Abstract
On the basis of the previous results on a histamine H(4) receptor agonist 4-methylhistamine and a cyclopropane-based conformationally restricted analog CEIC (3) with potent H(3)/H(4) receptor antagonistic effect, 4-methylhistamine analogs 4 and 5 of CEIC were designed and synthesized. Compound 4 showed strong affinity (K(i)=38.7 nM) for the H(3) receptor, which was more potent than a well-known H(3) antagonist thioperamide. Stable tautomer and conformation of 3 and 4, which can affect the pharmacological activity, were analyzed by ab initio calculations.
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cyclopropanes / chemical synthesis
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Cyclopropanes / chemistry*
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Cyclopropanes / pharmacology*
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Humans
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Methylhistamines / chemical synthesis
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Methylhistamines / chemistry*
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Methylhistamines / pharmacology*
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Molecular Conformation
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Receptors, G-Protein-Coupled / metabolism*
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Receptors, Histamine / metabolism*
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Receptors, Histamine H3 / metabolism*
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Receptors, Histamine H4
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Structure-Activity Relationship
Substances
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Cyclopropanes
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HRH4 protein, human
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Methylhistamines
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Receptors, G-Protein-Coupled
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Receptors, Histamine
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Receptors, Histamine H3
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Receptors, Histamine H4
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4-methylhistamine
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cyclopropane