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-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.
Fensome
Andrew
A
Chemical Sciences, Wyeth Research, Collegeville, PA 19426, USA. fensoma@wyeth.com
Bender
Reinhold
R
Cohen
Jeffrey
J
Collins
Mark A
MA
Mackner
Valerie A
VA
Miller
Lori L
LL
Ullrich
John W
JW
Winneker
Richard
R
Wrobel
Jay
J
Zhang
Puwen
P
Zhang
Zhiming
Z
Zhu
Yuan
Y
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
D003510:Cyclohexanes; D007211:Indoles; D011980:Receptors, Progesterone; D000469:Alkaline Phosphatase