New progesterone receptor antagonists: 3,3-disubstituted-5-aryloxindoles

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–activi...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 12; no. 23; pp. 3487 - 3490
Main Authors:	Fensome, Andrew, Bender, Reinhold, Cohen, Jeffrey, Collins, Mark A., Mackner, Valerie A., Miller, Lori L., Ullrich, John W., Winneker, Richard, Wrobel, Jay, Zhang, Puwen, Zhang, Zhiming, Zhu, Yuan
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 02-12-2002 Elsevier
Subjects:	Alkaline Phosphatase - metabolism Animals Binding, Competitive Biological and medical sciences Biological Assay Breast Neoplasms Cyclohexanes - chemistry Cyclohexanes - pharmacology Decidua - drug effects Female Hormones. Endocrine system Humans Indoles - chemistry Indoles - pharmacology Inhibitory Concentration 50 Medical sciences Pharmacology. Drug treatments Rats Receptors, Progesterone - antagonists & inhibitors Receptors, Progesterone - metabolism Structure-Activity Relationship Tumor Cells, Cultured Nitrile Rat Nitrogen heterocycle Rodentia Lactam Oral administration Antihormone Tricyclic compound Progesterone receptor In vitro Spiran In vivo Vertebrata Mammalia Structure activity relation Animal Antiprogesterone Aromatic compound Antagonist Fluorine Organic compounds Chemical synthesis Non steroid compound Hormonal receptor
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Summary:	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. The synthesis and SARs of a novel series of progesterone receptor antagonists 4 based upon a 5-aryl oxindole platform are discussed.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/S0960-894X(02)00746-1