Etynodiol

Etynodiol, or ethynodiol, is a steroidal progestin of the 19-nortestosterone group which was never marketed.[1][2][3] A diacylated derivative, etynodiol diacetate, is used as a hormonal contraceptive.[1][2] Etynodiol is sometimes used as a synonym for etynodiol diacetate.

Etynodiol
Clinical data
Other namesEthynodiol; 3β-Hydroxynorethisterone; 17α-Ethynylestr-4-ene-3β,17β-diol
Drug classProgestin; Progestogen
ATC code
Identifiers
IUPAC name
  • (3S,8R,9S,10R,13S,14S,17R)-17-ethynyl-13-methyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol
CAS Number
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.013.610
Chemical and physical data
FormulaC20H28O2
Molar mass300.442 g·mol−1
3D model (JSmol)
SMILES
  • O[C@@H]4/C=C3\[C@@H]([C@H]2CC[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)C)CC4
InChI
  • InChI=1S/C20H28O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,12,14-18,21-22H,4-11H2,2H3/t14-,15-,16+,17+,18-,19-,20-/m0/s1
  • Key:JYILPERKVHXLNF-QMNUTNMBSA-N

It was patented in 1955.[4]

Pharmacology

Etynodiol is a prodrug of norethisterone, and is converted immediately and completely into norethisterone.[5][6][7] Etynodiol is an intermediate in the conversion of the prodrug lynestrenol into norethisterone.[8]

Relative affinities (%) of norethisterone, metabolites, and prodrugs
CompoundTypeaPRARERGRMRSHBGCBG
Norethisterone67–751500–10–3160
5α-DihydronorethisteroneMetabolite252700 ? ? ?
3α,5α-TetrahydronorethisteroneMetabolite100–10 ? ? ?
3α,5β-TetrahydronorethisteroneMetabolite ?00 ? ? ? ?
3β,5α-TetrahydronorethisteroneMetabolite100–80 ? ? ?
EthinylestradiolMetabolite15–251–31121–300.180
Norethisterone acetateProdrug205100 ? ?
Norethisterone enanthateProdrug ? ? ? ? ? ? ?
NoretynodrelProdrug6020000
EtynodiolProdrug1011–180 ? ? ?
Etynodiol diacetateProdrug10000 ? ?
LynestrenolProdrug11300 ? ?
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 is a 19-nortestosterone derivative. Structurally, it is almost identical to norethisterone and lynestrenol, differing only in its C3 substituent. Whereas norethisterone has a ketone at C3 and lynestrenol has no substituent at C3, etynodiol has a hydroxyl group at the position.

Synthesis

Ethynodiol diacetate synthesis:[9] 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:[10]

Society and culture

Generic names

Etynodiol is the generic name of the drug and its INN, while ethynodiol is its BAN.[1][2]

References

  1. Macdonald F (1997). Dictionary of Pharmacological Agents. CRC Press. p. 1454. ISBN 978-0-412-46630-4. Retrieved 12 May 2012.
  2. Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 422. ISBN 978-3-88763-075-1. Retrieved 30 May 2012.
  3. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (December 2003). "Classification and pharmacology of progestins". Maturitas. 46 Suppl 1: S7–S16. doi:10.1016/j.maturitas.2003.09.014. PMID 14670641.
  4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 478. ISBN 9783527607495.
  5. Shoupe D, Haseltine FP (6 December 2012). Contraception. Springer Science & Business Media. pp. 21–. ISBN 978-1-4612-2730-4.
  6. Bhattacharya (1 January 2003). Pharmacology, 2/e. Elsevier India. pp. 378–. ISBN 978-81-8147-009-6.
  7. 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.
  8. Hammerstein J (December 1990). "Prodrugs: advantage or disadvantage?". American Journal of Obstetrics and Gynecology. 163 (6 Pt 2): 2198–203. doi:10.1016/0002-9378(90)90561-K. PMID 2256526.
  9. Klimstra PD, Colton FB (October 1967). "The synthesis of 3beta-hydroxyestr-4-en-17-one and 3beta-hydroxyandrost-4-en-17-one". Steroids. 10 (4): 411–24. doi:10.1016/0039-128X(67)90119-5. PMID 6064262.
  10. 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.
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