Structural refinement of inhibitors of urea-based soluble epoxide hydrolases

Christophe Morisseau, Marvin H. Goodrow, John W. Newman, Craig E. Wheelock, Deanna L. Dowdy, Bruce D. Hammock

Research output: Contribution to journalArticlepeer-review

155 Scopus citations


The soluble epoxide hydrolase (sEH) is involved in the metabolism of arachidonic, linoleic, and other fatty acid epoxides, endogenous chemical mediators that play an important role in blood pressure regulation and inflammation. 1,3-Disubstituted ureas, carbamates, and amides are new potent and stable inhibitors of sEH. However, the poor solubility of the lead compounds limits their use. Inhibitor structure-activity relationships were investigated to better define the structural requirements for inhibition and to identify points in the molecular topography that could accept polar groups without diminishing inhibition potency. Results indicate that lipophilicity is an important factor controlling inhibitor potency. Polar groups could be incorporated into one of the alkyl groups without loss of activity if they were placed at a sufficient distance from the urea function. The resulting compounds had a 2-fold higher water solubility. These findings will facilitate the rational design and optimization of sEH inhibitors with better physical properties.

Original languageEnglish (US)
Pages (from-to)1599-1608
Number of pages10
JournalBiochemical Pharmacology
Issue number9
StatePublished - May 1 2002


  • Blood pressure
  • Epoxide hydrolase
  • Immune response
  • Solubility
  • Structure-activity relationships
  • Urea inhibitors

ASJC Scopus subject areas

  • Pharmacology


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