Bicyclic analgesic compounds

Abstract

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 or at least partially preventing 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, —CH 3 , —CF 3  or a substituted or unsubstituted (C 2  to C 5 ) alkyl; 
         R 2  is H or —C(═Y)R 4 ; 
         R 3  is H, F, D, hydroxy, NH 2 , a (C 1  to C 10 ) alkoxy, a substituted or unsubstituted (C 1  to C 30 ) alkyl, a substituted or unsubstituted (C 2  to C 30 ) alkenyl, a substituted or unsubstituted (C 2  to C 30 ) alkynyl, a substituted or unsubstituted (C 3  to C 30 ) cycloalkyl, a substituted or unsubstituted (C 3  to C 30 ) cycloalkenyl, a substituted or unsubstituted (C 8  to C 30 ) cycloalkynyl, a substituted or unsubstituted (C 6  to C 30 ) aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl(C 1-6  alkyl), a substituted or unsubstituted heteroaryl(C 1-6  alkyl), a substituted or unsubstituted —N-linked amido, —(C═O)L or —O(C═O)R 5 , wherein —(C═O)L is a hydrolyzable prodrug ester leaving group, 
         R 4  is a substituted or unsubstituted (C 1  to C 10 ) alkyl; 
         R 5  is a substituted or unsubstituted (C 1  to C 6 ) alkyl, a substituted or unsubstituted aryl(C 1-6  alkyl) or 
       
       
         
           
           
               
               
           
         
       
       and
 Y is S or O. 
 
     
     
         2 .- 41 . (canceled) 
     
     
         42 . A compound of Formula (I), or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H, —CH 3 , —CF 3 , or a substituted or unsubstituted (C 2  to C 5 ) alkyl; 
         R 2  is —C(═Y)R 4 ; and 
         R 3  is H, F, D, hydroxy, NH 2 , a (C 1  to C 10 ) alkoxy, a substituted or unsubstituted (C 1  to C 30 ) alkyl, a substituted or unsubstituted (C 2  to C 30 ) alkenyl, a substituted or unsubstituted (C 2  to C 30 ) alkynyl, a substituted or unsubstituted (C 3  to C 30 ) cycloalkyl, a substituted or unsubstituted (C 3  to C 30 ) cycloalkenyl, a substituted or unsubstituted (C 8  to C 30 ) cycloalkynyl, a substituted or unsubstituted (C 6  to C 30 ) aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl(C 1-6  alkyl), a substituted or unsubstituted heteroaryl(C 1-6  alkyl), a substituted or unsubstituted —N-linked amido, —(C═O)L or —O(C═O)R 5 , wherein —(C═O)L is a hydrolyzable prodrug ester leaving group; or 
         R 1  is H, —CH 3 , —CF 3 , or a substituted or unsubstituted (C 2  to C 5 ) alkyl; 
         R 2  is H; 
         R 3  is H, D, a (C 1  to C 10 ) alkoxy, a substituted (C 1  to C 10 ) alkyl, an unsubstituted (C 2  to C 30 ) alkyl, a substituted or unsubstituted (C 2  to C 30 ) alkenyl, a substituted or unsubstituted (C 2  to C 30 ) alkynyl, a substituted or unsubstituted (C 3  to C 30 ) cycloalkyl, a substituted or unsubstituted (C 3  to C 30 ) cycloalkenyl, a substituted or unsubstituted (C 8  to C 30 ) cycloalkynyl, a substituted (C 6  to C 30 ) aryl, an unsubstituted (C 7  to C 30 ) aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl(C 1-6  alkyl), a substituted or unsubstituted heteroaryl(C 1-6  alkyl), a substituted or unsubstituted —N-linked amido or —O(C═O)R 5 ; 
         R 4  is or a substituted or unsubstituted (C 1  to C 10 ) alkyl; 
         R 5  is a substituted or unsubstituted (C 1  to C 6 ) alkyl, a substituted or unsubstituted aryl(C 1-6  alkyl) or 
       
       
         
           
           
               
               
           
         
       
       and
 Y is S or O; and 
 with the proviso that when R 3  hydrogen, then R 1  and R 2  cannot both be hydrogen. 
 
     
     
         43 .- 72 . (canceled) 
     
     
         73 . A pharmaceutical composition comprising an effective amount of a compound of  claim 42 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combination thereof.