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In this study, we reported the synthesis and biological characterization of a novel series of furan-carboxamide derivatives that were potent inhibitors of the influenza A H5N1 virus. The systematic structure–activity relationship (SAR) studies demonstrated that the 2,5-dimethyl-substituted heterocyclic moiety (furan or thiophene) had significant influence on the anti-influenza activity. In particular, 2,5-dimethyl-N-(2-((4-nitrobenzyl)thio)ethyl)-furan-3-carboxamide 1a showed the best activity against the H5N1 virus with an EC50 value of 1.25 μM. For the first time, the simple scaffold furan-carboxamide derivatives were identified as novel inhibitors of lethal H5N1 influenza A virus.

Furan-carboxamide derivatives as novel inhibitors of lethal H5N1 influenza A viruses