Spirolactone

Image:Potassium-sparing diuretics2.svge belong to spirolactone antimineralocorticoids.]]

{{Distinguish|Spironolactone}}

Spirolactones are a class of functional group in organic chemistry featuring a cyclic ester attached spiro to another ring system. The name is also used to refer to a class of synthetic steroids, called steroid-17α-spirolactones, 17α-spirolactosteroids, or simply 17α-spirolactones, which feature their spirolactone group at the C17α position.{{cite book|author=P. J. Bentley|title=Endocrine Pharmacology: Physiological Basis and Therapeutic Applications|url=https://books.google.com/books?id=W6M9AAAAIAAJ&pg=PA159|year=1980|publisher=CUP Archive|isbn=978-0-521-22673-8|pages=159–160}}{{cite book|author1=Gyorgy Szasz|author2=Zsuzsanna Budvari-Barany|title=Pharmaceutical Chemistry of Antihypertensive Agents|url=https://books.google.com/books?id=LMl4Sd38q4kC&pg=PA82%7CDATE%3D19+DECEMBER+1990%7CPUBLISHER%3DCRC+PRESS%7CISBN%3D978-0-8493-4724-5%7CPAGES%3D82%E2%80%9383%7D%7D%3C%2FREF%3E|date=19 December 1990|publisher=CRC Press|isbn=978-0-8493-4724-5|pages=82–}}{{cite journal|last1=Luther|first1=James M.|title=Is there a new dawn for selective mineralocorticoid receptor antagonism?|journal=Current Opinion in Nephrology and Hypertension|volume=23|issue=5|year=2014|pages=456–461|issn=1062-4821|doi=10.1097/MNH.0000000000000051|pmc=4248353|pmid=24992570}} They are antimineralocorticoids, or antagonists of the mineralocorticoid receptor (which is activated predominantly by the mineralocorticoid steroid hormone aldosterone), and have been employed clinically as potassium-sparing diuretics.{{cite book|author1=E. Buchborn|author2=K. D. Bock|title=Diuresis and Diuretics / Diurese und Diuretica: An International Symposium Herrenchiemsee, June 17th–20th, 1959 Sponsored by CIBA / Ein Internationales Symposium Herrenchiemsee, 17.–20. Juni 1959 Veranstaltet mit Unterstützung der CIBA|url=https://books.google.com/books?id=BJKhBgAAQBAJ&pg=PA261|date=14 December 2013|publisher=Springer-Verlag|isbn=978-3-642-49716-2|pages=261–}}{{cite book|author1=Rainer F. Greger|author2=H. Knauf|author3=E. Mutschler|title=Diuretics|url=https://books.google.com/books?id=zhHpCAAAQBAJ&pg=PA335|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-79565-7|pages=335–}} Some also possess progestogenic and/or antiandrogen properties, which have both contributed to side effects and been utilized for medical indications (e.g., spironolactone as an antiandrogen, and drospirenone as a progestin).{{cite book|author=Risto Erkkola|title=The Menopause|url=https://books.google.com/books?id=1AU_NI__fpUC&pg=PA188|year=2006|publisher=Elsevier|isbn=978-0-444-51830-9|pages=188–}} The spirolactones were developed by G. D. Searle & Company in the 1950s and thereafter and were denoted as "SC" compounds (e.g., SC-9420 for spironolactone).

The spirolactones include the marketed drugs spironolactone (SC-9420; Aldactone), canrenone (SC-9376; Cantaren, Luvion), potassium canrenoate (SC-14266; Venactone, Soldactone), eplerenone (SC-66110, CGP-30083; Inspra), and drospirenone (ZK-30595; Yasmin). Spirolactones that were not ever marketed include SC-5233, SC-8109, SC-11927 (Catatoxic Steroid 1; CS-1), spiroxasone, prorenone (SC-23133), prorenoate potassium (SC-23992), 7α-thiospironolactone (SC-24813), mexrenone (SC-25152, ZK-32055), dicirenone (SC-26304), 7α-thiomethylspironolactone (SC-26519), mexrenoate potassium (SC-26714), spirorenone (ZK-35973), ZK-91587 (15β,16β-methylenemexrenone), mespirenone (ZK-94679), and ZK-97894 (7α-thiomethylmespirenone). Oxprenoate potassium (RU-28318) is not a spirolactone by definition but is a closely related antimineralocorticoid that was never marketed.

SC-5233 (6,7-dihydrocanrenone), the C17α propanoic acid lactone of testosterone (androst-4-en-17β-ol-3-one), is the unsubstituted parent or prototype compound of the spirolactones, and is one of a few of the simplest members of the series along with SC-8109 (the 19-demethyl analogue of SC-5233) and canrenone (the 1,2-didehydro analogue of SC-5233).{{cite book|author1=Janos Fischer|author2=C. Robin Ganellin|title=Analogue-based Drug Discovery II|url=https://books.google.com/books?id=h2Kd8ci4Ln8C&pg=PA361|date=24 August 2010|publisher=John Wiley & Sons|isbn=978-3-527-63212-1|pages=361–}} Spironolactone is a derivative of SC-5233 with a 7α-acetylthio group (that is, SC-5233 is 7α-desthioacetylspironolactone).{{Spirolactone structures|align=left|caption=Chemical structures of progesterone and spirolactones (steroid-17α-spirolactones).}} {{Clear}}