Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors

Vladimir Burmistrov, Christophe Morisseau, Kin Sing Stephen Lee, Diyala S. Shihadih, Todd R. Harris, Gennady M. Butov, Bruce D. Hammock

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 (IC 50 = 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).

Original languageEnglish (US)
Pages (from-to)2193-2197
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number9
DOIs
StatePublished - May 1 2014

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Epoxide Hydrolases
Urea
Enzymes

Keywords

  • Adamantane
  • Diurea
  • Inhibitor
  • Isocyanate
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

Cite this

Burmistrov, V., Morisseau, C., Lee, K. S. S., Shihadih, D. S., Harris, T. R., Butov, G. M., & Hammock, B. D. (2014). Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors. Bioorganic and Medicinal Chemistry Letters, 24(9), 2193-2197. https://doi.org/10.1016/j.bmcl.2014.03.016

Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors. / Burmistrov, Vladimir; Morisseau, Christophe; Lee, Kin Sing Stephen; Shihadih, Diyala S.; Harris, Todd R.; Butov, Gennady M.; Hammock, Bruce D.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 9, 01.05.2014, p. 2193-2197.

Research output: Contribution to journalArticle

Burmistrov, V, Morisseau, C, Lee, KSS, Shihadih, DS, Harris, TR, Butov, GM & Hammock, BD 2014, 'Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 24, no. 9, pp. 2193-2197. https://doi.org/10.1016/j.bmcl.2014.03.016
Burmistrov V, Morisseau C, Lee KSS, Shihadih DS, Harris TR, Butov GM et al. Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors. Bioorganic and Medicinal Chemistry Letters. 2014 May 1;24(9):2193-2197. https://doi.org/10.1016/j.bmcl.2014.03.016
Burmistrov, Vladimir ; Morisseau, Christophe ; Lee, Kin Sing Stephen ; Shihadih, Diyala S. ; Harris, Todd R. ; Butov, Gennady M. ; Hammock, Bruce D. / Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2014 ; Vol. 24, No. 9. pp. 2193-2197.
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