[Synthesis and properties of 3,17-disubstituted estrogenic steroids].
In order to develop new radio protectors of low estrogenic activity and high potency and to study the structure-activity relationships, 10 estrogenic steroids were synthesized from the view point of drug latentiation, and by substitution with active groups in different positions of the steroidal skeleton. The compounds were tested in mice for estrogenic activity and radioprotective effect. The results showed that the introduction of hydroxyalkylimido or hydroxy group into 17-position resulted in reduction of estrogenic activity. Hydroxyalkylimides (2d, e) showed better protective effect in 750 rad of 60CO gamma-irradiation in mice by the reduction of radiation dose of 144-156 rads than estradiol (reduction of 62.2 rad). Whereas 2a-c and 4a, b showed weak or no protective 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 mouse 24 h before irradiation.
Tong
Z S
ZS
Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing.
Gan
G Z
GZ
Li
L
L
Tang
Z M
ZM
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D051379:Mice; D011837:Radiation-Protective Agents / Q000138:chemical synthesis*
D011837:Radiation-Protective Agents; D004958:Estradiol