Newly discovered orally active pure antiestrogens

In order to develop orally active pure antiestrogens, we incorporated the carboxy-containing side chains into the 7α-position of the steroid scaffold and found that 17-keto derivative CH4893237 (12b) functioned as a pure antiestrogen with its oral activity much superior to clinically used pure antiestrogen, ICI182,780. Results from the pharmacokinetic evaluation indicated that the potent antiestrogen activity at oral dosing in mice attributed to both improved absorption from the intestinal wall and metabolic stability in liver.

Graphical abstractSteroid derivatives bearing the carboxy moiety in the long side chain at the 7-α position exhibited remarkable antiestrogen activities when administered orally.Figure optionsDownload full-size imageDownload as PowerPoint slide