Synthesis and Antiplatelet Activity of Alkoxy Derivatives of 2- Phenylquinazolines

A series of 4-alkoxy-2-phenylquinazoline and N3-alky1-2- phenylquinazolinone derivatives were prepared by alkylation of various 2- phenylquinazolinones (1-5). The 4-alkoxy derivatives with lower alkyls, such as methyl and ethyl groups, significantly inhibited AA-induced platelet aggregation. In contrast, all the corresponding N3 -alkyl derivatives demonstrated very weak activity. Among the 4- alkoxy derivatives investigated, 4-ethoxy-2- phenylquinazoline (7) displayed the best activity with an IC 50 value of about 1.60 μM, about 13 times the potency of aspirin. Since the chemical structure of compound 7 is quite distinct from known anti platelet agents, the mechanism of action of compound 7 is currently under investigation