Abstract
To identify novel estrogen receptor ligands a series of substituted 17alpha-arylestradiols were synthesized using the catalytic [2 + 2 + 2]cyclotrimerization of 17alpha-ethynylestradiol with various 1,7-diynes in the presence of Wilkinson's catalysts [Rh(PPh(3))(3)Cl]. The compounds were subjected to competitive binding assays, cell-based luciferase reporter assays, and proliferation assays. These experiments confirmed their estrogenic character and revealed some interesting properties like mixed partial/full agonism for ERalpha/ERbeta and different selectivity as a result of differing potencies for either ER.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkynes / chemistry
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Binding, Competitive
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Cell Line
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cyclization
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Drug Partial Agonism
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Estradiol / analogs & derivatives*
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Estradiol / chemical synthesis*
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Estradiol / pharmacology
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Estrogen Receptor alpha / agonists*
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Estrogen Receptor alpha / genetics
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Estrogen Receptor beta / agonists*
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Estrogen Receptor beta / genetics
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Fluorescence Polarization
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Genes, Reporter
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Humans
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Ligands
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Luciferases / genetics
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Structure-Activity Relationship
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Transcriptional Activation
Substances
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Alkynes
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Ligands
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Estradiol
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Luciferases