Synthesis of Certain Quinolin-2(1H)-one α-Methylene-γ-butyrolactones as Potential Antiplatelet Agents

Abstract

Certain quinolin-2(1H)-one derivatives with various a-methylene-ybutyrolactones substituted at C(7)-position were synthesized and evaluated for their antiplatelet activity against arachidonic acid (AA)., and platelet-activating factor (PAR-induced aggregation in washed rabbit platelets.7-Hydroxyquinoline 1-oxide was treated with acetic anhydride followed by the hydrolysis of 1.0 N NaOH to afford 7-hydroxyquinolin-2(1H)-one (6).The desired 7-[(2,3,4,5-tetrahydro-4methylene-5-oxo-2-furanyl)methoxy]-quinolin-2(lff)-ones @a-e) were obtained from 6 via alkylation and the Reformatsky-type condensation.These quinolin-2(1N)-ones (8a-e), exhibited approximately five to seven times more potent than their coumarin counterparts against AA-and PAF-induced aggregation and are approximately two hundred times more potent than aspirin against AA-induced aggregation.