Design, Synthesis, and Evaluation of 3-((4-(t-Butyl)-2-(2-benzylidenehydrazinyl)thiazol-5-yl)methyl)quinolin-2(1H)-ones as Neuraminidase Inhibitors

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• 作者：Yilin Fang ; Mengwu Xiao ; Aixi Hu ; Jiao Ye ; Wenwen Lian and Ailin Liu
• 关键词：neuraminidase inhibitor ; 3-((4-(t-butyl)-2-(2-benzylidenehydrazinyl)thiazol-5-yl)methyl)quinolin-2(1H)-ones ; 2-(2-hydrazinyl)thiazole scaffold ; synthesis ; docking
• 刊名：Chinese Journal of Chemistry
• 出版年：2016
• 出版时间：April, 2016
• 年：2016
• 卷：34
• 期：4
• 页码：403-411
• 全文大小：1664K
• ISSN：1614-7065

文摘

A series of novel 3-((4-(t-butyl)-2-(2-benzylidenehydrazinyl)thiazol-5-yl)methyl)quinolin-2(1H)-ones (7a–7z) were designed, synthesized and evaluated for their ability of inhibiting neuraminidase (NA) of in?uenza H1N1 virus. Some compounds displayed moderate influenza NA inhibitory activity. Compound 7l with the scaffold of 2-(2-(2-methoxybenzylidene)hydrazinyl)thiazole was the best one, exhibiting moderate NA inhibitory activity with IC₅₀ of 44.66 µmol/L. Structure-activity relationship showed that compounds with methoxy or hydroxy groups at the ortho position, fluorine and nitro groups at the meta position and chlorine and bromine groups at the para position of phenyl ring were more active. Docking study indicated that compound 7l has important interactions with some key residues (including Asp151, Glu119, Arg292, Tyr406, and Asn347) and binds to 430-cavity adjacent to NA active site.