retroprogesterone

{{Short description|Chemical compound}}

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| IUPAC_name = (8S,9R,10S,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one

| image = Retroprogesterone.svg

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| class = Progestin; Progestogen

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| CAS_number = 2755-10-4

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = R94ZS616JR

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| PubChem = 92940

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| ChemSpiderID = 83898

| synonyms = 9β,10α-Progesterone; 9β,10α-Pregn-4-ene-3,20-dione

| C=21 | H=30 | O=2

| SMILES = CC(=O)C1CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C

| StdInChI = RJKFOVLPORLFTN-HQZYFCCVSA-N

| StdInChIKey = 1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19+,20+,21+/m0/s1

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Retroprogesterone, also known as 9β,10α-progesterone or as 9β,10α-pregn-4-ene-3,20-dione, is a progestin which was never marketed.{{cite book| vauthors = Horský J | chapter = Therapy of Anovolution | veditors = Horský J, Presl J |title=Ovarian Function and its Disorders: Diagnosis and Therapy|chapter-url=https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA329|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-8195-9|pages=305, 329}}{{cite book | vauthors = Sindhu SG | chapter = Endometrial Receptivity and Luteal Support | veditors = Talwar P, Sindhu SG |title=Step by Step: Protocols in Clinical Embryology and ART |chapter-url= https://books.google.com/books?id=KOP17hRq_YgC&pg=PA379 |date=18 May 2012|publisher=JP Medical Ltd|isbn=978-93-5025-765-4|pages=379–}} It is a stereoisomer of the naturally occurring progestogen progesterone, in which the hydrogen atom at the 9th carbon is in the α-position (below the plane) instead of the β-position (above the plane) and the methyl group at the 10th carbon is in the β-position instead of the α-position. In other words, the atom positions at the two carbons have been reversed relative to progesterone, hence the name retroprogesterone. This reversal results in a "bent" configuration in which the plane of rings A and B is orientated at a 60° angle below the rings C and D.{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | issue = Suppl 1 | pages = 3–63 | date = August 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 }} This configuration is ideal for interaction with the progesterone receptor, with retroprogesterone binding with high affinity to this receptor.{{cite book| vauthors = Litwack G |title=Biochemical Actions of Hormones|url=https://books.google.com/books?id=et3Lq-TitzAC&pg=PA193|date=2 December 2012|publisher=Elsevier|isbn=978-0-323-15189-4|pages=193–}} However, the configuration is not as ideal for binding to other steroid hormone receptors, and as a result, retroprogesterone derivatives have increased selectivity for the progesterone receptor relative to progesterone.{{cite journal | vauthors = Rižner TL, Brožič P, Doucette C, Turek-Etienne T, Müller-Vieira U, Sonneveld E, van der Burg B, Böcker C, Husen B | display-authors = 6 | title = Selectivity and potency of the retroprogesterone dydrogesterone in vitro | journal = Steroids | volume = 76 | issue = 6 | pages = 607–615 | date = May 2011 | pmid = 21376746 | doi = 10.1016/j.steroids.2011.02.043 | s2cid = 31609405 }}

Retroprogesterone is the parent compound of a group of progestins consisting of the marketed progestins dydrogesterone (6-dehydroretroprogesterone) and trengestone (1,6-didehydro-6-chlororetroprogesterone) and the never-marketed progestin Ro 6-3129, as well as the active metabolites of these progestins like 20α-dihydrodydrogesterone and 20α-dihydrotrengestone (i.e., the 20α-hydroxylated analogues).{{cite book| vauthors = Padubidri VG, Anand E | chapter = Hormonal Therapy in Gynecology |title=Gynaecology| chapter-url = https://books.google.com/books?id=6mvbRMT3_eoC&pg=PA207|date= January 2005|publisher=Elsevier India|isbn=978-81-8147-562-6|pages=207–}}{{cite journal| vauthors = Dixon R, Hudson S, Darragh A |title=Pharmacokinetics of the retro-steroid progestogen, 16α-ethylthio-9β,10α-pregna-4, 6-diene-3, 20-dione (Ro 6-3129), in man and the sheep|journal=Contraception|volume=8|issue=1|year=1973|pages=53–65|issn=0010-7824|doi=10.1016/0010-7824(73)90159-5}}