Synthesis of selective 11 beta-HSD1 inhibitors based on dammarane scaffold

doi:10.1016/j.ejmech.2017.04.059

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	Synthesis of selective 11 beta-HSD1 inhibitors based on dammarane scaffold
	Shao, Li-Dong 2; Bao, Ying 1,2; Shen, Yu 3; Su, Jia 2; Leng, Ying3 ; Zhao, Qin-Shi 2
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2017-07-28
卷号	135 页码:324-338
关键词	11 beta-HSD1 inhibitor Hupehenols Dammarane SAR
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2017.04.059
文献子类	Article
英文摘要	Inspired by natural 11 beta-HSD1 inhibitors hupehenols A - E, a ring-focused strategy was applied for the synthesis of 35 structurally diverse dammarane-type derivatives. These derivatives were effectively prepared from protopanaxadiol based on the modification of rings A and D. Among these compounds, ten were identified as selective 11 beta-HSD1 inhibitors (IC50 range: 101-1047 nM, SI range: 8-169) which exhibited inhibitory activities against human or mouse 11 beta-HSD1. Otherwise, we found 23a could selectively inhibit both human and mouse 11 beta-HSD1 with IC50 value of 994 and 213 nM (SI > 10 and > 47), respectively. Additionally, the molecular modelling results of 23a docking into the human and mouse 11 beta-HSD1 were in good agreement with the results from the enzyme inhibitory experiment. Moreover, valuable structural-activity relationship (SAR) information of dammarane-type 11 beta-HSD1 inhibitor was summarized. (C) 2017 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of China[U1502223] ; National Natural Science Foundation of China[81603000]
WOS关键词	11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 ; INSULIN-RESISTANCE ; GLUCOCORTICOID-RECEPTOR ; (+)-COLLETOIC ACID ; CARBENOXOLONE ; DISCOVERY ; SENSITIVITY ; HUPEHENOLS ; OBESITY
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:000403512100026
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272554]
专题	药理学第一研究室
通讯作者	Leng, Ying; Zhao, Qin-Shi
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Shao, Li-Dong,Bao, Ying,Shen, Yu,et al. Synthesis of selective 11 beta-HSD1 inhibitors based on dammarane scaffold[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,135:324-338.
APA	Shao, Li-Dong,Bao, Ying,Shen, Yu,Su, Jia,Leng, Ying,&Zhao, Qin-Shi.(2017).Synthesis of selective 11 beta-HSD1 inhibitors based on dammarane scaffold.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,135,324-338.
MLA	Shao, Li-Dong,et al."Synthesis of selective 11 beta-HSD1 inhibitors based on dammarane scaffold".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 135(2017):324-338.