Receptor Binding as a Tool in the Development of New Bioactive Steroids

Structural studies of thiophilic N-chloroazasteroids

“…Assuming that the phenolic ring is necessary for binding of estrogens to the estrogen receptor , 1987Hfihnel et al, 1973;Raynaud et al, 1979) and that irreversible covalent binding between the N-chlorolactam group and thiol groups on the receptor will occur, the O3...C1 distance can be used to assess the fit of the steroid in the receptor. The distance is about the same for both Dhomosteroids, 12.420 (3) and 12.390 (2)A in (1) and (2), respectively, and is 11.698 (4)A in steroid (3).…”

“…They, however, do not possess the 17/3-hydroxy function important for high-affinity binding; when the 17/3-hydroxy substituent is replaced with a 17-carbonyl group (e.g. in estrone), the affinity is decreased (H~ihnel el al., 1973;Raynaud et al, 1979;Katzenellenbogen, Heiman, Carlson, Payne & Lloyd, 1980). The binding affinity of steroids (2) and (3) to the estrogen receptor may therefore be similar to that of estrone.…”

“…These compounds, because of their similarity to estradiol and because of a common phenolic A ring , 1987Hfihnel, Twaddle & Ratajczak, 1973;Raynaud, Ojasoo, Bouton & Philibert, 1979), are expected to bind to the estrogen receptor. They, however, do not possess the 17/3-hydroxy function important for high-affinity binding; when the 17/3-hydroxy substituent is replaced with a 17-carbonyl group (e.g.…”

17β-Hydroxy-17α-methyl-4,9,11-estratrien-3-one

“…The title compound is one of the molecules which present a very pronounced affinity for androgen (Raynaud, Ojasoo, Bouton & Philibert, 1979) and progestin receptors (Ojasoo & Raynaud, 1978). A single crystal for the present investigation (pale yellow, 0.3 x 0.3 x 0.6 mm) was grown by slow evaporation of a methanol solution.…”

Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids

“…However, side-effects of ICS can be induced after absorption into the systemic circulatory system when they interact with systemic or peripheral GRs. Also, some of the endogenous glucocorticoids, such as corticosterone and deoxycorticosterone, have been reported to bind to the progesterone receptor (PR) [1]. Progesterone (PROG), in turn, has been shown to bind to the GR nonselectively [2].…”