C-Aryl glucoside SGLT2 inhibitors containing a biphenyl motif as potential anti-diabetic agents

Bioorg Med Chem Lett. 2015 Jul 15;25(14):2744-8. doi: 10.1016/j.bmcl.2015.05.040. Epub 2015 May 27.

Abstract

A series of highly active C-aryl glucoside SGLT2 inhibitors containing a biphenyl motif were designed and synthesized for biological evaluation. Among the compounds tested, compound 16l demonstrated high inhibitory activity against SGLT2 (IC50=1.9 nM) with an excellent pharmacokinetic profile. Further study indicated that the in vivo efficacy of compound 16l was comparable to that of dapagliflozin, suggesting that further development would be worthwhile.

Keywords: Biphenyl; C-Aryl glucoside; SGLT2 inhibitor; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry*
  • Biphenyl Compounds / pharmacokinetics
  • Glucose Tolerance Test
  • Glucosides / chemical synthesis
  • Glucosides / chemistry*
  • Glucosides / pharmacokinetics
  • Half-Life
  • Humans
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacokinetics
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors
  • Sodium-Glucose Transporter 1 / metabolism
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Structure-Activity Relationship

Substances

  • 2-(3-((1,1'-biphenyl)-4-ylmethyl)-4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
  • Biphenyl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • diphenyl