Studies on Antiplatelet Agents. I. Synthesis and Platelet Inhibitory Activity of 5-Alkyl-2-aryl-4-pyridylimidazoles

Abstract

5-Alkyl-2-aryl-4-pyridylimidazoles were synthesized and tested in rat ex vivo platelet aggregation studies. Among these compounds, 2-(2-fluorophenyl)-5-methyl-4-(3-pyridyl)imidazole (25) was most potent, and showed 98% inhibition at a dose of 10 mg/kg (p.o.). 25 had inhibitory activity on cyclooxygenase, thromboxane A₂ (TXA₂) synthetsase, and phosphodiesterase, and also showed inhibited KCl-induced contraction of rat aorta. All compounds have little acute toxicity and appear to be free of adverse effects on the stomach.