Abstract
In this work we report the synthesis of a set of labeled ligands targeting the human 5-HT(6) receptor (h5-HT(6)R). Among the synthesized compounds, fluorescent probe 10 (K(i) = 175 nM and Φ(f) = 0.21) and biotinylated derivative 15 (K(i) = 90 nM) deserve special attention because they enable direct observation of the h5-HT(6)R in cells. Thus, they represent the first molecular probes for 5-HT(6)R visualization. These results are the starting point for introducing a variety of tags in these or other 5-HT(6)R ligand scaffolds aimed at the development of optimized probes with tailored profiles in terms of fluorescence, affinity, or selectivity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding, Competitive
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Biotin / analogs & derivatives*
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Biotin / chemical synthesis
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Biotin / chemistry
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Biotin / metabolism
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Biotinylation
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Cell Line
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Dansyl Compounds / chemical synthesis
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Dansyl Compounds / chemistry
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Dansyl Compounds / metabolism
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Fluorescent Dyes / chemical synthesis*
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Fluorescent Dyes / chemistry
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Fluorescent Dyes / metabolism
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Humans
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Ligands
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Models, Molecular
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Molecular Probes / chemical synthesis*
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Molecular Probes / chemistry
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Molecular Probes / metabolism
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / metabolism
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Radioligand Assay
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Receptors, Serotonin / metabolism*
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Stereoisomerism
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
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Sulfonamides / metabolism
Substances
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5-(dimethylamino)-N-(3-(4-(4-(((5-(dimethylamino)-1-naphthyl)sulfonyl)amino)butyl)piperazin-1-yl)-4-methoxyphenyl)naphthalene-1-sulfonamide
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Dansyl Compounds
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Fluorescent Dyes
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Ligands
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Molecular Probes
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N-(6-(4-(5-(((5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl)amino)-2-methoxyphenyl)piperazin-1-yl)hexyl)-5-(-2-oxohexahydro-1H-thieno(3,4-d)imidazol-4-yl)pentanamide
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Piperazines
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Receptors, Serotonin
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Sulfonamides
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serotonin 6 receptor
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Biotin