Chemical synthesis and bioassay of anordrin and dinordrin I and II.
The chemical synthesis of 2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol dipropionate (Anordrin) and the corresponding diacetate is reported. Similarly, the preparation of the 2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-estrane-2 beta, 17 beta-diol, its diacetate and dipropionate (Dinordrin I), along with the corresponding 2 beta-epimer (Dinordrin II) from 17 beta-hydroxy-A-nor-5 alpha=estran-2-one is described. In rat uterotrophic activity bioassay, the slope of ethynylestradiol differed significantly from the slopes of the other three compounds, thus vitiating potency estimates with this reference compound. Dinordrin I was 20 times more potent than Anordrin and considerably more potent then Dinordrin II. The single-dose oral antifertility effect in rats generally paralleled uterotrophic activity. Immediate postovulatory contraceptive effectiveness was assessed in adult cycling female baboons given two doses daily for 4 days. Both Anordrin and Dinordrin I showed antifertility activity worthy of further study. Moreover, a definite luteolytic effect, with depression of both plasma estrogen and progesterone levels, was observed with these two steroids.
D000818:Animals; D003276:Contraceptives, Oral / Q000138:chemical synthesis*; D003280:Contraceptives, Oral, Synthetic / Q000138:chemical synthesis* / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects*; D004962:Estranes / Q000138:chemical synthesis* / Q000494:pharmacology; D004967:Estrogens / Q000097:blood; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D000882:Haplorhini; D008722:Methods; D009635:Norandrostanes / Q000138:chemical synthesis* / Q000494:pharmacology; D009654:Norsteroids / Q000138:chemical synthesis / Q000494:pharmacology; D010215:Papio; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D051381:Rats; D014599:Uterus / Q000187:drug effects
D003276:Contraceptives, Oral; D003280:Contraceptives, Oral, Synthetic; D004962:Estranes; D004967:Estrogens; D009635:Norandrostanes; D009654:Norsteroids; D004997:Ethinyl Estradiol; D011374:Progesterone; C020296:dinordrin; C010855:anordrin