ethynerone

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{{Short description|Chemical compound}}

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| IUPAC_name = (8S,13S,14S,17S)-17-(2-Chloroethynyl)-17-hydroxy-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one

| image = Ethynerone.svg

| width = 250

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| routes_of_administration = Oral

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| CAS_number = 3124-93-4

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

| UNII = CKM4S0R7LX

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| PubChem = 18403

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| ChemSpiderID = 8512249

| C=20 | H=23 | Cl=1 | O=2

| smiles = CC12CCC3=C4CCC(=O)C=C4CCC3C1CCC2(C#CCl)O

| StdInChI = 1S/C20H23ClO2/c1-19-8-6-16-15-5-3-14(22)12-13(15)2-4-17(16)18(19)7-9-20(19,23)10-11-21/h12,17-18,23H,2-9H2,1H3/t17-,18+,19+,20-/m1/s1

| StdInChIKey = KEOBKPHJNAILCW-FUMNGEBKSA-N

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Ethynerone (INN, USAN), also known as 17α-(2-chloroethynyl)estra-4,9-dien-17β-ol-3-one, is a steroidal progestin of the 19-nortestosterone group that was first reported in 1961 but was never marketed.{{cite book | vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA521|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=521–}} Under the developmental code name MK-665, it was studied in combination with mestranol as an oral contraceptive.{{cite book| vauthors = Runnebaum BC, Rabe T, Kiesel L |title=Female Contraception: Update and Trends|url=https://books.google.com/books?id=LtT6CAAAQBAJ&pg=PA134|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-73790-9|pages=134–135}} Development of the drug was discontinued due to concerns surrounding toxicity findings in dogs. It is a chloroethynylated derivative of norethisterone.{{cite book| vauthors = Diczfalusy E | collaboration = World Health Organization|title=Acta Endocrinologica: Supplementum| year = 1974 |url=https://books.google.com/books?id=0aMnAQAAIAAJ|publisher=Ejnar Munksgaard|page=261| isbn = 9788774940968 }}

In 1966, during its clinical development, ethynerone was found to produce mammary gland tumors in dogs treated with it at very high doses for prolonged periods of time.{{cite journal | vauthors = Geil RG, Lamar JK | title = FDA studies of estrogen, progestogens, and estrogen/progestogen combinations in the dog and monkey | journal = Journal of Toxicology and Environmental Health | volume = 3 | issue = 1–2 | pages = 179–93 | date = September 1977 | pmid = 411941 | doi = 10.1080/15287397709529557 | bibcode = 1977JTEH....3..179G }}{{cite journal | vauthors = Jacobs AC, Hatfield KP | title = History of chronic toxicity and animal carcinogenicity studies for pharmaceuticals | journal = Veterinary Pathology | volume = 50 | issue = 2 | pages = 324–33 | date = March 2013 | pmid = 22700852 | doi = 10.1177/0300985812450727 | s2cid = 22367595 }}{{cite book| vauthors = Lingeman CH |title=Carcinogenic Hormones|url=https://books.google.com/books?id=lOLnCAAAQBAJ&pg=PA149|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-81267-5|pages=149–}} Subsequent investigation found that 17α-hydroxyprogesterone derivatives included anagestone acetate, chlormadinone acetate, medroxyprogesterone acetate, and megestrol acetate produced similar mammary gland tumors, and that their ability to do so correlated directly with their progestogenic actions.{{cite book| vauthors = James VH, Pasqualini JR |title=Hormonal Steroids: Proceedings of the Fifth International Congress on Hormonal Steroids|url=https://books.google.com/books?id=p1AJAwAAQBAJ&pg=PA7|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4831-5895-2|pages=7–8}} In contrast, the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone, noretynodrel, and etynodiol diacetate, which are much less potent as progestogens, did not produce such effects at the dosages tested. Clinical development of ethynerone was discontinued, and many of the 17α-hydroxyprogesterone derivatives were withdrawn for the indication of hormonal contraception. Research later on revealed species differences between dogs and humans and established that there is no similar risk in humans.

File:Progestin-induced tumors in beagle dogs.pngs in beagle dogs treated by (left) MK-665 (ethynerone with mestranol) and (right) chloroethynylnorgestrel with mestranol for 4 years at a dosage of 1.05 mg/kg/day cyclically.]]{{Clear}}