Method of treating liver disorders

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 inhibiting liver steatosis, lobular inflammation, hepatic ballooning and hepatic scarring.

1 . A method of inhibiting steatosis in a patient suffering from non-alcoholic steatohepatitis comprising administering to the patient 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 inhibiting lobular inflammation in a patient suffering from non-alcoholic steatohepatitis comprising administering to the patient 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. 
     
     
         17 . A method of inhibiting hepatic ballooning in a patient suffering from non-alcoholic steatohepatitis comprising administering to the patient 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. 
     
     
         18 . The method of  claim 17 , in which the compound of Formula (I) is of Formula (IA) 
       
         
           
           
               
               
           
         
       
     
     
         19 . The method of  claim 17 , in which the metabolite of the compound of Formula (I) is a compound of Formula (IB): 
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 17 , in which the compound is administered orally. 
     
     
         21 . The method of  claim 20 , in which the compound is administered as a tablet or a capsule. 
     
     
         22 . The method of  claim 18 , in which the compound is present in an orthorhombic polymorphic form A that is substantially free of other polymorphic forms. 
     
     
         23 . The method of  claim 17 , in which the compound is administered as a liquid dosage form. 
     
     
         24 . The method of  claim 17 , in which the compound is administered in an amount from 100 to 4,000 mg/day, divided into one, two, or three portions. 
     
     
         25 . A method of inhibiting hepatic scarring in a patient suffering from non-alcoholic steatohepatitis comprising administering to the patient 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. 
     
     
         26 . The method of  claim 25 , in which the compound of Formula (I) is of Formula (IA) 
       
         
           
           
               
               
           
         
       
     
     
         27 . The method of  claim 25 , in which the metabolite of the compound of Formula (I) is a compound of Formula (IB): 
       
         
           
           
               
               
           
         
       
     
     
         28 . The method of  claim 25 , in which the compound is administered orally. 
     
     
         29 . The method of  claim 28 , in which the compound is administered as a tablet or a capsule. 
     
     
         30 . The method of  claim 26 , in which the compound is present in an orthorhombic polymorphic form A that is substantially free of other polymorphic forms. 
     
     
         31 . The method of  claim 25 , in which the compound is administered as a liquid dosage form. 
     
     
         32 . The method of  claim 25 , in which the compound is administered in an amount from 100 to 4,000 mg/day, divided into one, two, or three portions. 
     
     
         33 . A method of reducing and/or inhibiting elevated liver hydroxyproline levels in a patient suffering from non-alcoholic steatohepatitis comprising administering to the patient 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. 
     
     
         34 . The method of  claim 33 , in which the compound of Formula (I) is of Formula (IA) 
       
         
           
           
               
               
           
         
       
     
     
         35 . The method of  claim 33 , in which the metabolite of the compound of Formula (I) is a compound of Formula (IB): 
       
         
           
           
               
               
           
         
       
     
     
         36 . The method of  claim 33 , in which the compound is administered orally. 
     
     
         37 . The method of  claim 36 , in which the compound is administered as a tablet or a capsule. 
     
     
         38 . The method of  claim 34 , in which the compound is present in an orthorhombic polymorphic form A that is substantially free of other polymorphic forms. 
     
     
         39 . The method of  claim 33 , in which the compound is administered as a liquid dosage form. 
     
     
         40 . The method of  claim 33 , in which the compound is administered in an amount from 100 to 4,000 mg/day, divided into one, two, or three portions.