8-alkylthio-6-thio-substituted theophylline analogues as selective noncompetitive progesterone receptor antagonists.

ABSTRACT: The progesterone receptor (PR) plays a key role in reproduction and is important in cancers of the reproductive tract. Current PR antagonists usually compete for progestin binding in the PR ligand-binding pocket and often exhibit cross-binding with other members of the steroid receptor family. Using stably transfected cells expressing reporter genes, a set of ∼150 theophylline analogues were screened for their ability to inhibit progesterone, estrogen, glucocorticoid and androgen signaling. The structure-activity studies presented here identify branched 8-alkylthio-6-thio-substitutions of theophylline as selective PR inhibitors. 6-Thio-8-(2-ethylbutyl)thiotheophylline (51), the most extensively studied derivative, does not act by competing with progestins for binding in the ligand-binding

SUBMITTER: Aninye IO 

PROVIDER: S-EPMC3384716 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature