7α-Thioprogesterone

{{Short description|Chemical compound}}

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| IUPAC_name = (1S,3aS,3bS,4R,9aR,9bS,11aS)-1-Acetyl-9a,11a-dimethyl-4-sulfanyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one

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| CAS_number = 95286-04-7

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67810-32-6 (propionate)

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| C=21 | H=28 | O=2 | S=1

| SMILES = O=C(C)[C@]1CC[C@]([H])2[C@@]([H])3[C@](S[H])CC4=CC(CC[C@]4(C)[C@@]3([H])CC[C@@]21C)=O

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| StdInChI = 1S/C21H28O2S/c1-12(22)15-4-5-16-19-17(7-9-21(15,16)3)20(2)8-6-14(23)10-13(20)11-18(19)24/h10,16-17,19,24H,4-9,11H2,1-3H3/t16-,17-,19-,20-,21+/m0/s1

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| StdInChIKey = MTDUGSYXIPHNBV-JZTRKIHISA-N

| synonyms = 7α-TP4; SC-8365; 7α-Mercaptopregn-4-ene-3,20-dione

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7α-Thioprogesterone (7α-TP4; developmental code name SC-8365; also known as 7α-mercaptopregn-4-ene-3,20-dione) is a synthetic, steroidal, and potent antimineralocorticoid (putative) and antiandrogen which was developed by G. D. Searle & Co and was described in the late 1970s and early 1980s but was never developed or introduced for medical use.{{cite journal | vauthors = Cutler GB, Pita JC, Rifka SM, Menard RH, Sauer MA, Loriaux DL | title = SC 25152: A potent mineralocorticoid antagonist with reduced affinity for the 5 alpha-dihydrotestosterone receptor of human and rat prostate | journal = J. Clin. Endocrinol. Metab. | volume = 47 | issue = 1 | pages = 171–5 | year = 1978 | pmid = 263288 | doi = 10.1210/jcem-47-1-171 }}{{cite journal | vauthors = Pugeat MM, Dunn JF, Nisula BC | title = Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma | journal = J. Clin. Endocrinol. Metab. | volume = 53 | issue = 1 | pages = 69–75 | year = 1981 | pmid = 7195405 | doi = 10.1210/jcem-53-1-69 }}{{cite book|author=Ulrich Westphal|title=Steroid-Protein Interactions II|url=https://books.google.com/books?id=3DD6CAAAQBAJ&pg=PA501|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-82486-9|pages=501–}} It is a derivative of progesterone (pregn-4-ene-3,20-dione) with a thio (sulfur) substitution at the C7α position, and is related to the spirolactone group of drugs but lacks a γ-lactone ring.

As an antiandrogen, 7α-TP4 has approximately 8.5% of the affinity of dihydrotestosterone (DHT) for the rat ventral prostate androgen receptor (AR), which is similar to that of spironolactone and its active metabolite 7α-thiomethylspironolactone.{{cite journal | vauthors = Cutler GB, Pita JC, Rifka SM, Menard RH, Sauer MA, Loriaux DL | title = SC 25152: A potent mineralocorticoid antagonist with reduced affinity for the 5 alpha-dihydrotestosterone receptor of human and rat prostate | journal = J. Clin. Endocrinol. Metab. | volume = 47 | issue = 1 | pages = 171–5 | year = 1978 | pmid = 263288 | doi = 10.1210/jcem-47-1-171 }} The drug has also been assessed at steroid hormone-associated carrier proteins, and shows very low binding to sex hormone-binding globulin (SHBG) but high affinity for corticosteroid-binding globulin (CBG) approximately equal to that of progesterone.

7α-Acetylthio-17α-hydroxyprogesterone, a related derivative of progesterone and also of 17α-hydroxyprogesterone, has been found to possess potent antimineralocorticoid activity similarly.{{cite book|author=Ralph I. Dorfman|title=Steroidal Activity in Experimental Animals and Man|url=https://books.google.com/books?id=BbLfBAAAQBAJ&pg=PA395|date=5 December 2016|publisher=Elsevier Science|isbn=978-1-4832-7299-3|pages=395–}} Spironolactone is the derivative of this compound in which the acetyl group at the C17β position has been cyclized with the C17α hydroxyl group to form a spiro 21-carboxylic acid γ-lactone ring.{{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA1111|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|page=1111|url-status=live|archive-url=https://web.archive.org/web/20170215024945/https://books.google.com/books?id=0vXTBwAAQBAJ|archive-date=15 February 2017}}{{cite web |url=https://pubchem.ncbi.nlm.nih.gov/compound/5833 |title=Spironolactone |access-date=2017-07-04 |url-status=live |archive-url=https://web.archive.org/web/20160630101052/http://pubchem.ncbi.nlm.nih.gov/compound/5833/ |archive-date=2016-06-30 }}{{Cite web|url=http://www.chemspider.com/Chemical-Structure.5628.html?rid=b578a389-d64b-4ec2-ae20-309e5f3abd11|title = Spironolactone | C24H32O4S | ChemSpider}}