Pyridone amides as modulators of sodium channels
The invention relates to pyridone amide compounds of formula I and I′ or pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels: The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders, including pain.
1. A method of treating or lessening the severity in a subject of chronic pain, gut pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, or idiopathic pain comprising administering an effective amount of a compound selected from the group consisting of:
2-(4-fluoro-2-methylphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-4-(trifluoromethyl)benzamide;
2-(4-fluorophenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-5-(trifluoromethyl)benzamide;
4-chloro-2-(4-fluoro-2-methylphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)benzamide;
2-(4-fluoro-2-methoxyphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-4-(perfluoroethyl)benzamide; and
4,5-dichloro-2-(4-fluoro-2-methoxyphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)benzamide;
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the method comprises administering
2-(4-fluoro-2-methylphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-4-(trifluoromethyl)benzamide;
or a pharmaceutically acceptable salt thereof.
3. The method of claim 2 , wherein the method comprises treating or lessening the severity in a subject of neuropathic pain.
4. The method of claim 2 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
5. The method of claim 4 , wherein the musculoskeletal pain comprises osteoarthritis pain.
6. The method of claim 2 , wherein the method comprises treating or lessening the severity in a subject of inflammatory pain.
7. The method of claim 1 , wherein the method comprises administering
2-(4-fluorophenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-5-(trifluoromethyl)benzamide;
or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein the method comprises treating or lessening the severity in a subject of neuropathic pain.
9. The method of claim 7 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
10. The method of claim 9 , wherein the musculoskeletal pain comprises osteoarthritis pain.
11. The method of claim 7 , wherein the method comprises treating or lessening the severity in a subject of inflammatory pain.
12. The method of claim 1 , wherein the method comprises administering
4-chloro-2-(4-fluoro-2-methylphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)benzamide;
or a pharmaceutically acceptable salt thereof.
13. The method of claim 12 , wherein the method comprises treating or lessening the severity in a subject of neuropathic pain.
14. The method of claim 12 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
15. The method of claim 14 , wherein the musculoskeletal pain comprises osteoarthritis pain.
16. The method of claim 12 , wherein the method comprises treating or lessening the severity in a subject of inflammatory pain.
17. The method of claim 1 , wherein the method comprises administering
2-(4-fluoro-2-methoxyphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-4-(perfluoroethyl)benzamide;
or a pharmaceutically acceptable salt thereof.
18. The method of claim 17 , wherein the method comprises treating or lessening the severity in a subject of neuropathic pain.
19. The method of claim 17 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
20. The method of claim 19 , wherein the musculoskeletal pain comprises osteoarthritis pain.
21. The method of claim 17 , wherein the method comprises treating or lessening the severity in a subject of inflammatory pain.
22. The method of claim 1 , wherein the method comprises administering
4,5-dichloro-2-(4-fluoro-2-methoxyphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)benzamide;
or a pharmaceutically acceptable salt thereof.
23. The method of claim 22 , wherein the method comprises treating or lessening the severity in a subject of neuropathic pain.
24. The method of claim 22 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
25. The method of claim 24 , wherein the musculoskeletal pain comprises osteoarthritis pain.
26. The method of claim 22 , wherein the method comprises treating or lessening the severity in a subject of inflammatory pain.