Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists

doi:10.1016/j.ejmech.2013.12.018

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	Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists
	Han, Shuang 2; Zhang, Fei-Fei 1; Xie, Xin1 ; Chen, Jian-Zhong 2
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2014-03-03
卷号	74 页码:73-84
关键词	Cannabinoid receptors Antagonist 1,2,4-Triazolone Scaffold hopping Homology model
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2013.12.018
文献子类	Article
英文摘要	Cannabinoids are potentially useful for the treatment of several diseases. In the present work, we report the syntheses and biological evaluations of 1,2,4-triazolone derivatives designed using a combined approach of scaffold hopping and pharmacophore-oriented method. These compounds exhibited interesting antagonistic activity to the cannabinoid CBI receptor. The preliminary structure activity relationships were further discussed. In addition, docking simulations were performed on the good bioactive compound 5c and the low potent compound 5d, respectively, on the basis of homology models of the CBI and CB2 receptors, which were constructed based on human beta 2-adrenoreceptor and optimized in a membrane environment by MD simulations. Calculation of the binding modes gave us insights into the structural requirements for improving the cannabinoid receptor bioactivity and selectivity. (C) 2013 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of China[NSFC 30973637] ; Qianjiang talents project of Technology Office in Zhejiang Province[2010R10048]
WOS关键词	BINDING MODE PREDICTION ; 2 INVERSE AGONISTS ; CANNABINOID RECEPTOR ; ENDOCANNABINOID SYSTEM ; MOLECULAR-DYNAMICS ; OSTEOCLAST INHIBITORS ; SR 144528 ; IN-VIVO ; DERIVATIVES ; POTENT
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:000333780800009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277161]
专题	国家新药筛选中心
通讯作者	Chen, Jian-Zhong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Medico, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Beijing 100864, Peoples R China 2.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Han, Shuang,Zhang, Fei-Fei,Xie, Xin,et al. Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2014,74:73-84.
APA	Han, Shuang,Zhang, Fei-Fei,Xie, Xin,&Chen, Jian-Zhong.(2014).Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,74,73-84.
MLA	Han, Shuang,et al."Design, synthesis, biological evaluation, and comparative docking study of 1,2,4-triazolones as CB1 receptor selective antagonists".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 74(2014):73-84.