Abstract
Synthesis and biological evaluation of novel and potent cyclohexylamine-based histamine H3 receptor inverse agonists are described. Compounds in this newly identified series exhibited subnanomolar binding affinities for human receptor and no significant interaction with hERG channel. One derivative (10t) demonstrated enhanced in vivo efficiency and preferential brain distribution, both properties suitable for potential clinical evaluation.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Cyclohexylamines / chemical synthesis
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Cyclohexylamines / chemistry
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Cyclohexylamines / pharmacology*
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Dose-Response Relationship, Drug
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Histamine Agonists / chemical synthesis
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Histamine Agonists / chemistry
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Histamine Agonists / pharmacology*
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Humans
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Ligands
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Mice
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Models, Molecular
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Molecular Structure
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Receptors, Histamine H3 / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Trans-Activators / antagonists & inhibitors*
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Trans-Activators / metabolism
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Transcriptional Regulator ERG
Substances
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Cyclohexylamines
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ERG protein, human
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Histamine Agonists
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Ligands
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Receptors, Histamine H3
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Trans-Activators
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Transcriptional Regulator ERG