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

Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China.
Chemical Biology &amp Drug Design (Impact Factor: 2.51). 07/2011; 78(4):596-602. DOI: 10.1111/j.1747-0285.2011.01180.x
Source: PubMed

ABSTRACT 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 μm). The antiviral mechanism of action of these dihydro-alkyloxy-benzyl-oxopyrimidine derivatives must be quite different from that of the currently approved anti-influenza 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.