New progesterone receptor antagonists: Phosphorus-containing 11β-aryl-substituted steroids

A series of phosphorus-containing 11β-aryl-substituted steroids were synthesized and evaluated for their in vitro progesterone receptor and glucocorticoid receptor antagonist activities. Selected compounds were tested in rat in C3 assay for PR antagonist activities. A new series of phosphorus-containing 11β-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.