Abstract
Enlarging the 10-membered ring of 7-methyl-6,7,8,9,14,15-hexahydro-5H-indolo[3,2-f][3]benzazecine (1, LE 300) yielded two homologue antagonists. Their affinities and inhibitory activities at D(1)-D(5) receptors were measured by radioligand binding experiments and a functional Ca(2+) assay. Compared to 1, phenylpropyl homologue 3 was superior in selectivity and affinity for the D(5) subtype (K(i) = 0.6 nM), whereas the affinity of the indolylpropyl homologue 2 for all subtypes decreased. Compounds 2, 3, 10, 11, 17, and 18 are derivatives of novel heterocyclic ring systems.
MeSH terms
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Animals
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Calcium / metabolism
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Cell Line
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Cricetinae
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Cricetulus
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Dopamine D2 Receptor Antagonists*
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Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
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Heterocyclic Compounds, 4 or More Rings / chemistry
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Heterocyclic Compounds, 4 or More Rings / pharmacology
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Radioligand Assay
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Receptors, Dopamine D1 / antagonists & inhibitors*
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Receptors, Dopamine D3 / antagonists & inhibitors
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Receptors, Dopamine D4 / antagonists & inhibitors
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Receptors, Dopamine D5 / antagonists & inhibitors
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Structure-Activity Relationship
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 D2 Receptor Antagonists
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Heterocyclic Compounds, 4 or More Rings
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Indoles
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Receptors, Dopamine D1
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Receptors, Dopamine D3
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Receptors, Dopamine D4
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Receptors, Dopamine D5
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Calcium