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

Abstract

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. A series of novel 3-((4-(t-butyl)-2-(2-benzylidenehydrazinyl)thiazol-5-yl)methyl)qui-nolin-2(1H)-ones (7a-7z) were designed, syn-thesized and evaluated for their ability of inhibiting neuraminidase (NA) of influenza H1N1 virus. Compound 7l with the scaffold of 2-(2-(2-methoxybenzylidene)hydrazinyl)thiazole was the best one, exhibiting mod-erate NA inhibitory activity with IC50 of 44.66 μmol/L.