Design and synthesis of imidazole and triazole derivatives as Lp-PLA(2) inhibitors and the unexpected discovery of highly potent quaternary ammonium salts

doi:10.1016/j.bmcl.2013.01.029

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	Design and synthesis of imidazole and triazole derivatives as Lp-PLA(2) inhibitors and the unexpected discovery of highly potent quaternary ammonium salts
	Wang, Kai; Xu, Wenwei; Liu, Yang; Zhang, Wei; Wang, Wenyi; Shen, Jianhua; Wang, Yiping
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2013-03-01
卷号	23 期号:5 页码:1187-1192
关键词	Bioisosteric replacement Imidazole Triazole Lp-PLA(2) inhibitor Quaternary ammonium salt
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2013.01.029
文献子类	Article
英文摘要	New Lp-PLA2 inhibitors were synthesized by the bioisosteric replacement of the amide group of Darapladib with an imidazole or a triazole. Unfortunately, the inhibitory activities of these derivatives were lower than that of Darapladib. But interestingly, a series of quaternary ammonium salts that were isolated as by-products during this synthetic work were found with high potency. Of these by-products, compound 22c showed a similar profile to Darapladib both in vitro and in vivo. (C) 2013 Elsevier Ltd. All rights reserved.
资助项目	National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2012ZX09301001-001] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2012ZX09103101-008]
WOS关键词	CORONARY-ARTERY-DISEASE ; PHOSPHOLIPASE A(2) ; HEART-DISEASE ; LIPOPROTEIN ; ATHEROSCLEROSIS ; RISK ; MECHANISMS ; EVENTS
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000314693400005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277717]
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理学第一研究室
通讯作者	Shen, Jianhua
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Kai,Xu, Wenwei,Liu, Yang,et al. Design and synthesis of imidazole and triazole derivatives as Lp-PLA(2) inhibitors and the unexpected discovery of highly potent quaternary ammonium salts[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2013,23(5):1187-1192.
APA	Wang, Kai.,Xu, Wenwei.,Liu, Yang.,Zhang, Wei.,Wang, Wenyi.,...&Wang, Yiping.(2013).Design and synthesis of imidazole and triazole derivatives as Lp-PLA(2) inhibitors and the unexpected discovery of highly potent quaternary ammonium salts.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,23(5),1187-1192.
MLA	Wang, Kai,et al."Design and synthesis of imidazole and triazole derivatives as Lp-PLA(2) inhibitors and the unexpected discovery of highly potent quaternary ammonium salts".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 23.5(2013):1187-1192.