Discovery of potent, selective, and orally bioavailable pyridone-based dipeptidyl peptidase-4 inhibitors

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1346-9. doi: 10.1016/j.bmcl.2005.11.052. Epub 2005 Dec 5.

Abstract

anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. The optimized compound exhibited good pharmacokinetic profiles in three preclinical species.

MeSH terms

  • Adenosine Deaminase / metabolism
  • Adenosine Deaminase Inhibitors*
  • Administration, Oral
  • Amides / chemistry
  • Animals
  • Biological Availability
  • Dipeptidyl Peptidase 4 / metabolism
  • Dogs
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Macaca mulatta
  • Molecular Structure
  • Nitrogen / chemistry
  • Protease Inhibitors / administration & dosage*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacokinetics
  • Protease Inhibitors / pharmacology*
  • Pyridones / administration & dosage*
  • Pyridones / chemistry
  • Pyridones / pharmacokinetics
  • Pyridones / pharmacology*
  • Rats
  • Sensitivity and Specificity
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Adenosine Deaminase Inhibitors
  • Amides
  • Glycoproteins
  • Protease Inhibitors
  • Pyridones
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Adenosine Deaminase
  • Nitrogen