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
通讯作者地址：[Zhao, GL]Tianjin Inst Pharmaceut Res, Tianjin Key Lab Mol Design & Drug Discovery, Tianjin 300193, Peoples R China.
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.