Novel thiophenyl C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents

Bioorg Med Chem. 2011 Oct 1;19(19):5813-32. doi: 10.1016/j.bmc.2011.08.014. Epub 2011 Aug 22.

Abstract

Novel thiophene C-aryl glucoside SGLT2 inhibitors were designed and synthesized. Two different types of thiophene derivatives were readily prepared. Among the compounds tested, ethylphenyl at the distal ring 71p showed the best in vitro inhibitory activity in this series to date (IC(50)=4.47 nM) against SGLT2.

MeSH terms

  • Benzhydryl Compounds
  • Glucosides / chemical synthesis
  • Glucosides / chemistry*
  • Glucosides / pharmacology
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacology
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology

Substances

  • (2R,3R,4S,5S,6R)-2-(5-chloro-4-(4-ethylbenzyl)thiophen-2-yl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes
  • dapagliflozin