title: 7-aryl 1,5-dihydro-benzo[e][1,4]oxazepin-2-ones and analogs as non-steroidal progesterone receptor antagonists.
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.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. Zhangp@wyeth.com
authors.forename: Puwen
authors.initials: P
authors.lastname: Zhang
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Kern
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Terefenko
authors.forename: Andrew
authors.initials: A
authors.lastname: Fensome
authors.forename: Ray
authors.initials: R
authors.lastname: Unwalla
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cohen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Berrodin
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Yudt
authors.forename: Richard C
authors.initials: RC
authors.lastname: Winneker
authors.forename: Jay
authors.initials: J
authors.lastname: Wrobel
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D006900:Hydroxylation; D008958:Models, Molecular; D015394:Molecular Structure; D010077:Oxazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001552:Benzazepines; D010077:Oxazepines; D011980:Receptors, Progesterone; D000469:Alkaline Phosphatase