Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA(2) inhibitors

doi:10.1016/j.bmcl.2013.03.062

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	Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA(2) inhibitors
	Wang, Kai; Xu, Wenwei; Zhang, Wei; Mo, Mingguang; Wang, Yiping; Shen, Jianhua
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2013-05-15
卷号	23 期号:10 页码:2897-2901
关键词	Atherosclerosis Lp-PLA(2) inhibitor Imidazole Triazole
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2013.03.062
文献子类	Article
英文摘要	This Letter reports our efforts towards the optimization of our previously identified series of imidazole and triazole derivatives that lead to the discovery of a series of orally active Lp-PLA(2) inhibitors in C57 mice. These inhibitors are characterized by the presence of a diamine side chain in the molecules, such as 2c, 2f, and 4a. The introduction of the terminal-end amine succeeded in maintaining the in vitro activities at sub-nanomolar levels. The vivo activities could be greatly affected by variations in the two amines via modulating the metabolic stability and lipophilicity of the compounds. (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	PHOSPHOLIPASE A(2) ; ATHEROSCLEROSIS
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000318750000013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277618]
专题	药理学第一研究室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发现与设计中心
通讯作者	Wang, Yiping
作者单位	Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Kai,Xu, Wenwei,Zhang, Wei,et al. Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA(2) inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2013,23(10):2897-2901.
APA	Wang, Kai,Xu, Wenwei,Zhang, Wei,Mo, Mingguang,Wang, Yiping,&Shen, Jianhua.(2013).Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA(2) inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,23(10),2897-2901.
MLA	Wang, Kai,et al."Triazole derivatives: A series of Darapladib analogues as orally active Lp-PLA(2) inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 23.10(2013):2897-2901.