Synthesis and antiplatelet evaluation of alpha-methylene-gamma-butyrolactone bearing 2-methylquinoline and 8-hydroxyquinoline moieties

Abstract

In a search for inhibitors of platelet aggregation, some alpha-methylene-gamma-butyrolactones bearing 2-methylquinoline and 8-hydroxyquinoline moieties were synthesized and evaluated for antiplatelet activities against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. With the exception of 2-[[2,3,4,5-tetrahydro-4-methylene-5-oxo-2-(4-phenylphenyl)-2 -furanyl]methoxy]-8-hydroxyquinoline (8f), these alpha-methylene-gamma-butyrolactones completely inhibited the platelet aggregation induced by AA and Col. The 2-methylquinoline derivatives were also active against Thr- and PAF-induced aggregation, while their 8-hydroxyquinoline counterparts were relatively inactive.