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, idiopathic pain, or visceral 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.
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.
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 3 , wherein the neuropathic pain comprises idiopathic small-fiber neuropathy.
5. The method of claim 3 , wherein the neuropathic pain comprises post-herpetic neuralgia.
6. The method of claim 2 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
7. The method of claim 6 , wherein the musculoskeletal pain comprises osteoarthritis pain.
8. The method of claim 2 , wherein the method comprises treating or lessening the severity in a subject of acute pain.
9. The method of claim 8 , wherein the acute pain comprises acute post-operative pain.
10. The method of claim 2 , wherein the method comprises treating or lessening the severity in a subject of postsurgical pain.
11. The method of claim 2 , wherein the method comprises treating or lessening the severity in a subject of visceral pain.
12. The method of claim 1 , wherein the method comprises administering
2-(4-fluorophenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)-5-(trifluoromethyl)benzamide.
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 13 , wherein the neuropathic pain comprises idiopathic small-fiber neuropathy.
15. The method of claim 13 , wherein the neuropathic pain comprises post-herpetic neuralgia.
16. The method of claim 12 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
17. The method of claim 16 , wherein the musculoskeletal pain comprises osteoarthritis pain.
18. The method of claim 12 , wherein the method comprises treating or lessening the severity in a subject of acute pain.
19. The method of claim 18 , wherein the acute pain comprises acute post-operative pain.
20. The method of claim 12 , wherein the method comprises treating or lessening the severity in a subject of postsurgical pain.
21. The method of claim 12 , wherein the method comprises treating or lessening the severity in a subject of visceral pain.
22. 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.
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 23 , wherein the neuropathic pain comprises idiopathic small-fiber neuropathy.
25. The method of claim 23 , wherein the neuropathic pain comprises post-herpetic neuralgia.
26. The method of claim 22 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
27. The method of claim 26 , wherein the musculoskeletal pain comprises osteoarthritis pain.
28. The method of claim 22 , wherein the method comprises treating or lessening the severity in a subject of acute pain.
29. The method of claim 28 , wherein the acute pain comprises acute post-operative pain.
30. The method of claim 22 , wherein the method comprises treating or lessening the severity in a subject of postsurgical pain.
31. The method of claim 22 , wherein the method comprises treating or lessening the severity in a subject of visceral pain.
32. 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.
33. The method of claim 32 , wherein the method comprises treating or lessening the severity in a subject of neuropathic pain.
34. The method of claim 33 , wherein the neuropathic pain comprises idiopathic small-fiber neuropathy.
35. The method of claim 33 , wherein the neuropathic pain comprises post-herpetic neuralgia.
36. The method of claim 32 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
37. The method of claim 36 , wherein the musculoskeletal pain comprises osteoarthritis pain.
38. The method of claim 32 , wherein the method comprises treating or lessening the severity in a subject of acute pain.
39. The method of claim 38 , wherein the acute pain comprises acute post-operative pain.
40. The method of claim 32 , wherein the method comprises treating or lessening the severity in a subject of postsurgical pain.
41. The method of claim 32 , wherein the method comprises treating or lessening the severity in a subject of visceral pain.
42. 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.
43. The method of claim 42 , wherein the method comprises treating or lessening the severity in a subject of neuropathic pain.
44. The method of claim 43 , wherein the neuropathic pain comprises idiopathic small-fiber neuropathy.
45. The method of claim 43 , wherein the neuropathic pain comprises post-herpetic neuralgia.
46. The method of claim 42 , wherein the method comprises treating or lessening the severity in a subject of musculoskeletal pain.
47. The method of claim 46 , wherein the musculoskeletal pain comprises osteoarthritis pain.
48. The method of claim 42 , wherein the method comprises treating or lessening the severity in a subject of acute pain.
49. The method of claim 48 , wherein the acute pain comprises acute post-operative pain.
50. The method of claim 42 , wherein the method comprises treating or lessening the severity in a subject of postsurgical pain.
51. The method of claim 42 , wherein the method comprises treating or lessening the severity in a subject of visceral pain.