Abstract
A flexible, multistep parallel synthesis of spiperone analogues is described. A library of 4-substituted piperidines, assembled utilizing reductive amination and acylation protocols, was alkylated either homogeneously or heterogeneously, exploiting a product release only concept, to afford an oxa-series of spiperone analogues. Screening of the products at 5-HT2 and D2 receptors revealed 5-HT2A antagonists with improved selectivity compared to spiperone and AMI-193.
MeSH terms
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Antipsychotic Agents / chemical synthesis*
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Antipsychotic Agents / pharmacology
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Aza Compounds / pharmacology
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Biological Assay
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Cell Line
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Combinatorial Chemistry Techniques
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Humans
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Kinetics
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Magnetic Resonance Spectroscopy
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Molecular Structure
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Receptors, Serotonin / metabolism
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Serotonin Antagonists / chemical synthesis*
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Serotonin Antagonists / pharmacology
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Spectrometry, Mass, Electrospray Ionization
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Spiperone / analogs & derivatives*
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Spiperone / chemical synthesis*
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Spiperone / pharmacology
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Spiro Compounds / pharmacology
Substances
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Antipsychotic Agents
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Aza Compounds
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Receptors, Serotonin
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Serotonin Antagonists
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Spiro Compounds
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spiramide
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Spiperone