Abstract
The histamine H(4) receptor is a G protein-coupled receptor that has attracted much interest for its role in inflammatory and immunomodulatory functions. In our search for new H(4)R ligands, a low affinity isoquinoline fragment was optimized to 7-(furan-2-yl)-4-(piperazin-1-yl)quinazolin-2-amine (VUF11489), as a new H(4)R antagonist. Analysis of its binding kinetics at the human H(4)R showed this compound to have a very different dissociative half-life in comparison with reference antagonist JNJ7777120.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Biological Availability
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Chemistry, Pharmaceutical / methods
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Drug Design
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Histamine Antagonists / chemical synthesis*
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Histamine Antagonists / pharmacology
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Humans
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Hypersensitivity / drug therapy
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Inhibitory Concentration 50
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Kinetics
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Ligands
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Mice
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Models, Chemical
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Models, Molecular
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Molecular Conformation
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Rats
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Receptors, G-Protein-Coupled / antagonists & inhibitors*
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Receptors, G-Protein-Coupled / chemistry*
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Receptors, Histamine / chemistry*
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Receptors, Histamine H4
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Structure-Activity Relationship
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Time Factors
Substances
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HRH4 protein, human
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Histamine Antagonists
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Ligands
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Receptors, G-Protein-Coupled
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Receptors, Histamine
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Receptors, Histamine H4