C-nor-9,11-secoestranes as modified estrogens and fertility regulation.
The synthesis of C-nor-9,11-secoestradiol (4) has been achieved from 17 beta-acetoxy-11-chloro-3-methoxy-C-nor-9,11-secoestra-1,3,5(10)-tr ien-9-one (1) through a sequence of reactions without affecting the stereochemistry of estradiol-17 beta. Removal of the 9-keto function of 1 by hydrogenolysis and its subsequent treatment with Na/NH3 gives C-nor-9,11-secoestradiol 3-(methyl ether) (3), which has been demethylated under alkaline conditions to furnish C-nor-9,11-secoestradiol (4). Pyridinium chlorochromate oxidation of 3 gives the corresponding 17-ketone 6. Jones' oxidation of 4 to the ketone 5 and reaction of 5 and 6 with lithium acetylide gives corresponding 17 alpha-ethynyl derivatives 7 and 8. Relative binding affinity to estradiol-17 beta receptors and uterotropic, antiuterotrophic, and antiimplantation activities of compounds 3-8 have been studied. The effect of conformational flexibility on ligand-receptor interaction of these compounds is discussed.
Lal
K
K
Central Drug Research Institute, Lucknow, India.
Sharma
I
I
Agarwal
A K
AK
Agnihotri
A
A
Ray
S
S
D000818:Animals; D004962:Estranes / Q000138:chemical synthesis* / Q000494:pharmacology; D004967:Estrogens / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D005298:Fertility / Q000187:drug effects*; D008968:Molecular Conformation; D051381:Rats; D012632:Secosteroids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
D004962:Estranes; D004967:Estrogens; D012632:Secosteroids