DESIGN AND SYNTHESIS OF CYCLOHEXENYL-p-CARBORANE DERIVATIVES AS A NEW CLASS OF PROGESTERONE RECEPTOR ANTAGONISTS

摘要

We report here the synthesis and structure-activity relationships of a series of C-cyclohexenyl-p-carborane derivatives, which we designed as candidates for a novel class of progesterone receptor (PR) antagonists. Biological evaluation using T47D alkaline phosphatase assay revealed that several compounds exhibited potent PR-antagonistic activity. We also examined the selectivity of these compounds for PR over androgen receptor (AR). Among them, lib functioned as a PR-selective antagonist, while other compounds, such as 13b, acted as PR/AR dual antagonists. Notably, docking simulations indicated that 11b and 13b bind in similar orientations to the ligand-binding site of PR, but in opposite orientations to that of AR. These findings could helpful for developing more selective ligands for PR.