Abstract
3,3-Disubstituted piperidine-derived trisubstituted urea entA-2b was discovered as a highly potent and selective soluble epoxide hydrolase (sEH) inhibitor. Despite the good compound oral exposure, excellent sEH inhibition in whole blood, and remarkable selectivity, compound entA-2b failed to lower blood pressure acutely in spontaneously hypertensive rats (SHRs). This observation further challenges the premise that sEH inhibition can provide a viable approach to the treatment of hypertensive patients.
MeSH terms
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8,11,14-Eicosatrienoic Acid / analogs & derivatives
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8,11,14-Eicosatrienoic Acid / blood
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8,11,14-Eicosatrienoic Acid / metabolism
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Animals
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Blood Pressure / drug effects
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Epoxide Hydrolases / antagonists & inhibitors*
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Epoxide Hydrolases / metabolism*
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Humans
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Hypertension / drug therapy*
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Models, Molecular
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Piperidines / chemistry*
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Protein Binding
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Rats
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Rats, Inbred SHR
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Structure-Activity Relationship
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Urea / analogs & derivatives*
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Urea / pharmacology*
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Urea / therapeutic use
Substances
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14,15-dihydroxyeicosatrienoic acid
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Piperidines
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piperidine
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Urea
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Epoxide Hydrolases
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8,11,14-Eicosatrienoic Acid