Substituted hexahydropyrrolo[3,4-b]pyrroles and hexahydrocyclopenta[c]pyrroles as dopamine receptor modulators
View Patent ↗The disclosure provides compounds having formula (I), wherein the substituents are as defined herein. The compounds are useful for modulating the dopamine D 3 receptor and for treating conditions associated therewith, such as addictions, drug dependency, and psychiatric conditions.
1. A compound of Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5) or Formula (I-6):
or a pharmaceutically acceptable salt thereof,
wherein:
ring A of the bicyclic ring system is optionally substituted at one or more carbon atoms or the nitrogen atom by one or more C 1-4 alkyl;
ring B of the bicyclic ring system is optionally substituted at one or more carbon atoms by one or more C 1-4 alkyl;
G is phenyl or a 5-6 membered heteroaryl, each of which is optionally substituted by one, two, three or four substituents selected from the group consisting of halogen, SF 5 , CN, OH, NH 2 , NHC 1-4 alkyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl, C(═O)NH 2 and C(═O)OR 3 ;
G 1 is phenyl, a 5-6 membered heteroaryl or an 8-11 membered heteroaryl, each of which is optionally substituted by one, two, three or four substituents selected from the group consisting of halogen, SF 5 , CN, OH, NH 2 , NHC 1-4 alkyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C(═O)NH 2 and C(═O)(O) z R 3 ;
R is H, C 1-4 alkyl or C 1-4 alkoxy;
each R 1 is independently H, F, OH, C 1-4 alkyl or C 1-4 alkoxy;
each R 2 is independently H, F, OH, C 1-4 alkyl or C 1-4 alkoxy;
R 3 is H or C 1-4 alkyl;
R 4 is H, C 1-4 alkyl, C(═O)C 1-4 alkyl, C(═O)C 1-4 alkoxyC 1-4 alkyl or C(═O)cyclopropyl;
R 5 is H or C 1-4 alkyl;
R 6 is H or C 1-4 alkyl;
W is —CHR 2 —, —NR 3 —, —O—, —S— or —S(═O) 2 —;
Y is phenyl or an 8-11 membered heteroaryl, each of which is optionally substituted by one, two or three substituents selected from the group consisting of halogen, SF 5 , CN, OH, NR 5 R 6 , NHC 1-4 alkyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl and C(═O)(O) z R 3 ; or
Y is a 5-6 membered heteroaryl, which is optionally substituted by one, two or three substituents selected from the group consisting of halogen, ═O, SF 5 , CN, OH, NR 5 R 6 , NHC 1-4 alkyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl, C(═O)NH 2 , C(═O)(O) z R 3 and (CH 2 ) z C(═O)NR 4 R 5 , provided that ═O can only be a substituent for a carbon atom; or
Y is a monocyclic saturated 3-7 membered carbocyclyl, which is optionally substituted by one, two or three substituents selected from the group consisting of halogen, SF 5 , CN, OH, NR 5 R 6 , NHC 1-4 alkyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl, C(═O)NH 2 and C(═O)(O) z R 3 , and wherein one or more carbon atoms is optionally replaced by —N(R 4 ) z —, —O— or —S—; or
Y is a bicyclic 8-11 membered carbocyclyl, each of which is optionally substituted by one, two or three substituents selected from the group consisting of halogen, SF 5 , CN, OH, NR 5 R 6 , NHC 1-4 alkyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl, C(═O)NH 2 and C(═O)(O) z R 3 , and wherein one or more carbon atoms is optionally replaced by —N(R 4 ) z —, —O— or —S—;
m is 1 or 2;
n is 0 or 1;
p is 1 or 2; and
z is 0 or 1.
2. The compound of claim 1 , wherein the compound is of Formula (I-2):
wherein:
G is phenyl or a 6 membered heteroaryl, each of which is optionally substituted by one, two or three substituents selected from the group consisting of halogen, CN, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy and haloC 1-4 alkoxy;
G 1 is an optionally substituted 5-6 membered heteroaryl;
R is H;
each R 1 is independently H;
each R 2 is independently H;
W is —CH 2 —, —O— or —S—;
Y is a 5-6 membered heteroaryl, which is optionally substituted by one or two substituents selected from the group consisting of OH, C 1-4 alkyl, C(═O)NH 2 and (CH 2 ) z C(═O)NR 4 R 5 ;
m is 1;
n is 1; and
p is 1.
3. The compound of claim 1 , wherein:
G 1 is 4-methyl-4H-1,2,4-triazole; and
W is —S—.
4. The compound of claim 1 , wherein:
5. The compound of claim 1 , wherein:
6. The compound of claim 1 , wherein:
the compound of Formula (I-1) is:
and
the compound of Formula (I-3) is:
7. The compound of claim 1 , wherein:
the compound of Formula (I-2) is:
and
the compound of Formula (I-4) is:
8. The compound of claim 1 , wherein:
the compound of Formula (I-2) is:
and
the compound of Formula (I-4) is:
wherein:
G is phenyl or a 5-6 membered heteroaryl, each of which is optionally substituted by one, two, three or four substituents selected from the group consisting of halogen, SF 5 , CN, OH, NH 2 , NHC 1-4 alkyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl, C(═O)NH 2 and C(═O)OR 3 ;
G 1 is phenyl, a 5-6 membered heteroaryl or an 8-11 membered heteroaryl, each of which may be optionally substituted by one, two, three or four substituents selected from the group consisting of halogen, SF 5 , CN, OH, NH 2 , NHC 1-4 alkyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C(═O)NH 2 and C(═O)(O) z R 3 ; and
Y is a 5-6 membered heteroaryl, which is optionally substituted by one or two substituents selected from the group consisting of halogen, SF 5 , CN, OH, NH 2 , C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl, C(═O)NH 2 and C(═O)(O)R 3 ; or
Y is a monocyclic saturated 3-7 membered carbocyclyl, which is optionally substituted by one or two substituents selected from the group consisting of halogen, SF 5 , CN, OH, NH 2 , C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl, C(═O)NH 2 and C(═O)(O) z R 3 , and wherein one or more carbon atoms is optionally replaced by —N(R 4 )—, —O— or —S—; or
Y is a bicyclic 8-11 membered carbocyclyl, each of which may be optionally substituted by one or two substituents selected from the group consisting of halogen, SF 5 , CN, OH, NH 2 , C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl, C(═O)NH 2 and C(═O)(O)R 3 , and wherein one or more carbon atoms is optionally replaced by —N(R 4 )—, —O— or —S—.
9. The compound of claim 1 , wherein the compound is:
10. The compound of claim 1 , wherein the compound is selected from the group consisting of:
4-methyl-3-(4-methyl-1,3-oxazol-5-yl)-5-[(3-{1-[4(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-[5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-octahydropyrrolo[2,3-c]pyrrol-1-yl]benzonitrile;
3-[(3aS,6aS)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)-octahydropyrrolo[2,3-c]pyrrol-1-yl]benzonitrile;
3-[(3aS,6aS)-5-(3-{[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazol-3-yl]-sulfanyl}propyl)-octahydropyrrolo[2,3-c]pyrrol-1-yl]benzonitrile;
4-methyl-3-(4-methyl-1,3-oxazol-5-yl)-5-[(3-{1-phenyl-octahydropyrrolo[2,3-c]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-phenyl-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-[(3-{1-[2-fluoro-4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl}-propyl)sulfanyl]-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[1-(4-fluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}-sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}-sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
4-methyl-3-(4-methyl-1,3-oxazol-5-yl)-5-[(3-{1-[2-(trifluoromethoxy)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
3-({3-[1-(2,6-difluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[1-(3,5-dichlorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[1-(2,4-dichlorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[1-(3-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]-propyl}sulfanyl)-4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]-propyl}sulfanyl)-4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-phenyl-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazole;
3-({3-[1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}-sulfanyl)-4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}-sulfanyl)-4-methyl-5-(oxan-4-yl)-4H-1,2,4-triazole;
3-cyclopentyl-4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]-propyl}sulfanyl)-5-cyclopentyl-4-methyl-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]-propyl}sulfanyl)-5-cyclopentyl-4-methyl-4H-1,2,4-triazole;
3-cyclohexyl-4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol;
3-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]-propyl}sulfanyl)-5-cyclohexyl-4-methyl-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]-propyl}sulfanyl)-5-cyclohexyl-4-methyl-4H-1,2,4-triazole;
3-cyclohexyl-5-({3-[1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}-sulfanyl)-5-cyclohexyl-4-methyl-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}-sulfanyl)-5-cyclohexyl-4-methyl-4H-1,2,4-triazole;
1-methyl-2-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-1H-1,3-benzodiazole;
4-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}morpholine;
4-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]morpholine;
4-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]morpholine;
2-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyrazine;
2-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
3-[5-(3-{[4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-octahydropyrrolo[3,4-b]pyrrol-1-yl]benzonitrile;
2-[5-({3-[1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-{4-methyl-5-[(3-{1-[2-(trifluoromethoxy)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyrazine;
2-[5-({3-[1-(2,6-difluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[1-(3-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[1-(2,4-difluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[(3aS,6aS)-1-(2,4-difluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[(3aS,6aS)-1-(2,4-difluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[4-methyl-5-({3-[1-(4-methylphenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[1-(3-methoxyphenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-(3-{[4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}propyl)-octahydropyrrolo[3,4-b]pyrrol-1-yl]benzonitrile;
2-[4-methyl-5-({3-[1-(3-methylphenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyrazine;
2-{4-methyl-5-[(3-{1-[3-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyrazine;
2-{4-methyl-5-[(3-{1-[3-(trifluoromethoxy)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyrazine;
2-[5-({3-[(3aS,6aS)-1-[2-(propan-2-yloxy)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-{4-methyl-5-[(3-{1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyrazine;
2-[5-({3-[(3aS,6aS)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[1-(4-fluoro-3-methoxyphenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[(3aS,6aS)-1-(4-fluoro-3-methoxyphenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-[5-({3-[(3aS,6aS)-1-(4-fluoro-3-methoxyphenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrazine;
2-{5-[(3-{1-[2-fluoro-6-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4-methyl-4H-1,2,4-triazol-3-yl}pyrazine;
2-[4-methyl-5-({3-[1-(2,4,6-trifluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyrazine;
4-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyrimidine;
4-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrimidine;
4-[5-({3-[(3aR,6aR)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrimidine;
4-[5-({3-[(3aR,6aR)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrimidine;
4-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrimidine;
4-[5-({3-[1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyrimidine;
3-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyridine;
3-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine trihydrochloride;
3-[5-({3-[(3aR,6aR)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine trihydrochloride;
3-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine;
3-[5-({3-[(3aR,6aR)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine;
3-[5-({3-[1-(2,6-difluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine;
3-{4-methyl-5-[(3-{1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3yl}pyridine;
3-[5-({3-[(3aS,6aS)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine;
3-[5-({3-[(3aR,6aR)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine;
4-methyl-3-(1-methyl-1H-pyrazol-4-yl)-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
4-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyridine;
4-[5-({3-[1-(2,6-difluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine;
4-{4-methyl-5-[(3-{1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-thiazol-3-yl}pyridine;
4-[5-({3-[(3aS,6aS)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine;
4-[5-({3-[(3aR,6aR)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine;
2-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-thiazol-3-yl}pyridine;
2-{4-methyl-5-[(3-{1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-thiazol-3-yl}pyridine;
4-methyl-3-(1,3-thiazol-2-yl)-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
4-methyl-3-(3-methyl-1,2-oxazol-5-yl)-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
4-methyl-3-(4-methyl-1,3-thiazol-5-yl)-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
4-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-1,2-dihydropyridin-2-one;
4-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;
4-[5-({3-[1-(4-fluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;
4-[5-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}-sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;
5-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-1,2-dihydropyridin-2-one;
5-[5-({3-[1-(4-fluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;
5-{4-methyl-5-[(3-{1-[3-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-1,2-dihydropyridin-2-one;
5-{4-methyl-5-[(3-{1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-1,2-dihydropyridin-2-one;
5-[5-({3-[(3aS,6aS)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;
5-[5-({3-[(3aR,6aR)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;
3-({3-[1-(2,6-difluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(1-methyl-1H-pyrazol-5-yl)-4H-1,2,4-triazole;
4-methyl-3-(1-methyl-1H-pyrazol-5-yl)-5-[(3-{1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazole;
3-({3-[(3aS,6aS)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(1-methyl-1H-pyrazol-5-yl)-4H-1,2,4-triazole;
3-({3-[(3aR,6aR)-1-[2-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-5-(1-methyl-1H-pyrazol-5-yl)-4H-1,2,4-triazole;
1-methyl-5-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}-1,2-dihydropyridin-2-one;
5-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1-methyl-1,2-dihydropyridin-2-one;
5-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1-methyl-1,2-dihydropyridin-2-one;
5-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyridine-2-carboxamide;
5-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}-sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[(3aS,6aS)-1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}-sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[1-(2,6-difluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[(3aS,6aS)-1-(2,6-difluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[(3aS,6aS)-1-(2,6-difluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5 yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[4-methyl-5-({3-[1-(2,4,6-trifluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[(3aS,6aS)-1-(2,4,6-trifluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]-propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
5-[5-({3-[(3aS,6aS)-1-(2,4,6-trifluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]-propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]pyridine-2-carboxamide;
4-[5-({3-[1-(4-fluorophenyl)-octahydropyrrolo[3,4-b]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1-methyl-1,2-dihydropyridin-2-one;
1-methyl-4-[4-methyl-5-({3-[1-(2,4,6-trifluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4H-1,2,4-triazol-3-yl]-1,2-dihydropyridin-2-one;
4-[5-({3-[(3aS,6aS)-1-(2,4,6-trifluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]-propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1-methyl-1,2-dihydropyridin-2-one;
4-[5-({3-[(3aR,6aR)-1-(2,4,6-trifluorophenyl)-octahydropyrrolo[2,3-c]pyrrol-5-yl]-propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]-1-methyl-1,2-dihydropyridin-2-one;
4-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}cyclohexan-1-ol;
4-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]cyclohexan-1-ol;
4-[5-({3-[(3aS,6aS)-1-[4-(trifluoromethyl)phenyl]-octahydropyrrolo[2,3-c]pyrrol-5-yl]propyl}sulfanyl)-4-methyl-4H-1,2,4-triazol-3-yl]cyclohexan-1-ol;
4-methyl-3-(4-methyl-1,3-oxazol-5-yl)-5-({3-[(4S)-4-[4-(trifluoromethyl)phenyl]-octahydrocyclopenta[c]pyrrol-2-yl]propyl}sulfanyl)-4H-1,2,4-triazole; and
3-({3-[(4aS,7aS)-1-[4-(trifluoromethyl)phenyl]-octahydro-1H-pyrrolo[3,4-b]pyridin-6-yl]propyl}sulfanyl)-4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-4H-1,2,4-triazole.
11. The compound of claim 1 , wherein the compound is selected from the group consisting of:
12. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
13. A method for modulating a dopamine D 3 receptor in a patient, comprising administering to the patient in need thereof a therapeutically effective amount of the compound of claim 3 .
14. The method of claim 13 , wherein modulating the dopamine D 3 receptor is antagonizing the dopamine D 3 receptor.
15. The method of claim 13 , wherein modulating the dopamine D 3 receptor is treating a medical condition that is impacted by the dopamine D 3 receptor.
16. The method of claim 15 , wherein the medical condition is a psychiatric condition.
17. The method of claim 15 , wherein the medical condition is an opioid use disorder.
18. The method of claim 15 , wherein the medical condition is a drug dependency.
19. The method of claim 18 , wherein the drug dependency is alcohol dependency.
20. The method of claim 18 , wherein the drug dependency is opioid dependency.
21. The method of claim 15 , wherein the medical condition is an addiction.
22. The method of claim 21 , wherein the addiction is gambling.