Substituted piperazines as novel dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2004 Sep 20;14(18):4763-6. doi: 10.1016/j.bmcl.2004.06.065.

Abstract

Incorporation of a fluorophenyl beta-amino amide moiety into piperazine screening lead 2 has resulted in the discovery of a structurally novel series of potent and selective DP-IV inhibitors. Simplification of the molecule and incorporation of multiple fluorine atoms on the phenyl ring has provided low molecular weight analogs such as compound 32, which is a 19nM DP-IV inhibitor with >4000-fold selectivity over QPP.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Dipeptidyl Peptidase 4 / metabolism*
  • Half-Life
  • In Vitro Techniques
  • Male
  • Microsomes, Liver / metabolism
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Piperazines
  • Protease Inhibitors
  • Dipeptidyl Peptidase 4