Progestins progestational

Quantitative Structure—Activity Relationships. Many quantitative stmcture—activity relationship (QSAR) studies of progestins have appeared in the Hterature and an extensive review of this work is available (174). QSAR studies attempt to correlate electronic, steric, and/or hydrophobic properties to progestational activity or receptor binding affinity. A review focusing on the problems associated with QSAR of steroids has been pubUshed (175). 

Progestational activity. Effects elicited by progestins, principally a cessation of ovulation and other genital changes related to pregnancy. 

Oppenauer oxidation of the enol ether (34) affords the corresponding 17 ketone (37) (the enol ether is stable to the basic oxidation conditions). This ketone affords the corresponding 17a-ethynyl compound on reaction with metal acetylides. Hydrolysis of the enol ether under mild conditions leads directly to ethynodrel (39), an orally active progestin. This is the progestational component of the first oral contraceptive to be offered for sale. Treatment of the ethynyl enol ether with strong acid leads to yet another oral progestin employed as a contraceptive, norethindrone (40). ° In practice these and all other so-called combination contraceptives are mixtures of 1-2% mestranol... 

Therapeutic indications for the progestational drugs based on pregnanes described above are rather limited. This is particularly true when compared to the reduced estrane-based nor compounds that are used in oral contraceptives. This circumstance, combined with the availability of the half-dozen or so C-19 progestins, posed as a disincentive to further research on the synthesis of new compounds. This is reflected in the pubhcation dates of reports on the synthesis of these compounds. 

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