Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities

doi:10.1016/j.ejmech.2012.06.033

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	Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities
	Ye, Deju 1; Shin, Woo-Jin 3; Li, Ning 1; Tang, Wei1 ; Feng, Enguang 1; Li, Jian 1; He, Pei-Lan 1; Zuo, Jian-Ping1 ; Kim, Hanjo 2; Nam, Ky-Youb 2
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2012-08
卷号	54 页码:764-770
关键词	Neuraminidase (NA) Inhibitor Zanamivir Avian influenza virus (AIV) H5N1
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2012.06.033
文献子类	Article
英文摘要	With the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with C-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (H5N1 and H3N2) were determined. Compound 026 exerts the most potency, with IC50 values of 0.58 and 2.72 mu M against N2 and N1, respectively. Further preliminary anti-avian influenza virus (AIV, H5N1) activities against infected MDCK cells were evaluated, and D5 exerts similar to 58% protective against AIV infection, which was comparable to zanamivir (similar to 67%). In a rat pharmacokinetic study, compound D5 showed an increased plasma half-life (t(1/2)) compared to zanamivir following either intravenous or oral administration. This study may represent a new start point for the future development of improved anti-AIV agents. (C) 2012 Elsevier Masson SAS. All rights reserved.
资助项目	National Basic Research Program of China[2009CB918502] ; National Basic Research Program of China[2012CB518005] ; National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[81025017] ; National S&T Major Projects[2012ZX09103-101-072] ; Silver Project[260644] ; R&D Program of MKE/KEIT[10031969] ; Translational Research Center for Protein Function Control, NSF[2011-0001244] ; Ministry for Health, Welfare Family Affairs, Republic of Korea[A085105]
WOS关键词	INFLUENZA-A VIRUS ; DRUG DESIGN ; 4-GUANIDINO-NEU5AC2EN ; DISCOVERY ; SIALIDASE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000307920600078
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277996]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室药物化学研究室药理学第一研究室
通讯作者	Zuo, Jian-Ping
作者单位	1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Bioinformat & Mol Design Res Ctr, Seoul 120749, South Korea 3.Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biotechnol, Seoul 120749, South Korea;
推荐引用方式 GB/T 7714	Ye, Deju,Shin, Woo-Jin,Li, Ning,et al. Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2012,54:764-770.
APA	Ye, Deju.,Shin, Woo-Jin.,Li, Ning.,Tang, Wei.,Feng, Enguang.,...&Liu, Hong.(2012).Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,54,764-770.
MLA	Ye, Deju,et al."Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 54(2012):764-770.