Discovery of Dihydro-Alkyloxy-Benzyl- Oxopyrimidines as Promising Anti-Influenza Virus Agents

摘要

A series of novel dihydro-alkyloxy-benzyl-oxopyrimidine derivatives were synthesized and evaluated for their activity against influenza virus in Madin-Darby canine kidney cells. Four dihydro-alkyloxy- benzyl-oxopyrimidine derivatives (4a1, 4a2, 4a3, and 4d1) showed potent activity against influenza virus. Among them, compound 4a3 was the most promising lead with broad activity against influenza A (antiviral EC_(50) values of 9 and 18 μM for the A?H1N1 and A?H3N2 subtype, respectively) and influenza B viruses (EC_(50): 33 lM). The antiviral mechanism of action of these dihydro-alkyloxybenzyl- oxopyrimidine derivatives must be quite different from that of the currently approved antiinfluenza virus drugs that target the viral M2 or neuraminidase proteins. The dihydro-alkyloxy-benzyl- oxopyrimidine derivatives represent a new avenue for further optimization and development of novel anti-influenza virus agents.