Abstract
A series of conformationally restricted inhibitors of human soluble epoxide hydrolase (sEH) has been developed. Inhibition potency of the described compounds ranges from 4.2 microM to 1.1 nM against recombinant sEH. N-(1-Acetylpiperidin-4-yl)-N'-(adamant-1-yl) urea (5a) was found to be a potent inhibitor (IC(50) = 7.0 nM) that was also orally bioavailable in canines.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Antihypertensive Agents / chemical synthesis*
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Antihypertensive Agents / pharmacology
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Biological Availability
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Dogs
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Epoxide Hydrolases / antagonists & inhibitors*
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Inhibitory Concentration 50
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Molecular Conformation
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Structure-Activity Relationship
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Urea / analogs & derivatives*
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Urea / chemical synthesis
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Urea / pharmacokinetics
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Urea / pharmacology
Substances
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Antihypertensive Agents
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Enzyme Inhibitors
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Urea
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Epoxide Hydrolases