Synthesis and Evaluation of Coumarin α-Methylene-γ-butyrolactones : A New Class of Platelet Aggregation Inhibitors

Abstract

In a search for new inhibitors of platelet aggregation, certain coumarin-bearing α-methylene-γ-butyrolactones were synthesized and evaluated for inhibitory activity against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. These compounds were efficiently synthesized from commercially available 7-hydroxycoumarin or its derivative. Among them, 7-[(2, 3, 4, 5-tetrahydro-4-methylene-5-oxo-2-phenyl-2-furanyl)methoxy]-2H-1-benzopyran-2-one (3d) showed the most potent inhibition of AA- and PAF- induced aggregation, with IC₅₀ values of 3.65 and 16.36μM respectively.