Novel phosphorus-containing 17beta-side chain mifepristone analogues as progesterone receptor antagonists.
A novel series of steroidal compounds were designed and synthesized with various phosphorus-containing groups on the 17beta-side chain as progesterone receptor antagonists. The structure-activity relationships of these compounds are discussed. Selected compounds were tested in an rat progesterone-sensitive assay. Some of these compounds are more potent than mifepristone, with a better selectivity profile in differentiating progesterone receptor from glucocorticoid receptor.
Jiang
Weiqin
W
Johnson & Johnson Pharmaceutical Research & Development L.L.C., Drug Discovery, Raritan, NJ 08869, USA. wjiang1@prdus.jnj.com
Allan
George
G
Chen
Xin
X
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
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D005260:Female; D006727:Hormone Antagonists / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015735:Mifepristone / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D010758:Phosphorus / Q000737:chemistry*; D011374:Progesterone / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D010758:Phosphorus; D015735:Mifepristone; D011374:Progesterone