Progestins, discovery

Drospirenone (6/ ,7/ 15/ ,16/ -dimethylen-3-oxo-17a-pregn-4-en-21,17-carbolactone (Fig. 17.1) [1-3] is a progestin with a novel, advantageous biological profile. It originates from a project, the goal of which was the discovery of a new aldosterone antagonist. 

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. 

The discovery of nonsteroidal compounds with progestogenic activity, which at first sight have structurally nothing in common with the steroids, initiated new activities in the field of progestins with the aim to find new compounds with marked differences in their pharmacological profile. 

Klaus Schollkopf and Norbert Schmees give an overview of the biology of the progesterone receptor and of the development of research in the field of steroidal progestins and recent trends in discovery of nonsteroidal selective progesterone receptor modulators. 

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