Progestagen Derivatives

Due to the high similarity of the compounds, one-dimensional RDF descriptors are not able to describe such a complex property as the biological activity. On the one hand, they would react too sensitively to primary structural features (e.g., the 

FIGURE 6.32 Base structure for a set of 44 progestagen derivatives used for training a CPG neural network for the prediction of biological activity. 

FIGU RE 6.33 3D view of a charge-weighted 2D RDF descriptor for a progestagen derivative encoded with effective atom polarizability (a) in the second dimension (128 x 40 5120 components). 

The correlation coefficient is quite high but is less reliable. The few training compounds do not cover the range of effective concentrations appropriately, and the 

FIGURE 6.34 Correlation between calculated and predicted effective concentrations (ECjq) for 44 progestagen derivatives with the leave-one-out technique. The standard deviation of the error of prediction is 0.1 uM/L. 

---

Oral contraceptive preparations based upon EE and a progestagen derived from progesterone produce the anticipated effects upon lipids Table... 

Bottela, J., et al. 1986. Interaction of new 19-norprogesterone derivative with progestagen, miner-alocortoid and glucocorticoid receptors. J Pharmacol 17 699. 

In addition to bile salts, which facilitate the digestion of lipids, five major classes of steroid hormones are derived from cholesterol progestagens, glucocorticoids, mineralocorticoids, androgens, and estrogens. Hydroxylations by P450 monooxygenases that use NADPH and O2 play an important role in the synthesis of steroid hormones and bile salts from... 

Other 6-methylated progestagens followed in rapid succession. Spero [45, 46] prepared medroxyprogesterone acetate (XXV), which was the first 17a-hydroxyprogesterone derivative to find use in oral contraception. The related megesterol acetate (XXVI) [47] was prepared at about the same time... 

Mestranol and mestranol-containing oral contraceptive preparations seem to impair glucose tolerance possibly more than ethynyloestradioi and oral contraceptive preparations derived therefrom [208], particularly where there is a history of gestational (subclinical) diabetes. This situation may be reversed in the presence of progestagen (vide infra). 

Cholesterol (7), the major sterol in most animals, also is found in small amounts in many plants, where it serves as a precursor for other steroid derivatives, such as the progestagens and cardiac glycosides (Heftman, 1984). In plants, algae, and fiingi, a variety of other phytosterols may serve... 

---