Substituted pyrrolidine-2,4-dicarboxylic acid amides as potent dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3268-72. doi: 10.1016/j.bmcl.2006.03.037. Epub 2006 Apr 11.

Abstract

A series of substituted pyrrolidine-2,4-dicarboxylic acid amides were synthesized as potential antidiabetic agents, and many of them showed good in vitro DPP-IV inhibition (IC50 = 2-250 nM) with selectivity over DPP-II, DPP8, and FAP enzymes. Selected compounds 8c and 11a showed in vivo plasma DPP-IV inhibition after oral administration in Wistar rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology*
  • Animals
  • Dicarboxylic Acids / chemistry*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Drug Design
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Pyrrolidines / chemistry*
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Amides
  • Dicarboxylic Acids
  • Protease Inhibitors
  • Pyrrolidines
  • pyrrolidine-2,4-dicarboxylic acid
  • Dipeptidyl Peptidase 4