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

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.

SUBMITTER: Pecic S

PROVIDER: S-EPMC3541548 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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

Pecic Stevan S Pakhomova Svetlana S Newcomer Marcia E ME Morisseau Christophe C Hammock Bruce D BD Zhu Zhengxiang Z Rinderspacher Alison A Deng Shi-Xian SX

Bioorganic & medicinal chemistry letters 20121201 2

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 stab ...[more]

PMID: 23237835

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