Etynodiol

Etynodiol
Clinical data
Other names	Ethynodiol; 3β-Hydroxynorethisterone; 17α-Ethynylestr-4-ene-3β,17β-diol
Drug class	Progestin; Progestogen
ATC code	G03DC06 (WHO) ;
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	1231-93-2;
ChemSpider	14017;
CompTox Dashboard (EPA)	DTXSID1023025 ;
ECHA InfoCard	100.013.610
Chemical and physical data
Formula	C20H28O2
Molar mass	300.435 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	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;

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.

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
Compound	Type^a	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 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

F.. Macdonald (1997). Dictionary of Pharmacological Agents. CRC Press. p. 1454. ISBN 978-0-412-46630-4. Retrieved 12 May 2012.
Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 422. ISBN 978-3-88763-075-1. Retrieved 30 May 2012.
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.
Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 478. ISBN 9783527607495.
Donna Shoupe; Florence P. Haseltine (6 December 2012). Contraception. Springer Science & Business Media. pp. 21–. ISBN 978-1-4612-2730-4.
Bhattacharya (1 January 2003). Pharmacology, 2/e. Elsevier India. pp. 378–. ISBN 978-81-8147-009-6.
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.
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.
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.
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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[Macdonald1997-1] F.. Macdonald (1997). Dictionary of Pharmacological Agents. CRC Press. p. 1454. ISBN 978-0-412-46630-4. Retrieved 12 May 2012.

[IndexNominum2000-2] Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 422. ISBN 978-3-88763-075-1. Retrieved 30 May 2012.

[SchindlerCampagnoli2003-3] 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.

[Fis2006-4] Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 478. ISBN 9783527607495.

[ShoupeHaseltine2012-5] Donna Shoupe; Florence P. Haseltine (6 December 2012). Contraception. Springer Science & Business Media. pp. 21–. ISBN 978-1-4612-2730-4.

[Bhattacharya2003-6] Bhattacharya (1 January 2003). Pharmacology, 2/e. Elsevier India. pp. 378–. ISBN 978-81-8147-009-6.

[HumansOrganization2007-7] 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.

[pmid2256526-8] 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.

[9] 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.

[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.