Details for Patent: 7,217,714

Title:	CCR5 modulators
Abstract:	Compounds of Formula 1 [R.sub.egion .alpha.]-[R.sub.egion .beta.]-[R.sub.egion .gamma.]-[R.sub.egion .delta.] (I) which are useful as modulators of chemokine activity. The invention also provides pharmaceutical formulations and methods of treatment using these compounds.
Inventor(s):	Armour; Duncan Robert (Ramsgate, GB), Price; David Anthony (Ringwould Deal, GB), Stammen; Blanda Luzia Christa (Sandwich, GB), Wood; Anthony (Margate, GB), Perros; Manoussos (Ramsgate, GB), Edwards; Martin Paul (Ringwould Deal, GB)
Assignee:	Agouron Pharmaceuticals, Inc. (San Diego, CA)
Filing Date:	Nov 30, 1999
Application Number:	09/451,826
Claims:	1. A compound of the formula [Region .alpha.]-[Region .beta.]-[Region .gamma.]-[Region .delta.] or a pharmaceutically acceptable salt thereof, wherein [Region .alpha.] is a moiety of the formula ##STR00303## wherein the symbol `*` indicates the point of attachment of [Region .alpha.] to [Region .beta.]; R.sup.4 is H or C.sub.1 C.sub.2alkyl; R.sup.6 is H, C.sub.1 C.sub.2 alkyl, C.sub.1 C.sub.2 alkoxy, --CN, --OH, or --CONH.sub.2; A is phenyl optionally substituted by up, to 4 substituents independently selected from fluoro, chloro, --CO.sub.2R.sup.4, --OH, --CN, --CONR.sup.4.sub.aR.sup.4.sub.b, --NR.sup.4.sub.aR.sup.4.sub.b, --NR.sup.4.sub.aCOR.sup.4.sub.b, --NR.sup.4.sub.aCO.sub.2R.sup.4.sub.b, --NR.sup.4.sub.aS(O).sub.pR.sup.4.sub.b, --S(O).sub.pNR.sup.4.sub.aR.sup.4.sub.b, C.sub.1 C.sub.4 alkyl, C.sub.1 C.sub.4 alkoxy, C.sub.1 C.sub.2 alkoxycarbonyl, C.sub.1 C.sub.2 alkylcarbonyl and C.sub.1 C.sub.2 alkylcarbonyloxy, said C.sub.1 C.sub.4 alkyl and C.sub.1 C.sub.4 alkoxy being optionally substituted by up to 3 substituents independently selected from fluoro and chloro; p is 0, 1 or 2; R.sup.4.sub.a and R.sup.4.sub.b are each independently H or C.sub.1 C.sub.2 alkyl; R.sup.27 is: (i) C.sub.1 C.sub.6 alkyl, C.sub.2 C.sub.6alkenyl or C.sub.2 C.sub.6 alkynyl, each optionally substituted by up to 3 substituents R.sup.28; or (ii) --(CH.sub.2).sub.n--(C.sub.3 C.sub.7 cycloalkyl), wherein (a) said C.sub.3 C.sub.7 cycloalkyl is optionally substituted by up to 3 substituents R.sup.28; and (b) n is 0, 1 or 2, wherein: (1) where n is 0, the .alpha.-carbon of said C.sub.3 C.sub.7 cycloalkyl is optionally substituted by one substituent selected from C.sub.1 C.sub.4 alkyl and phenyl, wherein said C.sub.1 C.sub.4 alkyl and phenyl are optionally substituted by 1 or 2 substituents selected from --CH.sub.3, --OCH.sub.3, --OH and --NH.sub.2; and (2) where n is 1 or 2, the resulting methylene or ethylene is optionally substituted by 1 substituent selected from fluoro, --NH.sub.2, --N(CH.sub.3).sub.2, --OH, --OCH.sub.3, C.sub.1 C.sub.4 alkyl and phenyl, wherein said C.sub.1 C.sub.4 alkyl and phenyl are optionally substituted by 1 or 2 substituents selected from --CH.sub.3, --OCH.sub.3, --OH and --NH.sub.2; or (iii), phenyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl), thienyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrazinyl, pyridazinyl, piperazinyl, pyrimidinyl, pyranyl, -azetidinyl, morpholinyl, parathiazinyl, indolyl, indolinyl, benzofuranyl 2,3-dihydrobenzofuranyl, benzothienyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl or quinoxalinyl, each optionally substituted: (a) on any one or more carbon atoms by up to 3 substituents R.sup.28; or (b) on any one or more nitrogen atoms that is not a point of attachment of said heterocyclic moiety by up to 3 substituents R.sup.13.sub.b; or (c) on any sulphur atom that is not a point of attachment of said heterocyclic moiety by up to 2 oxygen atoms; R.sup.28 is phenyl, fluoro, chloro, oxo, --OH, C.sub.1 C.sub.2 alkyl, C.sub.1 C.sub.3 alkoxy, --CO.sub.2R.sup.29, --CO(C.sub.1 C.sub.4)alkyl, --SO.sub.2(C.sub.1 C.sub.4)alkyl, --CONR.sup.29R.sup.30, --NR.sup.29R.sup.30, --NR.sup.29COR.sup.30, --NR.sup.29CO.sub.2R.sup.30, --NR.sup.29S(O).sub.pR.sup.30 or --SO.sub.2NR.sup.29R.sup.30; R.sup.29 and R.sup.30 are each independently H or C.sub.1 C.sub.4 alkyl optionally substituted by up to 3 substituents selected from fluoro and chloro; R.sup.13.sub.b is H, C.sub.1 C.sub.4 alkyl, C.sub.2 C.sub.4 alkenyl, C.sub.1 C.sub.2 alkoxy, C.sub.3 C.sub.7 cycloalkyl, --CO(C.sub.1 C.sub.4)alkyl, --SO.sub.2(C.sub.1 C.sub.4)alkyl or phenyl, wherein said C.sub.1 C.sub.4 alkyl, C.sub.2 C.sub.4 alkenyl, C.sub.1 C.sub.2alkoxy, C.sub.3 C.sub.7cycloalkyl and phenyl are optionally substituted by up to 2 substituents R.sup.11; R.sup.11 is fluoro, chloro, --CO.sub.2R.sup.4, --OH, --CN, --CONR.sup.4.sub.aR.sup.4.sub.b, --NR.sup.4.sub.aR.sup.4.sub.b, --NR.sup.4.sub.aCOR.sup.4.sub.b, --NR.sup.4.sub.aCO.sub.2R.sup.4.sub.b, --NR.sup.4.sub.aS(O).sub.pR.sup.4.sub.b, --S(O).sub.pNR.sup.4.sub.aR.sup.4.sub.b, C.sub.1 C.sub.4 alkyl including dimethyl, C.sub.1 C.sub.4 alkoxy, C.sub.1 C.sub.2 alkoxycarbonyl, C.sub.1 C.sub.2 alkylcarbonyl or C.sub.1 C.sub.2 alkylcarbonyloxy, wherein said C.sub.1 C.sub.4 alkyl and C.sub.1 C.sub.4 alkoxy are each optionally substituted by up to 3; substituents independently selected from fluoro and chloro; [Region .beta.] is an alkyl bridging element of partial formula ##STR00304## wherein the symbol `*` indicates the point of attachment of [Region .beta.] to [Region .alpha.] and the symbol `.fwdarw.` indicates the point of attachment of [Region .beta.] to [Region .gamma.]; R.sup.40 and R.sup.41 are both H, C.sub.1 C.sub.2 alkyl including dimethyl, --OH, or C.sub.1 C.sub.3 alkoxy; [Region .gamma.] is piperidine being linked to [Region .delta.] through the ring nitrogen atom and each being linked to [Region .delta.] through any ring carbon atom, wherein said, piperidine is optionally substituted on a ring carbon atom by one substituent selected from C.sub.1 C.sub.4 alkyl including dimethyl, C.sub.3 C.sub.6 cycloalkyl, C.sub.1 C.sub.4 alkoxy, (C.sub.1 C.sub.2) alkoxy(C.sub.1 C.sub.2)alkyl, --CF.sub.3, --CO.sub.2R.sup.4, oxo, --OH, --CN, --CONR.sup.4.sub.aR.sup.4.sub.b, --NR.sup.4.sub.aR.sup.4.sub.b, --NR.sup.4.sub.aCOR.sup.4.sub.b, --NR.sup.4.sub.aCO.sub.2R.sup.4.sub.b, --NR.sup.4.sub.aS(O).sub.pR.sup.4.sub.b, --S(O).sub.pNR.sup.4.sub.aR.sup.4.sub.b, (C.sub.1 C.sub.2)alkyloxycarbonyl, (C.sub.1 C.sub.2)alkylcarbonyl, (C.sub.1 C.sub.2)alkylcarbonyloxy and optionally substituted on the ring nitrogen atom by substituent R.sup.46; R.sup.46 is H, C.sub.1 C.sub.4 alkyl or O, wherein said C.sub.1 C.sub.4 alkyl is optionally substituted by 1 substituent selected from C.sub.1 C.sub.2 alkoxy and --CO.sub.2R.sup.4; [R.sub.egion .delta.] is a (substituted)-heterocyclyl moiety selected from the group consisting of: (i) a heterocyclyl moiety of partial Formula (5.3.0): ##STR00305## wherein the symbol `*` indicates the point of attachment of partial Formula (5.3.0) to [R.sub.egion .gamma.] and wherein Q is N, O or S; and wherein partial Formula (5.3.0) is: is a member of the group consisting of triazoyl and oxadiazolyl, R.sup.90.sub.a and R.sup.90.sub.b are each a member independently selected from the group consisting of hydrogen, --(C.sub.1-C.sub.2)alkylcarbonyl, --(C.sub.1-C.sub.4)alkyl, --(CH.sub.2).sub.n-(C.sub.3-C.sub.7)cycloalkyl, --(C.sub.2-C.sub.3)alkenyl --(CH.sub.2).sub.n-(phenyl), and --(CH.sub.2).sub.n-(HET.sub.1), where n is an integer independently selected from 0, 1, and 2; wherein said (C.sub.1-C.sub.4)alkyl, alkenyl, cycloalkyl, phenyl, and HET.sub.1 groups are independently substituted with 0 to 3 substituents R.sup.91, where: j is 0, 1 or 2; HET.sub.1 is a heterocyclyl group selected from thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, parathiazinyl, and morpholinyl, where: R.sup.91 is selected from --F, --Cl, --CO.sub.2R.sup.4, -oxo, --OH, --C--N, --CONR.sup.93R.sup.94, --NR.sup.93R.sup.94, C(.dbd.O)(C.sub.1 C.sub.4)alkyl, --NR.sup.93C(.dbd.O)R.sup.94, --NR.sup.93C(.dbd.O)OR.sup.94, --NR.sup.93S(.dbd.O)R.sup.94, --S(.dbd.O)NR.sup.93R.sup.94, (C.sub.1-C.sub.4)alkyl, and (C.sub.1-C.sub.4)alkoxy, wherein said alkyl and alkoxy are each independently substituted with 0 to 3 substituents independently selected from F, Cl, (C.sub.1-C.sub.2)alkoxycarbonyl, (C.sub.1-C.sub.2)alkylcarbonyl, and (C.sub.1-C.sub.2)alkylcarbonyloxy; R.sup.93 and R.sup.94 are each a member independently selected from H and (C.sub.1-C.sub.2)alkyl; and (ii) a heterocyclyl moiety of partial Formula ##STR00306## wherein Q is N, O or S. 2. A compound according to claim 1, wherein R.sup.6 is H. 3. A compound according to claim 1, wherein A is phenyl. 4. A compound according to claim 1, wherein R.sup.27 is methyl, ethyl, isopropyl, tert-butyl or alkyl, each optionally substituted by one substituent selected from fluoro, chloro, --OH, --CF.sub.3, methyl, methoxy, --CN, --NH.sub.2, --NH(CH.sub.3), --N(CH.sub.3).sub.2, --NHCOCH.sub.3, and --N(CH.sub.3)COCH.sub.3. 5. A compound according to claim 1, wherein R.sup.27 is substituted or unsubstituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylethyl, cyclopentylpropylmethyl or cyclopentylmethyl. 6. A compound according to claim 1, wherein R.sup.27 is tetrahydropyranyl, oxetanyl, azetidinyl or tetrahydrofuranyl, each optionally substituted by up to three substituents R.sup.28. 7. A compound according to claim 1, wherein [Region .beta.] is unsubstituted ethylene. 8. A compound according to claim 1, wherein R.sup.46 is absent. 9. A compound according to claim 1, wherein the heterocycle constituting [Region .gamma.] is unsubstituted on any ring carbon atom. 10. A compound according to claim 1, wherein [Region .delta.] is selected from: ##STR00307## wherein the symbol `*` indicates the point of attachment to [Region .gamma.]. 11. A compound according to claim 1, wherein [Region .delta.] is selected from: ##STR00308## wherein the symbol `*` indicates the point of attachment to Region .gamma.. 12. A compound according to claim 1, which is selected from: N-{(1S)-3-[4-(3-Benzyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]-1-phenylpropy- l}cyclobutanecarboxamide; N-{1-Phenyl-3-[4-(4H-1,2,4-triazol-4-yl)-1-piperidinyl]-1-phenylpropyl}cy- clobutanecarboxamide; N-{3-[4-(1-Methyl-1H-1,2,4-triazol-5-yl)-1-piperidinyl]-1-phenylpropyl}cy- clobutanecarboxamide; N-{3-[4-(1-Methyl-1H-1,2,4-triazol-3-yl)-1-piperidinyl]-1-phenylpropyl}cy- clobutanecarboxamide; N-{3-[4-(3,5-Dimethyl-4H-1,2,4-triazol-4-yl)-1-piperidinyl]-1-phenylpropy- l}cyclobutanecarboxamide; N-{1-Phenyl-3-[4-(3-methyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]propyl}cyc- lobutanecarboxamide; N-{1-Phenyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]propyl}cyc- lobutanecarboxamide; N-{3-[4-(3-Benzyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]-1-phenylpropyl}cyc- lobutanecarboxamide; N-(3-{4-[3-(4-Methoxyphenyl)-1,2,4-oxadiazol-5-yl]-1-piperidinyl}-1-pheny- lpropyl)cyclobutanecarboxamide; N-{3-[4-(5-Methyl-1,2,4-oxadiazol-3-yl)-1-piperidinyl]-1-phenylpropyl}cyc- lobutanecarboxamide, N-{1-Phenyl-3-[4-(5-phenyl-1,2,4-oxadiazol-3-yl)-1-piperidinyl]propyl}cyc- lobutanecarboxamide; N-{3-[4-(5-Benzyl-1,2,4-oxadiazol-3-yl)-1-piperidinyl]-1-phenylpropyl}cyc- lobutanecarboxamide; N-{3-[4-(5-Methyl-1,3,4-oxadiazol-2-yl)-1-piperidinyl]-1-phenylpropyl}cyc- lobutanecarboxamide; N-{1-Phenyl-3-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)-1-piperidinyl]propyl}cyc- lobutanecarboxamide; N-{3-[4-(5-Benzyl-1,3,4-oxadiazol-2-yl)-1-piperidinyl]-1-phenylpropyl}cyc- lobutanecarboxamide; N-[(1S)-3-[4-(3-Benzyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]-1-(3-fluoroph- enyl)propyl]-2-cyclopropylacetamide; N-((1S)-3-{4-[3-(4-Methylbenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidinyl}-1-p- henylpropyl)cyclobutanecarboxamide; N-((1S)-3-{4-[3-(4-Trifluoromethylbenzyl)-1,2,4-oxadiazol-5-yl]-1-piperid- inyl}-1-phenylpropyl)cyclobutanecarboxamide; N-((1S)-3-{4-[3-(1,3-Benzodioxol-5-ylmethyl)-1,2,4-oxadiazol-5-yl]-1-pipe- ridinyl}-1-phenylpropyl)cyclobutanecarboxamide; N-((1S)-3-{4-[3-(3,5-Difluorobenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidinyl}- -1-phenylpropyl)cyclobutanecarboxamide; N-[(1S)-3-[4-(3-Benzyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]-1-(3-fluoroph- enyl)propyl]cyclobutanecarboxamide; N-{(1S)-3-[4-(3-{4-[(Methylsulfonyl)amino]benzyl}-1,2,4-oxadiazol-5-yl)-1- -piperidinyl]-1-phenylpropyl)cyclobutanecarboxamide; 4-{[5-(1-{(3S)-3-[(Cyclobutylcarbonyl)amino]-3-phenylpropyl}-4-piperidiny- l)-1,2,4-oxadiazol-3-yl]methyl}benzamide; N-((1S)-3-{4-[3-(2,5-Difluorobenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidinyl}- -1-phenylpropyl)cyclobutanecarboxamide; N-((1S)-3-{4-[3-(2,6-Difluorobenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidinyl}- -1-phenylpropyl)cyclobutanecarboxamide; N-((1S)-1-Phenyl-3-{4-[3-(3-pyridinylmethyl)-1,2,4-oxadiazol-5-yl]-1-pipe- ridinyl]propyl)cyclobutanecarboxamide; N-((1S)-1-Phenyl-3-{4-[3-(4-pyridinylmethyl)-1,2,4-oxadiazol-5-yl]-1-pipe- ridinyl}propyl)cyclobutanecarboxamide; N-{(1S)-3-[4-(3-{2-[(Methylsulfonyl)amino]benzyl}-1,2,4-oxadiazol-5-yl)-1- -piperidinyl]-1-phenylpropyl}cyclobutanecarboxamide; N-((1S)-1-Phenyl-3-{4-[3-(2-pyridinylmethyl)-1,2,4-oxadiazol-5-yl]-1-pipe- ridinyl}propyl)cyclobutanecarboxamide; N-(1S)-3-[4-(3-Isobutyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]-1-phenylprop- yl}cyclobutanecarboxamide; N-((1S)-3-{4-[3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidinyl}-1-p- henylpropyl)cyclobutanecarboxamide; N-((1S)-3-{4-[3-(1-Benzofuran-5-ylmethyl)-1,2,4-oxadiazol-5-yl]-1-piperid- inyl}-1-phenylpropyl)cyclobutanecarboxamide; N-[(1S)-1-Phenyl-3-(4-{3-[4-(trifluoromethoxy)benzyl]-1,2,4-oxadiazol-5-y- l}-1-piperidinyl)propyl]cyclobutanecarboxamide; N-{(1S)-3-[4-(3-{3-[(Methylsulfonyl)amino]benzyl}-1,2,4-oxadiazol-5-yl)-1- -piperidinyl]-1-phenylpropyl}cyclobutanecarboxamide; 3,3,3-Trifluoro-N-{(1S)-3-[4-(3-{4-[(methylsulfonyl)amino]benzyl}-1,2,4-o- xadiazol-5-yl)-1-piperidinyl]-1-phenylpropyl}propanamide; 2-Cyclopropyl-N-{(1S)-3-[4-(3-{4-[(methylsulfonyl)amino]benzyl}-1,2,4-oxa- diazol-5-yl)-1-piperidinyl]-1-phenylpropyl}acetamide; N-{(1S)-3-[4-(3-{4-[(Methylsulfonyl)amino]benzyl}-1,2,4-oxadiazol-5-yl)-1- -piperidinyl]-1-phenylpropyl}tetrahydro-2H-pyran-4-carboxamide; 1-Acetyl-N-{(1S)-3-[4-(3-{4-[(methylsulfonyl)amino]benzyl}-1,2,4-oxadiazo- l-5-yl)-1-piperidinyl]-1-phenylpropyl}-3-azetidinecarboxamide; N-{(1S)-3-[4-(3-Benzyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]-1-phenylpropy- l}tetrahydro-2H-pyran-4-carboxamide; 1-Acetyl-N-{(1S)-3-[4-(3-benzyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]-1-ph- enylpropyl}-3-azetidinecarboxamide; 1-(Acetylamino)-N-{(1S)-3-[4-(3-benzyl-1,2,4-oxadiazol-5-yl)-1-piperidiny- l]-1-phenylpropyl}cyclopentanecarboxamide; N-{(1S)-3-[4-(3-Benzyl-1,2,4-oxadiazol-5-yl)-1-piperidinyl]-1-phenylpropy- l}-1-methoxycyclobutanecarboxamide; 3-{[5-(1-(3S)-3-[(Cyclobutylcarbonyl)amino]-3-phenylpropyl}4-piperidinyl)- -1,2,4-oxadiazol-3-yl]methyl}benzamide; Ethyl 4-(3-benzyl-1,2,4-oxadiazol-5-yl)-1-((3S)-3-[(cyclobutylcarbonyl)amino]-3- -phenylpropyl}-4-piperidinecarboxylate; N-{(1S)-3-[4-(3-Benzyl-1,2,4-oxadiazol-5-yl).sub.4-cyano-1-piperidinyl]-1- -phenylpropyl}cyclobutanecarboxamide; N-[(1S)-3-[4-3-[3-(Aminosulfonyl)benzyl]-1,2,4-oxadiazol-5-yl}-1-piperidi- nyl)-1-phenylpropyl]cyclobutanecarboxamide; 1-{(3S)-3-[(Cyclobutylcarbonyl)amino]-3-phenylpropyl}-4-[3-(4-fluorobenzy- l)-1,2,4-oxadiazol-5-yl]-N-methyl-4-piperidinecarboxamide; N-((1S)-3-{4-[3-(4-Fluorobenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidinyl}-1-p- henylpropyl)tetrahydro-2H-pyran-4-carboxamide; 3,3,3-Trifluoro-N-((1S)-3-{4-[3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl]-1-- piperidinyl}-1-phenylpropyl)propanamide; N-((1S)-3-{4-[3-(4-Morpholinylmethyl)-1,2,4-oxadiazol-5-yl]-1-piperidinyl- }-1-phenylpropyl)cyclobutanecarboxamide; N-((1S)-3-{4-Cyano-4-[3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidi- nyl}-1-phenylpropyl)tetrahydro-2H-pyran-4-carboxamide; N-((1S)-3-{4-Cyano-4-[3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidi- nyl}-1-phenylpropyl)-2-cyclopropylacetamide; 1-Acetyl-N-((1S)-3-{4-cyano-4-[3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl]-1- -piperidinyl}-1-phenylpropyl)-3-azetidinecarboxamide; N-((1S)-3-{4-Cyano-4-[3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl]-1-piperidi- nyl}-1-phenylpropyl)-3,3,3-trifluoropropanamide; N-[(1S)-3-(4-{3-[4-(Aminosulfonyl)benzyl]-1,2,4-oxadiazol-5-yl}I---piperi- dinyl)-1-phenylpropyl]cyclobutanecarboxamide; N-{(1S)-3-[3-Benzyl-1,2,4-oxadiazol-5-yl)-1-azetidinyl]-1-phenylpropyl}te- trahydro-3-furancarboxamide; N-[(1S)-3-(4-{3-[(4-Acetyl-1-piperazinyl)methyl]-1,2,4-oxadiazol-5-yl}-1-- piperidinyl)-1-phenylpropyl]cyclobutanecarboxamide; N-{(1S)-3-[3-Benzyl-1,2,4-oxadiazol-5-yl)-1-azetidinyl]-1-phenylpropyl}te- trahydro-3-furancarboxamide; N-{(1S)-3-[4-[3-(4-Fluorobenzyl)-1,2,4-oxadiazol-5-yl]4-(methoxymethyl)-1- -piperidinyl]-1-phenylpropyl}acetamide; N-{3-[4-(3-Methyl-5-phenyl-4H-1,2,4-triazol-4-yl)-1-piperidinyl]-1-phenyl- propyl}cyclobutanecarboxamide; N-{(1S)-3-[4-(3-Benzyl-5-methyl-4H-1,2,4-triazol-4-yl)-1-piperidinyl]-1-p- henylpropyl}cyclobutanecarboxamide; N-{(1S)-3-[4-(5-Benzyl-4-methyl-4H-1,2,4-triazol-3-yl)-1-piperidinyl]-1-p- henylpropyl}cyclobutanecarboxamide; N-{(1S)-3-[4-(3-Benzyl-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-phenylprop- yl)-cyclobutanecarboxamide; N-{(1S)-3-[4-(5-Benzyl-1-methyl-1H-1,2,4-triazol-3-yl)-1-piperidinyl]-1-p- henylpropyl}cyclobutanecarboxamide; N-{3-[4-(5-Benzyl-1H-1,2,4-triazol-3-yl)-1-piperidinyl]-1-phenylpropyl}cy- clobutanecarboxamide; N-{(1S)-3-[4-(3-{4-[(methylsulfonyl)amino]benzyl}-1H-1,2,4-triazol-1-yl)-- 1-piperidinyl]-1-phenylpropyl}tetrahydro-2H-pyran-4-carboxamide; 2-Cyclopropyl-N-{(1S)-3-[4-(3-{4-[(methylsulfonyl)amino]benzyl}-1H-1,2,4-- triazol-1-yl)-1-piperidinyl]-1-phenylpropyl}acetamide; 3,3,3-Trifluoro-N-{(1S)-3-[4-(3-{4-[(methylsulfonyl)amino]benzyl}-1H-1,2,- 4-triazol-1-yl)-1-piperidinyl]-1-phenylpropyl}propanamide; N-(1S)-{3-[4-(3-Benzyl-1-methyl-1H-1,2,4-triazol-5-yl)-1-piperidinyl]-1-p- henylpropyl}cyclobutanecarboxamide; 4-{[1-(1-{(3S)-3-Phenyl-3-[(3,3,3-trifluoropropanoyl)amino]propyl}4-piper- idinyl)-1H-1,2,4-triazol-3-yl]methyl}benzamide; N-(1S)-3-[4-(3-Benzyl-5-methyl-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-ph- enylpropyl}tetrahydro-2H-pyran-4-carboxamide; N-{(1S)-3-[4-(3-Benzyl-5-methyl-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-p- henylpropyl}tetrahydro-3-furancarboxamide; 1-Amino-N-{(1S)-3-[4-(3-benzyl-5-methyl-1H-1,2,4-triazol-1-yl)-1-piperidi- nyl]-1-phenylpropyl}cyclopentanecarboxamide; N-{(1S)-3-[4-(3-Benzyl-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-phenylprop- yl}tetrahydro-3-furancarboxamide; N-{(1S)-3-[4-(3-Benzyl-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-phenylprop- yl}tetrahydro-2H-pyran-4-carboxamide; 1-Amino-N-{(1S)-3-[4-(3-benzyl-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-ph- enylpropyl}cyclopentanecarboxamide; 1-Acetyl-N-{(1S)-3-[4-(3-benzyl-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-p- henylpropyl}-3-azetidinecarboxamide; N-{(1S)-3-[4-(3-Benzyl-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-phenylprop- yl}-1-propionyl-3-azetidinecarboxamide; 1-Acetyl-N-{(1S)-3-[4-(3-benzyl-5-methyl-1H-1,2,4-triazol-1-yl)-1-piperid- inyl]-1-phenylpropyl}-3-azetidinecarboxamide; N-{(1S)-3-[4-(3-(4-Fluorobenzyl)-1H-1,2,4-triazol-1-yl)-1-piperidinyl]-1-- phenylpropyl}-1-propionyl-3-azetidinecarboxamide; 1-Acetyl-N-{(1S)-3-[4-(3-(4-fluorobenzyl)-1H-1,2,4-triazol-1-yl)-1-piperi- dinyl]-1-phenylpropyl}-3-azetidinecarboxamide; 2-Methoxy-N-{(1S)-3-[4-(3-(4-fluorobenzyl)-1H-1,2,4-triazol-1-yl)-1-piper- idinyl]-1-phenylpropyl}acetamide; and 3-Methoxy-N-{(1S)-3-[4-(3-(4-fluorobenzyl)-1H-1,2,4-triazol-1-yl)-1-piper- idinyl]-1-phenylpropyl}propanamide; and the pharmaceutically acceptable salts thereof. 13. A pharmaceutical composition comprising a compound of claim 1 together with a pharmaceutically acceptable excipient, diluent or carrier.