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

doi:10.1016/j.bmcl.2012.11.084

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

Entomology

Research output: Contribution to journal › Article › peer-review

20 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 language	English (US)
Pages (from-to)	417-421
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2012.11.084
State	Published - Jan 15 2013

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

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10.1016/j.bmcl.2012.11.084

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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 journal › Article › peer-review

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AU - Pecic, Stevan

AU - Pakhomova, Svetlana

AU - Newcomer, Marcia E.

AU - Morisseau, Christophe

AU - Hammock, Bruce D.

AU - Zhu, Zhengxiang

AU - Rinderspacher, Alison

AU - Deng, Shi Xian

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KW - Human liver microsomes stability

KW - Hypertension

KW - Non-urea inhibitors

KW - Soluble epoxide hydrolase

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

Abstract

Keywords

ASJC Scopus subject areas

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