The Synthesis of Novel 7, 19-Bifunctional Androstenediones as Aromatase Inhibitors

Both 7 and 19-substituted androstenediones exhibit good inhibitory activities against aromatase. The combination effects of those two functional groups were examined by comparing the activity of19-methylthiomethoxy-7-phenylthioandrost-4-en-3,17-dione (IC50591 nM) with 19methylthiomethoxy-androst-4,6-dien-3,17-dione (IC50389 nM). The addition of a 7-phenylthio functional group leads to a slight loss of inhibitory activity for this 7, 19-bifunctional androstenedione. These results indicate the relative location of the pharmacophores on C-19 and in the active center. The 7-position may not be compatible for the enhancement of inhibitory activity.