Fused heterocycles

Abstract

This invention provides fused heterocycles having the formula: in which R 1 is a member selected from the group consisting of H, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R 2 is a member selected from the group consisting of H substituted or unsubstituted alkenyl, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R 3 is a member selected from the group consisting of H, C 1 -C 6 substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R 4 is a member selected from OH and O − X + , in which X + is positive ion which is a member selected from organic positive ions and inorganic positive ions. Substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl moieties have the formula: in which Ar is a member selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The index n is an integer from 1 to 4.

1 . A method of treating pain in a subject, said method comprising administering to said subject a therapeutically effective amount of a D-amino oxidase inhibitor having the formula: 
     
       
         
         
             
             
         
       
     
     in which
 R 1  is a member selected from the group consisting of H, and substituted or unsubstituted arylalkyl; 
 R 2  is a member selected from the group consisting of H, and substituted or unsubstituted arylalkyl; and 
 R 4  is a member selected from OH and O − X +   
 wherein
 X +  is a positive ion which is a member selected from organic positive ions and inorganic positive ions, 
 
 wherein
 substituted or unsubstituted arylalkyl has the formula: 
 
 
     
       
         
         
             
             
         
       
       
         in which
 Ar is substituted or unsubstituted aryl; and 
 n is an integer from 1 to 4. 
 
       
     
   
   
       2 . The method according to  claim 1  wherein said pain is neuropathic pain. 
   
   
       3 . The method according to  claim 2  wherein said neuropathic pain in a member selected from diabetic peripheral neuropathic pain and post-herpetic neuralgia. 
   
   
       4 . The method according to  claim 1  wherein said D-amino oxidase inhibitor is administered to said subject as a pharmaceutical composition in unit dosage form comprising, per dosage unit, a pharmaceutically acceptable carrier and a daily dosage of said D-amino oxidase inhibitor in an amount from about 0.1 mg to about 7000 mg. 
   
   
       5 . The method according to  claim 4  wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 50 mg to about 500 mg. 
   
   
       6 . The method according to  claim 5  wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 1 mg to about 100 mg. 
   
   
       7 . The method according to  claim 6  wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 25 mg to about 50 mg. 
   
   
       8 . The method according to  claim 4  wherein said unit dosage is an oral dosage form. 
   
   
       9 . The method according to  claim 6  wherein oral dosage form is a member selected from a tablet and a capsule. 
   
   
       10 . A method of treating pain in a subject, said method comprising administering to said subject a therapeutically effective amount of a D-amino oxidase inhibitor as a pharmaceutical composition comprising, in single or divided doses, a pharmaceutically acceptable carrier and a daily dosage of about 0.1 mg to about 7000 mg of said D-amino oxidase inhibitor, said D-amino oxidase inhibitor having the formula: 
     
       
         
         
             
             
         
       
     
     in which
 R 1  is a member selected from the group consisting of H, and substituted or unsubstituted arylalkyl; 
 R 2  is a member selected from the group consisting of H, and substituted or unsubstituted arylalkyl; and 
 R 4  is a member selected from OH and O − X +   
 wherein
 X +  is a positive ion which is a member selected from organic positive ions and inorganic positive ions, 
 
 wherein
 substituted or unsubstituted arylalkyl has the formula: 
 
 
     
       
         
         
             
             
         
       
       
         in which
 Ar is substituted or unsubstituted aryl; and 
 n is an integer from 1 to 4. 
 
       
     
   
   
       11 . The method according to  claim 10  wherein said pain is neuropathic pain. 
   
   
       12 . The method according to  claim 11  wherein said neuropathic pain in a member selected from diabetic peripheral neuropathic pain and post-herpetic neuralgia. 
   
   
       13 . The method according to  claim 10  wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 50 mg to about 500 mg. 
   
   
       14 . The method according to  claim 13  wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 1 mg to about 100 mg. 
   
   
       15 . The method according to  claim 14  wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 25 mg to about 50 mg. 
   
   
       16 . The method according to  claim 10  wherein said unit dosage is an oral dosage form. 
   
   
       17 . The method according to  claim 16  wherein oral dosage form is a member selected from a tablet and a capsule. 
   
   
       18 . A method of  claim 1   wherein
 R 1  is H; 
 R 2  is H; and 
 R 4  is a member selected from OH and O − X +   
 wherein
 X +  is a positive ion which is a member selected from organic positive ions and inorganic positive ions. 
 
   
   
   
       19 . The method according to  claim 18  wherein said pain is neuropathic pain. 
   
   
       20 . The method according to  claim 19  wherein said neuropathic pain is a member selected from diabetic peripheral neuropathic pain and post-herpetic neuralgia.