Abstract
A series of 3-carboxamido-5-aryl-isoxazoles designed as CB2 agonists were evaluated as FAAH inhibitors. The pharmacological results led to identify structure-activity relationships enabling to switch cannabinoid response from CB2 agonists to FAAH inhibitors. Two compounds were selected for their FAAH and/or CB2 activity, and evaluated in a colitis model for their anti-inflammatory activity. Results showed that compounds 10 and 11 inhibit the development of DSS-induced acute colitis in mice and then, are interesting leads to explore new drug candidates for IBD.
Keywords:
CB(2); Cannabinoid; FAAH; IBD; Isoxazoles.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adamantane / analogs & derivatives*
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Adamantane / chemistry
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Adamantane / pharmacology
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Adamantane / therapeutic use
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Amidohydrolases / antagonists & inhibitors*
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Amidohydrolases / metabolism
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Animals
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Anti-Inflammatory Agents / chemistry*
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Anti-Inflammatory Agents / pharmacology
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Anti-Inflammatory Agents / therapeutic use
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Body Weight / drug effects
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Cannabinoids / chemistry*
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Cannabinoids / pharmacology
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Cannabinoids / therapeutic use
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Colitis / drug therapy
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Colitis / pathology
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Disease Models, Animal
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Isoxazoles / chemistry*
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Isoxazoles / pharmacology
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Isoxazoles / therapeutic use
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Male
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Mice
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Mice, Inbred C57BL
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Protein Binding
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Receptor, Cannabinoid, CB2 / agonists*
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Receptor, Cannabinoid, CB2 / metabolism
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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Cannabinoids
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Enzyme Inhibitors
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Isoxazoles
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Receptor, Cannabinoid, CB2
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Amidohydrolases
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fatty-acid amide hydrolase
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Adamantane