(3R,4S)-4-(2,4,5-Trifluorophenyl)-pyrrolidin-3-ylamine inhibitors of dipeptidyl peptidase IV: synthesis, in vitro, in vivo, and X-ray crystallographic characterization

Bioorg Med Chem Lett. 2007 Oct 15;17(20):5638-42. doi: 10.1016/j.bmcl.2007.07.081. Epub 2007 Aug 22.

Abstract

A series of pyrrolidine based inhibitors of dipeptidyl peptidase IV were developed from a high throughput screening hit for the treatment of type 2 diabetes. Potency, selectivity, and pharmacokinetic properties were optimized resulting in the identification of a pre-clinical candidate for further profiling.

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Dipeptidyl Peptidase 4 / chemistry
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors*
  • Dogs
  • Fluorine / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacokinetics
  • Protease Inhibitors / pharmacology*
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry*
  • Pyrrolidines / pharmacokinetics
  • Pyrrolidines / pharmacology*
  • Rats
  • Stereoisomerism

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Protease Inhibitors
  • Pyrrolidines
  • Fluorine
  • Dipeptidyl Peptidase 4
  • pyrrolidine