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

• DOI: 10.1016/j.ejmech.2012.07.008
• Publication Date: 2012-07-14T07:32:22Z
• Authors: Lan-hu Hao; Yan-ping Li; Wei-ying He; Hui-qiang Wang; Guang-zhi Shan; Jian-dong Jiang; Yu-huan Li; Zhuo-rong Li
• Keywords: Oseltamivir; Amide; Structure–activity relationship; Influenzavirus B

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 (IC(50)) 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 IC(50) values of 9.2 μM and 21.4 μM, respectively. Compound 1j is thus worth further investigation as an anti-influenza virus candidate.