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]
^ abcSherlock S (14 December 2013). "Diuretics in Liver Disease". In Buchborn E, Bock KD (eds.). 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. Springer-Verlag. pp. 224, 261. doi:10.1007/978-3-642-92756-0_11. ISBN978-3-642-49716-2.
^ abSzasz G, Budvari-Barany Z (19 December 1990). "Diuretics". Pharmaceutical Chemistry of Antihypertensive Agents. CRC Press. pp. 82–. ISBN978-0-8493-4724-5.
^ abDelcayre C, Fazal L, Ragot H, Prudhomme M, Azibani F, Samuel JL (6 November 2014). "The Renin-Angiotensin-Aldosterone System in Cardiovascular Disease". In Cokkinos DB (ed.). Introduction to Translational Cardiovascular Research. Springer. pp. 61–. ISBN978-3-319-08798-6.
^"Spironolactone". 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.
^Brandon ML (1 January 1962). Corticosteroids in medical practice. Thomas. p. 310. ISBN9780398002152.
^Kolkhof P, Bärfacker L (July 2017). "30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development". The Journal of Endocrinology. 234 (1): T125–T140. doi:10.1530/JOE-16-0600. PMC5488394. PMID 28634268.
^ abKagawa CM, Sturtevant FM, Van Arman CG (June 1959). "Pharmacology of a new steroid that blocks salt activity of aldosterone and desoxycorticosterone". The Journal of Pharmacology and Experimental Therapeutics. 126 (2): 123–130. PMID 13665517. [SC-5233] (total dose of 5 mg/rat) partially blocked the effects of testosterone propionate on the seminal vesicles and prostate in similar animals.
^Kalvoda J, de Gasparo M (24 August 2010). "Eplerenone: Selective Aldosterone Antagonist". In Fischer J, Ganellin CR (eds.). Analogue-based Drug Discovery II. John Wiley & Sons. pp. 361–. ISBN978-3-527-63212-1.
^Hertz R, Tullner WW (November 1958). "Progestational activity of certain steroid-17-spirolactones". Proceedings of the Society for Experimental Biology and Medicine. 99 (2): 451–452. doi:10.3181/00379727-99-24380. PMID 13601900. S2CID 20150966.
April 11, 2024
5233, also, known, dihydrocanrenone, spirox, dione, synthetic, steroidal, antimineralocorticoid, spirolactone, group, which, developed, searle, company, 1950s, never, marketed, first, synthetic, antagonist, mineralocorticoid, receptor, have, been, identified, . 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 amp 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 5233Clinical dataOther names6 7 Dihydrocanrenone 7 Desthioacetylspironolactone 20 Spirox 4 ene 3 20 dioneRoutes ofadministrationBy mouthDrug classAntimineralocorticoid Progestogen Steroidal antiandrogenATC codeNoneIdentifiersIUPAC name 8R 9S 10R 13S 14S 17R 10 13 dimethylspiro 2 6 7 8 9 11 12 14 15 16 decahydro 1H cyclopenta a phenanthrene 17 5 oxolane 2 3 dioneCAS Number976 70 5PubChem CID101931ChemSpider92091UNII3N8TCN29OPChEMBLChEMBL400534CompTox Dashboard EPA DTXSID10875403ECHA InfoCard100 012 321Chemical and physical dataFormulaC 22H 30O 3Molar mass342 479 g mol 13D model JSmol Interactive imageSMILES CC12CCC O C C1CCC3C2CCC4 C3CCC45CCC O O5 CInChI InChI 1S C22H30O3 c1 20 9 5 15 23 13 14 20 3 4 16 17 20 6 10 21 2 18 16 7 11 22 21 12 8 19 24 25 22 h13 16 18H 3 12H2 1 2H3 t16 17 18 20 21 22 m1 s1Key UWBICEKKOYXZRG WNHSNXHDSA NSC 5233 is the propionic acid lactone of testosterone androst 4 en 17b ol 3 one and is also known 3 3 oxo 17b hydroxyandrost 4 en 17a yl propionic acid g lactone or as 17a 2 carboxyethyl testosterone g 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 vte Chemical structures of spirolactones Progesterone Spirolactone Canrenone Spironolactone Drospirenone Spirorenone Chemical structures of progesterone and spirolactones steroid 17a spirolactones References edit a b c Sherlock S 14 December 2013 Diuretics in Liver Disease In Buchborn E Bock KD eds 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 Unterstutzung der CIBA Springer Verlag pp 224 261 doi 10 1007 978 3 642 92756 0 11 ISBN 978 3 642 49716 2 a b Szasz G Budvari Barany Z 19 December 1990 Diuretics Pharmaceutical Chemistry of Antihypertensive Agents CRC Press pp 82 ISBN 978 0 8493 4724 5 a b Delcayre C Fazal L Ragot H Prudhomme M Azibani F Samuel JL 6 November 2014 The Renin Angiotensin Aldosterone System in Cardiovascular Disease In Cokkinos DB ed Introduction to Translational Cardiovascular Research Springer pp 61 ISBN 978 3 319 08798 6 Spironolactone The British Encyclopaedia of Medical Practice Medical progress Butterworth amp Company 1961 p 302 Cena and Kagawa first synthesized 3 3 oxo 17b hydroxy 4 androsten 17a 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 Brandon ML 1 January 1962 Corticosteroids in medical practice Thomas p 310 ISBN 9780398002152 Kolkhof P Barfacker L July 2017 30 YEARS OF THE MINERALOCORTICOID RECEPTOR Mineralocorticoid receptor antagonists 60 years of research and development The Journal of Endocrinology 234 1 T125 T140 doi 10 1530 JOE 16 0600 PMC 5488394 PMID 28634268 a b Kagawa CM Sturtevant FM Van Arman CG June 1959 Pharmacology of a new steroid that blocks salt activity of aldosterone and desoxycorticosterone The Journal of Pharmacology and Experimental Therapeutics 126 2 123 130 PMID 13665517 SC 5233 total dose of 5 mg rat partially blocked the effects of testosterone propionate on the seminal vesicles and prostate in similar animals Kalvoda J de Gasparo M 24 August 2010 Eplerenone Selective Aldosterone Antagonist In Fischer J Ganellin CR eds Analogue based Drug Discovery II John Wiley amp Sons pp 361 ISBN 978 3 527 63212 1 Hertz R Tullner WW November 1958 Progestational activity of certain steroid 17 spirolactones Proceedings of the Society for Experimental Biology and Medicine 99 2 451 452 doi 10 3181 00379727 99 24380 PMID 13601900 S2CID 20150966 Retrieved from https en wikipedia org w index php title SC 5233 amp oldid 1199142932, wikipedia, wiki, book, books, library,
