Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine

Bioorg Med Chem Lett. 2004 Jan 5;14(1):95-8. doi: 10.1016/j.bmcl.2003.10.004.

Abstract

Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted.

MeSH terms

  • Administration, Oral
  • Animals
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Cyclooxygenase Inhibitors / chemistry*
  • Dogs
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Pyridines / administration & dosage*
  • Pyridines / chemistry*
  • Structure-Activity Relationship

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Pyridines
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases