Discovery of novel phosphorus-containing steroids as selective glucocorticoid receptor antagonist.

Article Details

Citation

Jiang W, Fiordeliso JJ, Allan G, Linton O, Tannenbaum P, Xu J, Zhu P, Gunnet J, Demarest K, Lundeen S, Sui Z

Discovery of novel phosphorus-containing steroids as selective glucocorticoid receptor antagonist.

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1471-4. Epub 2006 Oct 5.

PubMed ID
17258455 [ View in PubMed
]
Abstract

Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-diabetic activities. For glucocorticoid receptor (GR) program, we sought an unexplored, synthetically accessible phosphorus-containing steroidal mimetic of mifepristone, suitable for parallel synthesis of analogues. One compound 4a, with high oral bioavailability (59%) in rat, exhibited functional antagonism of GR in oral glucose tolerance test (OGTT). Thus this series of compounds might be potentially useful for the treatment of type II diabetes.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MifepristoneGlucocorticoid receptorKi (nM)1N/AN/ADetails
MifepristoneProgesterone receptorIC 50 (nM)2.6N/AN/ADetails