5-heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part 1: Structure-activity relationship studies of 5-alkylamino pyrazoles and discovery of a potent, selective, and orally active analog

Bioorg Med Chem Lett. 2006 Jan 15;16(2):288-92. doi: 10.1016/j.bmcl.2005.10.006. Epub 2005 Nov 3.

Abstract

Structure-activity relationship (SAR) studies of the novel 2-[3-di and trifluoromethyl-5-alkylamino pyrazo-1-yl]-5-methanesulfonyl (SO(2)Me)/sulfamoyl (SO(2)NH(2))-pyridine derivatives for canine COX enzymes are described. The studies led to the identification of 2e as lead with potent in vitro activity, selectivity, and in vivo activity in dogs and cats.

MeSH terms

  • Administration, Oral
  • Animals
  • Cats
  • Cyclooxygenase 2 / drug effects*
  • Cyclooxygenase 2 Inhibitors* / chemical synthesis
  • Cyclooxygenase 2 Inhibitors* / chemistry
  • Cyclooxygenase 2 Inhibitors* / pharmacokinetics
  • Disease Models, Animal
  • Dogs
  • Drug Evaluation, Preclinical
  • In Vitro Techniques
  • Molecular Structure
  • Pyrazoles* / chemical synthesis
  • Pyrazoles* / chemistry
  • Pyrazoles* / pharmacokinetics
  • Structure-Activity Relationship

Substances

  • 3-difluoromethyl-5-(cis-2,6-dimethylmorpholin-4-yl)-1-(5-methanesulfonyl-pyridin-2-yl)-1H-pyrazole-4-carbonitrile
  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • Cyclooxygenase 2