Abstract
A series of front bridged tricyclic 3beta-(4'-halo or 4'-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2beta-position was synthesized, and their binding affinities were determined in cells transfected to express human norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT) via competition binding assays. All compounds studied in this series exhibit a moderate to high potency at all three transporters with SERT or DAT selectivity. 3beta-(4'-iodo)phenyltropane bearing methylene on the bridge to the 2beta-position (24) presents a particularly attractive pharmacological profile, with very high SERT affinity (K(i) = 0.09 nM) and selectivity versus NET (65-fold) and DAT (94-fold).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Dopamine Plasma Membrane Transport Proteins / chemistry
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Dopamine Plasma Membrane Transport Proteins / metabolism*
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Molecular Structure
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Norepinephrine Plasma Membrane Transport Proteins / chemistry
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Norepinephrine Plasma Membrane Transport Proteins / metabolism*
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Polycyclic Compounds / chemical synthesis*
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Polycyclic Compounds / chemistry
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Polycyclic Compounds / metabolism*
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Serotonin Plasma Membrane Transport Proteins / chemistry
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Serotonin Plasma Membrane Transport Proteins / metabolism*
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Structure-Activity Relationship
Substances
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Dopamine Plasma Membrane Transport Proteins
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Norepinephrine Plasma Membrane Transport Proteins
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Polycyclic Compounds
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Serotonin Plasma Membrane Transport Proteins