Abstract
Joining aryl 8-azabicyclo[3.2.1]oct-3-enes with aryloxyethanes and aryloxypropanes produces novel series of compounds 11 and 12 with potent 5-HT-T affinity and moderately potent 5-HT(1A) affinity. Moreover, several of these compounds possess functional 5-HT(1A) antagonism. Optimal compounds are, 4-indolyloxyethane 21, 4-indolyloxypropanes 25, and 27, which possess potent 5-HT-T affinity (5-HT-T K(i): 21: 1.2nM, 25: 0.54nM, 27: 0.38nM) and good 5-HT(1A) affinity/antagonism (5-HT(1A)K(i), [(35)S]GTPgammaS: E(max) (%): 21: 111.1nM, 0%; 25: 173.2nM, 0%; 27: 107nM, 0%).
MeSH terms
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
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CHO Cells
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Cricetinae
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Cricetulus
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Humans
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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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Radioligand Assay
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Receptor, Serotonin, 5-HT1A / metabolism*
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Serotonin 5-HT1 Receptor Agonists
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Serotonin 5-HT1 Receptor Antagonists
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Serotonin Plasma Membrane Transport Proteins
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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SLC6A4 protein, human
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Serotonin 5-HT1 Receptor Agonists
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Serotonin 5-HT1 Receptor Antagonists
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Serotonin Plasma Membrane Transport Proteins
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Receptor, Serotonin, 5-HT1A