Abstract
A series of novel and potent pyrrolidino-tetrahydroisoquinolines with dual histamine H(3) antagonist/serotonin transporter inhibitor activity is described. A highly regio- and diastereoselective synthesis of the pyrrolidino-tetrahydroisoquinoline core involving acid mediated ring-closure of an acetophenone intermediate followed by reduction with NaCNBH(3) was developed. In vitro and in vivo data are discussed.
MeSH terms
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Animals
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Chemistry, Pharmaceutical / methods*
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Depression / drug therapy
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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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Kinetics
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Models, Chemical
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Molecular Conformation
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Rats
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Receptors, Histamine H3 / chemistry*
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Selective Serotonin Reuptake Inhibitors / chemical synthesis*
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Selective Serotonin Reuptake Inhibitors / pharmacology*
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Serotonin / chemistry*
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Tetrahydroisoquinolines / chemical synthesis*
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Tetrahydroisoquinolines / pharmacology*
Substances
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Histamine Antagonists
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Receptors, Histamine H3
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Serotonin Uptake Inhibitors
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Tetrahydroisoquinolines
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Serotonin