Chemical compound
Pharmaceutical compound
Etynodiol diacetate Clinical data Trade names Ovulen, Demulen, others Other names Ethynodiol diacetate; Norethindrol diacetate; 3β-Hydroxynorethisterone 3β,17β-diacetate;[ 1] License data Pregnancy Routes of By mouth Drug class Progestogen ;Progestin ;Progestogen ester ATC code Legal status Legal status Identifiers [(3S ,8R ,9S ,10R ,13S ,14S ,17R )-17-acetyloxy-17-ethynyl-13-methyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1H -cyclopenta[a ]phenanthren-3-yl] acetate
CAS Number PubChem CID DrugBank ChemSpider UNII KEGG ChEBI ChEMBL CompTox Dashboard (EPA) ECHA InfoCard 100.005.496 Chemical and physical data Formula C 24 H 32 O 4 Molar mass −1 3D model (JSmol ) InChI=1S/C24H32O4/c1-5-24(28-16(3)26)13-11-22-21-8-6-17-14-18(27-15(2)25)7-9-19(17)20(21)10-12-23(22,24)4/h1,14,18-22H,6-13H2,2-4H3/t18-,19-,20+,21+,22-,23-,24-/m0/s1
Key:ONKUMRGIYFNPJW-KIEAKMPYSA-N
Etynodiol diacetate , orethynodiol diacetate , sold under the brand nameOvulen among others, is aprogestin medication which is used inbirth control pills .[ 4] [ 5] [ 6] estrogen .[ 7] by mouth .[ 8]
Etynodiol diacetate is a progestin, or asynthetic progestogen , and hence is anagonist of theprogesterone receptor , thebiological target of progestogens likeprogesterone .[ 9] [ 10] androgenic andestrogenic activity and no other importanthormonal activity.[ 11] [ 12] [ 13] prodrug ofnorethisterone in the body, withetynodiol occurring as anintermediate .[ 9] [ 10] [ 14]
Etynodiol, a related compound, was discovered in 1954, and etynodiol diacetate was introduced for medical use in 1965.[ 15] [ 16] [ 17] [ 18]
In 2021, the combination withethinylestradiol was the 276th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.[ 19] [ 20]
Etynodiol diacetate is used in combination with anestrogen such as ethinylestradiol ormestranol incombined oral contraceptives for women for the prevention of pregnancy.[ 8]
Norethisterone (3-ketoetynodiol), theactive metabolite of etynodiol diacetate.Etynodiol diacetate is virtually inactive in terms ofaffinity for theprogesterone andandrogen receptors and acts as a rapidly convertedprodrug ofnorethisterone , withetynodiol occurring as anintermediate .[ 9] [ 10] [ 14] oral administration and duringfirst-pass metabolism in theliver , etynodiol diacetate is rapidly converted byesterases into etynodiol,[ 14] oxygenation of the C3hydroxyl group to produce norethisterone.[ 10] androgenic activity,[ 11] [ 12] noretynodrel ,[ 21] estrogenic activity.[ 12] [ 13]
Thepharmacokinetics of etynodiol diacetate have been reviewed.[ 22]
Relative affinities (%) ofnorethisterone , metabolites, and prodrugs Compound Typea PR Tooltip Progesterone receptor AR Tooltip Androgen receptor ER Tooltip Estrogen receptor GR Tooltip Glucocorticoid receptor MR Tooltip Mineralocorticoid receptor SHBG Tooltip Sex hormone-binding globulin CBG Tooltip Corticosteroid binding globulin Norethisterone – 67–75 15 0 0–1 0–3 16 0 5α-Dihydronorethisterone Metabolite 25 27 0 0 ? ? ? 3α,5α-Tetrahydronorethisterone Metabolite 1 0 0–1 0 ? ? ? 3α,5β-Tetrahydronorethisterone Metabolite ? 0 0 ? ? ? ? 3β,5α-Tetrahydronorethisterone Metabolite 1 0 0–8 0 ? ? ? Ethinylestradiol Metabolite 15–25 1–3 112 1–3 0 0.18 0 Norethisterone acetate Prodrug 20 5 1 0 0 ? ? Norethisterone enanthate Prodrug ? ? ? ? ? ? ? Noretynodrel Prodrug 6 0 2 0 0 0 0 Etynodiol Prodrug 1 0 11–18 0 ? ? ? Etynodiol diacetate Prodrug 1 0 0 0 0 ? ? Lynestrenol Prodrug 1 1 3 0 0 ? ? Notes: Values are percentages (%). Referenceligands (100%) werepromegestone for thePR Tooltip progesterone receptor ,metribolone for theAR Tooltip androgen receptor ,estradiol for theER Tooltip estrogen receptor ,dexamethasone for theGR Tooltip glucocorticoid receptor ,aldosterone for theMR Tooltip mineralocorticoid receptor ,dihydrotestosterone forSHBG Tooltip sex hormone-binding globulin , andcortisol forCBG Tooltip Corticosteroid-binding globulin .Footnotes: a =Active or inactivemetabolite ,prodrug , or neither of norethisterone.Sources: See template.
Etynodiol diacetate, also known as 3β-hydroxy-17α-ethynyl-19-nortestosterone 3β,17β-diaceate, 3β-hydroxynorethisterone 3β,17β-diacetate, or 17α-ethynylestr-4-ene-3β,17β-diol 3β,17β-diacetate, is asynthetic estrane steroid and aderivative oftestosterone .[ 1] [ 5] [ 6] 19-nortestosterone and17α-ethynyltestosterone , or ofnorethisterone (17α-ethynyl-19-nortestosterone), in which the C3ketone group has beendehydrogenated into a C3βhydroxyl group andacetate esters have been attached at the C3β and C17β positions.[ 5] [ 6] diacetate ester ofetynodiol (17α-ethynylestr-4-ene-3β,17β-diol).[ 5] [ 6]
Ethynodiol diacetate synthesis:[ 23] U.S. patent 2,843,609 Searle ). Prepn of the 3-acetate, 17-acetate, and diacetate: P. D. Klimstra,U.S. patent 3,176,013 [ 24]
Chemical syntheses of etynodiol diacetate have been published.[ 22]
Reduction ofnorethisterone (1 ) affords the 3,17-diol. The 3β-hydroxy compound is the desired product; since reactions at C3 do not show nearly thestereoselectivity as those at C17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium tri-tert-butoxyaluminum hydride. Acetylation of the 3β,17β-diol affords etynodiol diacetate (3 ).[ 23]
Etynodiol was firstsynthesized in 1954, viareduction ofnorethisterone , and etynodiol diacetate was introduced for medical use in 1965.[ 15] [ 16]
Society and culture [ edit ] Etynodiol diacetate is thegeneric name of the drug (theINN Tooltip International Nonproprietary Name of its free alcohol form is etynodiol), while ethynodiol diacetate is itsUSAN Tooltip United States Adopted Name ,BAN Tooltip British Approved Name , andJAN Tooltip Japanese Accepted Name .[ 5] [ 6] [ 7] [ 5] [ 6] [ 7]
Etynodiol diacetate is or has been marketed under brand names including Conova, Continuin, Demulen,[ 18] [ 25] [ 3] [ 25] [ 26] [ 27] [ 17] [ 25] [ 2] [ 5] [ 6] [ 7]
Etynodiol diacetate is marketed in only a few countries, including the United States, Canada, Argentina, and Oman.[ 7]
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Androgens AAS Tooltip anabolic–androgenic steroid )
Antiandrogens
AR Tooltip Androgen receptor antagonists Steroidogenesis
Antigonadotropins D2 receptor antagonists (prolactin releasers ) (e.g.,domperidone ,metoclopramide ,risperidone ,haloperidol ,chlorpromazine ,sulpiride )Estrogens (e.g.,bifluranol ,diethylstilbestrol ,estradiol ,estradiol esters ,ethinylestradiol ,ethinylestradiol sulfonate ,paroxypropione )GnRH agonists (e.g.,leuprorelin )GnRH antagonists (e.g.,cetrorelix )Progestogens (incl.,chlormadinone acetate ,cyproterone acetate ,hydroxyprogesterone caproate ,gestonorone caproate ,medroxyprogesterone acetate ,megestrol acetate )Others
Estrogens
ER Tooltip Estrogen receptor agonistsSteroidal: Alfatradiol Certainandrogens /anabolic steroids (e.g.,testosterone ,testosterone esters ,methyltestosterone ,metandienone ,nandrolone esters ) (via estrogenic metabolites) Certainprogestins (e.g.,norethisterone ,noretynodrel ,etynodiol diacetate ,tibolone ) Clomestrone Cloxestradiol acetate Conjugated estriol Conjugated estrogens Epiestriol Epimestrol Esterified estrogens Estetrol † Estradiol Estradiol esters (e.g.,estradiol acetate ,estradiol benzoate ,estradiol cypionate ,estradiol enanthate ,estradiol undecylate ,estradiol valerate ,polyestradiol phosphate ,estradiol ester mixtures (Climacteron ))Estramustine phosphate Estriol Estriol esters (e.g.,estriol succinate ,polyestriol phosphate )Estrogenic substances Estrone Estrone esters Ethinylestradiol # Hydroxyestrone diacetate Mestranol Methylestradiol Moxestrol Nilestriol Prasterone (dehydroepiandrosterone; DHEA) Promestriene Quinestradol Quinestrol Progonadotropins
Antiestrogens
ER Tooltip Estrogen receptor antagonistsSERMs Tooltip selective estrogen receptor modulators /SERDs Tooltip selective estrogen receptor downregulators )Aromatase inhibitors Antigonadotropins Androgens /anabolic steroids (e.g.,testosterone ,testosterone esters ,nandrolone esters ,oxandrolone ,fluoxymesterone )D2 receptor antagonists (prolactin releasers) (e.g.,domperidone ,metoclopramide ,risperidone ,haloperidol ,chlorpromazine ,sulpiride )GnRH agonists (e.g.,leuprorelin ,goserelin )GnRH antagonists (e.g.,cetrorelix ,elagolix )Progestogens (e.g.,chlormadinone acetate ,cyproterone acetate ,gestonorone caproate ,hydroxyprogesterone caproate ,medroxyprogesterone acetate ,megestrol acetate )Others
ER Tooltip Estrogen receptor
Agonists Steroidal: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol 3α-Androstanediol 3α,5α-Dihydrolevonorgestrel 3β,5α-Dihydrolevonorgestrel 3α-Hydroxytibolone 3β-Hydroxytibolone 3β-Androstanediol 4-Androstenediol 4-Androstenedione 4-Fluoroestradiol 4-Hydroxyestradiol 4-Hydroxyestrone 4-Methoxyestradiol 4-Methoxyestrone 5-Androstenediol 7-Oxo-DHEA 7α-Hydroxy-DHEA 7α-Methylestradiol 7β-Hydroxyepiandrosterone 8,9-Dehydroestradiol 8,9-Dehydroestrone 8β-VE2 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) 11β-Chloromethylestradiol 11β-Methoxyestradiol 15α-Hydroxyestradiol 16-Ketoestradiol 16-Ketoestrone 16α-Fluoroestradiol 16α-Hydroxy-DHEA 16α-Hydroxyestrone 16α-Iodoestradiol 16α-LE2 16β-Hydroxyestrone 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol) 17α-Estradiol (alfatradiol )17α-Dihydroequilenin 17α-Dihydroequilin 17α-Epiestriol (16α-hydroxy-17α-estradiol) 17α-Ethynyl-3α-androstanediol 17α-Ethynyl-3β-androstanediol 17β-Dihydroequilenin 17β-Dihydroequilin 17β-Methyl-17α-dihydroequilenin Abiraterone Abiraterone acetate Alestramustine Almestrone Anabolic steroids (e.g.,testosterone andesters ,methyltestosterone ,metandienone (methandrostenolone) ,nandrolone andesters , many others; via estrogenic metabolites)Atrimustine Bolandiol Bolandiol dipropionate Butolame Clomestrone Cloxestradiol Conjugated estriol Conjugated estrogens Cyclodiol Cyclotriol DHEA DHEA-S ent -EstradiolEpiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol) Epimestrol Equilenin Equilin ERA-63 (ORG-37663) Esterified estrogens Estetrol Estradiol Estramustine Estramustine phosphate Estrapronicate Estrazinol Estriol Estrofurate Estrogenic substances Estromustine Estrone Etamestrol (eptamestrol) Ethinylandrostenediol Ethinylestradiol Ethinylestriol Ethylestradiol Etynodiol Etynodiol diacetate Hexolame Hippulin Hydroxyestrone diacetate Lynestrenol Lynestrenol phenylpropionate Mestranol Methylestradiol Moxestrol Mytatrienediol Nilestriol Norethisterone Noretynodrel Orestrate Pentolame Prodiame Prolame Promestriene RU-16117 Quinestradol Quinestrol Tibolone Xenoestrogens: Anise -related (e.g.,anethole ,anol ,dianethole ,dianol ,photoanethole )Chalconoids (e.g.,isoliquiritigenin ,phloretin ,phlorizin (phloridzin) ,wedelolactone )Coumestans (e.g.,coumestrol ,psoralidin )Flavonoids (incl.7,8-DHF ,8-prenylnaringenin ,apigenin ,baicalein ,baicalin ,biochanin A ,calycosin ,catechin ,daidzein ,daidzin ,ECG ,EGCG ,epicatechin ,equol ,formononetin ,glabrene ,glabridin ,genistein ,genistin ,glycitein ,kaempferol ,liquiritigenin ,mirificin ,myricetin ,naringenin ,penduletin ,pinocembrin ,prunetin ,puerarin ,quercetin ,tectoridin ,tectorigenin )Lavender oil Lignans (e.g.,enterodiol ,enterolactone ,nyasol (cis -hinokiresinol) )Metalloestrogens (e.g.,cadmium )Pesticides (e.g.,alternariol ,dieldrin ,endosulfan ,fenarimol ,HPTE ,methiocarb ,methoxychlor ,triclocarban ,triclosan )Phytosteroids (e.g.,digitoxin (digitalis ),diosgenin ,guggulsterone )Phytosterols (e.g.,β-sitosterol ,campesterol ,stigmasterol )Resorcylic acid lactones (e.g.,zearalanone ,α-zearalenol ,β-zearalenol ,zearalenone ,zeranol (α-zearalanol) ,taleranol (teranol, β-zearalanol) )Steroid -like (e.g.,deoxymiroestrol ,miroestrol )Stilbenoids (e.g.,resveratrol ,rhaponticin )Synthetic xenoestrogens (e.g.,alkylphenols ,bisphenols (e.g.,BPA ,BPF ,BPS ),DDT ,parabens ,PBBs ,PHBA ,phthalates ,PCBs )Others (e.g.,agnuside ,rotundifuran ) MixedSERMs Tooltip Selective estrogen receptor modulators ) Antagonists Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
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 MixedSPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor PAQR Tooltip Progestin and adipoQ receptor )
