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.
Published by Elsevier Ltd.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Catalytic Domain
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Epoxide Hydrolases / antagonists & inhibitors*
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Humans
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Inhibitory Concentration 50
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Microsomes, Liver / enzymology
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Models, Molecular
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Molecular Structure
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology
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Protease Inhibitors / pharmacology
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Solubility
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Structure-Activity Relationship
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Urea / chemistry
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Urea / pharmacology
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Vasodilator Agents / chemical synthesis
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Vasodilator Agents / chemistry
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Vasodilator Agents / pharmacology
Substances
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Anti-Inflammatory Agents
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Piperidines
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Protease Inhibitors
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Vasodilator Agents
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piperidine
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Urea
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Epoxide Hydrolases