Steroidal progestins

Although the LBDs of the steroid receptors share only a low to medium sequence identity, the overall fold of the proteins is very similar and consists of a unique helical sandwich arrangement. The progesterone LBD contains 10 a-helices arranged in the same way and, as in the other receptors, the orientation ofhelix 12 differs whether an agonist or an antagonist is bound. 

The development and the properties of steroidal progestins have been described in several review articles [2, 22-24], therefore this chapter will give only a brief overview about the historical development in this field and will focus on the so-called new progestins [25]. 

The second structural class of steroidal progestins consists of pregnane derivatives like medroxyprogesterone acetate (MPA) (9), megestrol acetate (10) or cyproterone acetate (11). The introduction of a 17a-acetoxy group and different substituents in the 6-position of the parent molecule progesterone leads to an increase in metabolic stability and to orally active compounds. Cyproterone acetate was the first progestin 

Nestorone (12) is a member of the group of 19-nor-pregnane derivatives. It was developed by the Population Council and is one of the most potent progestins. Its profile at other steroid receptors is quite neutral. However, nesterone is not orally active, thus its use is limited to transdermal applications or implant devices. 

The antimineralocorticoidal activity of drospirenone is considered as a main benefit. It counteracts the salt and water retention effects of ethinylestradiol, the standard estrogen component in oral contraceptives [33]. 

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Progesterone Receptor Overview of Modern Steroidal Progestins and Developments in the Field of Nonsteroidal Selective Progesterone Receptor Modulators... 

Progesterone Receptor Overview of Modern Steroidal Progestins and Developments... 

In this chapter the biological function of PR, its structural properties and therapeutic indications for progestins will be described. Since steroidal progestins have now been in clinical use for several decades, the focus of this chapter will be more on the current developments, particularly in the area of nonsteroidal progestins mainly with a medicinal chemistry perspective. 

The development of steroidal progestins led to a variety of products with different pharmacological profiles. The use of progestins in combination with estrogens as oral contraceptives has had and still today has an enormous impact on the reproductive behavior in developed countries. This is also reflected in the global market volume of oral contraceptives, which was 5.35 billion in 2005 and is expected to grow to 7.55 billion in 2011. Additional indications for the use of progestins are... 

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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