Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration

Bioorg Med Chem. 2007 Apr 1;15(7):2631-50. doi: 10.1016/j.bmc.2007.01.041. Epub 2007 Jan 26.

Abstract

A series of 5beta-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure-activity relationships are also presented.

MeSH terms

  • Animals
  • Chromatography, Thin Layer
  • Dipeptidyl Peptidase 4 / blood
  • Dipeptidyl-Peptidase IV Inhibitors*
  • Dogs
  • Glucose Tolerance Test
  • Humans
  • Indicators and Reagents
  • Macaca fascicularis
  • Magnetic Resonance Spectroscopy
  • Male
  • Oxidation-Reduction
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology*
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Indicators and Reagents
  • Protease Inhibitors
  • Pyrrolidines
  • Dipeptidyl Peptidase 4