Comparative structure-activity relationship studies of 1-(5-methylsulfonylpyrid-2-yl)-5-alkyl and (hetero)aryl triazoles and pyrazoles in canine COX inhibition

Bioorg Med Chem Lett. 2008 Feb 1;18(3):1042-5. doi: 10.1016/j.bmcl.2007.12.025. Epub 2008 Jan 7.

Abstract

Structure-activity relationship (SAR) studies of novel 5-alkyl and 5-aryl/heteroaryl substituted 1,2,4-triazoles are described. The in vitro activity is compared to the pyrazole class of compounds with analogous side chains to delineate the contribution of the triazole ring nitrogen in binding to the active site. Both series are quite potent and selective in the canine whole blood (CWB) COX-2 assay, suggesting the increased binding contribution of the hydrophobic side chains.

MeSH terms

  • Alkylation
  • Animals
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / blood
  • Cyclooxygenase 2 Inhibitors / chemical synthesis*
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dogs
  • Ethers / chemistry*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Pyrazoles / blood
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / blood
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology*
  • Triazoles / blood
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Ethers
  • Pyrazoles
  • Sulfhydryl Compounds
  • Triazoles
  • Cyclooxygenase 2