SYNTHESIS AND PROPERTIES OF 3,17-DISUBSTITUTED ESTROGENIC STEROIDS

In order to develop new radio protectors of low estrogenic activity andhigh potency and to study the structure- activity relationships, 10 estrogenic steroids weresynthesized from the view point of drug latenfiation, and by substitution with activegroups in different positions of the steroidal skeleton. The compounds were tested in micefor estrogenic activity and radioprotective effect. The results showed that the introductionof hydroxyalkylimido or hydroxy group into 17-position resulted in reduction ofestrogenic activity. Hydroxyalkylimides (2d, e)showed better protective effect in 750 rad of⁶⁰CO γ-irradiation in mice by the reduction of radiation dose of 144～156 rads thanestradiol (reduction of 62.2 rad). Whereas 2a～c and 4a, b showed weak or no protec-tive effect. Compounds 1, 3, and 5a, b increased the 30-day survival rates by 35～80% in mice exposed to 900 rad of irradiation, when administered ip 0.1 mg per mouse24 h before irradiation.