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

作　　者：Yilin Fang Mengwu Xiao Aixi Hu Jiao Ye Wenwen Lian Ailin Liu 

机构地区：[1]College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China [2]Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beifing 100050, China

出　　处：《Chinese Journal of Chemistry》2016年第4期403-411,共9页中国化学（英文版）

摘　　要：A series of novel 3-（（4-（t-buty-）-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 influenza H1N1 virus. Some compounds displayed moderate influenza NA inhibitory activity. Compound 71 with the scaffold of 2-（2-（2-methoxybenzylidene）hydrazinyl）thiazole was the best one, exhibiting moderate NA inhibitory activity with ICs0 of 44.66 ~tmol/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 posi- tion of phenyl ring were more active. Docking study indicated that compound 71 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-buty-）-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 influenza H1N1 virus. Some compounds displayed moderate influenza NA inhibitory activity. Compound 71 with the scaffold of 2-（2-（2-methoxybenzylidene）hydrazinyl）thiazole was the best one, exhibiting moderate NA inhibitory activity with ICs0 of 44.66 ~tmol/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 posi- tion of phenyl ring were more active. Docking study indicated that compound 71 has important interactions with some key residues （including Asp151, Glu119, Arg292, Tyr406, and Asn347） and binds to 430-cavity adjacent to NA active site.

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 

分 类 号：TQ253.23[化学工程—有机化工] S855.3[农业科学—临床兽医学]