865670-66-2Relevant articles and documents
7-Aryl 1,5-dihydro-benzo[e][1,4]oxazepin-2-ones and analogs as non-steroidal progesterone receptor antagonists
Zhang, Puwen,Kern, Jeffrey C.,Terefenko, Eugene A.,Fensome, Andrew,Unwalla, Ray,Zhang, Zhiming,Cohen, Jeffrey,Berrodin, Thomas J.,Yudt, Matthew R.,Winneker, Richard C.,Wrobel, Jay
, p. 6589 - 6600 (2008/12/21)
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 (IC50 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.
Synthesis and structure-activity relationship of novel 6-aryl-1,4- dihydrobenzo[d][1,3]oxazine-2-thiones as progesterone receptor modulators leading to the potent and selective nonsteroidal progesterone receptor agonist tanaproget
Fensome, Andrew,Bender, Reinhold,Chopra, Rajiv,Cohen, Jeff,Collins, Mark A.,Hudak, Valerie,Malakian, Karl,Lockhead, Susan,Olland, Andrea,Svenson, Kristine,Terefenko, Eugene A.,Unwalla, Ray J.,Wilhelm, James M.,Wolfrom, Scott,Zhu, Yuan,Zhang, Zhiming,Zhang, Puwen,Winneker, Richard C.,Wrobel, Jay
, p. 5092 - 5095 (2007/10/03)
Tanaproget represents a potential first-in-class nonsteroidal PR agonist for contraception with improved safety and side effect profiles versus currently available steroidal oral contraceptives. Additional SAR, biological activity, and structural information from a tanaproget/hPR-LBD (hPR-LBD = human progesterone receptor ligand binding domain) cocrystal structure will also be presented.
