C-aryl glucosides substituted at the 4'-position as potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes

  • Bioorg Med Chem Lett. 2011 Aug 1;21(15):4465-70. doi: 10.1016/j.bmcl.2011.06.032.
Baihua Xu  1 ,  Yan Feng ,  Huawei Cheng ,  Yanli Song ,  Binhua Lv ,  Yuelin Wu ,  Congna Wang ,  Shengbin Li ,  Min Xu ,  Jiyan Du ,  Kun Peng ,  Jiajia Dong ,  Wenbin Zhang ,  Ting Zhang ,  Liangcheng Zhu ,  Haifeng Ding ,  Zelin Sheng ,  Ajith Welihinda ,  Jacques Y Roberge ,  Brian Seed ,  Yuanwei Chen
Affiliations
  • 1. Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan, PR China. [email protected]
PMID: 21737266 DOI: 10.1016/j.bmcl.2011.06.032
Abstract

A series of C-aryl glucosides with various substituents at the 4'-position of the distal aryl ring have been synthesized and evaluated for inhibition of hSGLT1 and hSGLT2. Introduction of alkyl or alkoxy substituents at the 4'-position was found to improve SGLT2 potency, whereas introduction of a hydrophilic group at this position was deleterious. Compounds with alkoxy-, cycloalkoxy- or cycloalkenyloxy-ethoxy scaffolds exhibited good inhibitory activity and high selectivity toward SGLT2. Selected compounds were investigated for in vivo efficacy.

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