Abstract
On the basis of the D(1/5)-selective dopamine antagonist LE 300 (1), an indolo[3,2-f]benzazecine derivative, we changed the annulation pattern of the heterocycles. The target compounds represent novel heterocyclic ring systems. The most constrained indolo[4,3a,3-ef]benzazecine 2 was inactive, but the indolo[4,3a,3-fg]benzazacycloundecene 3 showed antagonistic properties (functional Ca(2+) assay) with nanomolar affinities (radioligand binding) for all dopamine receptor subtypes, whereas the indolo[2,3-f]benzazecine 4 displayed a selectivity profile similar to 3 but with decreased affinities.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive
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CHO Cells
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Cell Line
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Cricetinae
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Cricetulus
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Dopamine Antagonists / chemistry
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Dopamine Antagonists / metabolism*
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Dopamine Antagonists / pharmacology
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Humans
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Indoles / chemistry
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Indoles / metabolism*
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Indoles / pharmacology
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Kinetics
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Ligands
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Models, Chemical
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Molecular Structure
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Radioligand Assay
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Receptors, Dopamine / metabolism*
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Receptors, Dopamine D1 / antagonists & inhibitors
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Receptors, Dopamine D1 / metabolism
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Receptors, Dopamine D5 / antagonists & inhibitors
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Receptors, Dopamine D5 / metabolism
Substances
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7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine
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Dopamine Antagonists
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Indoles
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Ligands
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Receptors, Dopamine
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Receptors, Dopamine D1
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Receptors, Dopamine D5