Abstract
17β-HSD1 is a novel target for the treatment of estrogen-dependent diseases, as it catalyzes intracellular estradiol formation. Starting from two recently described compounds, highly active and selective inhibitors were developed. Benzoyl 6 and benzamide 17 are the most selective compounds toward 17β-HSD2 described so far. They also showed a promising profile regarding activity in T47-D cells, selectivity toward ERα and ERβ, inhibition of hepatic CYP enzymes, metabolic stability, and inhibition of marmoset 17β-HSD1 and 17β-HSD2.
MeSH terms
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Animals
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Benzothiazoles / chemical synthesis*
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Benzothiazoles / chemistry
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Benzothiazoles / pharmacology
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Callithrix
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Cell Line
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Cytochrome P-450 Enzyme Inhibitors
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Estradiol Dehydrogenases / antagonists & inhibitors*
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Estrogen Receptor alpha / metabolism
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Estrogen Receptor beta / metabolism
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Female
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Humans
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In Vitro Techniques
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Microsomes, Liver / metabolism
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Placenta / enzymology
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Pregnancy
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Radioligand Assay
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Structure-Activity Relationship
Substances
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Benzothiazoles
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Cytochrome P-450 Enzyme Inhibitors
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Estradiol Dehydrogenases
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HSD17B1 protein, human
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HSD17B2 protein, human