Abstract
Eleven-membered heterocycles (dibenz[g,j]-1-oxa-4-azacycloundecenes) and open-chain analogues were synthesized and investigated for affinities to human dopamine receptor subtypes. The moderately rigidized rings displayed nanomolar and subnanomolar Ki values at D1-like receptors with a significant D1 to D2 and a slight D5 to D1 selectivity. The open-chain analogues showed lower affinities but significant D1 to D2 selectivities. Compound 3 (Ki(D5) = 0.57 nmol) showed antagonistic or inverse agonistic binding characteristics in a functional Ca assay.
Copyright 2004 American Chemical Society
Publication types
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Research Support, Non-U.S. Gov't
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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Heterocyclic Compounds, 2-Ring / chemical synthesis*
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Heterocyclic Compounds, 2-Ring / chemistry
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Heterocyclic Compounds, 2-Ring / pharmacology
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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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Ligands
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Oxygen*
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Radioligand Assay
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Receptors, Dopamine D1 / drug effects*
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Receptors, Dopamine D1 / metabolism
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Receptors, Dopamine D5
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Structure-Activity Relationship
Substances
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DRD5 protein, human
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Heterocyclic Compounds, 2-Ring
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Heterocyclic Compounds, 4 or More Rings
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Ligands
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Receptors, Dopamine D1
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Receptors, Dopamine D5
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Oxygen
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Calcium