Abstract
We describe here our attempts to optimise the human fatty acid amide hydrolase (FAAH) inhibition and physicochemical properties of our previously reported tetrasubstituted azetidine urea FAAH inhibitor, VER-156084. We describe the SAR of a series of analogues and conclude with the demonstration of in vivo dose-dependant FAAH inhibition in an anandamide-loading study in rats.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Amidohydrolases / antagonists & inhibitors*
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Amidohydrolases / metabolism
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Animals
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Azetidines / chemical synthesis
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Azetidines / chemistry
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Azetidines / pharmacology*
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Cytochrome P-450 Enzyme Inhibitors
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Cytochrome P-450 Enzyme System / metabolism
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Dose-Response Relationship, Drug
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ERG1 Potassium Channel
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
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Humans
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Models, Molecular
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Molecular Structure
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Rats
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Stereoisomerism
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Structure-Activity Relationship
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Urea / chemical synthesis
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Urea / chemistry
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Urea / pharmacology*
Substances
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Azetidines
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Cytochrome P-450 Enzyme Inhibitors
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ERG1 Potassium Channel
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Enzyme Inhibitors
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Ether-A-Go-Go Potassium Channels
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azetidine
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Urea
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Cytochrome P-450 Enzyme System
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Amidohydrolases
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fatty-acid amide hydrolase