Abstract
A novel series of oxa-steroids 6 derived from (8S, 13S, 14R)-7-oxa-estra-4,9-diene-3,17-dione 1 have been synthesized and identified as potent and selective progesterone receptor antagonists. These novel oxa-steroids showed similar potency to mifepristone. Preliminary SAR study resulted in the most potent 17-phenylethynyl oxa-steroid 6i wih an IC(50) of 1.4nM. In contrast to the equipotent mifepristone toward the progesterone receptor (PR) and glucocorticoid receptor (GR), compound 6i had over 200-fold selectivity for PR over GR.
MeSH terms
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Alkaline Phosphatase / biosynthesis
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Breast Neoplasms / enzymology
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Cell Line, Tumor
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Enzyme Induction / drug effects
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Female
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Genes, Reporter / drug effects
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Hormone Antagonists / chemical synthesis
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Hormone Antagonists / pharmacology
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Humans
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Mifepristone / chemical synthesis
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Mifepristone / pharmacology
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Receptors, Glucocorticoid / drug effects
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Receptors, Progesterone / antagonists & inhibitors*
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Stereoisomerism
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Steroids / chemical synthesis*
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Steroids / pharmacology*
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Structure-Activity Relationship
Substances
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Hormone Antagonists
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Receptors, Glucocorticoid
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Receptors, Progesterone
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Steroids
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Mifepristone
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Alkaline Phosphatase