Prorenone Explained

Prorenone (developmental code name SC-23133) is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone that was never marketed.^[1] It is the lactonic form of prorenoic acid (prorenoate), and prorenoate potassium (SC-23992), the potassium salt of prorenoic acid, also exists. Prorenoate potassium is about 8 times more potent than spironolactone as an antimineralocorticoid in animals, and it may act as a prodrug to prorenone. In addition to the mineralocorticoid receptor, prorenone also binds to the glucocorticoid, androgen, and progesterone receptors.^{[2] [3]} The antiandrogenic potency of prorenone in vivo in animals is close to that of spironolactone. Similarly to spironolactone, prorenone is also a potent inhibitor of aldosterone biosynthesis.^[4]

Chemistry

Synthesis

Prorenone can be synthesized via a Johnson–Corey–Chaykovsky reaction by reaction of canrenone with trimethylsulfoxonium iodide and sodium hydride.^[5]

See also

• Canrenone
• Mexrenone
• Prorenoate potassium
• Prorenoic acid
• Potassium canrenoate

Notes and References

1. Claire M, Rafestin-Oblin ME, Michaud A, Roth-Meyer C, Corvol P . Mechanism of action of a new antialdosterone compound, prorenone . Endocrinology . 104 . 4 . 1194–1200 . April 1979 . 436757 . 10.1210/endo-104-4-1194 .
2. Book: Szasz G, Budvari-Barany Z . Pharmaceutical Chemistry of Antihypertensive Agents. 19 December 1990. CRC Press. 978-0-8493-4724-5. 87–.
3. Kamata S, Matsui T, Haga N, Nakamura M, Odaguchi K, Itoh T, Shimizu T, Suzuki T, Ishibashi M, Yamada F . 6 . Aldosterone antagonists. 2. Synthesis and biological activities of 11,12-dehydropregnane derivatives . Journal of Medicinal Chemistry . 30 . 9 . 1647–1658 . September 1987 . 3040999 . 10.1021/jm00392a022 .
4. Netchitailo P, Delarue C, Perroteau I, Leboulenger F, Capron MH, Vaudry H . Relative inhibitory potency of five mineralocorticoid antagonists on aldosterone biosynthesis in vitro . Biochemical Pharmacology . 34 . 2 . 189–194 . January 1985 . 2981534 . 10.1016/0006-2952(85)90123-6 .
5. Chinn L . 19 October 1974 . US . 3845041 . 7-Halomethyl-17-hydroxy-3-oxo-17alpha-pregn-4-ene-21-carboxylic acid gamma-lactones . GD Searle LLC . . .