Synthesis and biological evaluation of novel C-aryl d-glucofuranosides as sodium-dependent glucose co-transporter 2 inhibitors

Bioorg Med Chem. 2013 Nov 1;21(21):6282-91. doi: 10.1016/j.bmc.2013.08.067. Epub 2013 Sep 8.

Abstract

Novel C-aryl-d-glucofuranosides were synthesized and evaluated for their capacity to inhibit human sodium-dependent glucose co-transporter 2 (hSGLT2) and hSGLT1. Compound 21q demonstrated the best in vitro inhibitory activity against SGLT2 in this series (EC50=0.62μM).

Keywords: Antidiabetics; Glucofuranosides; SGLT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / chemical synthesis*
  • Benzhydryl Compounds / chemistry
  • Benzhydryl Compounds / metabolism
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Glucosidases / chemical synthesis*
  • Glucosidases / chemistry
  • Glucosidases / metabolism
  • Glucosides / chemical synthesis
  • Glucosides / chemistry*
  • Glucosides / metabolism
  • Humans
  • Phlorhizin / chemistry
  • Protein Binding
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors
  • Sodium-Glucose Transporter 1 / genetics
  • Sodium-Glucose Transporter 1 / metabolism
  • Sodium-Glucose Transporter 2 / genetics
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Structure-Activity Relationship

Substances

  • 1,4-anhydro-1-(4-chloro-5-(4-ethylbenzyl)-2-methoxyphenyl)glucitol
  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Phlorhizin
  • Glucosidases