Spirocycles as inhibitors of 11-beta hydroxyl steroid dehydrogenase type 1
The present invention relates to certain spirocyclic compounds that are inhibitors of 11-β hydroxyl steroid dehydrogenase type 1 (11βHSD1), compositions containing the same, and methods of using the same for the treatment of diabetes, obesity and other diseases.
1. A compound of Formula II:
R 1 is F, Cl, Br, or I; and
R 2 and R 3 are independently selected from H, C 1-6 alkyl and C 3-7 cycloalkyl;
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is F or Cl.
3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 and R 3 are independently selected from H and C 1-4 alkyl.
4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein at least one of R 2 and R 3 is other than H.
5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is F or C 1 , R 2 and R 3 are independently selected from H and C 1-4 alkyl, and at least one of R 2 and R 3 is other than H.
6. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
7. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
8. A method of treating type II diabetes in a patient comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
9. A method according to claim 8 , wherein the compound is selected from the following compounds, and pharmaceutically acceptable salts thereof:
5-{3-Fluoro-4-[(5S)-2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]dec-7-yl]phenyl}-N,N-dimethylpyridine-2-carboxamide;
5-{3-Fluoro-4-[(5S)-2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]dec-7-yl]phenyl}-N-methylpyridine-2-carboxamide;
N-Ethyl-5-{3-fluoro-4-[(5S)-2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]dec-7-yl]phenyl}pyridine-2-carboxamide; and
5-{3-Chloro-4-[(5S)-2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]dec-7-yl]phenyl}-N-ethylpyridine-2-carboxamide.
10. A method according to claim 8 , wherein the compound is the following compound, or a pharmaceutically acceptable salt thereof:
5-{3-Fluoro-4-[(5S)-2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]dec-7-yl]phenyl}-N,N-dimethylpyridine-2-carboxamide.
11. A compound according to claim 1 , wherein the compound is:
N-Ethyl-5-{3-fluoro-4-[(5S)-2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]dec-7-yl]phenyl}pyridine-2-carboxamide; or a pharmaceutically acceptable salt thereof.
12. A compound according to claim 1 , wherein the compound is:
5-{3-Chloro-4-[(5S)-2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]dec-7-yl]phenyl}-N-ethylpyridine-2-carboxamide; or a pharmaceutically acceptable salt thereof.