Synthesis and evaluation of structurally constrained imidazolidin derivatives as potent dipeptidyl peptidase IV inhibitors

Eur J Med Chem. 2009 Aug;44(8):3318-22. doi: 10.1016/j.ejmech.2009.03.021. Epub 2009 Mar 26.

Abstract

To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine derivatives with constrained imidazolidin ring and tested their activities against DPP-IV. Most of them exhibited submicromolar inhibitory activities against DPP-IV. The most potent compound among these is (S)-1-(2-(2-(3-(3,4-dimethoxyphenyl)-2-oxoimidazolidin-1-yl)ethyl-amino)acetyl)pyrrolidine-2-carbonitrile (6n), which is a 2 nM DPP-IV inhibitor.

MeSH terms

  • Dipeptidyl-Peptidase IV Inhibitors* / chemical synthesis*
  • Dipeptidyl-Peptidase IV Inhibitors* / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors* / pharmacology*
  • Drug Design
  • Humans
  • Imidazolines / chemical synthesis*
  • Imidazolines / chemistry
  • Imidazolines / pharmacology*
  • Inhibitory Concentration 50
  • Pyrrolidines / chemistry

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Imidazolines
  • Pyrrolidines
  • pyrrolidine