SYNTHESIS OF COUMARIN DERIVATIVES AS INHIBITORS OF PLATELET-AGGREGATION

In a search for the inhibitors of platelet aggregation, certain coumar in derivatives were synthesized and evaluated for antiplatelet activit y against thrombin(Thr)-, arachidonic acid(AA)-, collagen(Col)-, and p latelet-activating-factor(PAF)-induced aggregation in washed rabbit pl atelets. These compounds were synthesized from 4-hydroxycoumarin (1) o r naphthalen-1-ol via alkylation and Reformatsky-type condensation (Sc hemes 1-3). Among them, -2-phenylfuran-2-yl)methoxy]-2H-1-benzopyran-2 -one (6b) showed potent antiplatelet effects on AA- and PAF-induced ag gregation with IC50 values of 8.21 and 103.67 mu M, respectively (see Tables 1 and 2). The antiplatelet potency of 6b against PAF-induced ag gregation could be further improved by introducing a proper substituen t at the 2-phenyl group of the lactone ring.