Synthesis and biological evaluation of pyrazoline analogues with beta-amino acyl group as dipeptidyl peptidase IV inhibitors

Eur J Med Chem. 2008 Sep;43(9):1889-902. doi: 10.1016/j.ejmech.2007.11.029. Epub 2007 Dec 14.

Abstract

A series of pyrazoline derivatives with beta-amino acyl group were synthesized and evaluated for their ability to inhibit dipeptidyl peptidase IV. Several pyrazoline derivatives exhibited submicromolar inhibitory activities against DPP-IV. X-ray co-crystal structure of initial hit compound 1h was determined. Among this series, carboxylic acid substituted pyrazoline derivative 2u was the most active and greatly decreased the inhibitory activity toward CYP3A4 enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Caco-2 Cells
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inhibitors
  • Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis*
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amines
  • Cytochrome P-450 CYP3A Inhibitors
  • Dipeptidyl-Peptidase IV Inhibitors
  • Pyrazoles
  • pyrazole
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human