1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors

Vladimir Burmistrov, Christophe Morisseau, Dmitry Danilov, Todd R. Harris, Igor Dalinger, Irina Vatsadze, Tatiana Shkineva, Gennady M. Butov, Bruce D. Hammock

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Adamantyl ureas are good soluble epoxide hydrolase (sEH) inhibitors; however they have limited solubility and rapid metabolism, thus limiting their usefulness in some therapeutic indications. Herein, we test the hypothesis that nodal substitution on the adamantane will help solubilize and stabilize the compounds. A series of compounds containing adamantane derivatives and isoxazole functional groups were developed. Overall, the presence of methyl on the nodal positions of adamantane yields higher water solubility than previously reported urea-based sEH inhibitors while maintaining high inhibition potency. However, it did not improve microsomal stability.

Original languageEnglish (US)
Pages (from-to)5514-5519
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number23
DOIs
StatePublished - Dec 1 2015

Keywords

  • Adamantane
  • Inhibitor
  • Isocyanate
  • Isoxazole
  • Soluble epoxide hydrolase
  • Urea

ASJC Scopus subject areas

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

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    Burmistrov, V., Morisseau, C., Danilov, D., Harris, T. R., Dalinger, I., Vatsadze, I., Shkineva, T., Butov, G. M., & Hammock, B. D. (2015). 1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors. Bioorganic and Medicinal Chemistry Letters, 25(23), 5514-5519. https://doi.org/10.1016/j.bmcl.2015.10.066