Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6379-83. doi: 10.1016/j.bmcl.2010.09.095. Epub 2010 Sep 19.


A novel series of pyrazole sEH inhibitors is reported. Lead optimization efforts to replace the aniline core are also described. In particular, 2-pyridine, 3-pyridine and pyridazine analogs are potent sEH inhibitors with favorable CYP3A4 inhibitory and microsomal stability profiles.

MeSH terms

  • Caco-2 Cells
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors / pharmacology*
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Humans
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Models, Molecular
  • Pyrazoles / pharmacology*


  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors
  • Pyrazoles
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Epoxide Hydrolases