Compounds for the treatment of pain
Provided herein are compounds that are useful in the treatment of pain in a subject.
1. A compound of Formula IV:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is C 1-2 alkoxy, wherein the C 1-2 alkoxy is optionally substituted with 1, 2, or 3 halo substituents;
R 2 is hydrogen, C 1-6 alkyl, C 3-10 cycloalkyl, 4- to 12-membered heterocycloalkyl, C 1-4 alkylene-CF 3 , C 1-4 alkylene-(C 3-10 cycloalkyl), C 1-4 alkylene-(4- to 12-membered heterocycloalkyl), C 1-4 alkylene-(5- to 14-membered heteroaryl), or (C 3-10 cycloalkylene)-(C 6-14 aryl);
wherein each of the C 1-6 alkyl, C 3-10 cycloalkyl, 4- to 12-membered heterocycloalkyl, C 1-4 alkylene, C 3-10 cycloalkylene, C 6-14 aryl, and 5- to 14-membered heteroaryl of R 2 is unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of —OH, halo, C 1-4 alkyl, C 1-4 alkoxy, —C(═O)—(C 1-4 alkyl), and —S(═O) 2 —(C 1-4 alkyl); or
wherein the C 3-10 cycloalkyl, 5- to 14-membered heteroaryl, or 4- to 12-membered heterocycloalkyl of R 2 is optionally substituted with 1, 2, or 3 oxo moieties; and
R 3 is hydrogen, OH, halo, C 1-4 alkyl, or C 1-4 alkoxy.
2. The compound of claim 1 , wherein R 2 is C 3-10 cycloalkyl or 4- to 12-membered heterocycloalkyl, wherein C 3-10 cycloalkyl, 4- to 12-membered heterocycloalkyl is unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of —OH, halo, C 1-4 alkyl, C 1-4 alkoxy, —C(═O)—(C 1-4 alkyl), and —S(═O) 2 —(C 1-4 alkyl).
3. The compound of claim 1 , wherein R 2 is C 1-6 alkyl or C 1-4 alkylene-CF 3 .
4. The compound of claim 3 , wherein R 2 is C 1-6 alkyl.
5. The compound claim 1 , wherein R 1 is unsubstituted C 1-2 alkoxy.
6. The compound of claim 1 , wherein R 1 is —OCH 3 .
7. The compound of claim 1 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
8. The compound of claim 7 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 7 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 7 , selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
12. A method of treating pain in a subject in need thereof comprising administering to the subject the compound of claim 1 .
13. The method of claim 12 , wherein the pain is inflammatory pain, thermal pain, acute pain, chronic pain, traumatic pain, chemical pain, ischemic pain, centrally mediated pain, peripherally mediated pain, prickling pain, visceral pain, progressive disease pain, musculoskeletal pain and neuropathic pain.
14. The method of claim 12 , wherein the pain is inflammatory pain, thermal pain, acute pain, chronic pain, musculoskeletal pain, and neuropathic pain.
15. The method of claim 12 , wherein the pain is chronic pain.
16. The method of claim 12 , wherein the pain is musculoskeletal pain.