Novel heteroaryl derivative

Abstract

A heteroaryl derivative of the formula (1): (wherein Ring Z is an optionally substituted heteroaryl, R 1 is a carboxyl group or an alkoxycarbonyl group, etc., W 1 and W 2 are an optionally substituted lower alkylene, Ar 1 is an optionally substituted arylene or an optionally substituted heteroarylene, W 3 is a single bond, a lower alkylene, a lower alkenylene, etc., W 4 is a single bond, —NR 10 —, etc., Ar 2 is an optionally substituted aryl or an optionally substituted heteroaryl), or a prodrug thereof, or a pharmaceutically acceptable salt thereof.

1 . A heteroaryl derivative of the formula (1): 
     
       
         
         
             
             
         
       
     
     wherein Ring Z is an optionally substituted heteroaryl;
 R 1  is a carboxyl group, an alkoxycarbonyl group, an optionally substituted carbamoyl group, an optionally substituted cyclic aminocarbonyl group, an optionally substituted alkylsulfonylcarbamoyl group, an optionally substituted arylsulfonylcarbamoyl group, or a tetrazolyl group; 
 W 1  and W 2  are an optionally substituted lower alkylene; 
 Ar 1  is an optionally substituted arylene or an optionally substituted heteroarylene; 
 W 3  is a single bond, a lower alkylene, a lower alkenylene, or —Y 1 —W 5 — in which Y 1  is an oxygen atom, a sulfur atom, —S(O)— or —S(O) 2 —, and W 5  is a lower alkylene or a lower alkenylene; 
 W 4  is a single bond, —NR 10 —, —NR 10 —W 6 —, in which R 10  is a hydrogen atom, or an optionally substituted lower alkyl, and W 6  is a lower alkylene), a lower alkylene, or a lower alkenylene; 
 Ar 2  is an optionally substituted aryl or an optionally substituted heteroaryl, 
 
     or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       2 . The heteroaryl derivative according to  claim 1 , wherein W 3  is a lower alkylene, a lower alkenylene, or —Y 1 —W 5 —, in which Y 1  is an oxygen atom, a sulfur atom, —S(O)— or —S(O) 2 —, and W 5  is a lower alkylene or a lower alkenylene, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       3 . The heteroaryl derivative according to  claim 1 , wherein Ring Z is an optionally substituted pyrazole ring, an optionally substituted imidazole ring, an optionally substituted triazole ring, an optionally substituted indole ring, an optionally substituted indazole ring, or an optionally substituted benzimidazole ring, W 3  is a C 1 -C 5  alkylene, a C 2 -C 5  alkenylene, or —Y 1 ′—W 5 ′— (in which Y 1 ′ is an oxygen atom or a sulfur atom, and W 5 ′ is a C 1 -C 5  alkylene or a C 2 -C 5  alkenylene), W 4  is a single bond, —NR 10 —, a C 1 -C 4  alkylene, or a C 2 -C 4  alkenylene, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       4 . The heteroaryl compound according to  claim 1 , wherein Ring Z is selected from the following formulae (2): 
     
       
         
         
             
             
         
       
     
     in which the number of R 2  may be one or more, and each is independently selected from a hydrogen atom, a halogen atom, an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted thiol, the number of R 3  may be one or more, and each is independently selected from a hydrogen atom, a halogen atom, an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted thiol, an optionally substituted hydroxy, an optionally substituted non-aromatic heterocyclic group, an optionally substituted amino, an optionally substituted acyl, and an alkylsulfonyl, and either of the binding direction of these groups may be acceptable), or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       5 . The heteroaryl compound according to  claim 1  or  claim 2 , wherein Ring Z is an optionally substituted imidazole ring, or an optionally substituted benzimidazole ring, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       6 . The heteroaryl compound according to any one of  claims 1  to  3 , wherein W 1  and W 2  are an optionally substituted straight chain C 1 -C 3  alkylene group, or an optionally substituted C 3 -C 6  alkylene group containing a cyclic structure, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       7 . The heteroaryl compound according to any one of  claims 1  to  3 , wherein W 1  and W 2  are an optionally substituted methylene or ethylene, W 3  is a straight chain C 2 -C 4  alkylene or C 3 -C 4  alkenylene, or —Y 1 ″—W 5 ″—, in which Y 1 ″ is an oxygen atom and W 5 ″ is a straight chain C 2 -C 4  alkylene, W 4  is a single bond, —NR 10 —, methylene, or transvinylene, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       8 . The heteroaryl compound according to any one of  claims 1  to  6 , wherein Ar 1  is an optionally substituted phenylene, and the binding position of W 2  is at meta-position or para-position with respect to the binding position of W 3 , or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       9 . (canceled) 
   
   
       10 . The heteroaryl derivative according to  claim 1 , wherein Ring Z is a group of the formula (4): 
     
       
         
         
             
             
         
       
     
     in which the number of R 2 ′ may be one or more, and each is independently selected from a hydrogen atom, methyl, an optionally substituted phenyl, and an optionally substituted heteroaryl, R 1  is a carboxyl group, an optionally substituted alkylsulfonylcarbamoyl group, or a tetrazolyl group, W 1  and W 2  are an optionally substituted methylene or ethylene, Ar 1  is an optionally substituted phenylene, W 3  is a straight chain C 2 -C 4  alkylene or C 3 -C 4  alkenylene, Ar 2  is an optionally substituted phenyl, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       11 . The heteroaryl derivative according to  claim 1 , wherein Ring Z is selected from the following formulae (5): 
     
       
         
         
             
             
         
       
     
     R 1  is a carboxyl group, W 1  is an optionally substituted methylene or ethylene, W 2  is methylene, Ar 1  is phenylene, W 3  is propenylene or propylene, Ar 2  is an optionally substituted phenyl, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       12 . The heteroaryl derivative according to  claim 1 , wherein Ring Z is selected from the following formulae (6): 
     
       
         
         
             
             
         
       
     
     in which the number of R 2 ′ may be one or more, and each is independently selected from a hydrogen atom, methyl, an optionally substituted phenyl, and an optionally substituted heteroaryl, R 1  is a carboxyl group, W 1  is an optionally substituted methylene, or ethylene, W 2  is methylene, Ar 1  is phenylene, W 3  is propenylene or propylene, Ar 2  is an optionally substituted phenyl, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       13 . (canceled) 
   
   
       14 . (canceled) 
   
   
       15 . The heteroaryl derivative according to  claim 1 , wherein Ring Z is selected from the following formulae (8): 
     
       
         
         
             
             
         
       
     
     R 1  is a carboxyl group, W 1  is a methylene optionally substituted by an alkyl group having 1 to 3 carbon atoms, W 2  is methylene, Ar 1  is phenylene, W 3  is propenylene or propylene, Ar 2  is a phenyl optionally substituted by an alkyl having 1 to 3 carbon atoms or an alkoxy having 1 to 3 carbon atoms, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       16 . The heteroaryl derivative according to  claim 1 , wherein Ring Z is a group of the formula (9): 
     
       
         
         
             
             
         
       
     
     R 1  is a carboxyl group, W 1  is a methylene optionally substituted by an alkyl group having 1 to 3 carbon atoms, W 2  is methylene, Ar 1  is phenylene, W 3  is propenylene, Ar 2  is a phenyl optionally substituted by an alkyl group having 1 to 3 carbon atoms or an alkoxy group having 1 to 3 carbon atoms, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 
   
   
       17 . The heteroaryl derivative according to  claim 1 , which is a compound selected from the following formulae (10): 
     
       
         
         
             
             
         
       
       or a prodrug thereof, or a pharmaceutically acceptable salt thereof.