2 Cl2) provided 2-benzyl-3-(4-chloro-phenyl)-2,6 dihydro-4H-pyrrolo[3,4-c]pyrazole-5-carboxylic acid tert-butyl ester. A solution of the ester and TFA (2 mL) in CH 2 Cl 2 (10 mL) was stirred at 25 0C for 4 h. 20 Concentration and purification by flash chromatography (2 M NH 3 in MeOH/CH 2 Cl 2 ) provided the desired compound (10 mg). MS (ESI): exact mass calculated for C1 8

H

1 6

CN

3 , 309.10; found, m/z 310.4 [M+H]. 'H NMR (500 MHz, CDC 3 ): 7.37-7.21 (m, 7H), 7.08-7.05 (m, 2H), 5.29 (s, 2H), 4.09 (s, 2H), 4.04 (s, 2H). 25 236 Example 332 " N-N cl Cl N H 1 -(4-Chloro-benzyl)-3-(4-chloro-phenyl)-1,4,5,6,7,8-hexahydro-1,2,5-triaza azulene. 5 The title compound (0.017 g), as a hydrochloride salt, was prepared from 3-(4 chloro-phenyl)-4,6,7,8-tetrahydro-1 H-1,2,5-triaza-azulene-5-carboxylic acid tert butyl ester (Example 59, Step C; 0.15 g) using 4-chlorobenzyl bromide (0.1 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for C 20

H

1 Cl 2

N

3 , 371.10; found, m/z 372.1 [M+H]*. 1 H NMR (500 10 MHz, CD 3 0D): 7.57-7.50 (m, 4H), 7.41-7.33 (m, 2H), 7.27-7.19 (m, 2H), 5.45 (s, 2H), 4.34 (s, 2H), 3.57-3.53 (m, 2H), 3.08-3.03 (m, 2H), 2.08-2.02 (m, 2H). Example 333 ' N-N N H 15 3-(4-Chloro-phenyl)-1 -(4-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,5-triaza azulene. The title compound (0.011 g), as a hydrochloride salt, was prepared from 3-(4 chloro-phenyl)-4,6,7,8-tetrahydro-1 H-1,2,5-triaza-azulene-5-carboxylic acid tert butyl ester (Example 59, Step C; 0.15 g) using 4-methylbenzyl bromide (0.09 g) 20 in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for C 21 H2CIN 3 , 351.15; found, m/z 352.2 [M+H)*. 1H NMR (500 MHz, CD 3 OD): 7.46-7.39 (m, 2H), 7.21-7.18 (m, 2H), 6.98-6.95 (m, 2H), 6.77 6.74 (m, 2H), 5.08 (s, 2H), 3.97 (s, 2H), 3.46-3.43 (m, 2H), 2.96-2.92 (m, 2H), 2.17 (s, 3H), 2.01-1.97 (m, 2H). 25 237 Example 334 Cl H 3-(4-Chloro-phenyl)-1-(3,4-dlfluoro-benzyl)-1,4,5,6,7,8-hexahydro-1,2,5-triaza azulene. 5 The title compound (0.005 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8 tetrahydro-1 H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 59, Step C; 0.07 g) using 3,4-difluorobenzyl bromide (0.06 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for

C

20

H

18

CIF

2

N

3 , 373.12; found, m/z 374.1 [M+H]. 'H NMR (500 MHz, CDOD): 10 7.39-7.34 (m, 4H), 7.16-7.10 (m, 1H), 6.98-6.97 (m, 1H), 6.89-6.88 (m, 1H), 5.27 (s, 2H), 3.81 (s, 2H), 3.09-3.06 (m, 2H), 2.80-2.76 (m, 2H), 1.75-1.70 (m, 2H). Example 335 '~N-N /ci 15 H 3-(4-Chloro-phenyl)-1-(3-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,5-triaza azulene. The title compound (0.012 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8 tetrahydro-1 H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 20 59, Step C; 0.1 g) using 3-methylbenzyl bromide (0.06 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for

C

21 H22CIN 3 , 351.15; found, n/z352.2 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 7.49-7.43 (m, 4H), 7.19 (t, J = 7.6 Hz, 1 H), 7.08 (d, J = 7.6 Hz, 1 H), 7.00 (s, 1H), 6.92 (d, J= 7.3 Hz, 1H), 5.34 (s, 2H), 3.88 (s, 2H), 3.16-3.13 (m, 2H), 25 2.88-2.85 (m, 2H), 2.30 (s, 3H), 1.80-1.77 (m, 2H). 238 Example 336 F N-N N H 3-(4-Chloro-phenyl)-1-(3-fluoro-4-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,5 triaza-azulene. 5 The title compound (0.002 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8 tetrahydro-1 H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 59, Step C; 0.1 g) using 3-fluoro-4-methylbenzyl bromide (0.09 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for C21H 21

CIFN

3 , 369.14; found, m/z370.1 [M+H]*. 1 H NMR (500 MHz, CD 3 OD): 10 7.49-7.43 (m, 4H), 7.19 (t, J= 7.9 Hz, 1H), 6.88-6.80 (m, 2H), 5.34 (s, 2H), 3.88 (s, 2H), 3.16-3.13 (m, 2H), 2.87-2.85 (m, 2H), 2.23 (d, J= 1.5 Hz, 3H), 1.81-1.78 (m, 2H). Example 337 N~N-N F N 15- H 3-(4-Chloro-phenyl)-1-(4-fluoro-3-methyl-benzyl)-1,4,5,6,7,8-hexahydro-1,2,5 triaza-azulene. The title compound (0.001 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8 tetrahydro-1 H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 20 59, Step C; 0.1 g) using 4-fluoro-3-methylbenzyl bromide (0.09 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for C21H 21

CIFN

3 , 369.14; found, m/z 370.1 [M+H]*. 'H NMR (500 MHz, CD 3 0D): 7.48-7.43 (m, 4H), 7.08-7.06 (m, 1 H), 6.99-6.97 (m, 2H), 5.32 (s, 2H), 3.88 (s, 2H), 3.16-3.14 (m, 2H), 2.89-2.86 (m, 2H), 2.22 (d, J= 1.6 Hz, 3H), 1.80 (m, 25 2H). 239 Example 338 N-N 4r-'D/ F HN 3

-(

4 -Fluoro-phenyl)-2-isopropyl-5,7-dimethyl-2,4,5,6,7,8-hexahydro-1,2,6 triaza-azulene. 5 The title compound was prepared in a manner analogous to those described above. Assay Methods 10 In vitro pharmacologv 1. Affinity for 5-HT 7 receptor binding sites The affinity of the compounds described in this invention for the 5-HT 7 receptor binding site was evaluated by single competition radioligand binding assay. The assay was performed on membranes prepared from HEK-293 cells 15 that had been subjected to stable transfection with the rat 5-HT 7 a receptor (GB: NM022938). Cells were scraped from the culture plates, suspended in Tris HCI 50 mM pH 7.5 and collected through centrifugation (1000 rpm for 5 min). The cell pellets were homogenized (Polytron, 15 s, setting 5) in 50 mM Tris-HCI (pH 7.5), 5 mM EDTA. Following centrifugation (15,000 rpm for 25 min), 20 membranes (135 pg protein/mL) were resuspended in the same buffer and incubated for 60 min at RT with 1 nM [ 3 H]5-CT in the presence of increasing concentration of test compounds. Nonspecific binding was defined in the presence of 10 IM 5-HT. Incubation was stopped by rapid filtration using the cell harvester (Packard). Radioactivity was counted in a TopCount-NXT 25 (Packard). Sigmoidal inhibition curves were generated and fitted by nonlinear regression analysis (GraphPad Prism). ICso values (concentration producing 50% inhibition of specific radioligand binding) were calculated. Ki values were 240 derived according to Cheng and Prussoff (Biochem. Pharmacol. (1973) 22: 3099-3108). Experiments were conducted in triplicate. Stock drug solutions (10 mM) were prepared in DMSO (the final assay concentration of DMSO not exceeding 0.4%). Drug dilutions were prepared in 5 assay buffer. Data are shown in Table 1 below. 2. Effect on adenylyl cyclase activity In vitro functional properties of the compounds described in this invention were evaluated in an adenylyl cyclase assay. HEK-293 cells stably tranfected with the rat 5-HT 7 a receptor were plated into 96-well plates. Cells 10 were washed with 200 gL DNEM/F12 and incubated for 10 min with 80 glL of 2 mM 3-isobutyl-1-methylxanthine. Compounds (10 gL) were added for another 10 min. Subsequently, 5-CT (10 4L) was added. After 20 min the incubation was stopped by the addition of 20 4L of 0.5 N HCl. Plates were incubated at 4 0 C for 30 min. Twenty pL of the supernatant were assayed for cAMP content 15 with a commercially available kit (Perkin Elmer) using 1 2 l1-cAMP. Sigmoidal curves of best fit were calculated by nonlinear regression analysis using GrapPad Prism. 5-CT-stimulated adenylyl cyclase activity in r5-HT 7 a/HEK-293 cells was inhibited by Example 59 with an estimated pKB - 8 in good agreement with the 20 Ki value determined from [ 3 H]5-CT binding studies. 3. Affinity for 5-HTPA receptor binding sites The affinity of the compounds for the rat 5-HT 2 A receptor was evaluated by competitive radioligand binding assay using [ 3 H]ketanserine as the radioligand. The assay was performed on membranes from rat cortex as 25 previously described (Schotte, A. et al., Psychopharmacology (1996) 124: 57 73). Briefly, brain tissue (rat cortex) was homogenized in 20 volumes per wet weight tissue of Tris-HCI buffer (50 mM, pH 7.4). The total membrane fraction was collected by centrifugation and washed by subsequent centrifugation runs (25 min at 25,000 g at 4 0 C). Membranes were re-suspended in Tris-HCI buffer 30 (50 mM, pH 7.4) containing 1 nM [ 3 H]ketanserin. Non-specific binding was estimated in the presence of 10 pM risperidone. The incubation was terminated by rapid filtration over Whatman GF/B filters pre-soaked in 0.1% polyethylenimine, and one washing step with 1 mL ice-cold Tris-HCI buffer, pH 241 7.4. pKi values for all compounds were calculated by pK = -log Ki where K, was calculated according to the method of Cheng and Prusoff (Biochem Pharmacol. (1973) 22: 3099-3108)

(IC

5 o/(1+[S]/Kd) were [S] = 1 nM; Kd = 0.42 nM). All values in Table 1 are listed in nM units. Data are shown in Table 1 5 below. 4. Affinity for 5HT2 receptor binding sites Receptor binding was performed using the human recombinant 5-HT 2 A (GB: X57830), 5-HT 2 B (GB: Z36748) and 5-HT 2 C (GB: M81778) receptors. The affinity of the compounds for the 3 different human 5-HT 2 receptor subtypes 10 was evaluated by competitive radioligand binding assays using [ 3 H]ketanserin (h5-HT 2 A) or [ 3 H]mesulergine (h5-HT 2 B and h5-HT 2 c). The assays were performed on membranes prepared from NIH3T3 stably transfected with h5 HT2A or CHO stably transfected with h5-HT 2 B and h5-HT 2 c. K, values for all compounds were calculated according to Cheng and Prusoff equation (Cheng 15 and Prusoff, Blochem. Pharmacol. (1973)22:3099-3108) (IC5o/(1+[S]/Kd) where [S] = 1 nM (5-HT 2 A), 4 nM (5-HT2B) and 3 nM (5-HT 2 c); Kd = 0.4 nM (5-HT2A), 3.5 nM (5-HT2B) and 3 nM (5-HT 2 c). Data are shown in Table 1 below. 5. In Vitro Functional Assay for 5-HT2 Receptor (Intracellular Calcium) In vitro functional properties of these compounds on the different 5-HT 2 20 receptor subtypes were determined using fluorometric imaging plate reader (FLIPR) based calcium assay as previously described (Porter et al., 1999, Jerman, J.C. et al. Eur. J. Pharmacol. (2001)414:23-30). The 5-HT 2 receptors are linked to the Gq family of G proteins and to subsequent activation of phospholipase C, induction of phosphoinositide metabolism and to an increase 25 in intracellular calcium concentration. The same cell lines as described in the previous section (receptor binding) were used for the FLIPR experiments. Table 1. Binding Affinities (nM) EX Ki Ki KI 5-HT 7 5-HT2A 5-HT 2 B 5-HT 2 c 1 120 NT NT NT 17 70 NT NT NT 18 25 NT NT NT 242 22 45 NT NT NT 26 18 NT NT NT 38, pKb7.8 NT NT NT 47 7-g 64 24 57 15 NT NT NT 5 9 6 280 160 74 64 19 18 NT NT 74 5 100 94 180 75 7 200 100 320 76 8 210 350 690 87' 33 NT NT NT 98 40 NT 1NT 8NT 100 30 NT NT NT E f03 E7.7J 60 44i 150 104- 9 8-0 5-2 360 108 9 NT -100- 800 111 17 NT NT NT 114 32 NT 90 400 117 20 NT NT NT 118 8 20 NT NT31NT 119 39 NT NT NT 120 40 NT NT NT 131 120 7 4.2 50 133 125 2.3 3.5 10 60 7 300 3520 3500 16 5 4 100 31l 0 180 1T66 8 80 0 590 16 7 7-5 NT 30 10000 1T72 3-7 NT NT NT 174 40 NT NT NT 1T77- 8-0 7 7 110 178 85 3 3 NT 243 180 10 1.5 1.4 12 181 37 1.5 1.8 11 182 90 0.74 1.4 18 183 240 7 54 70 184 120 1 17 15 186 61 1 24 20 190 16 10 22 51 191 30 NT NT NT 192 20 2.5 0.9 15 209 6 1.1 1.4 12 210 7 2 0.75 20 211 8.5 5 0.5 18 212 93 25 12 425 213 12 7.5 4.7 80 214 5 NT 2 170 215 30 8 95 NT 216 70 6 20 17 217 25 1 0.65 10 218 75 1.7 1.8 15 220 55 1.3 0.55 6.8 232 20 25 0.50 66 233 15 4 25 16 236 950 7 4.5 32 238 40 1 0.50 13 241 310 9 9.5 38 242 21 8 1.3 45 253 75 NT 25 625 255 60 NT NT NT 257 9 NT 2 110 273 5 400 NT NT 276 90 3 2.5 90 277 150 0.9 3 40 244 278 35 0.1 0.2 10 279 80 0.8 1 45 280 3300 1.5 6 120 282 100 6 20 200 283 5000 10 60 150 284 10 1 2 60 285 29 60 6 500 286 335 50 80 5000 298 50 5 6.5 60 299 35 1.7 9 26 300 10 0.3 0.8 12 301 40 1.6 3 100 302 100 0.2 1.3 21.5 305 600 20 60 2200 306 120 1 22 39 308 5200 2 3 162 309 130 30 15 130 310 475 0.2 0.4 30 311 80 140 100 3000 313 30 100 40 1000 315 12 9 3 300 316 9.1 60 530 5000 NT = not tested 245

Claims (24)

1. A compound having serotonin receptor modulating activity of formula (il): CYC-(ALK)q NAr N 1 (R3 ( III) wherein 5 m is 1 or 2; n is 1, 2 or 3; m+n is less than or equal to 4; q is 1; r is 0, 1, 2 3, 4, or 5; 10 R 3 is -C 4 alkyl, allyl, propargyl, or benzyl, each optionally substituted with -C 3 alkyl, 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 1 4 alkyleneO-, -(CH 2 ) 3 NH-, -(CH 2 ) 1 . 2 NH(CH 2 )~, 15 -(CH 2 ) 2 .. 3 N(C 4 alkyI)- or -(CH 2 4 2 N(Ct 4 alkyl)(CH 2 )-; R is selected from the group consisting of -OH, -C 1 -alkyl, -OC 1 ,alkyl, -C ealkenyl, -OCa 6 alkeny, -Calkynyl, -OCalkynyl, -CN, -NO 2 , -N(R )R' (wherein RY and R' are independently selected from H or 0 16 alkyl), -(C=0)N(R'}Rt -(N-Rt)COR -(N-R)SO 2 C 1 alkyl (wherein R1 is H or 20 C 1 ealkyl), -(C=0)C 1 alkyl, -(S=(O),)-Ceakyl (wherein n is selected from 0, 1 or 2), -S0 2 N(R)Rt -SCFa, halo, -CF 3 , -OCF -COOH and -COOC 6 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 25 ring, which moiety has one carbon atom replaced by >0, >S, >NH or >N(C 14 alkyi) 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'; 246 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/; 5 d) naphthyl, optionally mono-, di- or ti-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 4 alkyl), having up to one additional carbon atoms optionally replaced by -N=, optionally mono- or di-substituted 10 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 15 atoms replaced by -N=, optionally mono- or di-substituted with Rr 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 20 consisting of phenyl, pyridyl, thiophen-2-yl, thiophen-3-y, 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 1 alkylene, C 2 .8alkenylene, C 2 .zalkynylene or C,_cycloalkenylene, optionally mono-, di-, or tri-substituted with a substituent 25 independently selected from the group consisting of: -OH, -OCIalkyl, -OC 7 ,cycloalkyl -CN, -NO 2 , -N(Rt)R" (wherein R' and Rb are independently selected from H, Cb3alkyl or C 2 alkenyl), -(C=O)N(R)R, (N-RO)CORc, -(N-R)SO 2 C 1 6 alkyl (wherein R' is H or CO 1 alkyl), -(C=O)Calkyl, -(S=(O))-C 6 alkyl (wherein d is selected from 0, 1 or 2), -SO 2 N(R)Rb, -SCF 3 , 30 halo, -CF 3 ,, -OCFO 3 , -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 Rq or di-substituted on adjacent carbons with -OCalkyleneO-, -(CH)NH-, -CH2) 2 NH(CH 2 )-, 35 -(CH2)9'N(Cb.alkyl)- or -(CH2)wN( 4 alkyl)(CHJ)-; 247 R is selected from the group consisting of -OH, -C ,alkyl -O0ualkyl, -C3 6 cycloalkyl, -O..acycloalkyl, phenyl, -Ophenyl, benzyl, -Obenzyl. -CN, -NO 2 , -N(R")R (wherein R' and Rare independently selected from H, C 1 -alkyl or C 2 .. 6 alkenyl, or R' and Rb may be taken together with the 5 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 14 alkyl), optionally having one carbon substituted with -OH, and optionally having one or two unsaturated bonds in the ring), -(C=O)N(Ra)Rb, -(N-Rc)CORc, 10 ~(N-Rc)SO 2 C 1 . alkyl (wherein Re is H or Csalkyl or two Re in the same substituent may be taken together with the aide of attachment to form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -N(SO 2 0 C.alky), -(C=0)C 1 .. 6 alkyl, ~(S=(O),&Cj_%alkyl (wherein d is selected from 0, 1 or 2), -SO 2 N(R:)Rb, -SOF 3 , halo, -CF 3 ., 15 -OCF 3 . -COOH and -COOCI 6 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 4 alkyl) and which moiety has up to one additional carbon atom 20 optionally replaced by -N=, the fused rings optionally mono-, di- or tri-substituted with Rt 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 25 optionally mono-, di- or tri-substituted with R; iv) naphthyl, optionally mono-, di- or tri-substituted with RI; 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 1 4 alkyl), having up to one additional 30 carbon atoms optionally replaced by -N=, optionally mono- or di-substituted with R4 and optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono-, di-, or ti-substituted with Rt vi) a monocyclic aromatic hydrocarbon group having six ring atoms, having a 35 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 248 optionally benzofused or pyridofused at two adjacent carbon atoms, where the benzofused or pyridofused moiety is optionally mono- or di-substituted with Rq; vii) a 3-8 membered non-aromatic carbocyclic or heterocyclic ring said ring having 5 0, 1 or 2 non-adjacent heteroatom members 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, 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 10 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 0, S, -N=, >NH or >NR4 having 0, 1 or 2 unsaturated bonds, having 0, 1 or 2 carbon members which is a carbonyl and optionally having one carbon member 15 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 I possibly additional heteroatom member, not at the ring junction, selected from 0 S. -N=, >NH or >NRT having 0, 1 or 2 unsaturated 20 bonds, having 0, 1 or 2 carbon members which is a carbonyl and the fused rings having 0 to 5 substituents R R 1 is selected from the group consisting of H, Calkyl, C 2 alkenyi, C 2 7 alkynyl. C 3 ,cycloalkyl, Qocycloa lkylC 1 7 ualkyl, C 3 7cycloalkenyt, G 3 CcycloalkenyIO 1 .7aikyl and benzo-fusedCcycdoalkyl, each optionally mono-, di-, or tri-asubstituted with 25 RP; RI is selected from the group consisting of -OH, -OCu 6 alkyl, -%Ccycloalkyl, -OC 2 cycoalkyl, -CN, -NO 2 , phenyl, pyridyl, thienyl, furanyl, pyrrolyl, -N(Rs)R' (wherein R' and R' are independently selected from H or C 16 alkyl, or may be taken together with the nitrogen of attachment to form an otherwise 30 aliphatic hydrocarbon ring, said ring having 5 to 7 members, optionally having one carbon replaced with >0, N-, >NH or >N(C.1-alkyl) and optionally having one or two unsaturated bonds in the ring), -(C=O)N(R)R', -(N-R)COR', -(N-R)SO 2 CIalkyl (wherein R' is H or C 1 _alkyi or two R' in the same substituent may be taken together with the amide of attachment to 35 form an otherwise aliphatic hydrocarbon ring, said ring having 4 to 6 members), -(C=O)Calkyl, -(S=(O))-Calkyl (wherein n is selected from 0, 249 1 or 2), -SO 2 N(R")Ru, -SCF 3 , halo, -CF, -OCF 3 , -COOH and -COOCsalky, 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> 6 alky, 5 -OCalkyl, -CN, -NO 2 , -N(R")Rb (wherein R' and RW are independently selected from H, Csalkyl or C 2 alkenyl), -(C=O)N(R")Rb, -(N-R)COR, -(N-R)SO2Cjalkyl (wherein R is H or C-alkyl),(C=O)C 1 ualkyl, -(S=(O))-Cmakyl (wherein d is selected from 0, 1 or 2), -SO2N(R)R, -SCF, halo, -CF 3 , -OCF, -COOH and-COOC alky; 10 or an enantiomer, diastereomer, hydrate, solvate or pharmaceutically acceptable salt, ester or amide thereof.

2. The compound according to claim I wherein m is 1. 15 3. The compound of claim 1 or claim 2 wherein n is I or 2.

4. The compound of any one of claims I to 3 wherein m+n is 2 or 3.

5. A compound of any one of claims I to 4 wherein r is 0, 1 or 2. 20

6. A compound of any one of claims 1 to 4, wherein r is 4,

7. A compound of any one of claims 1 to 6 wherein R optionally substituted, is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, allyl, 25 propargyl, and benzylt

8. A compound of any one of claims I to 7 wherein R is methyl.

9. The compound of any one of claims 1 to 8 wherein Ar, optionally substituted, is 30 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-, 7lindolinyl, 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 35 benzofuranyl, 4-, 5-, 6- or 7-indolyl 4-, 5-, 6- or 7-benzthiazoly, 4-, 5-, 6- or 7 benzimidazolyl, 4-, 5-, 6- or 7-indazolyl, imidazoi ,2-ajpyridin-5, 6, 7 or 8-yl, 250 pyrazoo[1,5-a]pyridin-4, 5, 6 or 7-y, 1 H-pyrrolo[2,3-b]pyridin-4, 5 or 6-yl, 1 H-pyrrolo[3,2-c~pyridin-4, 6 or 7-yl, I H-pyrrolo[2,3-cjpyridin-4, 5 or 7-yt, 1 H-pyrroio[3,2-b]pyridin-5, 6 or 7-yt c) 5-, 6-, 7- or 8-isoquinoinyl, 5-, 6-, 7- or 8-quinolinyl, 5-, 6-, 7- or 8-quinoxalinyl, 5-, 5 6-, 7- or 8-quinazolinyl, d) naphthyl, e) furany, oxazolyl, isoxazolyl, 1,2,3-oxadiazolyl, 12,4-oxadiazolyl, 1,2,5 oxadiazolyl, 1,3,4-oxadiazoilyl, thiophenyl, thiazolyl, isothiazolyE, pyrrolyl, imidazolyl, pyrazoly, 12,3-triazolyl 1,2,4-triazolyl, 3indoxazinyl, 2 10 benzoxazolyl, 2- or 3-benzothiophenylE, 2- or 3-benzofuranyl, 2- or 3-indolyl, 2 benzthiazoly, 2-benzimidazolyL 3-indazolyl, f) pyridinyl, pyridinyl-N-oxide, pyrazinyl, pyrimidinyl, pyridaziny, 1-, 3- or 4 isoquinolinyl, 2-, 3- or 4-quinolinyl, 2- or 3-quinoxaliny, 2- or 4-quinazolinyl, [1,5], [1 6], [1,7], or [1,8]naphthyridin-2-, 3-, or 4-y, [2,53, [2,6], [2,7], [2,8]naphthyridin 15 1-, 3-, or 4-y, and g) biphenyl, 4-tetrazolylphenyl.

10. The compound of any one of claims 1 to 8 wherein Ar, optionally substituted, is selected from the group consisting of phenyl, pyridyl, thiophen-2-yl and thiophen-3-yl. 20

11. The compound of any one of claims 1 to 8 wherein Ar is selected from the group consisting of phenyl. 2-methoxypheny!, 3-methoxyphenyl, 4-methoxypheny, 2-methylphenyl; 3-methylpheny, 4-methylphenyl, 4-ethylphenyl 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyt, 3-fluorophenyl, 4-fluorophenyl, 25 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluorome thylphenyl, 3-trifluoromethoxypheny, 4-trifluoromethoxyphenylt 3-cyanophenyl, 4-cyanophenyl, 3-acetylphenyl, 4-acetylphenyl, 3,4-difluorophenyl, 3 4-dichlorophenyl, 2 3-difluorophenyl, 2,3-dichlorophenyl, 2,4-difiuorophenyt, 2 ,4-dichlorophenyl, 3-nitrophenyl, 4-nitrophenyl, 30 3-chlore-4-f4luoreophenyl, 3-fluoro-4-chlorophenyl, benzo[1,3]dioxol-4 or 5-ylI 3-hydroxyphenyl, 4-hydroxyphenyl, 4-hydroxy-2-methylphenyl, 4-hydroxy-3 fluorophenyl, 3,4-dihydroxyphenyl,4-dimethylaminophenyl, 4-carbamoylphenyl, 4-fluoro 3-rnethylphenyl, furan-2-yi, furan-3-y, thiophen-2-y, thiophen-3-yl, 5-chlorothiophen-2 yE, 5-methylthiophen-2-yl, 5-chlorothiophen-3-yl, 5-methylthiop he r-3-yl, 4' 35 chlorobiphenyl, and 4-tetrazolylpheny. 251

12. A compound of any one of claims I to 11, wherein ALK, optionally substituted, is selected from the group consisting of methylene, ethylene, propylene, butylene, tert butylene, pentylene, I -ethylpropylene, 2-ethylpropylene, 2-ethylbutylene, isopropylene but-3-enylene, isobutylene, 3-methylbutylene, allylene, and prop-2-ynylene 5

13. A compound of any one of clairns 1 to 11, wherein ALK is selected from the group consisting of methylene, trifluoromethylmethylene, methoxycarhonyimethy, methylcarbamoylmethyl, ethylene, propylene, 3-rnethoxycarbonyl propylene, 3-carboxy propylene, butylene, tert-butylene, 4-hydroxybutylene, 4-methoxycarbonyl butylene, 4 10 carboxy butylene, pentylene, 5-hydroxypentylene, 1-ethylpropylene, 2-ethylpropylene, 2-ethylbutylene, isopropylene, but-3-enylene, isobutylene, 3-methyibutylene, prop-2 ynylene, 2-dimethylaminoethylene, and 2-cyanoethylene.

14. A compound of any one of claims 1 to 13, wherein CYC, optionally substituted, 15 is hydrogen or is selected from the group consisting of: i) phenyl, 5-, 6-, 7-, 8-benzo-d4-dioxany, 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-benzoxazoyl, 4-, 5-j 6- or 7-benzothiophenyl, 4-, 5-, 6- or 7 20 benzofuranyl, 4-, 5-, 6- or 7-indolyi, 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, pyrazoio[1,5-a]pyridin-4, 5, 6 or 7-yi, 1 H-pyrrolo[2,3-b]pyridin-4, 5 or 6-yl, I H-pyrroio[3,2-c]pyridin-4, 6 or 7-yiz I H-pyrrolo[2,3-c]pyridin-4, 5 or 7-yi 1 H-pyrrolo[3,2 b]pyridin-5, 6 or 7-yl, 25 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-oxadiazolyi, 1,2,4-oxadiazolylt 1,2,5-oxadiazolyl, 1 3,4-oxadiazolyl, thiophenyl, thiazolyl, isothiazolyl, pyrrolyl, imidazolyi, pyrazolyl, 1,2,3 30 triazolyl, 1,2,4-triazolyl, 3-indoxazinyl, 2-benzoxazolyl, 2- or 3-benzothiophenyi, 2- or 3 benzofuranyl, 2- or 3-indolyl, 2-benzthiazoiyl, 2-benzinidazolyl, 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, [1,51, [1,6], [1,7l, or [1 ,8]naphthyridin-2-, 3-, or 4-yl, [2,5], [2,61, [2,7], [2,8]naphthyridin-1-, 3-, or 4-yl, 35 vii) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, adarnantyl, pyrrolinyl, pyrrolidinyl, pyrazolinyl, piperidinyl, hornopiperidinyl, 252 azepanyl, tetrahydrofuranyl, tetrahydropyranyl piperazinyl, morpholinyl, thiomorpholinyl, piperidinonyl, indanyl, dihydroindolyl, oxindolyl, dihydropyrrolopyridinyl, and viii) bicycIo[4.1.0]heptane, octahydroindolyl, octahydroisoindolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydropyrrolopyridinyb and octahydropyrrolopyrrolidinyl. 5

15. A compound of any one of claims 1 to 13, wherein CYC, optionally substituted, is selected from the group consisting of hydrogen, phenyl, indolyl, benzthiazoly, isoquinolyl, quinazolinyl, naphthalen-1 or 2-y thiophen-2-y, thiophen-3-yl, furan-2-y, furan-3-yl. pyridinyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 10 piperidin-2,3 or 4-yl 2-pyrrolin-2, 3, 4 or 5-yl, 3-pyrrolin-2 or 3-y, 2-pyrazolin-3, 4 or 5-y, morpholin-2, 3, 5 or 6-yl, thiomorpholin-2, 3, 5 or 6-yl, piperazin-2, 3, or 6-yl, pyrrolidin-2 or 3-yl, homopiperidinyl, adamantanyl, and octahydroindolyl.

16. A compound of any one of claims 1 to 13 wherein CYC, optionally substituted, is 15 selected from the group consisting of hydrogen, phenyl, pyridyl, cyclobutyl, cyclopentyl. cyclohexyl, thiophen-2-yi, thiophen-3-yl, tetrahyd ropyranyl, furan-2-yl, furan-3-yl and naphthalen-I or 2-ylt

17. A compound of any one of claims I to 13 wherein CYC is selected from the 20 group consisting of hydrogen, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-ethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluo rophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromopheny, 4-bromophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 25 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3-acetylpheny, 4-acetylphenyl. 3,4-difluorophenyl, 3,4-dichlorophenyl, 2,3-difluorophenyl, 2,3-dichlorophenyl, 2 4-difluorophenyl, 2,4-dichlorophenyl, 2,6-difluorophenyl, 2 6-dichlorophenyl, 2,6-dimethylphenyl, 2,4,6-trifluorophenyt, 2,4,6-trichlorophenyl, 3,4,5-trimethoxyphenyl, cyclobutyl, cyclohexyl, cyclopentyl, 4 30 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-a minophenyl, 4-carbomethoxyphenyl, 3-methanesulfo nylarmino-phenyl, 4-methanesulifonylamino-phenyl, 3-dimethanesulifonylamino-phenyl, 4-dimethanesulfonylamino-phenyl, thiophen-2-yl, thiophen-3-yl, 5-chlorothiophen-2-y 35 benzo[i,3]dioxol-4 or 5-yl, tetrahydropyrar-2,3 or 4-yt furan-2-y, furan-3-y 5 carboxyethyl-furan-2-yl, naphthalen-i or 2-yl, 3,4-bisbenzyloxyphenyl, 2-hydroxyphenyl 253 3-hydroxyphenyl, 4-hydroxyphenyl, 4-hydroxy-2-methylphenyl, 4-hydroxy-3-fluorophenyl and 3,4-dihydroxyphenyt

18. A compound of any one of claims 1 to 17 wherein R' is selected from the group 5 consisting of hydrogen, Cl 3 alkyl, C 2 4 jalkenyl C 4 akynyl, Ca 6 cycloalkyl, C 0 cycloa lkylOuakyl, C 6 cycloalkenyl, benzo-fusedC_ 6 cycloalkyl, each optionally mono-, d-, or tri-substituted with RP.

19. A compound of any one of claims 1 to 17 wherein R, optionally RP substituted, 10 is selected frorn the group consisting of hydrogen, methyl, ethyl, propyl, and isopropyL 20, A compound of any one of claims 1 to 17 wherein R' is selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, 3-hydroxypropyl benzyl, 3,4 dimethoxybenzyl, methoxycarbonyimethyl, carbamoylmethyl, phenethyl, phenpropyl, 15 and hydroxyethyl,

21. A compound 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; 64 314-Chloro-phenyl)-2-ethyl-2,4,5,6,7,8-hexahydr-i-12,6-triaza-azu lene 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; 70 3-(4-Chloro-phenyl)-2-(2-cyclohexyl-ethyl)-2,4,5,67, 8-hexahydro-i,2,6 triaza-azulene; 72 3-(4-Chlorro-phenyl)-2-phenethyl-2,4,5,6 ,7,8-hexahydro-1,26-triaza-azuilene; 82 5-[3-(4-Chloro-phenyl)-5,6 7 ,8-tetrahydro-4H-12,6-triaza-azulen-2-yl] pentanoic acid methyl ester; 5-[3-(4-Chloro-phenyl)-5,6, 7 8-tetrahydro-4H-1,2, 6-triaza-azulen-2-yl] 83 pentanoic acid; 84 5-[3-(4-Chloaro-phenyl)-5 ,6 7 ,8-tetrahydro-4H-1 ,2,6-triaza-azulen-2-yl] pentan1-ol; 4-[3-(4-Chloro-phenyl)-5,6,7 ,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yij-butyric acid methyl ester; 4-[3-(4-Chloro-phenyl)-5,6,7 ,8-tetrahydro-4H-1,2,6-Lriaza-azulen-2-y)-butyric 90 acid; 254 4-P3-(44--Ch laro,-phenyl )-5,6, 7 ,8tetrahyd rc-H1,2 ,6-triaza-azuleni-2-yl-butan 92 94 3.-(4-Chlora-phenyl)-21(3,4-dif luora-benzyl)-2,4,5,6,7,8-hexahyd ru-i ,2,6 triaza-azulene; 95 3-(4-Chlara-phenyl)-2-(4-rnettiyl-benzyl)j-2,4,5,6,7,6-hexahyd ros-i,2,6-triaza azulene; 974Coapey)2(-laa4mehx-ez~,5678hxhdo I ,2,6-triaza-azulene; 122 3-(4-.Ghlora-phenyl )-2-cyclahexylmethyl-2,,5,6 ,7,6-hexahyd re-I.2 ,6-triaza azulene; 126 3-(4-Chlara-phenyQ-2-(2-methyl-benzyl)-2,4,5,6,7,8--hex-ahydra-i ,2 ,6-triaza azuldene; 127 2-Benzyl1-3-(4-claro-pheniyl)-2,4,5,6,7,8-hexa hydra-I ,2,6-triaza-azulane;. 19 3-(4-Chlar--phenyl)-2-(2,4-ditluara-.benzy )-2,4,5,6,7,6-hexahydr-i -,2,6 triaza-azulene; 130 5[3-(4-Chla ra-phenyl)-5 ,6, 7,8-tetra hyd ra-4H-1,2 ,6-triaza-azuleni-2-ylrniethyl] furan-2-carbaxyhic acid ethyl ester; 131 3,-(4-Chlorar-phenyl)-2-isabutyl-2 ,4,5,6,7 .8-hexaqhyd ra- 1 ,2,6-triaza-azulene; 132 3-(4-Chiarao-phenyl)-2-(2-rnethaxy-benzyl)-2 4,5,6,7 ,&-hexa hydra-I 1,2,6- triaza-azulene; 133 2-Benzyl-3-phenyl-2,4,5,6,7,6-hexahydra-i ,2 ,6-triaza-azulczne; 136 3-(4-Chlara-phenlyl)-2-<niaophen-2-yrnehyl-2 ,4,5,6,7,3-hexahydra-1 ,2,6 iriaza-azulene; 139 3-(4-Chloro-phenyl )-2-(5-ch lara-thiaphen-2-yl methyl )-2 ,4,5,6,7 ,3-hexahyd ra 1 2,6-triaza-azulene; 140 3-(4-Chlaro-phenyl)-2-(2 ,6-difluaora-benzyl)-2 ,4,5,6,7,8-hexahydra.-1 ,2,o triaza-azuIene:

113-(4-Chlara)-phen.yl)-2-(2-tiluaramethyl-benzyl)-2, 4,5,6.,7, 8-hexahydra-1 ,2,6 iriaza-azulene; 143 3-(4-Ch lara-phenyl )-2-(2-ethyl-butyl)-2 ,4,5 ,6 ,7 ,3-hexa, yd re-i ,2,6-triaza azulene; 146 2-Benzaf I,3]d laxo l-5-yi methyl-3-(4-chloaro-phe nyl )-2 ,4, 5,6,7, 8-hexahyd ra I 2,6-triaza-azulene;,

193-(4-Ch lara-phenyl )-2-pe ntafluaraphenyi .methyl-2 ,4 ,5,6 ,7 .8-hexaohyd ra-1,2,6 triaza-azulene;, 255 151 3-(4-Chlioro-pheny)-2-naphthalen-1 -ylmethy-2,415,5,7,8-hexa hydro-1,2,6 tiaza-azulene; 153 3-(4-Chloro-phenyl)-2-(3,4,5-trimethoxy-benzy1)2,4,5,6,7 ,8-hexahydro-1 ,2,6 triaza-azulene; 2-(3 4-Bis-benzyloxy-benzy i)-3-(4-chloro-phenyl)-2, 4,56,7,8-hexahydro 155 1 ,2,6-triaza-azuIene; 4-[3-(4-Chloro-phenyl)-5 ,6,7 ,8-tetrahyd ro-4H-1,2 ,6-triaza-azulen-2-ylmethyl] 161 2-fluoro-phenol; 16 3 4-[3-(4-Chloro-phenyl)-5,6 ,7 8-tetrahyd ro-4H-1,2,6-triaza-azulen-2-ylmethyll 3-methyl-phenol; 164. 2-[3-(4-Chloro-phenyl)-5 6,7 ,8-tetrahyd ro-4H-1 ,2,6-triaza-azuLen-2-yethyl] 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; 3 4-Chloro-pheny)-2-cyclohexyl-2,4,5,6,7, 8-hexahydro-,2,6-triaza 178 \0 azulene; 179 2-Cyclohexyl-3-(4-trifluoromethyl-phenyl)-2 ,4, 56,7 8-hexahydro- ,2 ,6-triaza azulene; 180 2-Cyclopentyl-3-phenyi-2,5,6,7,8-hexahydro-12,6-triaza-azulene; 181 3-(4-Chloro-phenyl)-2-cyclopenty-2,4,5 ,6 8-hexahydro-1 ,2,6-triaza azulene; 183 2-Cyclopentyl3-(43-flunro-pheny)-2,4,5,6,7, 8-hexahydro-1,2,6-triaza azulene; 183 2-(1 -Ethyl-propyl)-3-(3-fluo ro-phe nyl)-2 ,45, 6 ,7, 8-hexahyd ro-1,2,6-triaza azulene; 2-(1 -Ethyl-prpyl)-3-(4-fluoro-phenyl)-2,4,5,6,7, 8-hexahydro-i ,2 6-triaza azulene; 186 2-(1 -Ethyl-propyl)-3-thiophen3-y2,4,5,678ahexahyd ro-1, 2,6triaza azulene; 186 2-(1-Ethy-propyl)-3-phenyl-2,4,5,67,8~hexahyldro-^1,2,6~triaza-azulene; 187 3-(4-Chloro-phenyl)-2-2,2,2-trifluoro-ethyl)p24,5,6,7-8-hexahydrod2,6 triaza-azuene; 24(2,2,2-Trifluoro-ethyi)-3-(4-tIriflu:orom,: ethy -phenyl)-2,4,5,6,7 ,8-hexahydro3 188 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-Fuoro-phenyl)-2-isoprnpyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 256 191 ~2-(lI -EtbyI-propyl)-3-diiopheni-2-yW-2,4,5,6 ,7,8-hexahydro-1 ,2,6-tr,,iaza azfl ene; 192 2-Cycoopen tyi.-3-thiophen-3-yL-2,4,5,6,7,3-hexahydro- 1,2,6-tria za-azulene; 193 2-EihyV--phenyk-2,4 5,6,7, 8-bexahyd rot ,2,6l-triaza-azulene; 194 .2-Ethvl-3-(4-fiLuoroD-pheny!)-2,4,5,6 ,7,8-hexabydro-i ,2,6-triaza -azulen-e; 195 2-Ethyl-3. -ihiophen-2-yi-2 .4,5:617,8-hexa hyd ro-I 2 ,6-triaza-azu iene; 196 2-(3-Chlere-phienyl )-3-phenyl-2,4 5 .6,7,8-hexahwd re-I,2 ,6-triaza-azuien-e;, 197 2-(3-Fiuore--phenyQ-3-phenyb.-2,4,5,6,7,8-hexahyd re-I,2 ,6-triaza-azulenie; 198 2-(2-Ghloro-phenyl)-3-phernyV-2 4, 5.6,7,8-hexahyr*- 1 ,2,6-tdaza-azuiene; 199 2-Phenyl-3-th iephen-2-yk-2, 4.5.6,7, 8-hex-ahyd re-1,2 .6-triaza-azulene; 200 3-(4-Fluore-phenyl)-2-phenyl-2,4,5,6,7 ,8-h exahydro-i ,2,6-triaza-azLdlene; 201 3-(4-Ch lero-phe nyl)-2-phenA-2 ,4,5,6,7, 8-hexahydre- 1,A,6-triaza-azu le fi; 202 3,-(3-Ohloro-phenyl>-2-phenyl-2,4,5,6,7 ,8-hexahydre-i .2,6-triaza-azulene; 203 2-Pheriyl-3-po-telyl-2 ,4,5,6,7,8-hexahydren-1 ,2,6-triz-a,,zuene; 204 2, 3-Diphenyl-4 .5,6 ,7-tetrahyd re-2Hi-pyrazeie[4 ,3-cjpyrid lee;

253-Phe nyh-2-(3-hifluerorrmethyl-phenyl )-2 .4,5,6,7 .8-hexahyd rn-I,2 .6-triaza azulene; 206 3-t4-Methexy-pheeyl)-2-pheeyl-2 ,4,5,6,7 .8-hexahydr--1,2 ,6-triaza-azu ieee; 207 2-(4-Chlere-pheeyQ)-3-phenyl-2,4,5,6,7,8-hexahiydre-1 ,2,6-triz-azulee; 208 6-Methyl-2,3-dipheeyl-2. 4,5,6,7, 8-hexahyd re-I,2,6-triaza-azulee 209 2-iseprepyl -3-p-tolyl-2,4,5,6,7,8-hexahydro- 1,2 ,6-t riaza-azuliee 210 3-(4-Ethyl1-p henyl )-2-i sop rpy-2 ,4:5,6,7,8-hex-a hyd ro- 1, 2,6-triaza-azu leee; 211 3-(4-Chlere-pheeyO1-2-iseprepyl-2 ,4,5,6,7,8-hexahyd re-I.6-triaza.-azulene: 212 4-(2- Ise pro pyl-2,4,5,6 ,7,8-h exa hyd ro-i 1,2,6-triaza--azu lee-3-yI)-benzori ble; 213 2i1soprpy-3-(4-trit lue reme thy -phenyl )-2 1 4,5,6,7,8-hexa h yd re-I, .2 6-triaza azulene; 214 2-Ethylk3-p-toiyl-2,4,5,6,7,8-h exahydre-i .2 0-trieza-azulene;$ 215 2-tert-Buityl-3-pheeyl-2,4,5,6,7,8-hexahydre-I .2 6-triaza-azulene;, 216 2-tert-Butyl-3-(4-fiuore-pheeyL)-2,4,5,6,7 ,8-hexahydre- 1.2 6-triaza9--azidene; 217 2-Cycoepee-l-y-3-p-lrlyl-2,t,5,6,7,8-hexahydre-1 .2,6-triaza-azulene; 218 2-CyclepeetyL-3-(4dtrifiue romethyl-phen-yl >-2,4,5.6,7,8-hexahyd re-I,2 ,6 trie za-aze ee:

2193-(3-Chlore-pheeyQ-2-cyc-iepeetyl-2, 4,5,6,7,8-hexabydre-1 ,2,6-triaz-a azulene;

2202-Cyelopeetyvl-3-(4-meh exy-phenyl )-2 .415,6,7 .8-hexahyd re-I .2 6-Pliaza azu ieee; 257 221 2-(3,3-Dirnethyl-cyclopentyi)-3-phenyk2,4, 5,67 ,Bhexahydro-1,2 6-triaza azulene; 2-(3 3-Dirnethyl-cyclopentyl)-3-(4-fluoro-phenyl-2,4,5,6,7, 8-hexahydro-1,2,6 222 triaza-azulene; .223 3-(4-Chloro-pheryl)-2-(3,3-dimethykcyclopentyl)-2 4,5,6,7,8-hexahydro 1,2,6-triaza-azulene; 224 2-Cyclohexy-3-(44-fluoro-phenyl)-24,5,6 ,T8-hexahydro-1,2,6-triaza-azulene; 225 2-Cycfohexyl-3-(3,4-difluoro-pheny)-2,4,5,6, 7,8-hexahyd ro-1,2 6-triaza azulene 226 2-Cyclohexyk3-p-toly-24,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene; 2-Cydohexyl-3-(4-methoxy-pheny)2,45,6,7,8-hexa hydro-1,2,6-riaza 227 azulene; 228 4-(2-Cydohexyl-2 ,4 ,5,6,7 8-hiexahydro1 ,2 ,6-triaza-azulen-3-yi)-benzonitrile; 3-(3-Chloro-phenyl)-2-cyclohexyl-2,4,5,6 7 8-hexahydr-1 2,6-triaza 229 azuIene; 3-(4-Fluoro-phenyl )-2-isopropyl-4,5,6 ,7-tetrahydro-2H-pyrazolo[4,3 231 c]pyridine; 232 2-Cyclopentyl-3furan-3-yV2,4,5,6,7,8-hexahydro- 1,2,6 -triaza-azulene; 233 2-Cyclopentyl-3-thiophen-2-y-24,5,6,7,8-hexahydro-1 2,6-triaza-azulene; 234 2-tert-Butyk3-thiophen-3-yl-2,4,5,6 ,7, 8-hexahydro-1 2, 6-triaza-azulene; 235 2tert-Butyl-3-furan-3-y-2,4,5,6 ,7,8-hexahydro- 1,2,6-triaza-azulene; 236 2-Cyclopentyi-3-(3,4-d ifluoro-phenyl)-2 415,6,7/8-hexahydroe-i,2,6-triaza azulene 238 3-(4-Chloro-phenyi)-2-cyclobutyl-2,4,5,6,7 ,8-hexahydro-1,2,6-triaza-azulene; 240 2-tert-Butyl-3-thiophen-2-yI-2,4A5,6,7,8-hexahydroe-I 2,6-triaza-azulene; 3-(3-Ch lo ra-4-fuI ori-phenyl)-2-cydopentyl-2,4,5,6,7,8-hexa hydro- 1,2,6 241 triaza-azulene; 242 2-Isopropyk3-(4-methoxy-phenyl)-2,4,5,687,-hexahydro-1,2 ,6-triaza azulene; 243 2-I-sopropyk3-(4-trifluoromethoxy-phenyl)-2 4,5,6,7 8-hexahydro- 1,2,6-triaza azulene; 2-Isopropyl-3-(4-isopropyl-phenyl)-2 4,5,6.7 ,8-hexahydro-1,2,6-triaza 244 azulene; 245 3-(4-tert-ButyI-phenyl)-2-isoprpyl-2 ,4,5,6 ,7,8-hexahydro-1,2 ,6-triaza. azulene; 246 2-Isopropyl-3-m-taolyl-2 4,5,6,7 ,8-hexahydro-1,2,6-triaza-azulene; 258 247 2-IsopropyL3-o-tolyi-2,4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene; 3-3 ,4-Dichloro-phenyl)-2-isopropy-2 4, 56 ,7,8-hexahydro~1,2 ,6-triaza 248 azuIene; 249 2-Benzyl-3-(4-fluoro-phenyl)-25,456 ,7,8-hexahyd ro-12,6-triaza-azulene; 250 2-iso propyl-3-thiophen-2-yI-2,4, 5,6 7,8-hexa hyd ro- 1,2 .6-triaza-azulene; 251 3-(2-Ch loro-phenyl)-2-isopropy-2 ,4,5,6,7,8-hexahyd ro-1 ,2 .6-triaza-azulene; 1-{4-(2-lsopropyl-2,4,5,6 ,7,8-hexahydro-1,2,6-triaza-azulen-3-yi)-phenyl] 252 ethanone; 253 2-Isopropyl-3-(4-nitro-phenyD-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 256 2-Benzyl-3-(4-chloro-pheny)-2, 4,4S6,7,8-hexahydro-1,2,5-triaza-azulene; 257 2-Ethyl-3-(4-ethyl-phenyl)-2,4,5,6,7,8-hexahyd ro- 1,2,6triaza-azulene; 258 4-(2-Ethyi-2,45,6 67,8-hexahydro-1 ,2,6-riaza-azulen-3-yl)-benzonitrile; 259 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-2,5,6 ,7, 8-hexa hyd ro-1,2,6~triaza azulene; 261 2-Ethyl-3-(4-isopropyl-phenyl)-2,4A,6,7,8-hexa hyd ro- 1,2,6-triaza-a zulene; 262 2-Ethyl-3-(4-methoxy-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 263 2-Ethyl-3-(4-trifluoromethyl-phenyl)-2;45,6,7,8-hexahydro-1 ,2,6-triaza azulene; 264 2-Ethyl-3-o-tolyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 265 3-(2-Chloro-phenyl)-2-ethyl-2,4,5 ,6,7,8-hexahydro-1,2,6-triaza-azule ne; 266 2-Ethyl-3-(24 luoro-phenyl)-2 4,5,6,7,8-hexahydro-1 ,2,6-triaza-azulene; 267 3-(2,4-Dichloro-pheny)-2-isopropyl-2 ,4,5,6,7,8-hexahyd ro- 1,2,6-triaza azulene; 268 {4-(2-Ethy-2 ,45,6,7,8-hexahydro- 1,2,6-triaza-azulen-3-yI)-phenyl-dimethyl~ amine; 269 6-Benzy-3-(4-fluoro-phenyl)-2-isopropyl-2, 4,5,6,78-hexahydro-1,2,6-triaza azulene; 3-(4-Fluoro-phenyl)-2-isopropyl-6-(3-phenyl-propyl)-2,4,5,6,7,8-hexahyd ro 270 1 ,2,6-triaza-azulene; 271 3-4-Fluoro-phenyl)-2-isopropyl-6-phenethyl-2,4,5,6,7,8-hexahyd ro~- ,2,6 triaza-azulene; and 272 3-(4-Fuoro-phenyl)-2-isopropyl-4,5,7 ,8-tetrahydro-2H- 1,2,6-triaza-azulene 6-carboxylic acid tet-butyl ester. 259 274 3-(4'-Chlo r-bipheny 4-yi)-2-(2,2,2-trif luoro-ethyl)-2,4,5,6,7,8-hexahyd ro 1,2,6-triaza-azulene; 275 3-(4-Chloro-biphenyk4-yI)-2-cyclopentyk2,4 5,6,7,8-hexahyd ro-,2,6-triaza azulene; 276 2-Cyclobutyl-3-phenyl-2,4,5,6, 7 ,8-hexahydro- 1,2,6-triaza-azuI ene; 277 2-Cycdobuty-3-(4-fluoro-phenyl)-2,4,5 6,7 8-hexahydro-1,2,6-triaza-azulene; 278 2-Cyclobutyl-3-p-to lyk2,4,5,6 7,8-hexahydro-1,2,6-riaza-azulene; 2-Cyclobutyk3-(4--trifluoromethyl-phenyl)-2,4,5,6 7,8-hexahydro-1 2,6-triaza azulene; 280 4-(2-Cyclobutyl-2,4,5,6,7,8-hexahydro-1 2 ,6-triaza-azulen-3-yI)-benzonitrile 281 2-Cyclopropyk3-pheny2, 4,5,6,7,8-hexahyd ro-1,2,6-triaza-azulene; 282 2-Cyclopropyl-3-(4-tluo r-phenyl)-2,4,5,6,7 ,8-hexahydr-i, 2,6-triaza azulene; 283 2-(1 -E thylI-propyl )-3-(4-fluoro-3-methyl-phenyl)-2,4,5,6,7,8-hexahydro-1,2,6 283 triaza-azulene; 284 2-Cyclopropy1-3-p-toly-2,4, 5,6,7,8-hexahyd ro- 1,2,6-triaza-azulene; 285 2-CyclopropylV3-thiophen-3-y'-2,4,5,6,7;8-hexahydro-1,2,6-triaza-azu lene; 286 4-(2-Cyclopropy-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulen-3-yl) benzonitrle; 287 6-Benzyl-2-isopro pyl-3-pheny 1-4,5,6,7-tetra hyd ro-2 H-pyrazo lo [3,4-cpyrid ine; 288 2-isopropyV~3-phenyl-4,56,7-tetrahydro-2H-pyrazolo[3,4-o]pyridine; 289 6-Benzyl-2-isopropyl-3-thiophen-3-y-4,5,6,7-tetra hydr2H-pyrazolo[3,4 ojpyridine; 290 6-Benzyl-2-isopropyl-3-p-toly-4,5,6 ,7-tetrabydro-2H-pyrazolo[3,4-cjpyridine, 291 6-Benzyl-3-(4-fluoro-phenyl)-2-iso propyl-4, 5,6,7-tetra hyd ro-2 H-pyrazo lo [3,4 c]pyridine; 292 3-(4-Fluoro-phenyl)-2-isopropyi-4,5,6 ,7-tetrahydro-2H-pyrazolo[3,4 cjpyridine; 293 2-Iso pro pyl-3-pdtoIy-4,5,6,7-tetrahyd ro-2 H-pyrazolo[3,4-cjpyrid ine; 2 9 4 2-Cyclopentyl-3-(4-fluoro-phenyl)Y5,5 7,7-tetramethyl-2,4,5,67,8-hexahyd ro 1,2,6-triaza-azulene; 295 2-Cyclopentyl-5,5,7 ,7-tetamethyl-3-phenyl-2,4 ,5,6,7,8-hexahydero-1,2,6 triaza-azulene; 2-Iso propyl-5,5,7,7-tetra methyl-3-phenyl-2,4 ,,6,7,8-hexahydre-1,2,6-tria za 296 azueri; 260 297 3-(4-Flunra-phenyl )-2-isnpropyl-5,5,7,Y-t etra rnethyt-2 ,4,5,6,7,8-hexahydro I ,2,6-triaza-azuiene; 298 2-sec-Butyl-3--phenyl-2,4,5.,7,8-hexahydro-I ,2 ,6-triaza-azulene; 299 2-s ,ec-Buty,-3-(4-flunrn-phenyQ)-2 .4 ,5fr7,8-hexahydro-1 ,2 ,Gdriaza-azulene; 300 2-sec-Buty-3-p-toik2 14516,716 -hexahyd rn -I,2,6-triaza--azulene;, 2-sec-Buityl-3-(4drifluoror-nethyl-pheniyQ-2 ,4,5,6r7,8-hexahydro-1 ,2,6dtriaza 301 afLdene; 302 2-Gyci npentyl-3-(4-f i u oro-p hen yl )-6- me thyb-2 14,516,7 ,8-hexa hyd rn.-I1 2,6 triaza-az7ulene; 303 4i21--so pro pyl-2,4,5,617 ,8-hexahyd ro-i .2,6-triaza-azu len-3-yD)-benzarnide;, 304 2-isapropyi-3-f4z-( 1 H ,etrazoW-5-yI )-phe-nyfl-2 ,4,5,6 ,7 1 8-hexa hydra- 1,2,6 triaza-azukine; 305 6-Benzyl;-3-(4-in ora-phenyi}-2-Lsaprapyl-8-rnethyl-2 ,4,5,6,7, 8-hexa hydra 1 ,2,6-triaza-azu fie; 36 3-(4-FILuarn-pheny9'-2-isaprapyl-8-rnethyl-2 ,4,5,6,7,8Stexahyd ro-i,2 ,6-triaza azulene;' 307 3-(4-Flua ro-phenyl)-2-isapropyl-4--methyl-2,4,.5,6 .7,8-hexahiyd ra- I,2,6-tdaza azulene; 303 2-Gycoapa rdy-3-(4-fluaira-phenyl )-7-r-nethyk-2 4,5,6,7, 8-hexahyd n- 1,2,6 triaza-azulene; 309 2-Cycoapent yl-3-(4-f luara-phenyl)-5-methyk-2,4,5,6,7,8-hiexahydra-i 2,6 triaza-azulene; 310 2-Cync pentyl-7-methyl-3-pda,,lyk-2,4 5,6,7 ,8-hexa hyd ro-i ,2 ,6-iriaza-azulene; 311 2-Isoprapyl-7-rnethyl-3-phenyl-2,4,5,6 ,7,8-hexahydra-1 ,2,6-triaza-azul iene 312 2Isa prapyk-5-methyb-3-phe:.nyl-2, 4,5,6,7, 8-hexahyd in- 1,2 ,6-triaza-azule ne; 313 3-(4-FI unra-phienyl )-2-isaprapyl-7-rnethyl-'2 4,5,617 ,8-hexathydra)-1,2 ,6-tria za azulene; 314 -{(4-Fluora-phe nyl )-2-isapinapyk-5-rethy1-2,4, 5,6,7 .8-hexahyd rn-I,2 ,6-triaza azulene;, 315 2-kaoprnpy-7-methyl-3-p-talykl2,4,5,6 ,7,8-hexahnydra-1 ,2,6-Uliaza-azulene; 31 3(4-Ch lo ra-phe nyl)-2-py rid in-2 -ylrnmethyI-1IA,4,5,6 ,7,8-hexahyd rn-I ,2,6-triaza azulene; 327 3-[3-(4-Ch larn-phenyl)-5,617 ,8-tetra hyid rn-4H-l ,2 ,6-triaza-azu Ian-2-yI] pro plan itia; 328 3-(4-Chiarn-phe, iyI)-2-cyclaheptyl-2,4,5,6 ,7,8-haxahydra-i ,2 ,6-tiaza azulene; 261 329 3}(4-Chloro-pheny})2-cycooctkyl-2,4,5,6 ,7,8-hexahyd ro-1 ,2,6-triaza-azulene; 330 3-(4-Chloro-phienyl)-2-(4-methyk--cdohexy >2,4,5,6,7, 8-.hexahyd ro.-1k2 triaza-azulene; 38 3-(4-Fluoro-pheriyl>-2-isopropyl-5,7-dimethyk-2,4,5,.6,7,8-hexahydro-1 ,226 triaza-azuiene, 22. A compound selecind from the group consisting of: 214 2-Ethyl,, -3-pAil-2,4,5,6,7 ,-hexahydz-o- I,2,6-triaza.--azuLene; 257 2-Ethv1-3-{z-ethy-phenyl-2,45,6,7,8-hexahyd ro-1 ,2,6-triaza-azuiene; 23, A compound selected froni the group consisting of; EX CHEMICAL NAME. 131 3-(4-Chloro-pheniyl)-2-isobutyi-2 .4,5,6,7 .8-hexahydro-1I,2,6-triaza-aZuLtene-; 133 2-Benzyk-3-phenyl-2 4,5,6,7 ,8-he-xahiyd to-I,2,6-triaza-a-zuliene; 177 2-Qyclohexyl-3-phenyl-2, 4,5,6,7, 8-hexa hydro-i ,2,6-triaza-azulenie; 183-(4-Ch lo ro-phenyi)-2-cyclohexy[-2,4 25,6,7 ,8-hiexa hyd to- 1,2.6-trilaza azuilene; 1813-(4-Chioro-phenyi)-2-cyclopenityl-2,4 .5,6,7, 8-hexa hydro-1 ,2, 6-triaza azuiene: 182 2-Cyclo pantyl-3-(4-f luoro-p henyl)-2,4,5 ,6,7, 8-hexahyd ro-1 ,2 ,6-triaza azulene; 183 219 -Ethyl-propyl)-31(3-fluoro--phe. yI)-2 .4,5,6,7,8-hexahyd to-I,2 ,6-triaza azulene; 14 2-(t Ethyk-propyQ-3-44iuoro-phienylj-2,4,5,6,7 ,3-hexahydro-1 .2,6-triaza azu lane; 186 2-(iSEthyl-propyl) -3-pheny[-2,4,5,6,7,8-hexahyd to-i ,2,6C-triaza-azulene; 191,2-(lI -Ethyl-pro pyl)-3-th iophen-2-yl-2 24,.5,6,7 ,8-hexahydto-I ,2 ,6-triaza azu lane; 215 2-teri-Butyl-3-phenyl-2 ,4,5,6,7,3-hexahyd to-1I,2,6-triaza-azulene:. 216 2-tert-Bu yl-3-(4-fluoro-pheny,-2 ,4,5,6,7 .8-hexahydro-i ,2 ,6-triaza-azuilene-; 217 2-Cyciopentyk-3-p-tolyl-2,4,,5,6 ,7 ,8-hexahydro-1 ,2,6-tria3za-azulen.e; 218 2yclopentyl-3-(4-trifluoromethyl-phenyl)-2,4,5,6,7 ,8-hexahydiro-1 ,2 ,6 triaza-azulene; 220 2-Cyclopentyk--(4-methoxy-phenyl)-2,4 ,5,6,7, 8-hexab yd ro-i,2,6-tnaza azulene; 262 2-Cyclopentyl-3-(3;4-d if iuo ro-phenyl)-2 A,5 ,6 ,7, 8-hexahydro-1,2,6-triaza 236 azulene; 238 3-(4-Chloro-phenyl)-2-cyclobutyl-2,45,6,7,8-hexahydro-1 2 26-triaza azulene; 3-(3-Chloro-4-fluoro-phenyl)-2-cyclopentyl-2 ,4, 5,6,7, 8-hexahydro-1,2,6 241 triaza-azulene; 2-Isopropyi-3-(4-methoxy-phenyl)-2 ,4, 5,6,7 ,8-hexahydro-1,2,6-triaza 242 azulene; 277 2-Cyclobutyk3-(4-fluora-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-iexahydroa-1,2,6-triaza-azulene; 2-Cyclobutyl-3-(4-triffu romethylkphenyl)-2 4 ,5,6,7,8-hexahydro-1,2,6 279 triaza-azulene; 284 2-Cyclopropyl-3-p-tolyV2,4,5,6,7,8-hexahydr-1 2 ,6-triaza-azulene; 300 2-sec-ButyL3-p-toly-2 ,4,5,6,7,8-hexahyd ro-i1,2,6-triaza-azulene; 2-Cyclopentyi-3-(4-fluoro-phenyl)-6-methyl-2,4,5,6,7,8-hexahydro-1,2,6 302 triaza-azulene; 3-(4-Fluoro-phenyi)~2-isopropyl-8-methyl-2 ,4,5,6,7,8-hexahydro-1,2 6 306 triaza-azulene; 310 2-Cycopentyl-7-methyl-3-p-tolyli-2 ,4, ,6,7, 8-hexahydr-1 ,2 ,6-triaza azulene; 24. A compound selected from the group consisting of: EX CHEMICAL NAME 64 3-(4-Chloro-phenyl)-2-ethyi-2,4,5,6,7,8-hexahydro-1,2 ,6-triaza-azulene; 180 2-Cyclopentyl-3-phenyk2,4,5,6 .7,8-hexahydro-1,2,6-triaza-azulene; 3-(4-FIuoro-phenIyl)-2-isopropyl-2,4,5,6,7, 8-hexahydro-1;2,6-friaza 190 azulene: 192 2-Cyclopentyi-3-thiophen-3-y-2,4,5,67,8-hexahydro-1, 2,6-triaza-azulene; 209 2-Isopropyl-3-p-toiyI-2,4,5,6,7,8-hexahydro- ,2 ,6-triaza-azulene; 210 3-(4-Ethyl-phenyl)-2-isopropyi-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 3-(4-Chlor-phenyl)-2-isopropy-2,4,5,6,7,8-hexahydro-1 2,6-triaza 211 azulene; 212 4-(2-lsopropyl-2 ,4,5,6,7,8-hexahydro- ,2,6-triaza-azulen-3-yi)-benzonitrile 213 2-Isapropyl-3-(4-trifluoromethykpheny)-2,4,5oQ7,8-hexaehydro-I,2,6-triaza azulene; 263 232 2-Cyclopentyk3-fu ran-3-yl2,45,6,7,8-hexa hydro- 1,2,6-triaza-azu lene; 233 2-Cyclopentyl-3-thiophen-2-y-2;4s5,6,7 ,8-hexahydro-1,2,6-triaza-azulene; 284 2-Cyclopropyl3-p-tolyk2,4,5,67,8-hexahydro- 1,2,6-triaza-azulene 300 2-sec-Butyl-3-p-toly-2 4,5,6,7,8-hexahydro-1,2,6-triaza-azu lene; 315 2-lsopropyl-7-methy-3-p-tolyl~2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene; 25. A compound selected from the group consisting of: 182 2-Cyclopentyl-3-(4-fluoro-phenyl)-2,4,5,67 ,8-hexahydro-1,2,6-triaza azulene and pharmaceutically acceptable salt thereof, 26. A compound selected from the group consisting of: 190 3-(4- Fluoro-phenyl)-2-isopropyl-2 4,5,67 ,8-hexahyd ro-1 ,2 6-triaza-azulene and a pharmaceutically acceptable salt thereof. 5 27, A compound according to claim 1, wherein said pharmaceutically acceptable salt is an effective amino addition salt. 28. The compound of to claim 1, wherein said pharmaceutically acceptable salt is 10 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 laurylsulfonae. 15 29, A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of compound according to any one of claims 1 to 28. 30. A compound according to any one of claims 1 to 28 for the treatment or prevention of a CNS disorder selected from the group consisting of: sleep disorders, 20 depression/anxiety, generalized anxiety disorder, schizophrenia, bipolar disorders, psychotic disorders, obsessive-compulsive disorder, mood disorders, post-traumatic stress and other stress-related disorders, migraine, pair, eating disorders, obesity, sexual dysfunction, metabolic disturbances, hormonal imbalance, alcohol abuse, addictive disorders, nausea, inflammation, centrally mediated hypertension, sleep/wake 25 disturbances, jetlag, and circadian rhythm abnormalities in mammals. 264 31. A compound according to claim 30 wherein said CNS disorder is selected from the group consisting of: depressionlanxiety, sleep disorders, and circadian rhythm abnormalities. 32. A compound according to any one of claims i to 28 for the treatment or 5 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, 10 33. A compound according to any one of claims 1 to 28 for the treatment or prevention of an ocular disorder selected from the group consisting of: glaucoma, optical neuritis, diabetic retinopathy, retinal edema, and age-related macular degeneration in mammals. 34. A compound according to any one of claims 1 to 28 for the treatment or 15 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, 35. A compound according to any one of claims 1 to 28 for the treatment or prevention of a disease or condition selected from the group consisting of: 20 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, additive disorders, and peripheral vascular disorders in mammals. 36 A compound of any one of claims 1 to 28 isotopically-labelied to be detectable 25 by PET or SPECT. 37. A method for studying serotonin-mediated disorders comprising the step of using an 1 F-labeled or "C-labelled compound of any one of claims 1 to 28 as a positron emission tomography (PET) molecular probe. 38. Use of a compound according to any one of claims 1 to 28 for the treatment or 30 prevention of a CNS disorder selected from the group consisting of: sleep disorders, 265 depressionanxiety, 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, 5 addictive disorders, nausea, inflammation, centrally mediated hypertension, sleep/wake disturbances, jetlag, and circadian rhythm abnormalities in mammals. 39. Use of a compound according to any one of claims I to 28 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, 10 diarrhea, spastic colon, irritable bowel disorders, ischemias, septic shock, urinary incontinence, and other disorders related to the gastrointestinal and vascular systems in mammals. 40. Use of a compound according to any one of claims 1 to 28 for the treatment or prevention of an ocular disorder selected from the group consisting of: glaucoma, optic 15 neuritis, diabetic retinopathy, retinal edema, and age-related macular degeneration in mammals. 41. Use of a compound according to any one of claims 1 to 28 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, 20 gastric motility, and irritable bowel disorders in mammals. 42. Use of a compound according to any one of claims 1 to 28 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 25 stress disorders, sleep disturbances, sexual dysfunction, eating disorders, migraine, addictive disorders, and peripheral vascular disorders in mammals, 43. A method of 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, 30 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 266 hypertension, sleep/wake disturbances, jetlag, and circadian rhythm abnormalities comprising administering to a mammal in need thereof a compound according to any one of claims I to 28, 44. A method of treatment or prevention of a disease or condition selected from the 5 group consisting of: hypotension, peripheral vascular disorders, cardiovascular shock, renal disorders, gastric motility, diarrhea, spastic colon, irritable bowel disorders, ischernias, septic shock, urinary incontinence, and other disorders related to the gastrointestinal and vascular systems comprising administering to a mammal in need thereof a compound according to any one of claims 1 to 28. 10 45. A method of 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 comprising administering to a mammal in need thereof a compound according to any one of claims 1 to 28. 46 A method of treatment or prevention of a disease or condition selected from te 15 group consisting of: depression/anxiety, sleep/wake disturbances, jetlag, migraine, urinary incontinence, gastric motility, and irritable bowel disorders in mammals comprising administering to a mammal in need thereof a compound according to any one of claims I to 28. 47 A method of treatment or prevention of a disease or condition selected from the 20 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 comprising administering to a mammal in need thereof a compound according to any one of claims 25 1 to 28, 48. A compound having serotonin receptor modulating activity of formula (l); A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound having serotonin receptor modulating activity of formula (Ilj); A cornpound according to any one of claims 30 to 35; A method 30 for studying serotonin-mediated disorders using an ' 8 F-labeled or "C-labelled compound of formula (1ll); Use of a compound having serotonin receptor modulating activity of formula (li) or a method according to any one of claims 43 to 47 substantially 267 as herein described with reference to any one of the embodiments of the invention illustrated in the accompanying examples. 268