Abstract
The design and synthesis of the novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole 5 is described. This azepinoindole has excellent affinity for 5-HT(2C) (K(i) 4.8 nM) and modest selectivity over 5-HT(2A) ( approximately 4-fold). Several N- and C(11)-substituted analogues of 5 were prepared, as were a number of biaryl indoline derivatives. The anxiolytic potential for the azepinoindole template 5 is demonstrated by activity in a mouse shock-aggression assay.
MeSH terms
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Aggression / drug effects
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Animals
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Anti-Anxiety Agents / chemical synthesis
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Anti-Anxiety Agents / pharmacology
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Ataxia / chemically induced
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Azepines / chemical synthesis*
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Azepines / pharmacology*
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Drug Design
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Electroshock
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Indicators and Reagents
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Indoles / chemical synthesis*
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Indoles / pharmacology*
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Kinetics
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Mice
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Receptor, Serotonin, 5-HT2A / drug effects
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Receptor, Serotonin, 5-HT2C / drug effects*
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Serotonin Receptor Agonists / chemical synthesis*
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Serotonin Receptor Agonists / pharmacology*
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Structure-Activity Relationship
Substances
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2,3,4,5,11,11a-hexahydro-1H-(1,4)diazepino(1,7-a)indole
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2,3,4,5-tetrahydro-1H-(1,4)diazepino(1,7-a)indole
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Anti-Anxiety Agents
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Azepines
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Indicators and Reagents
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Indoles
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Receptor, Serotonin, 5-HT2A
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Receptor, Serotonin, 5-HT2C
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Serotonin Receptor Agonists