Pharmaceutical composition for treating diabetes

Abstract

Provided is a compound represented by the following general formula (I), or a pharmaceutically acceptable salt thereof. This novel compound has a glycogen-synthase activation ability, but activates a receptor PPAR to a low degree and is highly safe. In the formula, Ar is an aromatic carbocyclic ring or a heterocyclic ring; and Ar 2 is represented by any one of the following rings and the like.

What is claimed is: 
     
         1 . A compound of formula (I), or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein Ar is an aromatic carbocyclic ring or a heterocyclic ring; 
         Ar 2  is represented by any one of the following rings 
       
       
         
           
           
               
               
           
         
         these rings may have a substituent, and 
         the substituent is selected from the group consisting of acetamido, aminocarbonyl, benzyl, benzyloxy, a halogen, hydroxyl-lower alkyl, lower alkyl, lower alkoxy-lower alkyl, phenoxy, phenyl, a formyl group, a cyano group, a cyanoalkyl group, a hydroxyiminomethyl group, a hydroxyamidino group, an amino group, an aminoalkyl group, an alkylaminoalkyl group, a dialkylaminoalkyl group, lower alkoxy, and trifluoro-methoxy; 
         R 2  and R 3  are independently selected from the group consisting of lower alkyl, lower alkoxy, trifluoromethyl, a halogen, hydroxy, a hydroxyl-lower alkyl group, amino, alkylamino, dialkylamino, cyano, and nitro; 
         R 4  is an amino acid residue bonded to C(O) through a nitrogen atom of the amino acid; 
         R 5  is a cyanoalkyl group or —CD3, or is represented by any one of the following substituents 
       
       
         
           
           
               
               
           
         
         R 6  is hydrogen, a lower alkyl group, a cyanoalkyl group, a hydroxyalkyl group, or an alkoxyalkyl group, or is represented by any one of the following substituents 
       
       
         
           
           
               
               
           
         
         R 7  and R 8  are each a cyanoalkyl group, a formyl group, an alkoxycarbonyl group, or a hydroxyiminomethyl group; 
         R 9  is hydrogen or a lower alkyl group; 
         m is 0, 1, 2, 3, or 4; 
         p is 0, 1, or 2; and 
         s is 0, 1, or 2. 
       
     
     
         2 . A compound of formula (I), or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein Ar is an aromatic carbocyclic ring or a heterocyclic ring; 
         Ar 2  is represented by any one of the following rings 
       
       
         
           
           
               
               
           
         
         these rings may have a substituent, and 
         the substituent is selected from the group consisting of acetamido, aminocarbonyl, benzyl, benzyloxy, a halogen, hydroxyl-lower alkyl, lower alkyl, lower alkoxy-lower alkyl, phenoxy, phenyl, lower alkoxy, and trifluoro-methoxy; 
         R 2  and R 3  are independently selected from the group consisting of lower alkyl, lower alkoxy, trifluoromethyl, a halogen, hydroxy, amino, alkylamino, dialkylamino, cyano, and nitro; 
         R 4  is an amino acid residue bonded to C(O) through a nitrogen atom of the amino acid; 
         R 5  is —CH2CN or —CD3, or is represented by any one of the following substituents 
       
       
         
           
           
               
               
           
         
         R 6  is hydrogen or a lower alkyl group; 
         m is 0, 1, 2, 3, or 4; 
         p is 0, 1, or 2; and 
         s is 0, 1, or 2. 
       
     
     
         3 . The compound according to  claim 2 , or a pharmaceutically acceptable salt thereof, wherein
 Ar is a phenyl group, and   R 4  represents a proline residue bonded to C(O) through a nitrogen atom of the proline.   
     
     
         4 . The compound according to  claim 2 , or a pharmaceutically acceptable salt thereof, wherein
 Ar is a phenyl group,   R 4  represents a proline residue bonded to C(O) through a nitrogen atom of the proline, and   Ar 2  is represented by any one of the following rings   
       
         
           
           
               
               
           
         
       
     
     
         5 . A pharmaceutical composition, comprising:
 the compound according to  claim 1  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         6 . A pharmaceutical composition, comprising:
 the compound according to  claim 2  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         7 . The compound according to  claim 2 , or a pharmaceutically acceptable salt thereof, wherein
 Ar is an aromatic carbocyclic ring.   
     
     
         8 . The compound according to  claim 2 , or a pharmaceutically acceptable salt thereof, wherein
 Ar is a heterocyclic ring.   
     
     
         9 . The compound according to  claim 2 , or a pharmaceutically acceptable salt thereof, wherein
 Ar 2  is represented by   
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound according to  claim 7 , or a pharmaceutically acceptable salt thereof, wherein
 Ar 2  is represented by   
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound according to  claim 8 , or a pharmaceutically acceptable salt thereof, wherein
 Ar 2  is represented by   
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound according to  claim 4 , or a pharmaceutically acceptable salt thereof, wherein
 Ar 2  is represented by   
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound according to  claim 4 , or a pharmaceutically acceptable salt thereof, wherein
 Ar 2  is represented by   
       
         
           
           
               
               
           
         
       
     
     
         14 . A pharmaceutical composition, comprising:
 the compound according to  claim 7  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         15 . A pharmaceutical composition, comprising:
 the compound according to  claim 8  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         16 . A pharmaceutical composition, comprising:
 the compound according to  claim 9  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         17 . A pharmaceutical composition, comprising:
 the compound according to  claim 10  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         18 . A pharmaceutical composition, comprising:
 the compound according to  claim 11  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         19 . A pharmaceutical composition, comprising:
 the compound according to  claim 12  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
     
     
         20 . A pharmaceutical composition, comprising:
 the compound according to  claim 13  or a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.