The COMPARATIVE CONTRACEPTIVE ACTIVITIES OF 10β-Hydroperoxy-17α-Ethynyl-4-Estren-17β-Ol-3-One (SCH 10015) AND NORETHYNODREL

Abstract

10\g=b\-Hydroperoxy-17\g=a\-ethynyl-4-estren-17\g=b\-ol-3-one(Sch 10015) was found to be less progestational than norethynodrel but equally potent as a contraceptive agent in rats. To prevent pregnancy in all the treated females, a minimum daily dose of 5 mg./kg. body weight (MPD 100) of either agent was required. At this dose, both agents had similar contraceptive mechanisms of action. They partially blocked the release of pituitary gonadotrophin and when given on the 2nd and 3rd day after coitus, i.e. after ovulation, prevented conception. Pituitary gonadotrophin inhibition is not considered to be the primary mechanism of contraception because significant numbers of rats ovulate when treated with the MPD 100 of either compound. It is concluded that the time of the primary contraceptive action of these agents at their respective MPD 100 is post-ovulatory.It would appear from these experiments that classical progestational activity is not required for the contraceptive action of these drugs.

Hydroperoxides as inactivators of aromatase: 10.beta.-hydroperoxy-4-estrene-3,17-dione, crystal structure and inactivation characteristics

“…Since its irreversible effects are abolished in the presence of NADPH, 10/3-OOH would not seem to have much utility as an in vivo inhibitor of estrogen biosynthesis. However, it is interesting to note that the 17/3-ethynyl-substituted analogue of 10/3-OOH has been prepared, evaluated in vivo, and found to have potent contraceptive properties (Jacob & Morris, 1969;Watnick et al, 1965). The 17a-methyl analogue of androstenedione is aromatized more slowly than androstenedione (Ryan, 1960;Braselton et al, 1974), possibly because the 17a-methyl substituent alters the alignment of the steroid in the aromatase active site.…”