Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors

Bioorg Med Chem Lett. 2014 May 1;24(9):2193-7. doi: 10.1016/j.bmcl.2014.03.016. Epub 2014 Mar 20.

Abstract

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing two urea groups has been developed. Inhibition potency of the described compounds ranges from 2.0 μM to 0.4 nM. 1,6-(Hexamethylene)bis[(adamant-1-yl)urea] (3b) was found to be a potent slow tight binding inhibitor (IC50=0.5 nM) with a strong binding to sEH (Ki=3.1 nM) and a moderately long residence time on the enzyme (koff=1.05 × 10(-3) s(-1); t1/2=11 min).

Keywords: Adamantane; Diurea; Inhibitor; Isocyanate; Soluble epoxide hydrolase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Epoxide Hydrolases / metabolism
  • Humans
  • Molecular Docking Simulation
  • Urea / analogs & derivatives*
  • Urea / pharmacology*

Substances

  • Enzyme Inhibitors
  • Urea
  • Epoxide Hydrolases
  • Adamantane