Pyrazolidine-3,5-dione derivatives as potent non-steroidal agonists of farnesoid X receptor: Virtual screening, synthesis, and biological evaluation

doi:10.1016/j.bmcl.2008.09.027

	Pyrazolidine-3,5-dione derivatives as potent non-steroidal agonists of farnesoid X receptor: Virtual screening, synthesis, and biological evaluation
	Deng, Guanghui 1; Li, Weihua 1; Shen, Jianhua1 ; Jiang, Hualiang1,2 ; Chen, Kaixian1 ; Liu, Hong1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2008-10-15
卷号	18 期号:20 页码:5497-5502
关键词	farnesoid X receptor pyrazolidine-3,5-dione virtual screening
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2008.09.027
文献子类	Article
英文摘要	The identification of a novel pyrazolidine-3,5-dione based scaffold hit compound as Farnesoid X receptor (FXR) partial or full agonist has been accomplished by means of virtual screening techniques. A series of pyrazolidine-3,5-dione derivatives (1a-u and 7) was designed, synthesized, and evaluated by a cell-based luciferase transactivation assay for their agonistic activities against FXR. Most of them showed agonistic potencies and 10 of them (1a, 1b, 1d-f, 1j, 1n, 1t, 5b, and 7) exhibited lower EC(50) values than the reference drug CDCA. Molecular modeling studies for the representative compounds 1a, 1d, 1f, 1j, 1n, 1u, 5b, and 7 were also presented. The novel structural scaffold has provided a new direction for finding potent and selective FXR partial and full agonists (referred to as 'selective bile acid receptor modulators', SBARMs). (c) 2008 Elsevier Ltd. All rights reserved.
资助项目	State Key Program of Basic Research of China[2006BAI01B02] ; National Natural Science Foundation of China[30672539] ; National Natural Science Foundation of China[20721003] ; 863 Hi-Tech Program of China[2006AA020602]
WOS关键词	ORPHAN NUCLEAR RECEPTOR ; BILE-ACID ; MOLECULAR DOCKING ; FXR ; LIGANDS ; IDENTIFICATION ; INHIBITORS ; DESIGN ; SERIES
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000259972800036
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272781]
专题	药物化学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	Shen, Jianhua
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Drug Discovery & Design Ctr,Grad Sch, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Deng, Guanghui,Li, Weihua,Shen, Jianhua,et al. Pyrazolidine-3,5-dione derivatives as potent non-steroidal agonists of farnesoid X receptor: Virtual screening, synthesis, and biological evaluation[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2008,18(20):5497-5502.
APA	Deng, Guanghui,Li, Weihua,Shen, Jianhua,Jiang, Hualiang,Chen, Kaixian,&Liu, Hong.(2008).Pyrazolidine-3,5-dione derivatives as potent non-steroidal agonists of farnesoid X receptor: Virtual screening, synthesis, and biological evaluation.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,18(20),5497-5502.
MLA	Deng, Guanghui,et al."Pyrazolidine-3,5-dione derivatives as potent non-steroidal agonists of farnesoid X receptor: Virtual screening, synthesis, and biological evaluation".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 18.20(2008):5497-5502.