SYNTHESIS AND ANTIPLATELET EVALUATION OF ALPHA-METHYLENE-GAMMA-BUTYROLACTONE BEARING 2-METHYLQUINOLINE AND 8-HYDROXYQUINOLINE MOIETIES

In a search for inhibitors of platelet aggregation, some alpha-methyle ne-gamma-butyrolactones bearing 2-methylquinoline and 8-hydroxyquinoli ne 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 tetrahydro-4-methylene-5-oxo-2-(4-ph enylphenyl)-2- furanyl]methoxy]-8-hydroxyquinoline (8f), these alpha-m ethylene-gamma-butyrolactones completely inhibited the platelet aggreg ation induced by AA and Col. The 2-methylquinoline derivatives were al so active against Thr- and PAP-induced aggregation, while their 8-hydr oxyquinoline counterparts were relatively inactive.