Heterocyclic derivatives which inhibit factor Xa

Abstract

The invention relates to heterocyclic derivatives of formula (I), or pharmaceutically-acceptable salts thereof, which possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the heterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.

1 . A compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein: 
 A is a 5- or 6-membered monocyclic aromatic ring containing 1, 2 or 3 ring heteroatoms selected from nitrogen, oxygen and sulphur atoms and is unsubstituted or is substituted by one, two or three atoms or groups selected from halo, oxo, carboxy, trifluoromethyl, cyano, amino, hydroxy, nitro, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 alkylamino, di-C 1-4 alkylamino or aminoC 1-4 alkyl;  
 B is N;  
 D is 2-benzimidazolyl, or 2-benzo[b]furanyl, and is unsubstituted or is substituted by one, two or three substituents selected from halo or a pharmaceutically-acceptable salts thereof.  
 
     
     
         2 . A compound of formula (I) as claimed in  claim 1  wherein A is a pyridyl, pyrimidinyl, imidazolyl or pyridazinyl ring;  
       or a pharmaceutically-acceptable salt thereof.  
     
     
         3 . A compound of formula (I) as claimed in  claim 2  wherein A is 2-pyridyl, 3-pyridyl, 4-pyridyl 3-pyradazinyl, 4-pyridazinyl, 4-pyrimidinyl, 5-pyrimidinyl, 1-imidazolyl, 2-imidazolyl or 4-imidazolyl;  
       or a pharmaceutically-acceptable salt thereof.  
     
     
         4 . A compound of formula (I) as claimed in  claim 1  wherein A is substituted by C 1-4 alkyl, amino and halo;  
       or a pharmaceutically-acceptable salt thereof.  
     
     
         5 . A compound of formula (I) as claimed in  claim 1  wherein A is unsubstituted;  
       or a pharmaceutically-acceptable salt thereof.  
     
     
         6 - 9 . (cancelled).  
     
     
         10 . A compound of formula (I) as claimed in  claim 1  wherein D is substituted by halo;  
       or a pharmaceutically-acceptable salt thereof.  
     
     
         11 . A compound of formula (I) as claimed in  claim 1  wherein D is substituted by bromo or chloro;  
       or a pharmaceutically-acceptable salt thereof.  
     
     
         12 . A compound of formula (I) as claimed in  claim 1  wherein: 
 A is pyridyl, pyrimidinyl, imidazolyl or pyridazinyl;  
 B is N;  
 D is 2-benzo[b]furanyl optionally substituted by fluoro, chloro or bromo;  
 or a pharmaceutically-acceptable salt thereof.  
 
     
     
         13 - 15 . (cancelled).  
     
     
         16 . A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically-acceptable salt thereof, as defined in any one of claims  1 - 5  or  10 - 12 , with a pharmaceutically-acceptable diluent or carrier.  
     
     
         17 . (cancelled).  
     
     
         18 . A method of treating a Factor Xa mediated disease or condition in a warm-blooded animal comprising administering an effective amount of a compound of formula (I), as defined in any one of claims  1 - 5  or  10 - 12 , or a pharmaceutically-acceptable salt thereof.