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Discovery and SAR study of hydroxyacetophenone derivatives as potent, non-steroidal farnesoid X receptor (FXR) antagonists

文献类型：期刊论文

作者Liu, Peng1; Xu, Xing2; Chen, Lili2; Ma, Lei1; Shen, Xu2; Hu, Lihong1,2
刊名BIOORGANIC & MEDICINAL CHEMISTRY
出版日期2014-03-01
卷号22期号:5页码:1596-1607
关键词FXR antagonist SAR study Hydroxyacetophenone derivatives Non-steroidal
ISSN号0968-0896
DOI10.1016/j.bmc.2014.01.032
文献子类Article
英文摘要Compound 1 (IC50 = 35.2 +/- 7.2 mu M), a moderate FXR antagonist was discovered via high-throughput screening. Structure-activity relationship studies indicated that the shape and the lipophilicity of the substituents of the aromatic ring affect the activity dramatically, increasing the shape and the lipophilicity of the substituents of the aromatic ring enhances the potency of FXR antagonists. Especially, when the OH at C2 position of the aromatic ring was replaced by the OBn substituent (analog 2b), its activity could be improved to IC50 = 1.1 +/- 0.1 mu M. Besides, the length of the linker and the tetrazole structure are essential for retaining the activity. (C) 2014 Elsevier Ltd. All rights reserved.
WOS关键词SALT EXPORT PUMP ; ORPHAN NUCLEAR RECEPTOR ; BILE-ACIDS ; BIOLOGICAL EVALUATION ; MEDICINAL CHEMISTRY ; ACTIVATED RECEPTOR ; NATURAL-PRODUCT ; AGONIST ; IDENTIFICATION ; LIGANDS
资助项目National Natural Science Foundation of China[81273397] ; National Natural Science Foundation of China[81373462] ; National Natural Science Foundation of China[81173105] ; Chinese National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2013ZX09508104] ; Chinese National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2012ZX09103-101-018] ; Chinese National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2014ZX09301-306-03] ; Science Foundation of Shanghai[12XD1405700] ; Fundamental Research Funds for the Central Universities[WY1114026]
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:000331729500009
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/277175]  
专题药理学第三研究室
通讯作者Shen, Xu
作者单位1.E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Peng,Xu, Xing,Chen, Lili,et al. Discovery and SAR study of hydroxyacetophenone derivatives as potent, non-steroidal farnesoid X receptor (FXR) antagonists[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2014,22(5):1596-1607.
APA Liu, Peng,Xu, Xing,Chen, Lili,Ma, Lei,Shen, Xu,&Hu, Lihong.(2014).Discovery and SAR study of hydroxyacetophenone derivatives as potent, non-steroidal farnesoid X receptor (FXR) antagonists.BIOORGANIC & MEDICINAL CHEMISTRY,22(5),1596-1607.
MLA Liu, Peng,et al."Discovery and SAR study of hydroxyacetophenone derivatives as potent, non-steroidal farnesoid X receptor (FXR) antagonists".BIOORGANIC & MEDICINAL CHEMISTRY 22.5(2014):1596-1607.

入库方式： OAI收割

来源：上海药物研究所

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