SYNTHSIS OF CERTAIN QUINOLIN-2(1H)-ONE (#alpha#)-METHYLENE-(#gamma#)-BUTYROLACTONES AS POTENTIAL ANTIPLATELET AGENTS

摘要

Certain quinolin-2(1H)-one derivatives with various (#alpha#)-methylene-(#gamma#)-butyroactones substituted at C(7)-position were synthesized and evaluated for their antiplatelet activity against arachidonic acid (AA)-,and platelte-activating factor (PAF)-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-4-methylene-5-oxo-2-furanyl)methoxy]-quinolin-2(1H)-one (8a-e) were obtained from 6 via alkylation and the Reformatsky-type condensation.These quinolin-2(1H)-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 aspirin against AA-induced aggregation.