Synthesis of Coumarin Derivatives as Inhibitors of Platelet Aggregation

In a search for the inhibitors of platelet aggregation, certain coumarin derivatives were synthesized and evaluated for antiplatelet activity against thrombin(Thr)‐, arachidonic acid(AA)‐, collagen(Col)‐, and platelet‐activating‐factor(PAF)‐induced aggregation in washed rabbit platelets. These compounds were synthesized from 4‐hydroxycoumarin (1) or naphthalen‐1‐ol via alkylation and Reformatsky‐type condensation (Schemes 1–3). Among them, 4‐[(2,3,4,5‐tetrahydro‐4‐methylidene‐5‐oxo‐2‐phenylfuran‐2‐yl)methoxy]‐2H‐1‐benzopyran‐2‐one (6b) showed potent antiplatelet effects on AA‐ and PAF‐induced aggregation with IC50 values of 8.21 and 103.67 m̈M, respectively (see Tables 1 and 2). The antiplatelet potency of 6b against PAF‐induced aggregation could be further improved by introducing a proper substituent at the 2‐phenyl group of the lactone ring.