Abstract
A series of tetrahydroisoquinolines acting as dual serotonin transporter inhibitor/histamine H(3) antagonists is described. The introduction of polar aromatic spacers as part of the histamine H(3) pharmacophore was explored. A convergent synthesis of the final products allowing late stage introduction of the aromatic side chain was developed. In vitro and in vivo data are discussed.
MeSH terms
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5-Hydroxytryptophan / pharmacology
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Animals
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Brain / metabolism
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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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Indicators and Reagents
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Rats
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Receptors, Histamine H3 / drug effects*
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Serotonin Antagonists / chemical synthesis*
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Serotonin Antagonists / pharmacology*
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Serotonin Plasma Membrane Transport Proteins / drug effects*
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Structure-Activity Relationship
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Tetrahydroisoquinolines / chemical synthesis*
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Tetrahydroisoquinolines / pharmacology*
Substances
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Histamine Antagonists
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Indicators and Reagents
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Receptors, Histamine H3
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Serotonin Antagonists
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Serotonin Plasma Membrane Transport Proteins
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Tetrahydroisoquinolines
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5-Hydroxytryptophan