chloroethynylnorgestrel

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc}}{{Drugbox

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| IUPAC_name = (1S,2R,10R,11S,14S,15S)-14-(2-chloroethynyl)-15-ethyl-14-hydroxytetracyclo[8.7.0.0^2,7.0^11,15]heptadec-6-en-5-one

| image = Chloroethynyl norgestrel.svg

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| CAS_number = 2415-28-3

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

| UNII = Q2YY22B0SV

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| PubChem = 22790422

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| ChemSpiderID = 18503812

| C=21 | H=27 | Cl=1 | O=2

| smiles = CC[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#CCl)O)CCC4=CC(=O)CC[C@H]34

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| StdInChI = 1S/C21H27ClO2/c1-2-20-9-7-17-16-6-4-15(23)13-14(16)3-5-18(17)19(20)8-10-21(20,24)11-12-22/h13,16-19,24H,2-10H2,1H3/t16-,17+,18+,19-,20-,21+/m0/s1

| StdInChIKey_Ref =

| StdInChIKey = MISOWVVRHHLGIK-ZUHHCLADSA-N

| synonyms = Chloroethynyl norgestrel; WY-4355; 17α-Chloroethynyl-13β-ethylgon-4-en-17β-ol-3-one; 17α-Chloroethynyl-18-methylestr-4-en-17β-ol-3-one; 17α-Chloroethynyl-18-methyl-19-nortestosterone

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Chloroethynylnorgestrel (developmental code name WY-4355) is a steroidal progestin of the 19-nortestosterone group related to norgestrel that was investigated as an oral contraceptive in the 1970s but was never marketed.{{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–}}{{cite journal | vauthors = Tavassoli FA, Casey HW, Norris HJ | title = The morphologic effects of synthetic reproductive steroids on the mammary gland of rhesus monkeys. Mestranol, ethynerone, mestranol-ethynerone, chloroethynyl norgestrel-mestranol, and anagestone acetate-mestranol combinations | journal = The American Journal of Pathology | volume = 131 | issue = 2 | pages = 213–234 | date = May 1988 | pmid = 3358452 | pmc = 1880606 }}{{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 = 179–193 | date = September 1977 | pmid = 411941 | doi = 10.1080/15287397709529557 | bibcode = 1977JTEH....3..179G }}{{cite book | vauthors = Casey HW, Giles RC, Kwapien RP | chapter = Mammary Neoplasia in Animals: Pathologic Aspects and the Effects of Contraceptive Steroids | title = Carcinogenic Hormones | journal = Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer | volume = 66 | pages = 129–160 | year = 1979 | pmid = 107546 | doi = 10.1007/978-3-642-81267-5_4 | isbn = 978-3-540-08995-7 }}

In combination with mestranol, similarly to ethynerone and anagestone acetate (and certain other progestogens, including progesterone and several other 17α-hydroxyprogesterone derivatives), chloroethynylnorgestrel was found to produce striking mammary tumors in beagle dogs after administration at very high dosages (10- to 25-fold human clinical dosages) for prolonged periods of time. This resulted in the discontinuation of its development, along with that of ethynerone and anagestone acetate, as well as the removal of several progestins, including chlormadinone acetate, medroxyprogesterone acetate, and megestrol acetate, from various markets as contraceptives (although medroxyprogesterone acetate has since been reintroduced).{{cite book | vauthors = Streffer C, Bolt H, Follesdal D, Hall P, Hengstler JG, Jacob P, Oughton D, Prieß K, Rehbinder E, Swaton E | chapter = Interspecies Extrapolation |title=Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation | chapter-url=https://books.google.com/books?id=eiL4CAAAQBAJ&pg=PA135 |date=11 November 2013 |publisher=Springer Science & Business Media |isbn=978-3-662-08422-9 |pages=135–}} Subsequent research revealed that the risk is species-dependent and unique to canines and that there is no similar risk for humans.{{cite book | vauthors = Neumann F, Düsterberg B, Laurent H | chapter = Development of progestogens. | veditors = Runnebaum B, Rabe T, Kiesel L |title=Female Contraception: Update and Trends | chapter-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–}}

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}}