Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase

In Hae Kim, Kosuke Nishi, Takeo Kasagami, Christophe Morisseau, Jun Yan Liu, Hsing Ju Tsai, Bruce D. Hammock

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Substituted ureas with a carboxylic acid ester as a secondary pharmacophore are potent soluble epoxide hydrolase (sEH) inhibitors. Although the ester substituent imparts better physical properties, such compounds are quickly metabolized to the corresponding less potent acids. Toward producing biologically active ester compounds, a series of esters were prepared and evaluated for potency on the human enzyme, stability in human liver microsomes, and physical properties. Modifications around the ester function enhanced in vitro metabolic stability of the ester inhibitors up to 32-fold without a decrease in inhibition potency. Further, several compounds had improved physical properties.

Original languageEnglish (US)
Pages (from-to)5889-5892
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number18
DOIs
StatePublished - Sep 15 2012

Fingerprint

Epoxide Hydrolases
Esters
Derivatives
Physical properties
Enzyme Stability
Liver Microsomes
Carboxylic Acids
Liver
Urea
Acids
Enzymes

Keywords

  • Metabolic stability
  • sEH
  • sEH inhibitors
  • Substituted urea-ester derivatives

ASJC Scopus subject areas

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

Cite this

Kim, I. H., Nishi, K., Kasagami, T., Morisseau, C., Liu, J. Y., Tsai, H. J., & Hammock, B. D. (2012). Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase. Bioorganic and Medicinal Chemistry Letters, 22(18), 5889-5892. https://doi.org/10.1016/j.bmcl.2012.07.074

Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase. / Kim, In Hae; Nishi, Kosuke; Kasagami, Takeo; Morisseau, Christophe; Liu, Jun Yan; Tsai, Hsing Ju; Hammock, Bruce D.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 18, 15.09.2012, p. 5889-5892.

Research output: Contribution to journalArticle

Kim, IH, Nishi, K, Kasagami, T, Morisseau, C, Liu, JY, Tsai, HJ & Hammock, BD 2012, 'Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 18, pp. 5889-5892. https://doi.org/10.1016/j.bmcl.2012.07.074
Kim, In Hae ; Nishi, Kosuke ; Kasagami, Takeo ; Morisseau, Christophe ; Liu, Jun Yan ; Tsai, Hsing Ju ; Hammock, Bruce D. / Biologically active ester derivatives as potent inhibitors of the soluble epoxide hydrolase. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 18. pp. 5889-5892.
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