Nitric oxide donors

Abstract

The present invention provides, in part a novel class of nonoate compounds which exhibit nitric oxide releasing activity and their pharmaceutically acceptable salts, esters and prodrugs. The compounds release nitric oxide upon activation by contact with plasma. The present invention also relates to the use of the disclosed compounds to deliver nitric oxide to treat disorders arising from nitric oxide dysregulation.

1 - 55 . (canceled) 
     
     
         56 . A composition comprising a compound represented by the Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester or prodrug thereof, where:
 X is CH 2 , m is 1; 
 R is alkyl, preferably having from 1 to 6 carbon atoms; 
 R 1  is alkyl, preferably having from 1 to 6 carbon atoms; 
 or R and R 1  taken together are carbon atoms to form a 5-7 member heterocyclic ring, said 5- 7 member heterocyclic ring being optionally substituted with —CH 2 OH; 
 A is —B(OR 2 )(OR 3 ), —(Y) p —C(═O)-R 4 , 
 
       
         
           
           
               
               
           
         
       
       1,3-dioxoisoindolin-2-yl, heterocycloalkyl, or a lipid, where
 Y is —CH 2 — and p is 0 or 1; 
 q is 0, 1 or 2; 
 R 2  and R 3  are the same or different and are alkyl, or aryl, optionally substituted with —OH; 
 R 4  is alkyl (optionally substituted with —NH 2 ), alkenyl, heteroalkyl (optionally substituted with one or more moieties independently selected from oxo, halo and 
 
       
         
           
           
               
               
           
         
       
       aryl, N-alkyl, N-aryl, O-alkyl or O-aryl; and with the proviso that R 4  is not methyl and Z is alkyl, aryl, N-alkyl, N-aryl, O-alkyl or O-aryl. 
     
     
         57 . The composition of  claim 56 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         58 . A composition comprising a compound selected from: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester or prodrug thereof. 
     
     
         59 . The compound of  claim 56 , wherein the compound is capable of releasing nitric oxide under physiological conditions. 
     
     
         60 . A pharmaceutical composition, comprising the compound of  claim 56  and a pharmaceutically acceptable carrier or excipient. 
     
     
         61 . A method for treating a disorder of nitric oxide dysregulation comprising administering a therapeutically effective amount of the compound of  claim 56  or a pharmaceutically acceptable salt, ester or prodrug thereof to a patient in need thereof. 
     
     
         62 . The method of  claim 61 , wherein the disorder of nitric oxide dysregulation is one or more of a cardiovascular disorder, vasodilation, and erectile dysfunction. 
     
     
         63 . The method of  claim 61 , wherein the disorder of nitric oxide dysregulation is a cardiovascular disorder. 
     
     
         64 . The method of  claim 61 , wherein the disorder of nitric oxide dysregulation is a metabolic-related disorder. 
     
     
         65 . The method of  claim 61 , wherein the disorder of nitric oxide dysregulation is a pulmonary disorder. 
     
     
         66 . The method of  claim 61 , wherein the disorder of nitric oxide dysregulation is an intraocular pressure-associated disorder. 
     
     
         67 . The method of  claim 66 , wherein the intraocular pressure-associated disorder is glaucoma. 
     
     
         68 . The method of  claim 61 , wherein the disorder of nitric oxide dysregulation is ischemia. 
     
     
         69 . The method of  claim 61 , wherein the disorder of nitric oxide dysregulation is infection, and optionally wherein the infection is bacterial infection. 
     
     
         70 . The method of  claim 61 , wherein the disorder of nitric oxide dysregulation is cancer. 
     
     
         71 . A method for enhancing or stimulating wound healing, comprising administering a therapeutically effective amount of the compound of  claim 56  or a pharmaceutically acceptable salt, ester or prodrug thereof to a patient in need thereof.