Provided are D 2 or D 3 antagonist compounds and pharmaceutical compositions of formula I and pharmaceutically acceptable salts thereof, or isomers thereof, wherein R 1 , R 2 and R 3 are as defined herein. The invention further comprises methods for making the compounds of the invention and methods for the treatment of conditions mediated by the dopamine D 2 or D 3 receptor from the compounds of the invention.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is
1-phenyl-1-oxo-(C 2 -C 6 ) optionally substituted at the 4 position of the phenyl with halo,
R 2 is cycloalkyl of three to seven carbon atoms optionally substituted with one to six halogens;
R 3 is
and
R 10 is H or alkyl of one to six carbons.
2. The compound of claim 1 , wherein R 3 is represented by formula A, C, D, or F and R 10 is H.
3. The compound of claim 2 , wherein R 3 is represented by formula A or D.
4. The compound of claim 1 , wherein R 2 is unsubstituted cycloalkyl of three to seven carbon atoms.
5. The compound of claim 4 , wherein R 2 is cyclohexyl.
6. The compound of claim 1 , wherein R 1 is
1-phenyl-1-oxo-propyl optionally substituted at the 4 position of the phenyl with halo.
7. The compound of claim 1 , wherein
R 1 is 1 phenyl-1-oxo-butyl optionally substituted at the 4 position of the phenyl with halo;
R 2 is cyclohexyl; and
R 3 is represented by formula A, C, D, or F and R 10 is H.
8. The compound of claim 7 , wherein R 3 is represented by formula A.
9. A compound of claim 1 chosen from the group consisting of
3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid, hydrochloride
2-((1-Cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid, hydrochloride
10. A composition comprising a compound of claim 1 and at feast one pharmaceutically acceptable excipient.
11. A compound which is 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid, hydrochloride
12. A composition comprising a compound of claim 11 and at least one pharmaceutically acceptable excipient.
13. A compound of claim 1 which is a pharmaceutically acceptable salt of 3-((1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoic acid wherein the pharmaceutically acceptable salt is selected from the salt of fumaric or maleic acid.
14. A composition comprising a compound of claim 13 and at least one pharmaceutically acceptable excipient.