Steroid Hormones Adrenocorticoids—Glucocorticoids

Most glucocorticoids have some mineralocorticoid effect, which is usually considered an undesirable activity. Through structural chemistry and structure-activity relationship (SAR) studies, molecular modifications can separate the two activities. 

The structure-activity relationships of glucocorticoids are based on two natural hormones, cortisol (3.8) and corticosterone (5.61). The characteristic structural features of these hormones are the conjugated 3-ketone, the 11-OH group, and the up-ketol side chain. Molecular modifications have been aimed at deriving compounds with glucocorticoid 

Halogenation. 9a-Flnorocortisone is only about 10 times more active than its parent compound, but its mineralocorticoid activity is 300-600 times greater. This is undesirable since it leads to edema thns, the compound fludrocortisone (5.62) is used only topically, in ointments. 

Additional double bonds. A -componnds (where A indicates the position of a double bond) were introduced, like prednisone (3.7), a A -ll-ketone, and prednisolone, its 11-hydroxy analogne. Changing the geometry of the A ring increased the potency without augmenting mineralocorticoid activity. 

The introdnction of a methyl group in methylprednisolone (5.63) resnlted in a slight increase in activity however, the greatest improvements in activity came from the combination of a double bond, halogen, and methyl substitnents. Triamcinolone (5.64), in 

---

Adrenal glands are small monnds of tissue located at the top of each kidney. The outer layer of the gland, the adrenal cortex, produces a number of potent steroid hormones, the adrenocorticoids. They are classified into two groups according to function Mineralocor-ticoids regulate the concentration of ions (mainly Na ) in body fluids, and glucocorticoids enhance carbohydrate metabolism. 

---