Progestins modifications

It should be noted that the stereochemistry of the B/C and C/D junctions has remained inviolate in all the modifications discussed to date. It was in fact assumed that changing either of these was a quick path to loss of activity. Just such a modification, however, led to a progestin with a unique pharmacologic profile. 

In some cases, the simple modification of a drug structure can essentially modify the biological activity profile, whilst preserving some part of the original activity. Drospirenone (see Chapter 11-17), an orally active progestin contraceptive with antimineralcorticoid properties, is an example of an analogue-based drug discovery process that started from the diuretic spironolactone. 

Dr. Babcock To get the ball rolling, Dr. Pincus, I would like to ask a simple question that has puzzled me for some time. Can an estrogen or progestin alone do the job that combinations are doing so successfully now Since we have had estrogens and progestins available for 30 years, is it possible that they could have been used as successfully as the newer molecular modifications of these compounds now appear to be ... 

Ethisterone (Fig. 46.14), a 17a-ethynyl derivative of testosterone, is one of the first synthetic progestins to be used therapeutically. In 1937, this agent was synthesized from male sex hormones (androstanes) in an attempt to find an orally active androgen (53). Ethisterone later proved to be an effective oral progestin and became useful in the treatment of menstrual dysfunctions (49). Several molecular modifications... 

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