Glucopyranosyloxybenzylbenzene derivatives and medicinal compositions containing the same

Abstract

The present invention relates to glucopyranosyloxy-benzylbenzene derivatives represented by the general formula: wherein P represents a group forming a prodrug; and R represents a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group or a lower alkoxy-substituted (lower alkylthio) group, which have an improved oral absorption and can exert an excellent inhibitory activity in human SGLT2 in vivo and which are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutical compositions comprising the same.

1 - 2 . (canceled).  
     
     
         3 . A method as claimed in  claim 14 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  represents a lower alkyl group or a lower alkoxy group; and P 1  represents a lower acyl group, a lower alkoxy-substituted (lower acyl) group, a lower alkoxycarbonyl-substituted (lower acyl) group, a lower alkoxycarbonyl group or a lower alkoxy-substituted (lower alkoxycarbonyl) group.  
       
     
     
         4 . A method as claimed in  claim 14 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the general formula:  
       
         
           
           
               
               
           
         
         wherein R represents a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group or a lower alkoxy-substituted (lower alkylthio) group; and P 2  represents a lower acyl group or a lower alkoxycarbonyl group.  
       
     
     
         5 . A method as claimed in  claim 14 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  represents a lower alkyl group or a lower alkoxy group; and P 2  represents a lower acyl group or a lower alkoxycarbonyl group.  
       
     
     
         6 . A method as claimed in  claim 14 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the formula:  
       
         
           
           
               
               
           
         
       
     
     
         7 . A method as claimed in  claim 14 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the formula:  
       
         
           
           
               
               
           
         
       
     
     
         8 - 13 . (canceled).  
     
     
         14 . A method for the prevention of a disease associated with hyperglycemia, which comprises administering to a patient in need of the prevention of a disease associated with hyperglycemia a therapeutically effective amount of a glucopyranosyloxybenzylbenzene derivative represented by the general formula:  
       
         
           
           
               
               
           
         
       
       wherein R represents a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group or a lower alkoxy-substituted (lower alkylthio) group; and P 1  represents a lower acyl group, a lower alkoxy-substituted (lower acyl) group, a lower alkoxycarbonyl-substituted (lower acyl) group, a lower alkoxycarbonyl group or a lower alkoxy-substituted (lower alkoxycarbonyl) group.  
     
     
         15 . (canceled).  
     
     
         16 . A method for providing a preventing effect on a disease associated with hyperglycemia, which comprises administering to a patient in need of the preventing effect a therapeutically effective amount of a glucopyranosyloxybenzylbenzene derivative represented by the general formula:  
       
         
           
           
               
               
           
         
         wherein R represents a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group or a lower alkoxy-substituted (lower alkylthio) group; and P 1  represents a lower acyl group, a lower alkoxy-substituted (lower acyl) group, a lower alkoxycarbonyl-substituted (lower acyl) group, a lower alkoxycarbonyl group or a lower alkoxy-substituted (lower alkoxycarbonyl) group.  
       
     
     
         17 . A method as claimed in  claim 16 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  represents a lower alkyl group or a lower alkoxy group; and P 1  represents a lower acyl group, a lower alkoxy-substituted (lower acyl) group, a lower alkoxycarbonyl-substituted (lower acyl) group, a lower alkoxycarbonyl group or a lower alkoxy-substituted (lower alkoxycarbonyl) group.  
       
     
     
         18 . A method as claimed in  claim 16 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the general formula:  
       
         
           
           
               
               
           
         
         wherein R represents a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a lower alkoxy-substituted (lower alkyl) group, a lower alkoxy-substituted (lower alkoxy) group or a lower alkoxy-substituted (lower alkylthio) group; and P 2  represents a lower acyl group or a lower alkoxycarbonyl group.  
       
     
     
         19 . A method as claimed in  claim 16 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  represents a lower alkyl group or a lower alkoxy group; and P 2  represents a lower acyl group or a lower alkoxycarbonyl group.  
       
     
     
         20 . A method as claimed in  claim 16 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the formula:  
       
         
           
           
               
               
           
         
       
     
     
         21 . A method as claimed in  claim 16 , wherein the glucopyranosyloxybenzylbenzene derivative is represented by the formula: