Etynodiol diacetate
![]() | |
Clinical data | |
---|---|
Trade names | Continuin, Demulen, Femulen, Luteonorm, Luto-Metrodiol, Metrodiol, Ovulen, others |
Other names | Ethynodiol diacetate; Norethindrol diacetate; 3β-Hydroxynorethisterone 3β,17β-diacetate;[1] 17α-Ethynylestr-4-ene-3β,17β-diyl diacetate; CB-8080; SC-11800 |
Routes of administration | By mouth |
Drug class | Progestogen; Progestin; Progestogen ester |
ATC code | |
Legal status | |
Legal status |
|
Identifiers | |
IUPAC name
| |
CAS Number |
|
PubChem CID | |
PubChem SID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.005.496 ![]() |
Chemical and physical data | |
Formula | C24H32O4 |
Molar mass | 384.516 g·mol−1 |
3D model (JSmol) | |
SMILES
| |
InChI
|
Etynodiol diacetate, or ethynodiol diacetate, sold under the brand names Demulen and Femulen among others, is a progestin medication which is used in birth control pills.[2][3][4] The medication is available only in combination with an estrogen.[5] It is taken by mouth.[6]
Etynodiol diacetate is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[7][8] It has weak androgenic and estrogenic activity and no other important hormonal activity.[9][10][11] The medication is a prodrug of norethisterone in the body, with etynodiol occurring as an intermediate.[7][8][12]
Etynodiol, a related compound, was discovered in 1954, and etynodiol diacetate was introduced for medical use in 1965.[13][14] The medication remains available today only in the United States, Canada, and a few other countries.[4][5]
Medical uses[]
Etynodiol diacetate is used in combination with an estrogen such as ethinylestradiol or mestranol in combined oral contraceptives for women.[6]
Side effects[]
Pharmacology[]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/d/d4/Norethisterone.svg/225px-Norethisterone.svg.png)
Etynodiol diacetate is virtually inactive in terms of affinity for the progesterone and androgen receptors and acts as a rapidly converted prodrug of norethisterone, with etynodiol occurring as an intermediate.[7][8][12] Upon oral administration and during first-pass metabolism in the liver, etynodiol diacetate is rapidly converted by esterases into etynodiol,[12] which is followed by oxygenation of the C3 hydroxyl group to produce norethisterone.[8] In addition to its progestogenic activity, etynodiol diacetate has weak androgenic activity,[9][10] and, unlike most progestins but similarly to norethisterone and noretynodrel,[15] also has some estrogenic activity.[10][11]
The pharmacokinetics of etynodiol diacetate have been reviewed.[16]
Compound | Typea | PR | AR | ER | GR | MR | SHBG | CBG |
---|---|---|---|---|---|---|---|---|
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 (%). Reference ligands (100%) were promegestone for the PR, metribolone for the AR, estradiol for the ER, dexamethasone for the GR, aldosterone for the MR, dihydrotestosterone for SHBG, and cortisol for CBG. Footnotes: a = Active or inactive metabolite, prodrug, or neither of norethisterone. Sources: See template. |
Chemistry[]
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 a synthetic estrane steroid and a derivative of testosterone.[1][3][4] It is specifically a derivative of 19-nortestosterone and 17α-ethynyltestosterone, or of norethisterone (17α-ethynyl-19-nortestosterone), in which the C3 ketone group has been dehydrogenated into a C3β hydroxyl group and acetate esters have been attached at the C3β and C17β positions.[3][4] Etynodiol diacetate is the 3β,17β-diacetate ester of etynodiol (17α-ethynylestr-4-ene-3β,17β-diol).[3][4]
Synthesis[]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/2/29/Ethynodiol_diacetate_synthesis.svg/700px-Ethynodiol_diacetate_synthesis.svg.png)
Chemical syntheses of etynodiol diacetate have been published.[16]
Reduction of norethisterone (1) affords the 3,17-diol. The 3β-hydroxy compound is the desired product; since reactions at C3 do not show nearly the stereoselectivity 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).[17]
History[]
Etynodiol was first synthesized in 1954, via reduction of norethisterone, and etynodiol diacetate was introduced for medical use in 1965.[13][14]
Society and culture[]
Generic names[]
Etynodiol diacetate is the generic name of the drug (the INN of its free alcohol form is etynodiol), while ethynodiol diacetate is its USAN, BAN, and JAN.[3][4][5] It is also known by its former developmental code names CB-8080 and SC-11800.[3][4][5]
Brand names[]
Etynodiol diacetate is or has been marketed under brand names including Conova, Continuin, Demulen, Femulen, Kelnor, Luteonorm, Luto-Metrodiol, Metrodiol, Ovulen, Soluna, Zovia, and others.[3][4][5]
Availability[]
Etynodiol diacetate remains marketed in only a few countries, including the United States, Canada, Argentina, and Oman.[5]
References[]
- ^ a b Schindler, Adolf E; Campagnoli, Carlo; Druckmann, René; Huber, Johannes; Pasqualini, Jorge R; Schweppe, Karl W; Thijssen, Jos HH (2003). "Classification and pharmacology of progestins". Maturitas. 46: 7–16. doi:10.1016/j.maturitas.2003.09.014. ISSN 0378-5122. PMID 14670641.
- ^ Donna Shoupe; Florence P. Haseltine (6 December 2012). Contraception. Springer Science & Business Media. pp. 21–. ISBN 978-1-4612-2730-4.
- ^ a b c d e f g J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 522–. ISBN 978-1-4757-2085-3.
- ^ a b c d e f g h Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 422. ISBN 978-3-88763-075-1. Retrieved 30 May 2012.
- ^ a b c d e f https://www.drugs.com/international/etynodiol.html
- ^ a b Robert W. Blum (22 October 2013). Adolescent Health Care: Clinical Issues. Elsevier Science. pp. 216–. ISBN 978-1-4832-7738-7.
- ^ a b c Hammerstein J (1990). "Prodrugs: advantage or disadvantage?". Am. J. Obstet. Gynecol. 163 (6 Pt 2): 2198–203. doi:10.1016/0002-9378(90)90561-K. PMID 2256526.
- ^ a b c d IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 146–. ISBN 978-92-832-1291-1.
- ^ a b Armen H. Tashjian; Ehrin J. Armstrong (21 July 2011). Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Lippincott Williams & Wilkins. pp. 523–. ISBN 978-1-4511-1805-6.
- ^ a b c Kenneth L. Becker (24 April 2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. p. 1004. ISBN 978-0-7817-1750-2. Retrieved 30 May 2012.
- ^ a b Allan H. Goroll; Albert G. Mulley (27 January 2009). Primary Care Medicine: Office Evaluation and Management of the Adult Patient. Lippincott Williams & Wilkins. p. 876. ISBN 978-0-7817-7513-7. Retrieved 30 May 2012.
- ^ a b c Stanczyk FZ (2002). "Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception". Rev Endocr Metab Disord. 3 (3): 211–24. doi:10.1023/A:1020072325818. PMID 12215716. S2CID 27018468.
- ^ a b Progress in Medicinal Chemistry. Butterworth-Heinemann. 21 September 2011. pp. 180–. ISBN 978-0-08-086256-9.
- ^ a b William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1516–. ISBN 978-0-8155-1856-3.
- ^ Benno Clemens Runnebaum; Thomas Rabe; Ludwig Kiesel (6 December 2012). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 36–. ISBN 978-3-642-73790-9.
- ^ a b Die Gestagene. Springer-Verlag. 27 November 2013. pp. 14–15, 286. ISBN 978-3-642-99941-3.
- ^ a b Klimstra, P.; Colton, F. (1967). "The synthesis of 3β-hydroxyestr-4-en-17-one and 3β-hydroxiandrost-4-en-17-one". Steroids. 10 (4): 411–424. doi:10.1016/0039-128X(67)90119-5. PMID 6064262.
- ^ Sondheimer, F.; Klibansky, Y. (1959). "Synthesis of 3β-hydroxy analogues of steroidal hormones, a biologically active class of compounds". Tetrahedron. 5: 15–26. doi:10.1016/0040-4020(59)80066-1.
- Acetate esters
- Alkyne derivatives
- Androgens and anabolic steroids
- Merck brands
- Estranes
- Prodrugs
- Progestogen esters
- Progestogens
- Synthetic estrogens