AMPK-activating heterocyclic compounds and methods for using the same
View Patent ↗Disclosed are substituted pyridine compounds as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure wherein E, J, T, the ring system denoted by “B”, T, R 3 , R 4 , w and x are as described herein. In certain embodiments, a compound disclosed herein activates the AMPK pathway, and can be used to treat metabolism-related disorders and conditions.
1. N-((trans)-1-(4-cyanobenzyl)-3-fluoropiperidin-4-yl)-6-(4-(4-methoxybenzoyl)piperidine-1-carbonyl)nicotinamide or a pharmaceutically acceptable salt or N-oxide thereof.
2. A pharmaceutical composition comprising:
at least one pharmaceutically acceptable carrier, diluent or excipient; and
a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
3. A method for activating the AMPK pathway in a cell, the method comprising contacting the cell with an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
4. A method for treating type II diabetes in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
5. A method for treating atherosclerosis in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
6. A method for improving exercise efficiency in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
7. A method for treating intermittent claudication, the method comprising administering to the subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
8. The compound of claim 1 , having the structural formula
9. A pharmaceutical composition comprising:
at least one pharmaceutically acceptable carrier, diluent or excipient; and
a compound according to claim 8 or a pharmaceutically acceptable salt or N-oxide thereof.
10. A method for activating the AMPK pathway in a cell, the method comprising contacting the cell with an effective amount of a compound according to claim 8 or a pharmaceutically acceptable salt or N-oxide thereof.
11. A method for treating type II diabetes in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 8 or a pharmaceutically acceptable salt or N-oxide thereof.
12. A method for treating atherosclerosis in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 8 or a pharmaceutically acceptable salt or N-oxide thereof.
13. A method for improving exercise efficiency in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 8 or a pharmaceutically acceptable salt or N-oxide thereof.
14. A method for treating intermittent claudication, the method comprising administering to the subject an effective amount of a compound according to claim 8 or a pharmaceutically acceptable salt or N-oxide thereof.
15. The compound of claim 1 , having the structural formula
16. A pharmaceutical composition comprising:
at least one pharmaceutically acceptable carrier, diluent or excipient; and
a compound according to claim 15 or a pharmaceutically acceptable salt or N-oxide thereof.
17. A method for activating the AMPK pathway in a cell, the method comprising contacting the cell with an effective amount of a compound according to claim 15 or a pharmaceutically acceptable salt or N-oxide thereof.
18. A method for treating type II diabetes in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 15 or a pharmaceutically acceptable salt or N-oxide thereof.
19. A method for treating atherosclerosis in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 15 or a pharmaceutically acceptable salt or N-oxide thereof.
20. A method for improving exercise efficiency in a subject, the method comprising administering to the subject an effective amount of a compound according to claim 15 or a pharmaceutically acceptable salt or N-oxide thereof.
21. A method for treating intermittent claudication, the method comprising administering to the subject an effective amount of a compound according to claim 15 or a pharmaceutically acceptable salt or N-oxide thereof.
22. A compound according to claim 1 , wherein the compound is racemic.
23. A compound according to claim 8 , wherein the compound is substantially enantiomerically pure.
24. A compound according to claim 15 , wherein the compound is substantially enantiomerically pure.