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 method of treating obesity; diabetes; glucose intolerance; insulin resistance; hyperglycemia; hypertension; or hyperlipidemia; in a patient, comprising administering to said patient a therapeutically effective amount of a compound selected from the group consisting of:
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;
or a pharmaceutically acceptable salt thereof.
2. The method according to claim 1 , 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.
3. The method according to claim 1 , 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-methylpyridine-2-carboxamide.
4. The method according to claim 1 , wherein the compound is the following compound, or a pharmaceutically acceptable salt thereof:
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.
5. The method according to claim 1 , wherein the compound is the following compound, or a pharmaceutically acceptable salt thereof:
5-{3-Chloro-4-[(5S)-2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]dec-7-yl]phenyl}-N-ethylpyridine-2-carboxamide.
6. The method of according to claim 2 , wherein the method is a method of treating obesity.
7. The method according to claim 2 , wherein the method is a method of treating diabetes.
8. The method according to claim 2 , wherein the method is a method of treating glucose intolerance.
9. The method according to claim 2 , wherein the method is a method of treating insulin resistance.
10. The method according to claim 2 , wherein the method is a method of treating hyperglycemia.
11. The method according to claim 2 , wherein the method is a method of treating hypertension.
12. The method according to claim 2 , wherein the method is a method of treating hyperlipidemia.