Abstract
The discovery and synthesis of dihydrobenzoxathiins as potent, ERalpha subtype selective ligands are described. The most active analogue, 4-D, was found to be 50-fold selective in a competitive binding assay and 100-fold selective in a transactivation assay in HEK-293 cells. The alpha selectivity was postulated to lie in the interaction of the sulfur atom of the benzoxathiin ring with the two discriminating residues in the binding pocket of the receptor isoforms.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Binding, Competitive
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Cell Line
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Crystallography, X-Ray
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Female
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Humans
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Ligands
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Models, Molecular
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Molecular Conformation
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Organ Size / drug effects
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Oxathiins / chemical synthesis*
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Oxathiins / chemistry
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Oxathiins / pharmacology
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Receptors, Estrogen / drug effects
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Receptors, Estrogen / metabolism
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Selective Estrogen Receptor Modulators / chemical synthesis*
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Selective Estrogen Receptor Modulators / chemistry
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Selective Estrogen Receptor Modulators / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Transcriptional Activation
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Uterus / drug effects
Substances
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Ligands
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Oxathiins
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Receptors, Estrogen
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Selective Estrogen Receptor Modulators