Glucopyranosyloxypyrazole derivatives, medicinal compositions containing the same and intermediates in the production thereof

Abstract

The present invention relates to glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R 1 represents a hydrogen atom or a lower alkyl group; one of Q 1 and T 1 represents a group represented by the general formula: while the other represents a lower alkyl group or a halo(lower alkyl) group; and R 2 represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom, or pharmaceutically acceptable salts thereof, which have an inhibitory activity in human SGLT2 and are useful as agents for the prevention or treatment of diabetes, diabetic complications or obesity, and to pharmaceutical compositions comprising the same and intermediates thereof.

1 - 9 . (canceled)  
     
     
         10 . A method for preventing diabetes in a subject, which comprises administering to the subject an amount of the glucopyranosyloxypyrazole derivative of formula (I), or a pharmaceutically acceptable salt thereof, effective to prevent diabetes in the subject:  
       
         
           
           
               
               
           
         
       
       wherein R 1  represents a hydrogen atom or a lower alkyl group; one of Q 1  and T 1  represents a group represented by the formula:  
       
         
           
           
               
               
           
         
       
       while the other represents a lower alkyl group or a halo(lower alkyl) group; R 2  represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom, or a pharmaceutically acceptable salt thereof.  
     
     
         11 . A method as claimed in  claim 10 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is represented by the formula (II):  
       
         
           
           
               
               
           
         
       
       wherein R 11  represents a hydrogen atom or a straight-chained or branched alkyl group having 1 to 3 carbon atoms; one of Q 11  and T 11  represents a group represented by the formula:  
       
         
           
           
               
               
           
         
       
       while the other represents a straight-chained or branched alkyl group having 1 to 3 carbon atoms; and R 21  represents a straight-chained or branched alkyl group having 1 to 4 carbon atoms, a straight-chained or branched alkoxy group having 1 to 3 carbon atoms or a straight-chained or branched alkylthio group having 1 to 3 carbon atoms, or a pharmaceutically acceptable salt thereof.  
     
     
         12 . A method as claimed in  claim 10 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is represented by the formula (III):  
       
         
           
           
               
               
           
         
       
       wherein R 12  represents a hydrogen atom, an ethyl group, a propyl group or an isopropyl group; one of Q 12  and T 12  represents a group represented by the formula:  
       
         
           
           
               
               
           
         
       
       while the other represents a methyl group; and R 22  represents an ethyl group, an ethoxy group, an isopropoxy group or a methylthio group, or a pharmaceutically acceptable salt thereof.  
     
     
         13 . A method as claimed in  claim 10 , wherein the composition is a human SGLT2 inhibitor.  
     
     
         14 . A method as claimed in  claim 10 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is represented by the formula (IV):  
       
         
           
           
               
               
           
         
         wherein R 1  represents a hydrogen atom or a lower alkyl group; one of Q 2  and T 2  represents a 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy group, while the other represents a lower alkyl group or a halo(lower alkyl) group; and R 2  represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom, or a salt thereof.  
       
     
     
         15 . A method for preventing obesity in a subject, which comprises administering to the subject an amount of the glucopyranosyloxypyrazole derivative of formula (I), or a pharmaceutically acceptable salt thereof, effective to prevent obesity in the subject:  
       
         
           
           
               
               
           
         
       
       wherein R 1  represents a hydrogen atom or a lower alkyl group; one of Q 1  and T 1  represents a group represented by the formula:  
       
         
           
           
               
               
           
         
       
       while the other represents a lower alkyl group or a halo(lower alkyl) group; R 2  represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom, or a pharmaceutically acceptable salt thereof.  
     
     
         16 . A method as claimed in  claim 15 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is represented by the formula (II):  
       
         
           
           
               
               
           
         
       
       wherein R 11  represents a hydrogen atom or a straight-chained or branched alkyl group having 1 to 3 carbon atoms; one of Q 11  and T 11  represents a group represented by the formula:  
       
         
           
           
               
               
           
         
       
       while the other represents a straight-chained or branched alkyl group having 1 to 3 carbon atoms; and R 21  represents a straight-chained or branched alkyl group having 1 to 4 carbon atoms, a straight-chained or branched alkoxy group having 1 to 3 carbon atoms or a straight-chained or branched alkylthio group having 1 to 3 carbon atoms, or a pharmaceutically acceptable salt thereof.  
     
     
         17 . A method as claimed in  claim 15 , wherein the glucopyranosyloxypyrazole derivative in formula (I) is represented by the formula (III)  
       
         
           
           
               
               
           
         
       
       wherein R 12  represents a hydrogen atom, an ethyl group, a propyl group or an isopropyl group; one of Q 12  and T 12  represents a group represented by the formula:  
       
         
           
           
               
               
           
         
       
       while the other represents a methyl group; and R 22  represents an ethyl group, an ethoxy group, an isopropoxy group or a methylthio group, or a pharmaceutically acceptable salt thereof.  
     
     
         18 . A method as claimed in  claim 15 , wherein the composition is a human SGLT2 inhibitor.  
     
     
         19 . A method as claimed in  claim 15 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is represented by the formula (IV):  
       
         
           
           
               
               
           
         
         wherein R 1  represents a hydrogen atom or a lower alkyl group; one of Q 2  and T 2  represents a 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy group, while the other represents a lower alkyl group or a halo(lower alkyl) group; and R 2  represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom, or a salt thereof.  
       
     
     
         20 . A method as claimed in  claim 10 , wherein R 1  is a hydrogen atom, or a pharmaceutically acceptable salt thereof.  
     
     
         21 . A method as claimed in  claim 10 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is 3-(β-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)methyl]-1-isopropyl-5-methylpyrazole or a pharmaceutically acceptable salt thereof.  
     
     
         22 . A method as claimed in  claim 10 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is 3-(β-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)methyl]-5-methyl-1H-pyrazole.  
     
     
         23 . A method as claimed in  claim 15 , wherein R 1  is a hydrogen atom, or a pharmaceutically acceptable salt thereof.  
     
     
         24 . A method as claimed in  claim 15 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is 3-(β-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)methyl]-1-isopropyl-5-methylpyrazole or a pharmaceutically acceptable salt thereof.  
     
     
         25 . A method as claimed in  claim 15 , wherein the glucopyranosyloxypyrazole derivative of formula (I) is 3-(β-D-glucopyranosyloxy)-4-[(4-isopropoxyphenyl)methyl]-5-methyl-1H-pyrazole.