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Design, Synthesis, and Evaluation of 3‐((4‐( t ‐Butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1 H )‐ones as Neuraminidase Inhibitors
Author(s) -
Fang Yilin,
Xiao Mengwu,
Hu Aixi,
Ye Jiao,
Lian Wenwen,
Liu Ailin
Publication year - 2016
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201500738
Subject(s) - chemistry , thiazole , neuraminidase , stereochemistry , nitro , chlorine , medicinal chemistry , bromine , structure–activity relationship , combinatorial chemistry , enzyme , organic chemistry , biochemistry , in vitro , alkyl
A series of novel 3‐((4‐( t ‐butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1 H )‐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 IC 50 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.