7 alpha-Alkyltestosterone derivatives: synthesis and activity as androgens and as aromatase inhibitors

The 7 alpha-ethyl,propyl,butyl,3'-t-butoxypropyl,allyl,3'-hydroxypropyl 17-acetate, and 3'-chloropropyl 17-acetate derivatives of testosterone and the 7 alpha-3'-t-butoxypropyl, 3'-hydroxypropyl,3'-acetoxypropyl,3'-bromoacetoxypropyl, 3'-chloropropyl, and 2'-oxo-3'-bromopropyl derivatives of 4-androstene-3,17-dione were synthesized. The testosterone derivatives were found to lose androgenic and anabolic activity rapidly as the size of the group at the 7 position increased. Many of the compounds were tested as inhibitors of aromatase. The 17-keto compounds were more active than the corresponding alcohols and the enzyme was found to tolerate at least the bulk of a hydroxypropyl group at the C-7 alpha position.