Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease

doi:10.1016/j.bmc.2014.09.057

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物安全性评价中心

	Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease
	Liu, Hailong 1,3; Wu, Ruoming 2; Sun, Yanyan 2; Ye, Yan 1; Chen, Jing1 ; Luo, Xiaomin1 ; Shen, Xu1 ; Liu, Hong1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2014-11-15
卷号	22 期号:22 页码:6344-6352
关键词	Thiadiazo Dengue virus NS2B/NS3
ISSN号	0968-0896
DOI	10.1016/j.bmc.2014.09.057
文献子类	Article
英文摘要	Dengue virus is endemic throughout tropical and subtropical regions, and cause severe epidemic diseases. The NS2B/NS3 protease is a promising drug target for dengue virus. Herein, we report the discovery and modification of a novel class of thiadiazoloacrylamide derivatives with potent inhibitory activity against the NS2B/NS3 protease. Thiadiazolopyrimidinone 1 was firstly determined as a new chemical structure against NS2B/NS3 from a commercial compound library. Then, we sought to identify similar compounds with the thiadiazoloacrylamide core that would exhibit better activity. A series of analogues were synthesized and fourteen of them were identified with strong inhibitory activities, in which the nitrile group in the linker part was discovered as an essential group for the inhibitory activity. The best of these (8b) demonstrated an IC50 at 2.24 mu M based on in vitro DENV2 NS2B-NS3pro assays. (C) 2014 Published by Elsevier Ltd.
资助项目	National Natural Science Foundation of China[81220108025] ; National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81025017] ; National S&T Major Projects[2012ZX09103101-072] ; National S&T Major Projects[2012ZX09301001-005] ; National S&T Major Projects[2013ZX09507-001] ; Program of Shanghai Subject Chief Scientist[12XD1407100] ; Silver Project[260644]
WOS关键词	TETRAPEPTIDE ALDEHYDE INHIBITORS ; PEPTIDE INHIBITORS ; NS2B-NS3 PROTEASE ; NS3 PROTEASE ; SERINE-PROTEASE ; DERIVATIVES ; DESIGN ; SAR
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000344472600004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276834]
专题	药物安全性评价中心药物化学研究室
通讯作者	Chen, Jing
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 3.China Pharmaceut Univ, Sch Pharm, Nanjing 200237, Jiangsu, Peoples R China;
推荐引用方式 GB/T 7714	Liu, Hailong,Wu, Ruoming,Sun, Yanyan,et al. Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2014,22(22):6344-6352.
APA	Liu, Hailong.,Wu, Ruoming.,Sun, Yanyan.,Ye, Yan.,Chen, Jing.,...&Liu, Hong.(2014).Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease.BIOORGANIC & MEDICINAL CHEMISTRY,22(22),6344-6352.
MLA	Liu, Hailong,et al."Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease".BIOORGANIC & MEDICINAL CHEMISTRY 22.22(2014):6344-6352.