Etynodiol

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Etynodiol
Etynodiol.svg
Clinical data
SynonymsEthynodiol; 3β-Hydroxynorethisterone; 17α-Ethynylestr-4-ene-3β,17β-diol
Drug classProgestin; Progestogen
ATC code
Identifiers
CAS Number
ChemSpider
ECHA InfoCard100.013.610 Edit this at Wikidata
Chemical and physical data
FormulaC20H28O2
Molar mass300.435 g/mol
3D model (JSmol)

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] While etynodiol is sometimes used as a synonym for etynodiol diacetate, it usually refers to etynodiol diacetate, not etynodiol.

Pharmacology[edit]

Etynodiol is a prodrug of norethisterone, and is converted immediately and completely into norethisterone.[4][5][6] In addition, etynodiol is an intermediate in the conversion of the prodrug lynestrenol into norethisterone.[7]

Relative affinities (%) of norethisterone, metabolites, and prodrugs

Compound PR AR ER GR MR SHBG CBG
Norethisterone 67–75 15 0 0–1 0–3 16 0
  5α-Dihydronorethisteronea 25 27 0 0 ? ? ?
  3α,5α-Tetrahydronorethisteronea 1 0 0–1 0 ? ? ?
  3α,5β-Tetrahydronorethisteronea ? 0 0 ? ? ? ?
  3β,5α-Tetrahydronorethisteronea 1 0 0–8 0 ? ? ?
  Ethinylestradiol 15–25 1–3 112 1–3 0 0.18 0
Norethisterone acetateb 20 5 1 0 0 ? ?
Norethisterone enanthateb ? ? ? ? ? ? ?
Noretynodrelb 6 0 2 0 0 0 0
Etynodiolb 1 0 11–18 0 ? ? ?
Etynodiol diacetateb 1 0 0 0 0 ? ?
Lynestrenolb 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. Foonotes: a = Metabolite of norethisterone. b = Prodrug of norethisterone and/or other active metabolites. Sources: [8][9][10][11][12]

Chemistry[edit]

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[edit]

Ethynodiol diacetate synthesis:[13] 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:[14]

Society and culture[edit]

Generic names[edit]

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

References[edit]

  1. ^ a b c F.. Macdonald (1997). Dictionary of Pharmacological Agents. CRC Press. p. 1454. ISBN 978-0-412-46630-4. Retrieved 12 May 2012.
  2. ^ a b c Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 422. ISBN 978-3-88763-075-1. Retrieved 30 May 2012.
  3. ^ Schindler, Adolf E; Campagnoli, Carlo; Druckmann, René; Huber, Johannes; Pasqualini, Jorge R; Schweppe, Karl W; Thijssen, Jos H.H (2003). "Classification and pharmacology of progestins". Maturitas. 46: 7–16. doi:10.1016/j.maturitas.2003.09.014. ISSN 0378-5122. PMID 14670641.
  4. ^ Donna Shoupe; Florence P. Haseltine (6 December 2012). Contraception. Springer Science & Business Media. pp. 21–. ISBN 978-1-4612-2730-4.
  5. ^ Bhattacharya (1 January 2003). Pharmacology, 2/e. Elsevier India. pp. 378–. ISBN 978-81-8147-009-6.
  6. ^ 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.
  7. ^ Hammerstein J (1990). "Prodrugs: advantage or disadvantage?". Am. J. Obstet. Gynecol. 163 (6 Pt 2): 2198–203. PMID 2256526.
  8. ^ Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947.
  9. ^ Kuhl H (September 1990). "Pharmacokinetics of oestrogens and progestogens". Maturitas. 12 (3): 171–97. doi:10.1016/0378-5122(90)90003-O. PMID 2170822.
  10. ^ Philibert D, Bouchoux F, Degryse M, Lecaque D, Petit F, Gaillard M (October 1999). "The pharmacological profile of a novel norpregnance progestin (trimegestone)". Gynecol. Endocrinol. 13 (5): 316–26. doi:10.3109/09513599909167574. PMID 10599548.
  11. ^ Raynaud, J.P.; Ojasoo, T.; Bouton, M.M.; Philibert, D. (1979). "Receptor Binding as a Tool in the Development of New Bioactive Steroids": 169–214. doi:10.1016/B978-0-12-060308-4.50010-X.
  12. ^ Pugeat MM, Dunn JF, Nisula BC (July 1981). "Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma". J. Clin. Endocrinol. Metab. 53 (1): 69–75. doi:10.1210/jcem-53-1-69. PMID 7195405.
  13. ^ 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.
  14. ^ 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.