Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase

Bioorg Med Chem Lett. 2010 Jan 15;20(2):571-5. doi: 10.1016/j.bmcl.2009.11.091. Epub 2009 Nov 22.


Inhibition of sEH is hypothesized to lead to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects. In an effort to explore sEH inhibition as an avenue for the development of vasodilatory and cardio- or renal-protective agents, a lead identified through high-throughput screening was optimized, guided by the determination of a solid state co-structure with sEH. Replacement of potential toxicophores was followed by optimization of cell-based potency and ADME properties to provide a new class of functionally potent sEH inhibitors with attractive in vitro metabolic profiles and high and sustained plasma exposures after oral administration in the rat.

MeSH terms

  • Administration, Oral
  • Animals
  • Binding Sites
  • Computer Simulation
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacokinetics
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Epoxide Hydrolases / metabolism
  • Humans
  • Microsomes, Liver / metabolism
  • Piperidines / chemistry*
  • Rats
  • Urea / analogs & derivatives*
  • Urea / chemistry
  • Urea / pharmacokinetics


  • Enzyme Inhibitors
  • Piperidines
  • piperidine
  • Urea
  • Epoxide Hydrolases