Synthesis of certain quinolin-2(1H)-one alpha-methylene-gamma-butyrolactones as potential antiplatelet agents

Certain quinolin-2(1H)-one derivatives with various alpha-methylene-gamma-b utyrolactones substituted at C(7)-position were synthesized and evaluated f or their antiplatelet activity against arachidonic acid (AA)-, and platelet -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 des ired 7-[(2,3,4,5-tetrahydro-4-methylene-5-oxo-2-furanyl)methoxy]-quinolin-2 (1H)-ones (8a-e) were obtained from 6 via alkylation and the Reformatsky-ty pe condensation. These quinolin-2(IH)-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.