Deuterated pyridone amides and prodrugs thereof as modulators of sodium channels
Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. The compounds have the formula (I) wherein R is H or CH 2 OPO(OH) 2 . Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein R is H or CH 2 OPO(OH) 2 .
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of formula I is
3. The compound of claim 1 , wherein the compound of formula I is
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of formula I is
5. The compound of claim 1 , wherein the compound of formula I is
6. A pharmaceutical composition comprising a therapeutically effective amount of the compound or pharmaceutically acceptable salt of claim 1 and one or more pharmaceutically acceptable carriers or vehicles.
7. A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt of claim 1 and one or more pharmaceutically acceptable carriers or vehicles.
8. A method of inhibiting a voltage-gated sodium channel in a subject comprising administering to the subject the compound or pharmaceutically acceptable salt of claim 1 .
9. The method of claim 8 , wherein the voltage-gated sodium channel is Nav1.8.
10. 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, postsurgical pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia comprising administering to the subject an effective amount of the compound or pharmaceutically acceptable salt of claim 1 .
11. The method of claim 10 , where the method comprises treating or lessening the severity in the subject of neuropathic pain.
12. The method of claim 11 , wherein the neuropathic pain comprises post-herpetic neuralgia, idiopathic small-fiber neuropathy, or diabetic neuropathy.
13. The method of claim 10 , wherein the method comprises treating or lessening the severity in the subject of musculoskeletal pain.
14. The method of claim 13 , wherein the musculoskeletal pain comprises osteoarthritis pain.
15. The method of claim 10 , wherein the method comprises treating or lessening the severity in the subject of acute pain.
16. The method of claim 15 , wherein the acute pain comprises acute post-operative pain.
17. The method of claim 10 , wherein the method comprises treating or lessening the severity in the subject of postsurgical pain.
18. The method of claim 17 , wherein the postsurgical pain comprises bunionectomy pain or abdominoplasty pain.
19. The method of claim 10 , wherein the method comprises treating or lessening the severity in the subject of visceral pain.
20. The method of claim 10 , wherein said subject is treated with one or more additional therapeutic agents administered concurrently with, prior to, or subsequent to treatment with the compound, pharmaceutically acceptable salt, or pharmaceutical composition.