Fluorine-Containing Steroids

Effect of ACTH, corticoids and PCN (pregnenolone-16α-carbonitrile) on drug responses and disposition

“…The introduction of a fluoro radical in the 9a position of cortisol enhances not only the hormonal (gluco-and mineralocorticoid) actions, but also the pharmacologie (e.g., anti-inflammatory) effects of the steroid (Fried & Sabo, 1954). The high electronegativity of fluor appears to be the most important factor in protecting the metabolic inactivation of the 11j3 group and/or increasing binding in the target organ (Chen, Jr. & Borrevang, 1970). Dehydrogenation in the 1 and 2 positions of cortisol (prednisolone and triamcinolone) results in higher hormonal activities and in prolonged half-lives in blood (Bernstein et al, 1956).…”

“…For instance, 16/3-carbonitriles and betamethasone are not active, whereas dexamethasone is effective(Selye, 1971a,b). Here, the presence of 9a-fluoro group (e.g., in dexamethasone and CS-1) might be relevant as well, since the importance of the electronegativity of this radical is well-known in steroid chemistry and pharmacology(Chen, Jr. & Borrevang, 1970). ACTH and PCN most probably act through different mechanisms, PCN-pretreatment is known to induce the synthesis of hepatic microsomal drug-metabolizing enzymes(Solymoss et al, 1971c;Garg et aL, 1971c), and to increase the level of cytochrome P-450 in the liver(Werringloer, 1971(Werringloer, ,1972Lu et al, 1972).…”

Biological Magnetic Resonance

“…A large number of fluorine-substituted steroids have been synthesized (Taylor and Kent, 1965;Chen and Borrevang, 1970;Kent, 1972;Wettstein, 1972;Herz and Montalvo, 1973). …”

Fluoro-organic biochemistry

“…Fluorinated corticoids (dexamethasone) are of great importance because they possess superior anti-inflammatory action. Fluorinated androgens, estrogens, and progestens are currently used in the treatment of disorders of the reproductive system (24).…”