Probing the hydrophobic pocket of the active site of aromatase with 4-phenoxy-7 alpha-(phenylthio)-4-androstene-3,17-dione.

In order to examine the nature of the hydrophobic pocket at the active site of aromatase, we carried out the synthesis, biochemical evaluation, and molecular modeling studies on 4-phenoxy-7α-(phenylthio)-4-androstenedione 2. Aromatase inhibitory activity of 2 was found to be significantly weaker than that of the 4- and 7α-mono(phenylthio)-substituted derivatives of androstenedione. These results along with those obtained from the modeling studies suggest the existence of a single hydrophobic pocket corresponding to the α-face in the C4, C6, C7 region of androstenedione.