Synthesis and identification of novel oxa-steroids as progesterone receptor antagonists.

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Kang FA, Allan G, Guan J, Jain N, Linton O, Tannenbaum P, Xu J, Zhu P, Gunnet J, Chen X, Demarest K, Lundeen S, Sui Z

Synthesis and identification of novel oxa-steroids as progesterone receptor antagonists.

Bioorg Med Chem Lett. 2007 Feb 15;17(4):907-10. Epub 2006 Dec 1.

PubMed ID
17169557 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MifepristoneGlucocorticoid receptorIC 50 (nM)1.6N/AN/ADetails
MifepristoneProgesterone receptorIC 50 (nM)1.4N/AN/ADetails