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Issue 40, 2014
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Discovery and SAR study of piperidine-based derivatives as novel influenza virus inhibitors

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Abstract

A series of piperidine-based derivatives were identified as novel and potent inhibitors of the influenza virus through structural modification of a compound that was selected from a high-throughput screen. Various analogues were synthesized and confirmed as inhibitors. The structure–activity relationship (SAR) studies suggested that the ether linkage between the quinoline and piperidine is critical for the inhibitory activity. The optimized compound tert-butyl 4-(quinolin-4-yloxy)piperidine-1-carboxylate 11e had an excellent inhibitory activity against influenza virus infection from a variety of influenza virus strains, with EC50 values as low as 0.05 μM. The selectivity index value (SI = MLD50/EC50) of 11e is over 160 000 based on cytotoxicity, measured by MTT assays of three cell lines. We carried out a time-of-addition experiment to delineate the mechanism of inhibition. The result indicates that 11e interferes with the early to middle stage of influenza virus replication.

Graphical abstract: Discovery and SAR study of piperidine-based derivatives as novel influenza virus inhibitors

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Publication details

The article was received on 26 May 2014, accepted on 06 Aug 2014 and first published on 07 Aug 2014


Article type: Paper
DOI: 10.1039/C4OB01079E
Citation: Org. Biomol. Chem., 2014,12, 8048-8060
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    Discovery and SAR study of piperidine-based derivatives as novel influenza virus inhibitors

    G. Wang, L. Chen, T. Xian, Y. Liang, X. Zhang, Z. Yang and M. Luo, Org. Biomol. Chem., 2014, 12, 8048
    DOI: 10.1039/C4OB01079E

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