Synthesis and antiplatelet activity of 3,5,6,7,8,2 prime ,3 prime and 4 prime -disubstituted 2-phenyl-4-quinolones

To further define the structure-activity relationships (SAR) of 2-phenyl-4-quinolone derivatives, a series of disubstituted derivatives were synthesized and their inhibitory effects against arachidonic acid (AA)-induced platelet aggregation were evaluated. The test results did not lead to a definite SAR but will be used as a guideline for further development of quantitative structure-activity relationship studies. Some of the tested compounds did show significant antiplatelet activity. Among them, 5,7-dimethyl-2-phenyl-4-quinolone (32) exhibited the highest activity (IC50 = 1.03 μmol) with about 20 times the potency of aspirin, and was hence chosen as a new lead compound for further structural modification.