Solid-phase combinatorial approach for the optimization of soluble epoxide hydrolase inhibitors

Bioorg Med Chem Lett. 2006 Nov 15;16(22):5773-7. doi: 10.1016/j.bmcl.2006.08.078. Epub 2006 Sep 1.

Abstract

A 192-member library of N,N'-disubstituted urea inhibitors was synthesized by a solid-phase method. The ureas were tested for their inhibitory activities against recombinant human soluble epoxide hydrolase. Simple carbocyclic or para/meta-substituted phenyl groups showed inhibition potencies that were equal to or greater than adamantane-based sEH inhibitors, while the presence of bulky or ionizable groups close to the urea group dramatically decreased their activities.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Combinatorial Chemistry Techniques*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Inhibitory Concentration 50
  • Kinetics
  • Solubility
  • Structure-Activity Relationship
  • Urea / chemistry*

Substances

  • Enzyme Inhibitors
  • Urea
  • Epoxide Hydrolases