Abstract
This Letter describes the identification of a series of novel non-acetylenic mGluR5 negative allosteric modulators based on the alpha-substituted acylamine structure. An initial structure-activity relationship study suggested that (R)-19b and (R)-19j might have good in vitro activity. When administered orally, these compounds were found to have an anxiolytic-like effect in a mouse model of stress-induced hyperthermia.
Keywords:
Acylamines; Metabotropic glutamate receptor; mGluR5 negative allosteric modulators.
Copyright © 2015 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Allosteric Regulation
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Amines / chemical synthesis
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Amines / chemistry*
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Amines / pharmacology
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Animals
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Anti-Anxiety Agents / chemical synthesis*
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Anti-Anxiety Agents / chemistry
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Anti-Anxiety Agents / pharmacology
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Crystallography, X-Ray
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Disease Models, Animal
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Hyperthermia, Induced
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Mice
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Molecular Conformation
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Receptor, Metabotropic Glutamate 5 / chemistry*
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Receptor, Metabotropic Glutamate 5 / metabolism
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Rectum / drug effects
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Rectum / physiology
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Stereoisomerism
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Structure-Activity Relationship
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Temperature
Substances
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Amines
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Anti-Anxiety Agents
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Receptor, Metabotropic Glutamate 5