17-Desoxy estrogen analogues.
A series of 17-substituted, 17-desoxyestratrienes have been synthesized and tested as potential postcoital antifertility agents. Estrogen-relative binding affinities were determined, in vivo assays for estrogenic and postcoital antifertility activity were conducted in rats, and selected candidate compounds were further tested for estrogenic activity in monkeys. In the rat, the 17-desoxyestratriene derivatives 8a, 8b, and 30 have shown low estrogenic activity while retaining potent antifertility activity. Structural modifications at the outset included a variety of 17-substituents and an omission of the 17-oxygen functionality, which was previously thought to be necessary for potent activity. The 17 beta-ethyl side chain exhibited the greatest antifertility activity with the largest separation ratio to estrogenicity. Nuclear modification of 17-desoxyethylestrane derivatives at positions 7 and 11 further increased the desired separation of activity, with the 11-hydroxy moiety enhancing separation more than other features.
Peters
R H
RH
Bio-Organic Chemistry Laboratory, SRI International, Menlo Park, California 94025.
Crowe
D F
DF
Avery
M A
MA
Chong
W K
WK
Tanabe
M
M
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003271:Contraceptive Agents, Female; D045166:Estradiol Congeners / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008253:Macaca mulatta; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology; D012453:Saimiri; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
D003271:Contraceptive Agents, Female; D045166:Estradiol Congeners; D011960:Receptors, Estrogen