Dicarboxamide derivatives

Abstract

The invention is concerned with novel dicarboxamide derivatives of formula (I) wherein A, B, R c , D and E are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the coagulation factor Xa and can be used as medicaments.

1 . A compound of formula (I) 
     
       
         
         
             
             
         
       
     
     wherein
 A is —CONH— or —NHCO—; 
 B is optionally substituted phenyl, optionally substituted heteroaryl or optionally substituted heterocyclyl; 
 R c  is optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl, one or two carbon atoms of said aryl, heteroaryl or heterocyclyl ring optionally being replaced with a carbonyl group; 
 D is aryl optionally substituted by one, two or three halogen atoms independently selected from chlorine, fluorine and bromine or heteroaryl optionally substituted by one, two or three halogen atoms independently selected from chlorine, fluorine and bromine; 
 E is E-3: 
 
     
       
         
         
             
             
         
       
       R 7 , R 8 , R 9  and R 10  are independently from each other hydrogen, C 1-6  alkyl or hydroxy. 
     
   
   
       2 . A compound according to  claim 1 , wherein D is aryl optionally substituted by one halogen atom selected from chlorine and bromine or heteroaryl optionally substituted by one halogen atom selected from chlorine and bromine. 
   
   
       3 . A compound according to  claim 1 , wherein D is phenyl, pyridyl, thienyl, pyrimidinyl, pyridazinyl or indolyl, said phenyl, pyridyl, thienyl, pyrimidinyl, pyridazinyl or indolyl being optionally substituted by one halogen atom selected from chlorine and bromine. 
   
   
       4 . A compound according to  claim 1 , wherein D is chlorophenyl or chloropyridyl. 
   
   
       5 . A compound according to  claim 1 , wherein B is optionally substituted phenyl or optionally substituted heteroaryl. 
   
   
       6 . A compound according to  claim 1 , wherein B is phenyl or pyridyl, said phenyl or pyridyl being optionally substituted by one or two halogen atoms selected independently from the group consisting of chlorine, fluorine and bromine. 
   
   
       7 . A compound according to  claim 1 , wherein B is phenyl substituted by one or two fluorine. 
   
   
       8 . A compound according to  claim 1 , wherein B is fluorophenyl. 
   
   
       9 . A compound according to  claim 1 , wherein B is 2-fluorophenyl. 
   
   
       10 . A compound according to  claim 1 , wherein R c  is aryl, heteroaryl or heterocyclyl, one carbon atom of said aryl, heteroaryl or heterocyclyl ring optionally being replaced with a carbonyl group, and said aryl, heteroaryl or heterocyclyl ring optionally being substituted by hydroxy, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  alkyl sulfonyl, amino C 1-6  alkyl, mono-C 1-6  alkyl substituted amino-C 1-6  alkyl or di-C 1-6  alkyl substituted amino-C 1-6  alkyl. 
   
   
       11 . A compound according to  claim 1 , wherein R c  is aryl, heteroaryl or heterocyclyl, one carbon atom of said aryl, heteroaryl or heterocyclyl ring being replaced with a carbonyl group at ortho position with respect to B, and said aryl, heteroaryl or heterocyclyl ring optionally being substituted by hydroxy, C 1-6  alkyl, C 1-6  alkoxy, C 1-6  alkyl sulfonyl, amino C 1-6  alkyl, mono-C 1-6  alkyl substituted amino-C 1-6  alkyl or di-C 1-6  alkyl substituted amino-C 1-6  alkyl. 
   
   
       12 . A compound according to  claim 1 , wherein R c  is 2-oxo-2H-pyridin-1-yl optionally substituted by C 1-6  alkyl or C 1-6  alkoxy. 
   
   
       13 . A compound according to  claim 1 , wherein —B—R c  is 2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl. 
   
   
       14 . A compound according to  claim 1 , wherein A is —CONH—. 
   
   
       15 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable excipient.