Synthesis and biological evaluation of azobicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3565-8. doi: 10.1016/j.bmcl.2010.04.120. Epub 2010 May 18.

Abstract

A series of novel azobicyclo[3.3.0]octane derivatives were synthesized and evaluated as dipeptidyl peptidase 4 (DPP-4) inhibitors. The effort resulted in the discovery of inhibitor 2a, which exhibited excellent efficacies in an oral glucose tolerance test. Introduction of methyl group (2j) could prolong the inhibition of serum DPP-4 activity.

MeSH terms

  • Animals
  • Azo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / chemical synthesis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl Peptidase 4 / blood
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Glucose Tolerance Test
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Mice
  • Mice, Inbred ICR
  • Octanes / chemical synthesis*
  • Octanes / pharmacology
  • Octanes / therapeutic use*
  • Pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Azo Compounds
  • Bridged Bicyclo Compounds
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Octanes
  • Dipeptidyl Peptidase 4