Synthesis and antiviral activity of substituted bisaryl amide compounds as novel influenza virus inhibitors

The influenza virus is a persistent cause of mortality and morbidity on an annual basis and thus presents itself as an important target for pharmaceutical investigation. In this work, substituted bisaryl amide compounds were found to be a new class of potential anti-influenza agents, and a series of substituted bisaryl amide compounds were synthesised and evaluated for their anti-influenza virus activities. The analysis of the results produced a preliminary structure–activity relationship study (SAR). Compounds 1a, 1g, 1h, 1j, 1l and 1n exhibited clear antiviral activities against the influenza A (A/Guangdong Luohu/219/2006, H1N1) virus with 50% inhibitory concentrations (IC50) for virus growth ranging from 12.5 to 59.0 μM. Specifically, compound 1j also possessed antiviral activity against both oseltamivir-resistant influenza (A/Jinnan/15/2009) virus and influenza B (B/Jifang/13/97) virus with IC50 values of 9.2 μM and 21.4 μM, respectively. Compound 1j is thus worth further investigation as an anti-influenza virus candidate.

A total of 25 novel bisaryl amide compounds were synthesised and screened for their inhibitory activity against influenza virus. Moreover, the data were analysed to produce a preliminary SAR.Figure optionsDownload as PowerPoint slideHighlights
► Substituted bisaryl amide compounds were found to be a new class of potential anti-influenza agents.
► The title compounds were screened for inhibitory activity against influenza viruses.
► A preliminary SAR of the novel influenza virus inhibitor was produced.
► Some compounds were evaluated for inhibitory activity against influenza B and oseltamivir resistant influenza virus.
► 1j exhibited the highest antiviral activity against three influenza virus strains.