New pyrazole derivatives and diabetic medicine containing them

Abstract

The present invention provides pyrazole-O-glycoside derivatives represented by the following formulae, used as a diabetic medicine.

1 . A pyrazole compound of formula (1A) or a pharmaceutically acceptable salt thereof: 
     
       
         
         
             
             
         
       
     
     wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated or β-D-glucuronyl group, of which one or more hydroxyl groups may be acylated and a carboxyl group may be esterified; 
 Y represents a lower alkyl group or a perfluoro lower alkyl group; 
 Z represents a hydrogen atom, a lower alkyl group, a perfluoro lower alkyl group, an aralkyl group or a phenyl group; 
 R1, R2, R4, and R5 may be the same or different and each represents a hydrogen atom, a lower alkyl group, a perfluoro lower alkyl group, a lower alkoxy group, a perfluoro lower alkoxy group, a lower alkylthio group, a perfluoro lower alkylthio group, a lower alkyl amino group, a halogeno group, a lower alkanoyl group, a lower alkenyl group or a lower alkynyl group; and 
 n represents an integer from 1 to 3, 
 wherein at least one of R1, R2, R4, and R5 represents a lower alkyl group having 1 to 6 carbon atoms, lower alkylthio group having 1 to 6 carbon atoms, halogeno atom, lower alkoxy group, lower alkenyl group or lower alkynyl group; and 
 R3 represents a lower alkyl group having 1 to 6 carbon atoms, a lower alkylthio group having 1 to 6 carbon atoms, a halogeno atom, a lower alkoxy group, a lower alkenyl group, or a lower alkynyl group. 
 
   
   
       2 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 Y and Z each represent a lower alkyl group; and   each of R1, R2, R3, R4, and R5 may be the same or different and represents a hydrogen atom, a lower alkoxy group, or a halogeno group.   
   
   
       3 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 Y is a methyl group;   Z represent an isopropyl group; and   each of R1, R2, R3, R4, and R5 may be the same or different and represents a hydrogen atom, a lower alkoxy group, or a halogeno group.   
   
   
       4 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 Y and Z each represent a lower alkyl group;   R1 is a halogeno group;   R3 is a lower alkoxy group; and   each of R2, R4, and R5 is a hydrogen atom.   
   
   
       5 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 Y and Z each represent a lower alkyl group;   R1 is a fluorine atom;   R3 is a methoxy group; and   each of R2, R4, and R5 is a hydrogen atom.   
   
   
       6 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated;   Y and Z each represent a lower alkyl group; and   each of R1, R2, R3, R4, and R5 may be the same or different and represents a hydrogen atom, a lower alkoxy group, or a halogeno group.   
   
   
       7 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated;   Y is a methyl group;   Z represent an isopropyl group; and   each of R1, R2, R3, R4, and R5 may be the same or different and represents a hydrogen atom, a lower alkoxy group, or a halogeno group.   
   
   
       8 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated;   Y and Z each represent a lower alkyl group;   R1 is a halogeno group;   R3 is a lower alkoxy group; and   each of R2, R4, and R5 is a hydrogen atom.   
   
   
       9 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated;   Y and Z each represent a lower alkyl group;   R1 is a fluorine atom;   R3 is a methoxy group; and   each of R2, R4, and R5 is a hydrogen atom.   
   
   
       10 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 Y and Z each represent a lower alkyl group;   each of R1, R2, R3, R4, and R5 may be the same or different and represents a hydrogen atom, a lower alkoxy group, or a halogeno group; and   n is 1.   
   
   
       11 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 Y is a methyl group;   Z represent an isopropyl group;   each of R1, R2, R3, R4, and R5 may be the same or different and represents a hydrogen atom, a lower alkoxy group, or a halogeno group; and   n is 1.   
   
   
       12 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 Y and Z each represent a lower alkyl group;   R1 is a halogeno group;   R3 is a lower alkoxy group;   each of R2, R4, and R5 is a hydrogen atom; and   n is 1.   
   
   
       13 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 Y and Z each represent a lower alkyl group;   R1 is a fluorine atom;   R3 is a methoxy group;   each of R2, R4, and R5 is a hydrogen atom; and   n is 1.   
   
   
       14 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated;   Y and Z each represent a lower alkyl group;   each of R1, R2, R3, R4, and R5 may be the same or different and represents a hydrogen atom, a lower alkoxy group, or a halogeno group; and   n is 1.   
   
   
       15 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated;   Y is a methyl group;   Z represent an isopropyl group;   each of R1, R2, R3, R4, and R5 may be the same or different and represents a hydrogen atom, a lower alkoxy group, or a halogeno group; and   n is 1.   
   
   
       16 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated;   Y and Z each represent a lower alkyl group;   R1 is a halogeno group;   R3 is a lower alkoxy group;   each of R2, R4, and R5 is a hydrogen atom; and   n is 1.   
   
   
       17 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 X represents a β-D-glucopyranosyl group, of which one or more hydroxyl groups may be acylated;   Y and Z each represent a lower alkyl group;   R1 is a fluorine atom;   R3 is a methoxy group;   each of R2, R4, and R5 is a hydrogen atom; and   n is 1.   
   
   
       18 . The pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein said pyrazole compound is
 4-[(2-fluoro-4-methoxyphenyl)methyl]-1-isopropyl-5-methyl-1H-pyrazole-3-O-β-D-glucopyranoside, or a pharmaceutically acceptable salt thereof.   
   
   
       19 . A pharmaceutical composition comprising the pyrazole compound or a pharmaceutically acceptable salt thereof according to  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       20 . A method for treating diabetes which comprises administering an effective amount of a pharmaceutical composition according to  claim 19  to a patient in need thereof.