Compositions and methods of use of gamma-ketoaldheyde scavengers for treating, preventing or improving fibrosis of the liver

Abstract

Methods and compositions for use in treating, attenuating, preventing or improving liver fibrosis in a subject are described. The compounds of the present invention are gamma-ketoaldehyde scavengers.

We claim: 
     
         1 . A method for treating hepatic fibrosis, comprising:
 identifying a subject in need of treatment for hepatic fibrosis;   administering to said subject an effective isoLG scavenging amount of at least one compound of the following formula:   
       
         
           
           
               
               
           
         
       
       wherein:
 R 2  is independently chosen from H, substituted or unsubstituted alkyl; 
 R 3  is H, halogen, alkyl, alkoxy, hydroxyl, nitro; 
 R 4  is H, substituted or unsubstituted alkyl, carboxyl; and pharmaceutically acceptable salts thereof. 
 
     
     
         2 . The method of  claim 1 , wherein R 2  is independently chosen from H, ethyl, methyl. 
     
     
         3 . The method of  claim 1 , wherein the compound is 2-hydroyxbenzylamine, methyl-2-hydroyxbenzylamine, ethyl-2-hydroyxbenzylamine. 
     
     
         4 . The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         5 . The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         6 . The method of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         7 . The method of  claim 1 , wherein the treating step inhibits the progression of hepatic fibrosis. 
     
     
         8 . The method of  claim 1 , wherein the treating step attenuates the severity of hepatic fibrosis. 
     
     
         9 . The method of  claim 1 , wherein the treating step mitigates the damaging effects of hepatic fibrosis in the subject. 
     
     
         10 . The method of  claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered in a composition that comprises said compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 
     
     
         11 . The method of  claim 1 , wherein the subject in need of treatment for hepatic fibrosis has or is at risk of developing hepatic fibrosis due to an etiology unrelated to alcohol consumption. 
     
     
         12 . The method of  claim 11 , wherein the etiology is selected from the list consisting of nonalcoholic fatty liver disease (NAFLD), hepatitis, toxins, genetic conditions, autoimmune diseases and nonalcoholic steatohepatitis (NASH).