Bicyclic analgesic compounds
Analgesic compounds for treatment of pain or fever that include a bicyclopentane moiety linked to an amine, combinations of the compounds with opioid analgesic drugs, and methods for treating pain or fever by administering a compound described herein.
1. A method for reducing pain or fever comprising administering an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein Formula (I) has the structure:
wherein
R 1 is H or —CH 3 ;
R 2 is H or —C(═Y)R 4 ;
R 3 is H, hydroxy, NH 2 , an unsubstituted (C 1 to C 10 ) alkoxy, an unsubstituted (C 1 to C 6 )alkyl, an unsubstituted mono-cyclic (C 3 to C 6 ) cycloalkyl, an unsubstituted —NC(═O)—C 1-6 alkyl, (C═O)OR 6 or O(C═O)R 5 ;
R 4 is an unsubstituted (C 1 to C 10 ) alkyl or CF 3 ;
R 5 is an unsubstituted (C 1 to C 6 ) alkyl, a substituted or unsubstituted benzyl or
R 6 is an unsubstituted (C 1 to C 30 ) alkyl; and
Y is O.
2. The method of claim 1 , further comprising administering an opioid analgesic.
3. The method of claim 2 , wherein the opioid analgesic is selected from the group consisting of morphine, codeine, hydrocodone, oxycodone, fentanyl, pethidine, methadone, pentazocine, sufentanil, levorphanol, dihydrocodeine, nalbuphine, butorphanol, tramadol, meptazinol, buprenorphine, dipipanone, alfentanil, remifentanil, oxymorphone, tapentadol, propoxyphene and hydromorphone.
4. The method of claim 1 , wherein the administration is intravenous or topical.
5. The method of claim 1 , wherein the pain is post-operative pain.
6. The method of claim 1 , wherein R 2 is —C(═Y)R 4 ; and R 1 is H.
7. The method of claim 1 , wherein R 2 is H; and R 1 is H.
8. The method of claim 1 , wherein R 3 is H.
9. The method of claim 1 , wherein R 3 is hydroxy or an unsubstituted (C 1 to C 10 ) alkoxy.
10. The method of claim 1 , wherein R 3 is an unsubstituted (C 1 to C 6 )alkyl.
11. The method of claim 1 , wherein R 3 is an unsubstituted mono-cyclic (C 3 to C 6 ) cycloalkyl.
12. The method of claim 1 , wherein R 3 is NH 2 or an unsubstituted —NC(═O)—C 1-6 alkyl.
13. The method of claim 1 , wherein R 3 is —(C═O)OR 6 , wherein R 6 is an unsubstituted (C 1 to C 30 ) alkyl; or —O(C═O)R 5 , wherein R 5 is an unsubstituted (C 1 to C 6 ) alkyl, a substituted or unsubstituted benzyl or
14. A compound of Formula (I), or a pharmaceutically acceptable salt thereof:
wherein
R 1 is H or —CH 3 ;
R 2 is —C(═Y)R 4 ; and
R 3 is H, hydroxy, NH 2 , an unsubstituted (C 1 to C 10 ) alkoxy, an unsubstituted (C 1 to C 6 )alkyl, an unsubstituted mono-cyclic (C 3 to C 6 ) cycloalkyl, an unsubstituted —NC(═O)—C 1-6 alkyl, —(C═O)OR 6 or —O(C═O)R 5 ; or
R 1 is H;
R 2 is H;
R 3 is an unsubstituted (C 1 to C 10 ) alkoxy or an unsubstituted (C 2 to C 6 ) alkyl;
R 4 is an unsubstituted (C 1 to C 10 ) alkyl or CF 3 ;
R 5 is a substituted benzyl or
R 6 is an unsubstituted (C 1 to C 30 ) alkyl; and
Y is O.
15. The compound of claim 14 , wherein R 2 is —C(═Y)R 4 ; and R 1 is H.
16. The compound of claim 14 , wherein R 2 is H; and R 1 is H.
17. The compound of claim 14 , wherein R 3 is H.
18. The compound of claim 14 , wherein R 3 is hydroxy or an unsubstituted (C 1 to C 10 ) alkoxy.
19. The compound of claim 15 , wherein R 3 is an unsubstituted (C 1 to C 6 )alkyl.
20. The compound of claim 14 , wherein R 3 is an unsubstituted mono-cyclic (C 3 to C 6 ) cycloalkyl.
21. The compound of claim 14 , wherein R 3 is NH 2 or an unsubstituted —NC(═O)—C 1-6 alkyl.
22. The compound of claim 14 , wherein R 3 is —(C═O)OR 6 , wherein R 6 is an unsubstituted (C 1 to C 30 ) alkyl; or —O(C═O)R 5 , wherein R 5 is a substituted benzyl or
23. A pharmaceutical composition comprising an effective amount of a compound of claim 14 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof.
24. The compound of claim 16 , wherein R 3 is an unsubstituted (C 2 to C 6 )alkyl.