Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity.

European Journal of Medicinal Chemistry
Ruifang JiaXinyong Liu


Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C5-NH2 of oseltamivir targeting 150-cavity. Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1-H274Y). Specifically, there was 30-fold loss of activity against the wild-type strain H1N1. However, 5c displayed 4.85-fold more potent activity than OSC against H5N1-H274Y NA. Also, 5c demonstrated low cytotoxicity in vitro and no acute toxicity in mice. Molecular docking studies provided insights into the high potency of 5c against N1 and N1-H274Y mutant NAs. Besides, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability of representative compounds were conducted to evaluate their drug-like properties.


Nov 7, 1999·Drugs·C J Dunn, K L Goa
Feb 1, 2000·Drug Discovery Today·D E Clark, S D Pickett
Apr 25, 2000·Annual Review of Medicine·N J Cox, K Subbarao
Mar 29, 2001·Drugs·K McClellan, C M Perry
Apr 18, 2009·Biochemical and Biophysical Research Communications·Pasqualina D'UrsiLuciano Milanesi
May 9, 2009·The New England Journal of Medicine·Fatimah S DawoodTimothy M Uyeki
Jun 23, 2009·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·J S Malik PeirisYi Guan
Feb 4, 2010·Bioorganic & Medicinal Chemistry·Ying WuHoon Cho
Sep 21, 2010·Biochemical and Biophysical Research Communications·Shu-Qing WangKuo-Chen Chou
Sep 21, 2010·Nature Structural & Molecular Biology·Qing LiGeorge F Gao
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Qing LiGeorge F Gao
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xueyong ZhuIan A Wilson
Oct 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Adolfo García-Sastre
Mar 26, 2013·Antiviral Research·Mélanie SamsonGuy Boivin
Sep 13, 2013·Virus Research·Bryan S Kaplan, Richard J Webby
Oct 5, 2013·The Journal of Organic Chemistry·Pal John Pal AdabalaB Mario Pinto
Apr 5, 2014·Cellular and Molecular Life Sciences : CMLS·Arianna LoregianGiorgio Palù
Aug 1, 2014·Acta Pharmaceutica Sinica. B·Qian GaoShan Cen
Nov 19, 2015·Acta Pharmaceutica Sinica. B·Zuyuan ShenWei Wang
Apr 12, 2016·Frontiers in Microbiology·Malak M AlameHassan Zaraket
Aug 9, 2016·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Takuji KomedaJingoro Shimada
Sep 28, 2017·Scientific Reports·Kai-Cheng HsuJinn-Moon Yang
Feb 7, 2018·European Journal of Medicinal Chemistry·Han JuXinyong Liu
Jun 9, 2019·European Journal of Medicinal Chemistry·Ruifang JiaXinyong Liu

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Jun 4, 2021·European Journal of Medicinal Chemistry·Hongqian ZhaoYongshou Tian

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