Abstract
We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (K(I)=15nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low apparent bioavailability in dogs and rats, this series of compounds revealed that sEH inhibitor structures could accept large groups that could lead to better orally available drugs.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Area Under Curve
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Biological Availability
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Dogs
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacokinetics*
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Epoxide Hydrolases / antagonists & inhibitors*
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Humans
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Mice
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Molecular Structure
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Peptides / chemistry*
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Rats
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Solubility
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Stereoisomerism
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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*
Substances
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Enzyme Inhibitors
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Peptides
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Urea
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Epoxide Hydrolases