Glycoprotein IIb/IIIa antagonists

Abstract

This invention relates to certain bicyclic compounds having a nucleus formed of two fused six membered rings, for example, isoquinoline, isoquinolone, tetrahydronaphthalene, dihydronaphthalene, or tetralone, substituted with both basic and acidic functionality, which are useful in inhibition of platelet aggregation.

1 . A bicyclic compound having a nucleus formed from two fused six membered rings, A and B, represented by the formula (I), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof:  
       
         
           
           
               
               
           
         
       
       wherein; 
 B 1 , B 2 , B 3 , B 4  are independently selected from carbon, oxygen, sulfur, and nitrogen, with the proviso that at least two of B 1 , B 2 , B 3 , B 4  are carbon;  
 R 3  is an acidic group;  
 n is a number from 2 to 6;  
 R 0  is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; with the proviso that if R 0  is ═O or ═S, then only one of B 1 , B 2 , B 3 , and B 4  may be nitrogen.  
 A 1 , A 2 , A 3 , and A 4  may be independently selected from carbon, oxygen, sulfur, and nitrogen, with the proviso that at least two of A 1 , A 2 , A 3 , and A 4  are carbon.  
 m is a number from 2 to 6;  
 R 10  is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; with the proviso that only one R 10  may be ═O or ═S;  
 linking group -(L)- is a bond or a divalent substituted or unsubstituted chain of from 1 to 10 atoms selected from the group consisting of carbon, nitrogen, sulfur, and oxygen; and;  
 Q is an organic group comprising a basic group.