2. Academic Validation
  3. 7-aryl 1,5-dihydro-benzo[e][1,4]oxazepin-2-ones and analogs as non-steroidal progesterone receptor antagonists

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.
Puwen Zhang 1,  Jeffrey C Kern,  Eugene A Terefenko,  Andrew Fensome,  Ray Unwalla,  Zhiming Zhang,  Jeffrey Cohen,  Thomas J Berrodin,  Matthew R Yudt,  Richard C Winneker,  Jay Wrobel
Affiliations

Affiliation

  • 1 Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. Zhangp@wyeth.com
PMID: 18504132 DOI: 10.1016/j.bmc.2008.05.018
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.

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