Method of treating non-alcoholic fatty liver disease and steatohepatitis

Abstract

A compound of Formula (I): or a metabolite thereof, or an ester of the compound of Formula (I) or the metabolite thereof, or a pharmaceutically acceptable salt of each thereof, wherein m, n, X 1 and X 2 are as defined herein, is useful for treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).

1 . A method of reducing hepatic fibrosis in a patient suffering from non-alcoholic steatohepatitis (NASH) comprising administering to a patient in need thereof an effective amount of a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
       or a metabolite thereof, or an ester of the compound of Formula (I) or the metabolite thereof, or a pharmaceutically acceptable salt of each thereof, wherein m is an integer from 2 to 5, and n is an integer from 3 to 8, X 1  and X 2  each independently represent a sulfur atom, oxygen atom, sulfinyl group or a sulfonyl group, provided that X 1  and X 2  are not simultaneously oxygen atom. 
     
     
         2 . The method of  claim 1 , in which the compound of Formula (I) is of Formula (IA) 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , in which the metabolite of the compound of Formula (I) is a compound of Formula (IB): 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method of  claim 1 , in which the compound is administered orally. 
     
     
         5 . The method of  claim 4 , in which the compound is administered as a tablet or a capsule. 
     
     
         6 . The method of  claim 2 , in which the compound is present in an orthorhombic polymorphic form A that is substantially free of other polymorphic forms. 
     
     
         7 . The method of  claim 1 , in which the compound is administered as a liquid dosage form. 
     
     
         8 . The method of  claim 1 , in which the compound is administered in an amount from 100 to 4,000 mg/day, divided into one, two, or three portions. 
     
     
         9 . A method of reducing damage to liver cells in a patient suffering from non-alcoholic steatohepatitis (NASH) comprising administering to a patient in need thereof an effective amount of a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
       or a metabolite thereof, or an ester of the compound of Formula (I) or the metabolite thereof, or a pharmaceutically acceptable salt of each thereof, wherein m is an integer from 2 to 5, and n is an integer from 3 to 8, X 1  and X 2  each independently represent a sulfur atom, oxygen atom, sulfinyl group or a sulfonyl group, provided that X 1  and X 2  are not simultaneously oxygen atom. 
     
     
         10 . The method of  claim 9 , in which the compound of Formula (I) is of Formula (IA) 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 9 , in which the metabolite of the compound of Formula (I) is a compound of Formula (IB): 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 9 , in which the compound is administered orally. 
     
     
         13 . The method of  claim 12 , in which the compound is administered as a tablet or a capsule. 
     
     
         14 . The method of  claim 10 , in which the compound is present in an orthorhombic polymorphic form A that is substantially free of other polymorphic forms. 
     
     
         15 . The method of  claim 9 , in which the compound is administered as a liquid dosage form. 
     
     
         16 . The method of  claim 9 , in which the compound is administered in an amount from 100 to 4,000 mg/day, divided into one, two, or three portions.