Abstract
A series of octahydro- and 6,7-dimethoxy-3,4-dihydro- isoquinolin-2(1H)-yl-alkyl derivatives of imidazo- and pyrimidino[2,1-f]purines were synthesized and biologically evaluated in in vitro competition binding experiments for serotonin 5-HT(1A), 5-HT(6), 5-HT(7), and dopamine D2 receptors and inhibitory potencies for phosphodiesterases - PDE4B1 and PDE10A. The structure-activity relationships allowed to determine the structural features responsible for receptor and enzyme activity. Compound 5 (8-(4-(6,7-dimethoxy-3,4-dihydroiso- quinolin-2(1H)butyl)1,3-dimethyl-H-imidazo[2,1-f]purine-2,4(3H,8H)-dione) could be regarded as promising structure for further modification and detailed mechanistic study for obtained hybrid ligands.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding, Competitive
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HEK293 Cells
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Humans
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Imidazoles / chemistry
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Imidazoles / metabolism*
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Imidazoles / pharmacology
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Ligands
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Molecular Structure
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Phosphodiesterase 4 Inhibitors / chemistry
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Phosphodiesterase 4 Inhibitors / metabolism*
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Phosphodiesterase 4 Inhibitors / pharmacology
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Phosphoric Diester Hydrolases / chemistry
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Phosphoric Diester Hydrolases / metabolism*
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Protein Binding
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Pyrimidinones / chemistry
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Pyrimidinones / metabolism*
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Pyrimidinones / pharmacology
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Radioligand Assay
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Receptors, Dopamine D2 / drug effects
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Receptors, Dopamine D2 / genetics
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Receptors, Dopamine D2 / metabolism*
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Receptors, Serotonin / drug effects
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Receptors, Serotonin / genetics
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Receptors, Serotonin / metabolism*
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Structure-Activity Relationship
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Transfection
Substances
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DRD2 protein, human
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Imidazoles
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Ligands
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Phosphodiesterase 4 Inhibitors
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Pyrimidinones
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Receptors, Dopamine D2
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Receptors, Serotonin
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Phosphoric Diester Hydrolases