Abstract
Metallocene-derived bioisosteres lead to exceptionally strong binding G-protein-coupled receptor ligands, indicating substantial plasticity of the receptor excluded volume. Novel binding profiles of ferrocenylcarboxamides combining subnanomolar Ki values for the dopamine D4 receptor (1a, 0.52 nM; 1b, 0.63 nM) with superpotent serotonin 5-hydroxytryptamine1A (1a, 0.50 nM) and dopamine D3 receptor binding (1b, 0.64 nM) and selective D4 agonist properties of the ruthenocene 1c may be a starting point for highly beneficial central nervous system active drugs.
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 Sites
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Binding, Competitive
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CHO Cells
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Cricetinae
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Cricetulus
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Cyclopentanes / chemical synthesis
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Cyclopentanes / chemistry
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Cyclopentanes / pharmacology
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Ferrous Compounds / chemical synthesis
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Ferrous Compounds / chemistry
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Ferrous Compounds / pharmacology
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Ligands
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Metallocenes
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Mitosis / drug effects
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Models, Molecular
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Organometallic Compounds / chemical synthesis*
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Organometallic Compounds / chemistry
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Organometallic Compounds / pharmacology
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Radioligand Assay
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Receptor, Serotonin, 5-HT1A / metabolism
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Receptors, Dopamine D2 / metabolism
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Receptors, Dopamine D3
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Receptors, Dopamine D4
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Receptors, G-Protein-Coupled / metabolism*
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Ruthenium
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Structure-Activity Relationship
Substances
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Cyclopentanes
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Ferrous Compounds
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Ligands
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Metallocenes
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Organometallic Compounds
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Receptors, Dopamine D2
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Receptors, Dopamine D3
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Receptors, G-Protein-Coupled
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metallocene
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Receptor, Serotonin, 5-HT1A
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ruthenocene
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Receptors, Dopamine D4
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Guanosine 5'-O-(3-Thiotriphosphate)
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Ruthenium
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ferrocene