Syntheses and antigestagenic activity of mifepristone derivatives

A series of mifepristone derivatives with different "linker groups" in position 4' of the phenyl ring in the 11beta-position of the steroid scaffold (2-41) have been synthesized. Their antigestagenic activites were determined in a cell-based assay (alkali Phosphatase assay in T47-D breast Cancer cells) and compared with that of the parent compound mifepristone. SAR and QSAR studies reveal the influence of both lipophilicity and partial charge based van der Waals surface area descriptors on biological activity. Within the series of compounds described in this study, three mifepristone derivatives are identified with considerably high antigestagenic activity. These compounds are regarded as useful starting Materials for the synthesis of either physiologically stable or cleavable progesterone receptor-binding conjugates for therapeutic or diagnostic purposes.