SC-5233, also known as 6,7-dihydrocanrenone or 20-spirox-4-ene-3,20-dione, is a synthetic, steroidalantimineralocorticoid of the spirolactone group which was developed by G. D. Searle & Company in the 1950s but was never marketed.[1][2] It was the first synthetic antagonist of the mineralocorticoid receptor to have been identified and tested in humans.[1][3] The drug was found to lack appreciable oral bioavailability and to be of low potency when administered parenterally,[4] but it nonetheless produced a mild diuretic effect in patients with congestive heart failure.[1]SC-8109, the 19-nor (19-demethyl) analogue, was developed and found to have improved oral bioavailability and potency, but still had low potency.[5]Spironolactone (SC-9420; Aldactone) followed and had both good oral bioavailability and potency, and was the first synthetic antimineralocorticoid to be marketed.[3] It has about 46-fold higher oral potency than SC-5233.[6]
SC-5233 is the propionic acidlactone 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.[7] It is the unsubstituted parent or prototype compound of the spirolactone family of steroidal antimineralocorticoids.[2][8]
Similarly to other spirolactones like canrenone and spironolactone, SC-5233 has some antiandrogenic activity and antagonizes the effects of testosterone in animals.[7] In addition, along with SC-8109, it has been found to possess potent progestogenic activity.[9]
v
t
Chemical structures of spirolactones
Progesterone
Spirolactone
Canrenone
Spironolactone
Drospirenone
Spirorenone
Chemical structures of progesterone and spirolactones (steroid-17α-spirolactones).
^The British Encyclopaedia of Medical Practice: Medical progress. Butterworth & Company. 1961. p. 302. 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.
^ abKAGAWA CM, STURTEVANT FM, VAN ARMAN CG (1959). "Pharmacology of a new steroid that blocks salt activity of aldosterone and desoxycorticosterone". J. Pharmacol. Exp. Ther. 126 (2): 123–30. PMID13665517. [SC-5233] (total dose of 5 mg/rat) partially blocked the effects of testosterone propionate on the seminal vesicles and prostate in similar animals.
^Janos Fischer; C. Robin Ganellin (24 August 2010). Analogue-based Drug Discovery II. John Wiley & Sons. pp. 361–. ISBN978-3-527-63212-1.
^Hertz R, Tullner WW (1958). "Progestational activity of certain steroid-17-spirolactones". Proc. Soc. Exp. Biol. Med. 99 (2): 451–2. doi:10.3181/00379727-99-24380. PMID13601900. S2CID20150966.