Exploration of SAR regarding glucose moiety in novel C-aryl glucoside inhibitors of SGLT2

Bioorg Med Chem Lett. 2011 Jan 15;21(2):742-6. doi: 10.1016/j.bmcl.2010.11.115. Epub 2010 Dec 3.

Abstract

In order to investigate SAR regarding glucose moiety in novel C-aryl glucoside SGLT2 inhibitors containing a thiazole motif, a series of chemical modifications on glucose was conducted to explore potential utility as a suitable replacement of glucose per se. Among the compounds prepared, deshydroxy 29 (IC(50)=7.01nM) demonstrated the best in vitro inhibitory activity against SGLT2 in this series to date. But, none of the compounds were better than the parent molecule 5 (IC(50)=1.75nM).

MeSH terms

  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / enzymology
  • Glycosides / chemistry*
  • Glycosides / pharmacology*
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacology*
  • Sodium-Glucose Transporter 2 / metabolism*
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology

Substances

  • Glycosides
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiazoles