Granted Patent B2

US 10,000,477 · App. 15/522,863 · Granted Jun 19, 2018

Abstract

Claims (217)

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein

A is a saturated 3-6 membered carbocyclic ring, optionally substituted by one or more C 1-4 alkyl;

B is a saturated 4-6 membered heterocyclic ring, in which one or two carbon atoms are optionally replaced by a heteroatom selected from nitrogen and oxygen; wherein the ring may optionally be substituted by one or more C 1-4 alkyl;

G is aryl or a 5-6 membered heteroaromatic group or 8-11 membered heteroaromatic group, which may optionally be benzofused or optionally substituted by 1, 2, 3, 4, or 5 substituents selected from the group consisting of: halogen, cyano, hydroxyl, amino, C 1-4 alkylamino, C 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkyl, haloC 1-4 alkoxy, SF 5 , C(═O)NH 2 , and C(═O)(O) z R 3 ;

W is S, SO 2 , O, CHR 2 , or NR 3 ;

n is 0 or 1;

m is 1 or 2;

p is 1 or 2;

z is each independently 0 or 1;

R is hydrogen, C 1-4 alkoxy, or C 1-4 alkyl;

R 1 is each independently hydrogen, OH, C 1-4 alkoxy, F, or C 1-4 alkyl;

R 2 is each independently hydrogen, OH, C 1-4 alkoxy, F, or C 1-4 alkyl;

R 3 is each independently hydrogen or C 1-4 alkyl;

R 4 is each independently hydrogen; C 1-4 alkyl; —C(═O)C 1-4 alkyl; —C(═O)C 1-4 alkoxyC 1-4 alkyl; or —C(═O)C 3-6 cycloalkyl;

R 5 is each independently hydrogen or C 1-4 alkyl;

R 6 is each independently hydrogen or C 1-4 alkyl;

R 7 is each independently halogen, C 1-4 alkyl; OH, or C 1-4 alkoxy;

G 1 is a phenyl or a 5-6-membered heteroaromatic group or a 8-11 membered heteroaromatic group; any of which groups may be optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, hydroxyl, amino, C 1-4 alkylamino, C 1-4 alkyl, haloC 1-4 alkyl, haloC 1-4 alkoxy, C 1-4 alkoxy, SF 5 , C(═O)NH 2 , and C(═O)(O) z R 3 ;

Y is phenyl or a moiety selected from the group consisting of: a 5-6 membered heteroaromatic group, a 8-11 membered heteroaromatic group, a saturated mono 3-7 membered carbocyclic group and a 8-11 membered bicyclic carbocyclic group, and for any of such groups one or more ring carbons may optionally be replaced by N(R 4 ) z , O, S; any of which groups may be optionally substituted by 1, 2 or 3 substituents selected from: halogen, cyano, hydroxyl, C 1-4 alkylamino, C 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkyl, haloC 1-4 alkoxy, oxo, —NHC(═O)C 1-4 alkyl, —NR 5 R 6 , SF 5 , (CH 2 ) z C(═O)NR 5 R 6 , —C(═O)(O) z R 3 , —C 1-4 alkylCN, —SO 2 NR 5 R 6 , Y′, or OY′;

Y′ is phenyl, or a 5-6-membered heteroaromatic group optionally substituted by 1 or 2 R 7 groups; provided that Y, Y′ and G 1 are not simultaneously phenyl.

2. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein A and B are:

3. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein A and B are:

4. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , of formula (IIA):

5. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , of formula (IIB):

6. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , of formula (IIIA):

7. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , of formula (IIIB):

8. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , of formula (VA):

9. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , of formula (VB):

10. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , of formula (IIC):

11. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein W is S, and R, R 1 , and R 2 are hydrogen.

12. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein G is phenyl or pyridyl, optionally substituted by 1, 2 or 3 groups independently selected from halo, C 1-4 alkyl, and haloC 1-4 alkyl.

13. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein G is selected from: phenyl, 4-trifluoromethyl-phenyl, 2-fluoro-4-trifluoromethyl-phenyl, 2,4-difluorophenyl, 4-fluorophenyl, 2-trifluoromethyl-phenyl, 2-trifluoromethyl-4-fluorophenyl, and 3,5-dichlorophenyl.

14. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein G 1 is a 5-6-membered heteroaromatic group containing at least one ring nitrogen, wherein the heteroaromatic group is optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of: halogen, cyano, hydroxyl, amino, C 1-4 alkylamino, C 1-4 alkyl, haloC 1-4 alkyl, haloC 1-4 alkoxy, C 1-4 alkoxy, —C(═O)NH 2 and —C(═O)(O) z R 3 .

15. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein G 1 is:

and wherein R a is H or C 1-4 alkyl.

16. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein Y is selected from the group consisting of:

a phenyl optionally substituted by one or two substituents selected from: cyano, —C(═O)NH 2 , sulphonamide, acetyl, —CH 2 CN, —CH 2 C(═O)NH 2 , and Y′;

a saturated mono 3-7 membered carbocyclic group in which 0 or 1 or 2 carbon atoms are replaced by a heteroatom independently selected from O and NR 3 ;

a 8-11 membered bicyclic carbocyclic group, optionally substituted by one or more C 1-4 alkyl;

a 5-6 membered heteroaromatic group optionally substituted by one or two substituents selected from: halogen, cyano, hydroxyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, —(CH 2 ) z C(═O)N(R 4 R 5 ), Y′, and OY′; and

a 8-11 membered heteroaromatic group in which 1 or 2 or 3 atom carbons may optionally be replaced by N, and optionally substituted by one or more C 1-4 alkyl.

17. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein Y is phenyl substituted by 1 or 2 substituents selected from cyano, —CH 2 CN, —C(═O)R 3 , (CH 2 ) z C(═O)NR 5 R 6 , —SO 2 NH 2 , and Y′, and wherein Y′ is selected from oxadiazolyl, tetrazolyl, triazolyl and oxazolyl, which Y′ is optionally substituted by C 1-4 alkyl.

18. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein Y is selected from pyridyl, pyrimidinyl and pyrazinyl, any of which groups may be optionally substituted by 1 or 2 substituents selected from: fluoro, cyano, C 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkyl, and —C(═O)NR 5 R 6 .

19. The compound, or the pharmaceutically acceptable salt thereof, according to claim 1 , wherein —(CHR) n (CR 1 R 2 ) m (CR 1 R 2 ) p W— is

20. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

(1R,3R or 1S,3S)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}-propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-phenyl-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-phenyl-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3R or 1R,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S or 1S,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-1-(2,4-difluorophenyl)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S)-1-(2,4-difluorophenyl)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-1-(4-fluorophenyl)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S)-1-(4-fluorophenyl)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)-1-[2-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S or 1R,3R)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}- propyl)-1-[2-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3R or 1R,3S)-1-[4-fluoro-2-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S or 1R,3R)-1-[4-fluoro-2-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-1-(3,5-dichlorophenyl)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-1-(3,5-dichlorophenyl)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)- 1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3R or 1S,3S)-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S or 1R,3R)-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl] sulfanyl} propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3R or 1R,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-{3-[(4-methyl-5-{8-oxabicyclo[3.2.1]octan-3-yl}-4H-1,2,4-triazol-3-yl)sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-{3-[(4-methyl-5-{8-oxabicyclo[3.2.1]octan-3-yl}-4H-1,2,4-triazol-3-yl)-sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-5-{3-[(5-cyclohexyl-4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3R or 1S,3S)-5-{3-[(5-cyclohexyl-4-methyl-4H-1,2,4-triazol-3-yl)-sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S or 1R,3R)-5-{3-[(5-cyclohexyl-4-methyl-4H-1,2,4-triazol-3-yl)-sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-{3-[(5-cyclohexyl-4-methyl-4H-1,2,4-triazol-3-yl)-sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-{3-[(5-cyclohexyl-4-methyl-4H-1,2,4-triazol-3-yl)-sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

1-{4-[4-methyl-5-({3-[(1R,3S/1S,R3)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]piperidin-1-yl}ethan-1-one;

1-{4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]piperidin-1-yl}ethan-1-one;

1-{4-[5-({3-[(1S,3S/1R,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]piperidin-1-yl}ethan-1-one;

1-{4-[5-({3-[(1S,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]piperidin-1-yl}ethan-1-one;

3-methoxy-1-{4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]piperidin-1-yl}propan-1-one;

(1R,3S)-5-(3-{[5-(1-cyclopropanecarbonylpiperidin-4-yl)-4-methyl-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

N-{4-[4-methyl-5-({3-[(1R,3S/1S,3R)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}acetamide;

N-{4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}acetamide;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(morpholin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(morpholin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]piperidin-2-one;

5-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]piperidin-2-one;

6-[4-methyl-5-({3-[(1R,3S/1S,3R)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

5-[4-methyl-5-({3-[(1R,3S/1S,3R)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

5-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

5-[5-({3-[(1S,3S/1R,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

5-[5-({3-[(1S,3S/1R,3R)-1-(2,4-difluorophenyl)-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

5-[5-({3-[(1R,3S/1S,3R)-1-(4-fluorophenyl)-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

5-[4-methyl-5-({3-[(1S,3S/1R,3R)-1-[2-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

1-methyl-5-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

4-[4-methyl-5-({3-[(1R,3S/1S,3R)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

4-[4-methyl-5-({3-[(1S,3S/1R,3R)-1-[2-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

1-methyl-4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;

4-[5-({3-[(1S,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1-methyl-1,2-dihydropyridin-2-one;

(1S,3S/1R,3S)-5-(3-{[4-methyl-5-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-1-(2,4-difluorophenyl)-5-(3-{[4-methyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S)-1-(2,4-difluorophenyl)-5-(3-{[4-methyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-1-(4-fluorophenyl)-5-(3-{[4-methyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S)-1-(4-fluorophenyl)-5-(3-{[4-methyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-5-(3-{[4-methyl-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(2-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(2-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-5-(3-{[4-methyl-5-(2-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[2-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(6-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(3-methylpyridin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[5-(2,6-dimethylpyridin-3-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[5-(2-fluoropyridin-3-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-[3-({4-methyl-5-[2-(trifluoromethyl)pyridin-3-yl]-4H-1,2,4-triazol-3-yl}-sulfanyl)propyl]-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[5-(2-methoxypyridin-3-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[5-(2-methoxypyridin-3-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

5-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile;

4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carbonitrile;

5-[4-methyl-5-({3-[(1S,3S/1R,3R)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

5-[4-methyl-5-({3-[(1S,3S or 1R,3R)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

5-[4-methyl-5-({3-[(1R,3R or 1S,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

5-[4-methyl-5-({3-[(1R,3S/1S,3R)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

5-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

5-[5-({3-[1S,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

6-methyl-5-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

6-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-3-carboxamide;

6-[5-({3-[(1S,3 S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-3-carboxamide;

4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

5-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-3-carboxamide;

6-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

N-methyl-6-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(pyridazin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(pyridazin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-5-(3-{[4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S or 1R,3R)-5-(3-{[4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3R or 1S,R3)-5-(3-{[4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1S,3S or 1R,3R)-5-(3-{[4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3R or 1S,R3)-5-(3-{[4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-(3-{[4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(6-methylpyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(5-methylpyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(3-methylpyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(3-methylpyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

5-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyrazine-2-carboxamide;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(3-methyl-1,2-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(3-methyl-1,2-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(4-methyl-1,3-thiazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(4-methyl-1,3-thiazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(1,3-thiazol-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(1,3-thiazol-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)5-(3-{[4-methyl-5-(1-methyl-1H-pyrazol-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}-propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(1-methyl-1H-pyrazol-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(1-methyl-1H-pyrazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}-propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(1-methyl-1H-pyrazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[5-(furan-2-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[5-(furan-3-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(thiophen-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(1-methyl-1H-pyrrol-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S/1R,3R)-5-(3-{[4-methyl-5-(1,2,3-thiadiazol-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(1,2,3-thiadiazol-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(1,2,3-thiadiazol-4-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(4-methyl-1,2,3-thiadiazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}-propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-[3-({4-methyl-5-[2-(pyridin-3-yl)-1,3-oxazol-5-yl]-4H-1,2,4-triazol-3-yl}-sulfanyl)propyl]-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-(3-{[4-methyl-5-(6-phenoxypyridin-3-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-{3-[(4-methyl-5-{[1,2,4]triazolo[4,3-a]pyridin-6-yl}-4H-1,2,4-triazol-3-yl)sulfanyl]-propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-{3-[(4-methyl-5-{[1,2,4]triazolo[4,3-a]pyridin-7-yl}-4H-1,2,4-triazol-3-yl)-sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1S,3S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-5-{3-[(4-methyl-5-{[1,2,4]triazolo[4,3-a]pyridin-7-yl}-4H-1,2,4-triazol-3-yl)sulfanyl]propyl}-5-azaspiro[2.4]heptane;

(1R,3S)-5-{3-[(4-methyl-5-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl}-4H-1,2,4-triazol-3-yl)sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-{3-[(5-{1H-imidazo[4,5-b]pyridin-5-yl}-4-methyl-4H-1,2,4-triazol-3-yl)-sulfanyl]propyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-[3-({4-methyl-5-[4-(1H-1,2,3,4-tetrazol-5-yl)phenyl]-4H-1,2,4-triazol-3-yl}-sulfanyl)propyl]-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-[3-({4-methyl-5-[4-(1,3,4-oxadiazol-2-yl)phenyl]-4H-1,2,4-triazol-3-yl}sulfanyl)-propyl]-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-[3-({4-methyl-5-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-4H-1,2,4-triazol-3-yl}-sulfanyl)propyl]-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-[3-({4-methyl-5-[4-(4H-1,2,4-triazol-4-yl)phenyl]-4H-1,2,4-triazol-3-yl}sulfanyl)-propyl]-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-[3-({4-methyl-5-[4-(1,3-oxazol-2-yl)phenyl]-4H-1,2,4-triazol-3-yl}sulfanyl)propyl]-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S)-5-[3-({4-methyl-5-[3-(1,3-oxazol-2-yl)phenyl]-4H-1,2,4-triazol-3-yl}sulfanyl)propyl]-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]benzamide;

4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]benzonitrile

1-{4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]phenyl}ethan-1-one;

4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]benzamide;

2-{4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]phenyl}acetonitrile;

2-{4-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]phenyl}acetamide;

3-[4-methyl-5-({3-[(1R,3S)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]-propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]benzamide;

(1S,3S)-1-[2-fluoro-4-(trifluoromethyl)-phenyl]-5-{4-[4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazol-3-yl]butyl}-5-azaspiro[2.4] heptane;

(1R,3S)-5-{4-[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]butyl}-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane;

(1R,3S/1S,3R)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.5]octane; and

(1S,3R or 1R,3S)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}-propyl)-1-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.5]octane.

21. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

22. A method of modulating dopamine D 3 receptors in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the compound of claim 1 .

23. A method for treating a psychosis or a psychotic condition in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the compound of claim 1 to treat the psychosis or the psychotic condition.

24. A method for treating substance abuse in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the compound of claim 1 to treat the substance abuse.

25. A method for treating schizophrenia in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the compound of claim 1 to treat the schizophrenia.

26. The compound of claim 1 , wherein Y is phenyl substituted by 1 substituent selected from cyano, CH 2 CN, acetyl, —CH 2 C(═O)NH 2 , —C(═O)NH 2 , —SO 2 NH 2 and Y′; and wherein Y′ is oxadiazolyl, tetrazolyl, triazolyl or oxazolyl, and Y′ is optionally substituted by methyl.

27. The compound of claim 1 , wherein Y is pyridyl optionally substituted by 1 or 2 substituents selected from: C 1-4 alkyl and —C(═O)NH 2 .

28. The compound of claim 10 enriched in configuration (1R,3S) or (1S,3S).

29. A pharmaceutical composition comprising the compound of claim 20 and a pharmaceutically acceptable carrier.

30. A method of modulating dopamine D 3 receptors in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the compound of claim 20 .

31. A method for treating a psychosis or a psychotic condition in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the compound of claim 20 to treat the psychosis or the psychotic condition.

32. A method for treating substance abuse in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the compound of claim 20 to treat the substance abuse.

33. A method for treating schizophrenia in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the compound of claim 20 to treat the schizophrenia.

Assignments (7)