New progesterone receptor antagonists: phosphorus-containing 11beta-aryl-substituted steroids.
A new series of phosphorus-containing 11beta-aryl-substituted steroids have been synthesized in an eight-step sequence involving a palladium-catalyzed coupling reaction to introduce a phosphorus group onto the aromatic ring. The compounds were evaluated for progesterone receptor (PR) antagonist activity in a T47D cell-based assay and for glucocorticoid receptor (GR) antagonist activity in an A549 cell-based assay. The structure-activity relationships of these compounds are discussed. Selected compounds were tested in vivo in a rat complement C3 assay.
Jiang
Weiqin
W
Johnson & Johnson Pharmaceutical Research & Development L.L.C., Drug Discovery, 1000 Route 202, Raritan, NJ 08869, USA. wjiang1@prdus.jnj.com
Allan
George
G
Fiordeliso
James J
JJ
Linton
Olivia
O
Tannenbaum
Pamela
P
Xu
Jun
J
Zhu
Peifang
P
Gunnet
Joseph
J
Demarest
Keith
K
Lundeen
Scott
S
Sui
Zhihua
Z
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D002384:Catalysis; D045744:Cell Line, Tumor; D003176:Complement C3 / Q000378:metabolism; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010052:Ovariectomy; D010165:Palladium; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D013256:Steroids / Q000138:chemical synthesis* / Q000494:pharmacology*
D003176:Complement C3; D007202:Indicators and Reagents; D011980:Receptors, Progesterone; D013256:Steroids; D010165:Palladium; D000469:Alkaline Phosphatase