Abstract
A series of estrogen receptor ligands based on a dihydrobenzoxathiin scaffold is described and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. The most active analogue, 22, was found to be 40-fold ERalpha selective in a competitive binding assay, and 22 demonstrated very potent in vivo antagonism of estradiol driven proliferation in an immature rat uterine weight gain assay.
MeSH terms
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Animals
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Binding, Competitive
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Estrogen Receptor alpha / chemistry*
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Estrogen Receptor beta / chemistry
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Female
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Heterocyclic Compounds, 4 or More Rings / chemical synthesis
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Heterocyclic Compounds, 4 or More Rings / pharmacokinetics
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Heterocyclic Compounds, 4 or More Rings / pharmacology
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Humans
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Ligands
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Organ Size
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Oxathiins / chemical synthesis
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Oxathiins / pharmacokinetics
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Oxathiins / pharmacology*
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Protein Binding
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Rats
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Rats, Sprague-Dawley
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Selective Estrogen Receptor Modulators / chemical synthesis*
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Selective Estrogen Receptor Modulators / pharmacokinetics
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Selective Estrogen Receptor Modulators / pharmacology
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Structure-Activity Relationship
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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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Heterocyclic Compounds, 4 or More Rings
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Ligands
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Oxathiins
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Selective Estrogen Receptor Modulators
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syn-dihydrobenzoxathiin