SYNTHESIS OF 11-SUBSTITUTED ANDROSTENEDIONES AND TESTOSTERONES AS HUMAN DECIDUAL CELL-GROWTH INHIBITORS

11 alpha-Hydroxytestosterone (1a), 11 beta-hydroxytestosterone (1b), 1 1 alpha-methoxytestosterone (1c), 11 beta-methoxytestosterone (1d), 11 -ketotestosterone (1e), and Delta(9(11))-testosterone (1f) were synthe sized from hydrocortisone (4b) or 11-epi-hydrocortisone (4a). The six target compounds, together with 11 alpha-methoxyandrostenedione (2c), 11 beta-methoxyandrostenedione, (2d) and their lead compound, testoste rone (1), were found to effectively inhibit the growth and differentia tion of human decidual cells in culture. There is no observable bindin g of these compounds to estrogen receptor of rabbit uterus. The introd uction of apolar group (e.g., hydroxyl and carbonyl) to C-11 of andros tenes decreases both the relative binding affinities to progesterone r eceptor and the inhibitory effects on human decidual cell growth, whil e the methylation of 11-hydroxyl group minimizes these effects. The si milar effects of a polar group at C-11 of testosterone (1) on the inhi bitory effects on human decidual cell growth and the relative binding affinities to progesterone receptor of rabbit uterus may suggest that one of the mechanisms of human decidual cell growth inhibition by thes e compounds is the anti-progestational activity of these androgens.