Discovery of DA-1229: a potent, long acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3809-12. doi: 10.1016/j.bmcl.2011.04.029. Epub 2011 Apr 13.

Abstract

A series of β-amino amide containing substituted piperazine-2-one derivatives was synthesized and evaluated as inhibitors of dipeptidyl pepdidase-4 (DPP-4) for the treatment of type 2 diabetes. As results of intensive SAR study of the series, (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-(t-butoxymethyl)-piperazin-2-one (DA-1229) displayed potent DPP-4 inhibition pattern in several animal models, was selected for clinical development.

MeSH terms

  • Administration, Oral
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis*
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Disease Models, Animal
  • Humans
  • Inhibitory Concentration 50
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • 4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one
  • Dipeptidyl-Peptidase IV Inhibitors
  • Piperazines