title: New progesterone receptor antagonists: 3,3-disubstituted-5-aryloxindoles.
abstract: A new series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this communication, the synthesis and structure-activity relationships (SARs) of various 3,3-substituents are discussed where it is clear that small alkyl and spiroalkyl groups are required to achieve better PR antagonist activity.
authors.affiliation: Chemical Sciences, Wyeth Research, Collegeville, PA 19426, USA. fensoma@wyeth.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Fensome
authors.forename: Reinhold
authors.initials: R
authors.lastname: Bender
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cohen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Collins
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Mackner
authors.forename: Lori L
authors.initials: LL
authors.lastname: Miller
authors.forename: John W
authors.initials: JW
authors.lastname: Ullrich
authors.forename: Richard
authors.initials: R
authors.lastname: Winneker
authors.forename: Jay
authors.initials: J
authors.lastname: Wrobel
authors.forename: Puwen
authors.initials: P
authors.lastname: Zhang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D001943:Breast Neoplasms; D003510:Cyclohexanes / Q000737:chemistry* / Q000494:pharmacology*; D003656:Decidua / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051381:Rats; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D003510:Cyclohexanes; D007211:Indoles; D011980:Receptors, Progesterone; D000469:Alkaline Phosphatase