Abstract
Design, synthesis and properties of a new tricyclic series of selective 5-HT2C receptor antagonists are reported. Conformational analysis of a 2-phenyl-dihydropyrrolone scaffold suggested that ring fusion, locking coplanarity between the rings of this moiety, might be tolerated by the 5-HT2C receptor. An interesting effect of this is the change of the nature of the carbon-carbon double bond of the lactam ring from vinylic to aromatic. The changes were found to result in a favourable profile at both, receptor and in vivo level.
MeSH terms
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Alkylation
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Animals
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Biological Availability
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Drug Design
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Heterocyclic Compounds / chemical synthesis*
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Heterocyclic Compounds / pharmacokinetics
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Heterocyclic Compounds / pharmacology*
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Humans
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Indicators and Reagents
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Male
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Models, Molecular
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Molecular Conformation
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Rats
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Receptor, Serotonin, 5-HT2A / drug effects
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Receptor, Serotonin, 5-HT2B / drug effects
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Receptor, Serotonin, 5-HT2C / drug effects*
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Serotonin Antagonists / pharmacology*
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Structure-Activity Relationship
Substances
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Heterocyclic Compounds
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Indicators and Reagents
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Receptor, Serotonin, 5-HT2A
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Receptor, Serotonin, 5-HT2B
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Receptor, Serotonin, 5-HT2C
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Serotonin Antagonists