Chemical compounds containing a superoxide scavenger and an organic nitrate or nitrite moiety

Abstract

Compounds for use in the treatment of heart disease include a superoxide scavenger and an organic nitrate or nitrite moiety. The compounds can be represented by the formula (A)n(B)m, in which A is a superoxide scavenger, B is an organic nitrate or organic nitrite moiety, and n and m are values between 1 and 8. These compounds do not suffer from the problem of patient tolerance that is associated with the use of conventional agents such as organic nitrates.

1 . A compound comprising a superoxide scavenger and an organic nitrate or nitrite moiety.  
     
     
         2 . A compound according to  claim 1 , which is represented by formula (I):  
         (A)n(B)m  (I)  
       where A is a superoxide scavenger, B is an organic nitrate or organic nitrite moiety, n and m are values between 1 and 8.  
     
     
         3 . A compound according to  claim 2 , wherein in formula (I), n and m are integers.  
     
     
         4 . A compound according to  claim 3 , wherein the values of n and m are both 1.  
     
     
         5 . A compound according to  claim 2  wherein A and B are stably linked.  
     
     
         6 . A compound according to  claim 2 , wherein said organic nitrate or nitrite moiety forms nitric oxide in the body of an animal.  
     
     
         7 . A compound according to  claim 6 , wherein the nitric oxide is formed by enzymatic conversion of said organic nitrate or nitrite moiety by endogenous enzymes in the body of an animal.  
     
     
         8 . A compound according to  claim 7 , wherein said enzymatic conversion is by xanthine oxidase.  
     
     
         9 . A compound according to  claim 6 , wherein the superoxide scavenger remains effective in trapping superoxide upon enzymatic conversion of the organic nitrate or nitrite moiety to form nitric oxide  
     
     
         10 . A compound according to  claim 2 , wherein the superoxide scavenger is a low molecular mass superoxide dismutase analog.  
     
     
         11 . A compound according to  claim 2 , wherein the superoxide scavenger is a spin trap capable of trapping superoxide.  
     
     
         12 . A compound according to  claim 2  wherein the superoxide scavenger contains one or more thiol groups.  
     
     
         13 . A compound according to  claim 2 , wherein said superoxide scavenger is linked to the organic nitrate or nitrite moiety by a linkage that is stable S under physiological conditions.  
     
     
         14 . A compound according to  claim 13 , wherein said linkage is a thiol linkage.  
     
     
         15 . A compound having the formula  
       
         
           
           
               
               
           
         
       
     
     
         16 . A composition comprising a compound according to  claim 2  in conjunction with a pharmaceutically-acceptable excipient.  
     
     
         17 . A method of treating heart disease comprising administering a compound according to  claim 2  in a therapeutically effective amount to a patient in need thereof.