|Other names||6,7-Dihydrocanrenone; 7-Desthioacetylspironolactone; 20-Spirox-4-ene-3,20-dione|
|Drug class||Antimineralocorticoid; Progestogen; Steroidal antiandrogen|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||342.4718 g/mol g·mol−1|
|3D model (JSmol)|
SC-5233, also known as 6,7-dihydrocanrenone or 20-spirox-4-ene-3,20-dione, is a synthetic, steroidal antimineralocorticoid of the spirolactone group which was developed by G. D. Searle & Company in the 1950s but was never marketed. It was the first synthetic antagonist of the mineralocorticoid receptor to have been identified and tested in humans. The drug was found to lack appreciable oral bioavailability and to be of low potency when administered parenterally, but it nonetheless produced a mild diuretic effect in patients with congestive heart failure. SC-8109, the 19-nor (19-demethyl) analogue, was developed and found to have improved oral bioavailability and potency, but still had low potency. Spironolactone (SC-9420; Aldactone) followed and had both good oral bioavailability and potency, and was the first synthetic antimineralocorticoid to be marketed. It has about 46-fold higher oral potency than SC-5233.
SC-5233 is the propionic acid lactone of testosterone (androst-4-en-17β-ol-3-one) and is also known 3-(3-oxo-17β-hydroxyandrost-4-en-17α-yl)propionic acid γ-lactone or as 17α-(2-carboxyethyl)testosterone γ-lactone. It is the unsubstituted parent or prototype compound of the spirolactone family of steroidal antimineralocorticoids.
Similarly to other spirolactones like canrenone and spironolactone, SC-5233 has some antiandrogenic activity and antagonizes the effects of testosterone in animals. In addition, along with SC-8109, it has been found to possess potent progestogenic activity.
Chemical structures of spirolactones
Cena and Kagawa first synthesized 3-(3-oxo-17β-hydroxy-4-androsten-17α-yl)-propionic acid-gamma-lactone and later prepared its 19-nor analogue. These compounds were designated SC-5233 and SC-8109, respectively. Both have anti-aldosterone activity and most of the early work on aldosterone antagonism was done with their aid. SC-5233 is not appreciably absorbed when given by mouth and the parenteral dose is large. As in the case of certain other steroids the 19-nor derivative was an improvement on the parent compound (Klyne, 1959). SC-8109 is well absorbed from the alimentary tract, but the dose is about 2 g daily.
[SC-5233] (total dose of 5 mg/rat) partially blocked the effects of testosterone propionate on the seminal vesicles and prostate in similar animals.