Abstract
Preparation of cocaine analogues has been aimed largely at development of stable compounds with high affinity and selectivity for the dopamine transporter (DAT). We now report the synthesis and monoamine transporter affinity of 10 new 2beta-carbomethoxy-3beta-[4-(substituted thiophenyl)]phenyltropanes. Among these, compound 4b exhibited very high affinity for the serotonin transporter (SERT: K(i)=17 pM) and good selectivity over dopamine (DAT: 710-fold) and norepinephrine transporters (NET: 11,100-fold).
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cerebral Cortex / cytology
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Dopamine Plasma Membrane Transport Proteins
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Dose-Response Relationship, Drug
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Membrane Glycoproteins / metabolism
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Membrane Transport Proteins / metabolism
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Nerve Tissue Proteins / metabolism
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Norepinephrine Plasma Membrane Transport Proteins
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Rats
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Selective Serotonin Reuptake Inhibitors / chemical synthesis*
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Selective Serotonin Reuptake Inhibitors / pharmacology
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Serotonin Plasma Membrane Transport Proteins
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Structure-Activity Relationship
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Symporters / metabolism
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Tropanes / chemical synthesis*
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Tropanes / pharmacology
Substances
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Dopamine Plasma Membrane Transport Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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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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Slc6a2 protein, rat
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Slc6a3 protein, rat
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Slc6a4 protein, rat
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Symporters
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Tropanes