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 Citations (Scopus)

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

Fingerprint

Epoxide Hydrolases
Structure-Activity Relationship
Lead compounds
Amides
Liver
Assays
Screening
Anti-Inflammatory Agents
Throughput
Acids
piperidine
Pharmaceutical Preparations

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

Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors. / Pecic, Stevan; Pakhomova, Svetlana; Newcomer, Marcia E.; Morisseau, Christophe; Hammock, Bruce D.; Zhu, Zhengxiang; Rinderspacher, Alison; Deng, Shi Xian.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 2, 15.01.2013, p. 417-421.

Research output: Contribution to journalArticle

Pecic, S, Pakhomova, S, Newcomer, ME, Morisseau, C, Hammock, BD, Zhu, Z, Rinderspacher, A & Deng, SX 2013, 'Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 2, pp. 417-421. https://doi.org/10.1016/j.bmcl.2012.11.084
Pecic, Stevan ; Pakhomova, Svetlana ; Newcomer, Marcia E. ; Morisseau, Christophe ; Hammock, Bruce D. ; Zhu, Zhengxiang ; Rinderspacher, Alison ; Deng, Shi Xian. / Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 2. pp. 417-421.
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