Deuterium-enriched pioglitazone

Abstract

The present application describes deuterium-enriched pioglitazone, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

1 . A method of treating diabetes mellitus type 2, comprising administering a therapeutically effective amount of a deuterium-enriched compound of formula Ito a patient in need thereof to treat the diabetes mellitus type 2, wherein formula I is represented by: 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, wherein R 1  and R 3 -R 20  are independently H or D. 
       
     
     
         2 . The method of  claim 1 , wherein R 1  and R 3 -R 20  are H. 
     
     
         3 . The method of  claim 1 , wherein the deuterium-enriched compound is 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method of  claim 3 , wherein R 1  and R 3 -R 20  are H. 
     
     
         5 . The method of  claim 1 , wherein the deuterium-enriched compound is represented by 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of  claim 5 , wherein R 1  and R 3 -R 20  are H. 
     
     
         7 . The method of  claim 1 , wherein the deuterium-enriched compound is 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 1 , wherein the deuterium-enriched compound is represented by 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 8 , wherein R 1  and R 3 -R 20  are H. 
     
     
         10 . The method of  claim 1 , wherein the deuterium-enriched compound is 
       
         
           
           
               
               
           
         
       
     
     
         11 . A method of treating non-alcoholic steatohepatitis, comprising administering a therapeutically effective amount of a deuterium-enriched compound of formula Ito a patient in need thereof to treat the non-alcoholic steatohepatitis, wherein formula I is represented by: 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof, wherein R 1  and R 3 -R 20  are independently H or D. 
       
     
     
         12 . The method of  claim 1   1 , wherein R 1  and R 3 -R 20  are H. 
     
     
         13 . The method of  claim 11 , wherein the deuterium-enriched compound is 
       
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 13 , wherein R 1  and R 3 -R 20  are H. 
     
     
         15 . The method of  claim 11 , wherein the deuterium-enriched compound is represented by 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 15 , wherein R 1  and R 3 -R 20  are H. 
     
     
         17 . The method of  claim 11 , wherein the deuterium-enriched compound is 
       
         
           
           
               
               
           
         
       
     
     
         18 . The method of  claim 11 , wherein the deuterium-enriched compound is represented by 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of  claim 8 , wherein R 1  and R 3 -R 20  are H. 
     
     
         20 . The method of  claim 11 , wherein the deuterium-enriched compound is