Abstract
EM-652 (acolbifene) analogs have been synthesized as selective estrogen receptor modulators. Substitution on the nitrogen atom of these 2H-1-benzopyran derivatives has been studied for its influence on antiestrogenic activity. Binding to the rat estrogen receptor, inhibition of estradiol-stimulated proliferation of T-47D breast cancer cells, as well as antiuterotrophic and uterotrophic activities in ovariectomized mice have been evaluated. 2H-1-Benzopyran 1b (EM-343, racemic form of EM-652), which contains a piperidine ring, shows the best pharmacological profile; RBA = 380, IC50 value = 0.110 nM (in T-47D cells), as well as 63% and 84% antiuterotrophic inhibitions at the 7.5 and 75 nmol doses, respectively.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzopyrans / chemistry
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Cattle
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Cell Line, Tumor
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Cell Proliferation
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Cells, Cultured
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Enzyme Inhibitors / pharmacology*
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Estrogen Receptor Modulators / metabolism*
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Estrogen Receptor Modulators / pharmacology*
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Estrogens / metabolism
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Female
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Humans
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Inhibitory Concentration 50
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Insulin / metabolism
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Magnetic Resonance Spectroscopy
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Mice
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Mice, Inbred BALB C
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Models, Chemical
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Nitrogen / chemistry*
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Piperidines / chemical synthesis*
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Protein Binding
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Rats
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Rats, Sprague-Dawley
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Receptors, Estrogen / metabolism
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Structure-Activity Relationship
Substances
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Benzopyrans
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Enzyme Inhibitors
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Estrogen Receptor Modulators
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Estrogens
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Insulin
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Piperidines
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Receptors, Estrogen
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ritetronium
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Nitrogen