标题:Design, synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors
作者:Zhang, Shuo; Wang, Yu-Li; Wei, Qun-Chao; Xu, Wei-Ren; Tang, Li-Da; Zhao, Gui-Long; Wang, Jian-Wu
作者机构:[Zhang Shuo] School of Chemistry and Chemical Engineering, Shandong University, Tianjin Key Laboratory of Molecular Design and Drug Discovery, Ji'nan, 更多
通讯作者:Zhao, GL(zhao_guilong@126.com)
通讯作者地址:[Zhao, GL]Tianjin Inst Pharmaceut Res, Tianjin Key Lab Mol Design & Drug Discovery, Tianjin 300193, Peoples R China.
来源:中国化学快报
出版年:2013
卷:24
期:5
页码:429-432
DOI:10.1016/j.cclet.2013.03.026
关键词:Synthesis; C-Glucoside; SGLT2 inhibitor; Urinary glucose excretion;; Cyclohexane-bearing
摘要:Seven cyclohexane-bearing C-glucoside derivatives (7, 9, 12, 13 and 17-19) were designed and synthesized as SGLT2 inhibitors starting from a potent SGLT2 inhibitor we discovered in earlier work, (1S)-1-deoxy-1-[4-methoxy-3-(trans-n-propylcyclohexyl)methylphenyl]-D-glucose (1). The in vitro and in vivo biological activities were evaluated by hSGLT2/hSGLT1 inhibition and urinary glucose excretion (UGE), respectively. Among the synthesized compounds 12, the 6-deoxy derivative of 1 was the most active and selective SGLT2 inhibitor (IC50 = 1.4 nmol/L against hSGLT2; selectivity = 1576). Compound 12 was a potent SGLT2 inhibitor, which could induce more urinary glucose than 1 and dapagliflozin in UGE. (C) 2013 Gui-Long Zhao, Jian-Wu Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
收录类别:CSCD;SCOPUS;SCIE
WOS核心被引频次:5
Scopus被引频次:6
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84877702187&doi=10.1016%2fj.cclet.2013.03.026&partnerID=40&md5=ad24088dc3692643a992cdcae03b147b
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