Norethindrone and norethynodrel

Table II Medical Session Reports (Singapore) on Norethindrone and Norethynodrel Combinations...

Although norethindrone, norethindrone acetate, and norethynodrel differ slightly in biological properties in animal experiments, all three agents are known to be converted, at least in part, to 17-ethinyl-19-nortestosterone in vivo (8,25, 26,68). 

By 1956, clinical studies led by John Rock, a gynecologist, showed that progesterone, in combination with norethindrone, was an effective oral contraceptive. G.D. Searle was the first on the market with Enovid, a combination of mestranol and norethynodrel. In 2005. approximately 11 million American women, and approximately 100 million women worldwide, were using oral contraceptive pills. In 1993, the British weekly The Economist considered the pill to be one of the seven... 

In 1953, G. D. Searle and Co. patented a related compound, norethynodrel. This steroid is also an active contraceptive when taken orally. This fact is not at all surprising to an experienced organic chemist because it is well known that a CC double bond such as the one in norethynodrel is readily isomerized into conjugation with a carbonyl group. This acid-catalyzed isomerization occurs via an enol intermediate, and the equilibrium favors the more stable, conjugated compound. The acidic conditions in the human gastric system are quite sufficient to accomplish the transformation of norethynodrel to norethindrone. It seems that chemical reactions do not care much about patents ... 

In 1951, Djerassi, Miramontes and Rosenkranz [29] converted 19-nortestosterone into 19-norandrostenedione (XIV) and thence into norethindrone (19-norethisterone) (XVIII). Two years later, Colton [30] prepared norethynodrel (XIX). These two 19-nor steroids achieved immediate success as orally active progestagens. In retrospect, the enhanced biological potency of (XVIII) over ethisterone (XVI) is not surprising as 19-nor steroids form the biogenetic link between the androgens and the quantitatively more potent oestrogens. At the time, however, the results were baffling. 

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