Abstract
Synthetic methods were developed for the synthesis of the 3beta-(4-substituted phenyl)-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes (4a-s). The compounds were evaluated for their monoamine transporter binding and monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. In general, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin and norepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potency relative to [3H]serotonin and [3H]norepinephrine uptake inhibition. Several compounds were DAT selective relative to the SERT and NET in the monoamine transporter binding assays. The most potent and selective analog in the functional monoamine uptake inhibition test was 3beta-(4-methylphenyl-2 beta-[5-(3-nitrophenyl)thiazol-2-yl]tropane (4p).
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adrenergic Uptake Inhibitors / chemical synthesis
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Adrenergic Uptake Inhibitors / chemistry
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Adrenergic Uptake Inhibitors / pharmacology
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Animals
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Binding, Competitive
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Cell Line
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Corpus Striatum / metabolism
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Dopamine Plasma Membrane Transport Proteins / metabolism*
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Dopamine Uptake Inhibitors / chemical synthesis
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Dopamine Uptake Inhibitors / chemistry
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Dopamine Uptake Inhibitors / pharmacology
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Frontal Lobe / metabolism
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Humans
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In Vitro Techniques
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Male
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Mesencephalon / metabolism
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Norepinephrine Plasma Membrane Transport Proteins / metabolism
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Selective Serotonin Reuptake Inhibitors / chemical synthesis
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Selective Serotonin Reuptake Inhibitors / chemistry
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Selective Serotonin Reuptake Inhibitors / pharmacology
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Serotonin Plasma Membrane Transport Proteins / metabolism
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology
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Tropanes / chemical synthesis*
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Tropanes / chemistry
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Tropanes / pharmacology
Substances
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3-(4-methylphenyl)-2-(5-(3-nitrophenyl)thiazol-2-yl)tropane
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Adrenergic Uptake Inhibitors
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Dopamine Plasma Membrane Transport Proteins
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Dopamine Uptake Inhibitors
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Norepinephrine Plasma Membrane Transport Proteins
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Serotonin Plasma Membrane Transport Proteins
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Serotonin Uptake Inhibitors
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Thiazoles
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Tropanes