Abstract
Starting from a series of ureas that were determined to be mechanism-based inhibitors of FAAH, several spirocyclic ureas and lactams were designed and synthesized. These efforts identified a series of novel, noncovalent FAAH inhibitors with in vitro potency comparable to known covalent FAAH inhibitors. The mechanism of action for these compounds was determined through a combination of SAR and co-crystallography with rat FAAH.
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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Binding Sites
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Computer Simulation
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Crystallography, X-Ray
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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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Humans
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Lactams / chemical synthesis
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Lactams / chemistry
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Lactams / pharmacokinetics
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Rats
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Spiro Compounds / chemistry
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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 / pharmacokinetics
Substances
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Enzyme Inhibitors
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Lactams
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Spiro Compounds
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Urea
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Amidohydrolases
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fatty-acid amide hydrolase