Lead optimisation of pyrazoles as novel FPR1 antagonists

Bioorg Med Chem Lett. 2012 Jan 1;22(1):532-6. doi: 10.1016/j.bmcl.2011.10.090. Epub 2011 Nov 4.

Abstract

Optimisation of a series of pyrazole inhibitors of the human FPR1 receptor has been achieved. The use of an in vitro media loss assay was utilised to identify sub-series with more robust DMPK profiles. These were subsequently improved to generate analogues with attractive overall profiles.

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical / methods
  • Chemistry, Physical / methods
  • Drug Design
  • Hepatocytes / cytology
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Microsomes, Liver / metabolism
  • Models, Chemical
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Formyl Peptide / antagonists & inhibitors*
  • Receptors, Formyl Peptide / chemistry

Substances

  • FPR1 protein, human
  • Pyrazoles
  • Receptors, Formyl Peptide