STEROIDAL, ALDOSTERONE ANTAGONISTS - INCREASED SELECTIVITY OF 9-ALPHA,11-EPOXY DERIVATIVES

In the search for aldosterone antagonists with an optimal activity pro file, twelve 9 alpha,11-epoxy-steroids were prepared and compared with their 9 alpha,11 alpha-unsubstituted analogues in terms of steroid re ceptor binding in vitro and electrolyte excretion in vivo. Substitutio n of the parent structures by an epoxy group at positions 9 alpha,11 r esulted in marginal effects on mineralocorticoid receptor binding and electrolyte excretion, but greatly reduced androgen and gestagen recep tor binding. This finding is reflected in the largely lacking unwanted anti-androgenic and gestagenic side effects in animal models of the t hree most interesting 9 alpha,11-epoxy-spirolactones 4(CGP 33 033), 18 (CGP 29 245), and 25(CGP 30 083).