Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors

Stevan Pecic, Svetlana Pakhomova, Marcia E. Newcomer, Christophe Morisseau, Bruce D. Hammock, Zhengxiang Zhu, Alison Rinderspacher, Shi Xian Deng

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.

Original languageEnglish (US)
Pages (from-to)417-421
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number2
DOIs
StatePublished - Jan 15 2013

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Keywords

  • Human liver microsomes stability
  • Hypertension
  • Non-urea inhibitors
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

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

Cite this

Pecic, S., Pakhomova, S., Newcomer, M. E., Morisseau, C., Hammock, B. D., Zhu, Z., Rinderspacher, A., & Deng, S. X. (2013). Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors. Bioorganic and Medicinal Chemistry Letters, 23(2), 417-421. https://doi.org/10.1016/j.bmcl.2012.11.084