5-Heteroatom-substituted pyrazoles as canine COX-2 inhibitors: Part 2. Structure-activity relationship studies of 5-alkylethers and 5-thioethers

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1202-6. doi: 10.1016/j.bmcl.2005.11.110. Epub 2005 Dec 27.

Abstract

Structure-activity relationship (SAR) studies of novel 2-[3-trifluoromethyl-5-alkyl(thio)ether pyrazo-1-yl]-5-methanesulfonyl pyridine derivatives for canine COX enzymes are described. The 4-cyano-5-alkyl ethers were found to have excellent potency and selectivity, whereas the 5-thioethers were potent but less selective than the ether analogs in a canine whole blood (CWB) COX-2 assay.

MeSH terms

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

Substances

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