7-aryl 1,5-dihydro-benzo[e][1,4]oxazepin-2-ones and analogs as non-steroidal progesterone receptor antagonists.

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Zhang P, Kern JC, Terefenko EA, Fensome A, Unwalla R, Zhang Z, Cohen J, Berrodin TJ, Yudt MR, Winneker RC, Wrobel J

7-aryl 1,5-dihydro-benzo[e][1,4]oxazepin-2-ones and analogs as non-steroidal progesterone receptor antagonists.

Bioorg Med Chem. 2008 Jul 1;16(13):6589-600. doi: 10.1016/j.bmc.2008.05.018. Epub 2008 May 10.

PubMed ID
18504132 [ View in PubMed
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Abstract

Novel 7-aryl benzo[1,4]oxazepin-2-ones were synthesized and evaluated as non-steroidal progesterone receptor (PR) modulators. The structure activity relationship of 7-aryl benzo[1,4]oxazepinones was examined using the T47D cell alkaline phosphatase assay. A number of 7-aryl benzo[1,4]oxazepinones such as 10j and 10v demonstrated good in vitro potency (IC(50) of 10-30 nM) and selectivity (over 100-fold) at PR over other steroidal receptors such as glucocorticoid and androgen receptors (GR and AR). Several 7-aryl benzo[1,4]oxazepinones were active in the rat uterine decidualization model. In this in vivo model, compounds 10j and 10u were active at 3 mg/kg when dosed orally.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MifepristoneGlucocorticoid receptorIC 50 (nM)0.6N/AN/ADetails
MifepristoneProgesterone receptorIC 50 (nM)0.2N/AN/ADetails