Exploration of O-spiroketal C-arylglucosides as novel and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

  • Bioorg Med Chem Lett. 2009 Dec 15;19(24):6877-81. doi: 10.1016/j.bmcl.2009.10.088.
Binhua Lv  1 ,  Baihua Xu ,  Yan Feng ,  Kun Peng ,  Ge Xu ,  Jiyan Du ,  Lili Zhang ,  Wenbin Zhang ,  Ting Zhang ,  Liangcheng Zhu ,  Haifeng Ding ,  Zelin Sheng ,  Ajith Welihinda ,  Brian Seed ,  Yuanwei Chen
Affiliations
  • 1. Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, PR China. [email protected]
PMID: 19896374 DOI: 10.1016/j.bmcl.2009.10.088
Abstract

A series of novel O-spiroketal C-arylglucosides have been prepared and evaluated in cell-based functional assays for activity against human sodium-dependent glucose co-transporters 1 and 2 (SGLT1 and 2). The core spiro[isobenzofuran-1,2'-pyran] structure proved to be an effective scaffold for diversification and a number of compounds with single digit nanomolar potency and high selectivity have been synthesized. Compound 5a promoted glucosuria when administered in vivo in rats and produced a significant blood glucose reduction effect.