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Chemical compound
Ethynerone
Routes of administration
Oral
(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
CAS Number
PubChem
CID
ChemSpider
UNII
CompTox Dashboard (
EPA )
Formula C 20 H 23 Cl O 2
Molar mass 330.85 g·mol−1 3D model (
JSmol )
CC12CCC3=C4CCC(=O)C=C4CCC3C1CCC2(C#CCl)O
InChI=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
Key:KEOBKPHJNAILCW-FUMNGEBKSA-N
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.
[1] Under the developmental code name MK-665 , it was studied in
combination with
mestranol as an
oral contraceptive .
[2] Development of the drug was discontinued due to concerns surrounding toxicity findings in dogs.
[2] It is a
chloroethynylated derivative of
norethisterone .
[3]
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.
[4]
[5]
[6] 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.
[6]
[7] 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.
[6] Clinical development of ethynerone was discontinued, and many of the 17α-hydroxyprogesterone derivatives were withdrawn for the indication of
hormonal contraception .
[6]
[7] Research later on revealed species differences between dogs and humans and established that there is no similar risk in humans.
[2]
Mammary tumors 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.
Synthesis
Ethynerone synthesis.
[8] J. Fried and T. S. Bry
U.S. patent 3,096,353 (1963,
Merck & Co. Inc).
See also
References
PR Tooltip Progesterone receptor
Agonists
Testosterone derivatives: Progestins:
6,6-Difluoronorethisterone
6,6-Difluoronorethisterone acetate
17α-Allyl-19-nortestosterone
Allylestrenol
Altrenogest
Chloroethynylnorgestrel
Cingestol
Danazol
Desogestrel
Dienogest
Ethinylandrostenediol
Ethisterone
Ethynerone
Etonogestrel
Etynodiol
Etynodiol diacetate
Gestodene
Gestrinone
Levonorgestrel
Levonorgestrel esters (e.g.,
levonorgestrel butanoate )
Lynestrenol
Lynestrenol phenylpropionate
Metynodiol
Metynodiol diacetate
Norelgestromin
Norethisterone (norethindrone)
Norethisterone esters (e.g.,
norethisterone acetate ,
norethisterone enanthate )
Noretynodrel
Norgesterone
Norgestimate
Norgestrel
Norgestrienone
Norvinisterone
Oxendolone
Quingestanol
Quingestanol acetate
Tibolone
Tigestol
Tosagestin ; Anabolic–androgenic steroids:
11β-Methyl-19-nortestosterone
11β-Methyl-19-nortestosterone dodecylcarbonate
19-Nor-5-androstenediol
19-Nor-5-androstenedione
19-Nordehydroepiandrosterone
Bolandiol
Bolandiol dipropionate
Bolandione
Dimethisterone
Dienedione
Dienolone
Dimethandrolone
Dimethandrolone buciclate
Dimethandrolone dodecylcarbonate
Dimethandrolone undecanoate
Dimethyldienolone
Dimethyltrienolone
Ethyldienolone
Ethylestrenol (ethylnandrol)
Methyldienolone
Metribolone (R-1881)
Methoxydienone (methoxygonadiene)
Mibolerone
Nandrolone
Nandrolone esters (e.g.,
nandrolone decanoate ,
nandrolone phenylpropionate )
Norethandrolone
Normethandrone (methylestrenolone, normethandrolone, normethisterone)
RU-2309
Tetrahydrogestrinone
Trenbolone (trienolone)
Trenbolone esters (e.g.,
trenbolone acetate ,
trenbolone enanthate )
Trendione
Trestolone
Trestolone acetate
Mixed (
SPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor (
PAQR Tooltip Progestin and adipoQ receptor )