Ethinylandrostenediol

{{Short description|Chemical compound}}

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| IUPAC_name = (3S,8R,9S,10R,13S,14S,17R)-17-ethynyl-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-diol

| image = ethinylandrostenediol.svg

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| class = Estrogen; Progestogen; Progestin

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| CAS_number = 3604-60-2

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| ChemSpiderID = 96678

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| ChEMBL = 410519

| synonyms = SKF-2856; 17α-Ethynyl-5-androstenediol; 17α-Ethynylandrost-5-ene-3β,17-diol; 17α-Pregn-5-en-20-yne-3β,17-diol; NSC-17098

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

| SMILES = C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC[C@]4(C#C)O)C)O

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| StdInChI = 1S/C21H30O2/c1-4-21(23)12-9-18-16-6-5-14-13-15(22)7-10-19(14,2)17(16)8-11-20(18,21)3/h1,5,15-18,22-23H,6-13H2,2-3H3/t15-,16+,17-,18-,19-,20-,21-/m0/s1

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| StdInChIKey = VGJUOWGYQZYCII-TVWVXWENSA-N

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Ethinylandrostenediol (developmental code name SKF-2856), also known as 17α-ethynyl-5-androstenediol, is a synthetic estrogen, progestogen, and androgen which was never marketed.{{cite thesis | vauthors = Tan VY | date = 2010 | title = Characterization of the estrogenic activity of a synthetic adrenal steroid 17-α ethinyl androstenediol and its potential use in hormone replacement therapy | hdl = 10356/45321 | degree = Ph.D. | url = http://hdl.handle.net/10356/45321 }}{{cite journal | vauthors = Beyler AL, Clinton RO | title = Uterine growth stimulating and testicular growth suppressing activities of 17alpha-ethinylandrostane-3beta, 17beta-diol, its delta 5-analog and derivatives | journal = Proc. Soc. Exp. Biol. Med. | volume = 92 | issue = 2 | pages = 404–8 | date = June 1956 | pmid = 13350363 | doi = 10.3181/00379727-92-22493 | s2cid = 87469965 }}{{cite journal | vauthors = Masson G, Selye H | date = 1945 | title = Additional steroids with luteoid activity. | journal = Journal of Pharmacology and Experimental Therapeutics | volume = 84 | issue = 1 | pages = 46–52 | jstor = 1671439 }}{{cite journal | vauthors = Overbeek GA | title = Luteoid activity of ethinyl-androstenediol | journal = Acta Brevia Neerl Physiol Pharmacol Microbiol e A | volume = 15 | issue = 5–7 | pages = 68 | date = 1948 | pmid = 18873577 }}{{cite journal | vauthors = Mardones E, Iglesias R, Lipschutz A | title = The antiluteinizing potency of five derivatives of progesterone | journal = Endocrinology | volume = 58 | issue = 2 | pages = 212–9 | date = February 1956 | pmid = 13285465 | doi = 10.1210/endo-58-2-212 }}{{cite book| vauthors = Neumann F |title=Die Gestagene|chapter=Chemische Konstitution und pharmakologische Wirkung|series=Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology |year=1968|pages=680–1025|publisher=Springer |doi=10.1007/978-3-642-99941-3_6|isbn=978-3-642-99942-0}} It is the C17α ethynyl derivative of the androgen precursor and prohormone 5-androstenediol.

Ethinylandrostenediol was first synthesized in the late 1930s and along with its close analogue ethisterone (17α-ethynyltestosterone) was one of the first progestins (synthetic progestogens) to be developed.{{cite journal| vauthors = Stavely HE |title=Preparation of a Pregnane Compound from Dehydroandrosterone|journal=Journal of the American Chemical Society|volume=61|issue=1|year=1939|pages=79–80|issn=0002-7863|doi=10.1021/ja01870a023|bibcode=1939JAChS..61...79S }}{{cite journal| vauthors = Stavely HE |title=The Preparation of Δ5-Pregnenediol-3,17-one-20 from Δ5-17-Ethynyl-androstenediol-3,17|journal=Journal of the American Chemical Society|volume=62|issue=3|year=1940|pages=489–491|issn=0002-7863|doi=10.1021/ja01860a007|bibcode=1940JAChS..62..489S }}{{cite book| vauthors = Emmens CW |title=Hormone Assay|url=https://books.google.com/books?id=cCzgBAAAQBAJ&pg=PA422|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4832-7286-3|pages=422–}} Ethinylandrostenediol is orally active similarly to ethisterone and shows about half its progestogenic potency. Ethinylandrostenediol was an intermediate in the initial synthesis of ethisterone.{{cite book| vauthors = Sneader W |title=Drug Discovery: A History|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA200|date=23 June 2005|publisher=John Wiley & Sons|isbn=978-0-471-89979-2|pages=200–}}

Ethinylandrostenediol shows tissue selectivity in its estrogenic effects in animals and doesn't seem to have estrogenic effects in the uterus. The androgenic activity of ethinylandrostenediol is weak.

An ester of ethinylandrostenediol, ethandrostate (17α-ethynyl-5-androstenediol 3β-cyclohexylpropionate), has been studied clinically in men and women with prostate cancer and breast cancer, respectively.{{cite journal | vauthors = Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J | title = 17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism | journal = Invest New Drugs | volume = 30 | issue = 1 | pages = 59–78 | date = February 2012 | pmid = 20814732 | doi = 10.1007/s10637-010-9517-0 | s2cid = 24785562 }}{{cite book| vauthors = Shipley EG |chapter=Anti-gonadotropic steroids, inhibition of ovulation and mating|pages=179–274| veditors = Dorfman RI |title=Bioassay|chapter-url=https://books.google.com/books?id=WS_LBAAAQBAJ&pg=PA179|date=1962|publisher=Elsevier|isbn=978-1-4832-7276-4}}{{cite journal | vauthors = Boccabella A, Bakritges C | title = Effects of ethandrostate on pituitary and sex organs of rats | journal = Anatomical Record | date = January 1956 | volume = 124 | issue = 2 | pages = 260 }}{{cite journal| vauthors = Clinton R, Neumann H, Laskowski S, Christiansen R |title= Esters of 17α-Ethinyl-androstane-3β,17β-diol and 17 α-Ethinylandrost-5-ene-3β, 17β-diol|journal=The Journal of Organic Chemistry|volume=22|issue=4|year=1957|pages=473–475|issn=0022-3263|doi=10.1021/jo01355a627}}{{cite journal | vauthors = Olson KB, Frawley TF, Stein AA, Shields D | title = Ethandrostate: endocrine effects and studies in treatment of cancer | journal = Cancer | volume = 11 | issue = 3 | pages = 537–45 | date = 1958 | pmid = 13523561 | doi = 10.1002/1097-0142(195805/06)11:3<537::aid-cncr2820110313>3.0.co;2-w | s2cid = 738607 | doi-access = }}

Notable structural analogues of ethinylandrostenediol include 5-androstenediol, 17α-ethynyl-3β-androstanediol, 17α-ethynyl-3α-androstanediol, ethisterone (17α-ethynyltestosterone), and methandriol (17α-methyl-5-androstenediol), as well as ethinylestradiol (17α-ethynylestradiol or 17α-ethynylestra-1,3,5(10)-triene-3,17β-diol).

{{Affinities of estrogen receptor ligands for the ERα and ERβ}}