Abstract
A new family of Histamine H(3) receptor antagonists (5a-t) has been prepared based on the structure of the natural product Conessine, a known H(3) antagonist. Several members of the new series are highly potent and selective binders of rat and human H(3) receptors and display inverse agonism at the human H(3) receptor. Compound 5n exhibited promising rat pharmacokinetic properties and demonstrated functional antagonism of the H(3) receptor in an in-vivo pharmacological model.
MeSH terms
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Alkaloids / chemical synthesis*
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Alkaloids / chemistry
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Alkaloids / pharmacology*
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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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CHO Cells
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Cricetinae
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Cricetulus
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Drug Design
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Histamine Agonists / pharmacology
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Histamine H3 Antagonists / chemical synthesis*
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Histamine H3 Antagonists / metabolism
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Histamine H3 Antagonists / pharmacology*
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Humans
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Kinetics
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Pyrrolidines / chemical synthesis
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Pyrrolidines / chemistry
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Pyrrolidines / pharmacology
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Rats
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Receptors, Histamine H3 / metabolism
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Structure-Activity Relationship
Substances
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Alkaloids
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Amines
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Histamine Agonists
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Histamine H3 Antagonists
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Pyrrolidines
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Receptors, Histamine H3
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conessine