Discovery and pharmacological characterization of N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor

Bioorg Med Chem. 2011 Dec 1;19(23):7221-7. doi: 10.1016/j.bmc.2011.09.043. Epub 2011 Oct 2.

Abstract

In the course of our program for discovery of novel DPP-IV inhibitors, a series of pyrazolo[1,5-a]pyrimidines were found to be novel DPP-IV inhibitors. We identified N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (4a) and described its pharmacological profiles.

MeSH terms

  • Animals
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dogs
  • Humans
  • Male
  • Pyrimidines / administration & dosage
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Pyrimidines
  • Dipeptidyl Peptidase 4
  • anagliptin