Substituted gamma lactams as therapeutic agents

Abstract

A compound comprising or a pharmaceutically acceptable salt, prodrug, or a metabolite thereof is disclosed herein. Y, A, and B are as described herein. Methods, compositions, and medicaments related to these compounds are also disclosed.

1 . A method for treating inflammation comprising administering to a subject in need thereof a therapeutically effective amount of a compound having the structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof;
 wherein
 A is —(CH 2 ) 6 —, cis —CH 2 CH═CH—(CH 2 ) 3 —, or —CH 2 C≡C—(CH 2 ) 3 —, wherein 1 or 2 carbon atoms may be substituted with S or O; or A is —(CH 2 ) m —Ar—(CH 2 ) o —wherein Ar is interarylene or heterointerarylene, the sum of m and o is from 1 to 4, and wherein one CH 2  may be substituted with S or O; 
 R 1  is C 1  to C 6  alkyl; and 
 B is optionally substituted aryl or optionally substituted heteroaryl. 
 
 
     
     
         2 . The method of  claim 1  wherein B is phenyl. 
     
     
         3 . The method of  claim 2  wherein B is alkylphenyl. 
     
     
         4 . The method of  claim 2  wherein B is p-t-butylphenyl. 
     
     
         5 . The method of  claim 2  wherein B is hydroxyalkylphenyl. 
     
     
         6 . The method of  claim 1  wherein R 1  is C 3  alkyl. 
     
     
         7 . The method of  claim 1  wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 1  wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 1  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof;
 wherein 
 G is 1,3-interaryl or interheteroaryl, or —(CH 2 ) 3 —; 
 R 1  is C 1  to C 6  alkyl; and 
 B is optionally substituted aryl or optionally substituted heteroaryl. 
 
     
     
         10 . The method of  claim 9  wherein B is phenyl. 
     
     
         11 . The method of  claim 10  wherein B is alkylphenyl. 
     
     
         12 . The method of  claim 10  wherein B is p-t-butylphenyl. 
     
     
         13 . The method of  claim 10  wherein B is hydroxyalkylphenyl. 
     
     
         14 . The method of  claim 9  wherein R, is C 3  alkyl. 
     
     
         15 . The method of  claim 1  wherein the compound has the structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof;
 wherein 
 a dashed line indicates the presence or absence of a bond; 
 R 1  is C 1  to C 6  alkyl; 
 R 2  is C 1  to C 12  hydrocarbyl or C 1  to C 12  hydroxyhydrocarbyl; 
 X is CH 2 , O, or S; and 
 G is 1,3-interaryl or interheteroaryl, or —(CH 2 ) 3 —. 
 
     
     
         16 . The method of  claim 15 , wherein R 1  is C 3  alkyl. 
     
     
         17 . The method of  claim 15  wherein R 1  is isopropyl.