Etynodiol diacetate

Source: Wikipedia, the free encyclopedia.

Etynodiol diacetate
Clinical data
Trade namesOvulen, Demulen, others
Other namesEthynodiol diacetate; Norethindrol diacetate; 3β-Hydroxynorethisterone 3β,17β-diacetate;[1] 17α-Ethynylestr-4-ene-3β,17β-diyl diacetate; CB-8080; SC-11800
License data
Pregnancy
category
  • Contraindicated
Progestin; Progestogen ester
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only[2][3]
  • In general: ℞ (Prescription only)
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
JSmol)
  • O=C(O[C@@H]4/C=C3\[C@@H]([C@H]2CC[C@]1([C@@H](CC[C@]1(C#C)OC(=O)C)[C@@H]2CC3)C)CC4)C
  • 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, or ethynodiol diacetate, sold under the brand name Ovulen among others, is a

birth control pills.[4][5][6] The medication is available only in combination with an estrogen.[7] It is taken by mouth.[8]

Etynodiol diacetate is a progestin, or a

hormonal activity.[11][12][13] The medication is a prodrug of norethisterone in the body, with etynodiol occurring as an intermediate.[9][10][14]

Etynodiol, a related compound, was discovered in 1954, and etynodiol diacetate was introduced for medical use in 1965.[15][16] The combination ethynodiol with mestranol (Ovulen) was approved for medical use in the United States in 1966.[17] The combination ethinylestradiol with ethynodiol (Demulen) was approved for medical use in the United States in 1970.[18]

In 2021, the combination with ethinylestradiol was the 276th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.[19][20]

Medical uses

Etynodiol diacetate is used in combination with an

combined oral contraceptives for women for the prevention of pregnancy.[8]

Side effects

See also:
Progestin § Side effects

Pharmacology

Norethisterone (3-ketoetynodiol), the active metabolite of etynodiol diacetate.

Etynodiol diacetate is virtually inactive in terms of

hydroxyl group to produce norethisterone.[10] In addition to its progestogenic activity, etynodiol diacetate has weak androgenic activity,[11][12] and, unlike most progestins but similarly to norethisterone and noretynodrel,[21] also has some estrogenic activity.[12][13]

The pharmacokinetics of etynodiol diacetate have been reviewed.[22]

Relative affinities (%) of norethisterone, metabolites, and prodrugs
Compound Typea PRTooltip Progesterone receptor ARTooltip Androgen receptor ERTooltip Estrogen receptor GRTooltip Glucocorticoid receptor MRTooltip Mineralocorticoid receptor SHBGTooltip 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 (%). Reference
CBGTooltip Corticosteroid-binding globulin. Footnotes: a = Active or inactive metabolite, prodrug
, or neither of norethisterone. Sources: See template.

Chemistry

See also: List of progestogens, Progestogen ester, and List of progestogen esters

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

hydroxyl group and acetate esters have been attached at the C3β and C17β positions.[5][6] Etynodiol diacetate is the 3β,17β-diacetate ester of etynodiol (17α-ethynylestr-4-ene-3β,17β-diol).[5][6]

Synthesis

Ethynodiol diacetate synthesis:[23] F. B. Colton, U.S. patent 2,843,609 (1958 to Searle). Prepn of the 3-acetate, 17-acetate, and diacetate: P. D. Klimstra, U.S. patent 3,176,013 (1965 to Searle); see also:[24]

Chemical syntheses of etynodiol diacetate have been published.[22]

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).[23]

History

Etynodiol was first synthesized in 1954, via reduction of norethisterone, and etynodiol diacetate was introduced for medical use in 1965.[15][16]

Society and culture

Generic names

Etynodiol diacetate is the

INNTooltip International Nonproprietary Name of its free alcohol form is etynodiol), while ethynodiol diacetate is its USANTooltip United States Adopted Name, BANTooltip British Approved Name, and JANTooltip Japanese Accepted Name.[5][6][7] It is also known by its former developmental code names CB-8080 and SC-11800.[5][6][7]

Brand names

Etynodiol diacetate is or has been marketed under brand names including Conova, Continuin, Demulen,[18][25] Femulen, Kelnor,[3][25] Lo-Malmorede,[26] Luteonorm, Luto-Metrodiol, Malmorede,[27] Metrodiol, Ovulen,[17][25] Soluna, Zovia,[2] and others.[5][6][7]

Availability

Etynodiol diacetate is marketed in only a few countries, including the United States, Canada, Argentina, and Oman.[7]

References

  1. ^
    PMID 14670641
    .
  2. ^ a b "Zovia 1/35- ethynodiol diacetate and ethinyl estradiol tablets kit". Archived from the original on 28 September 2022. Retrieved 20 January 2024.
  3. ^ a b "Kelnor 1/35- ethynodiol diacetate and ethinyl estradiol kit". Archived from the original on 29 March 2023. Retrieved 20 January 2024.
  4. ISBN 978-1-4612-2730-4
    .
  5. ^
    ISBN 978-1-4757-2085-3
    .
  6. ^
    ISBN 978-3-88763-075-1
    . Retrieved 30 May 2012.
  7. ^ a b c d e "Etynodiol". Drugs.com. Archived from the original on 5 February 2018. Retrieved 4 February 2018.
  8. ^
    ISBN 978-1-4832-7738-7
    .
  9. ^
    PMID 2256526
    .
  10. ^
    ISBN 978-92-832-1291-1
    .
  11. ^
    ISBN 978-1-4511-1805-6. Archived
    from the original on 11 January 2023. Retrieved 11 October 2016.
  12. ^
    ISBN 978-0-7817-1750-2
    . Retrieved 30 May 2012.
  13. ^
    ISBN 978-0-7817-7513-7
    . Retrieved 30 May 2012.
  14. ^
    S2CID 27018468
    .
  15. ^
    PMID 4947236
    .
  16. ^
    ISBN 978-0-8155-1856-3. Archived
    from the original on 20 January 2024. Retrieved 4 February 2018.
  17. ^ a b "Ovulen: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 8 December 2022. Retrieved 20 January 2024.
  18. ^ a b "Demulen: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 10 May 2021. Retrieved 20 January 2024.
  19. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  20. ^ "Ethinyl Estradiol; Ethynodiol - Drug Usage Statistics". ClinCalc. Archived from the original on 18 January 2024. Retrieved 14 January 2024.
  21. ISBN 978-3-642-73790-9
    .
  22. ^
    ISBN 978-3-642-99941-3
    .
  23. ^
    PMID 6064262
    .
  24. doi:10.1016/0040-4020(59)80066-1
    .
  25. ^ a b c "Estrogen and Progestin (Oral Contraceptives)". Archived from the original on 18 January 2024. Retrieved 20 January 2024.
  26. ^ "Lo-Malmorede". Archived from the original on 24 March 2021. Retrieved 20 January 2024.
  27. ^ "Malmorede". Archived from the original on 1 October 2023. Retrieved 20 January 2024.