Anagestone acetate

Anagestone acetate
Clinical data
Trade namesAnatropin, Neo-Novum
Other namesORF-1658; Anapregnone acetate; 3-Deketo-6α-methyl-17α-acetoxyprogesterone; 6α-Methyl-17α-hydroxypregn-4-en-20-one acetate
Routes of
administration		By mouth
Drug classProgestogen; Progestin; Progestogen ester
Identifiers
IUPAC name
  • [(6S,8R,9S,10R,13S,14S,17R)-17-acetyl-6,10,13-trimethyl-1,2,3,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] acetate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.019.578
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Chemical and physical data
FormulaC24H36O3
Molar mass372.549 g·mol−1
3D model (JSmol)
SMILES
  • C[C@H]1C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)OC(=O)C)C)[C@@]4(C1=CCCC4)C
InChI
  • InChI=1S/C24H36O3/c1-15-14-18-20(22(4)11-7-6-8-19(15)22)9-12-23(5)21(18)10-13-24(23,16(2)25)27-17(3)26/h8,15,18,20-21H,6-7,9-14H2,1-5H3/t15-,18+,20-,21-,22-,23-,24-/m0/s1
  • Key:KDLNOQQQEBKBQM-DICPTYMLSA-N

Anagestone acetate, sold under the brand names Anatropin and Neo-Novum, is a progestin medication which was withdrawn from medical use.[1][2]

Medical uses

Anagestone acetate was used in combination with the estrogen mestranol as a combined birth control pill.[3][4]

Pharmacology

Based on its chemical structure, namely the lack of a C3 ketone, it is probable that anagestone acetate is a prodrug of medroxyprogesterone acetate (the 3-keto analogue).[5][6]

Chemistry

Anagestone acetate, also known as 3-deketo-6α-methyl-17α-acetoxyprogesterone or as 6α-methyl-17α-acetoxypregn-4-en-20-one, is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone.[1] It is the C17α acetate ester of anagestone, which, in contrast to anagestone acetate, was never marketed.[1] Anagestone acetate is closely related structurally to medroxyprogesterone acetate (6α-methyl-17α-acetoxyprogesterone).[1]

History

Anagestone acetate was introduced in combination with mestranol as a birth control pill in 1968 by Ortho Pharmaceutical.[3][4] It was withdrawn in 1969.[4][7]

In 1969, along with a variety of other progestogens including progesterone, chlormadinone acetate, megestrol acetate, medroxyprogesterone acetate, ethynerone, and chloroethynyl norgestrel, anagestone acetate was found to induce the development of mammary gland tumors in Beagle dogs after extensive treatment (2–7 years) with very high doses (10–25 times the recommended human dose), though notably not with 1–2 times the human dosage.[4][8][7] In contrast, the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone, noretynodrel, and etynodiol diacetate were not found to produce such nodules.[7] Because of these findings, anagestone acetate was voluntarily withdrawn from the market by the manufacturer in 1969.[4][7][9] The findings also led to the virtual disappearance of most 17α-hydroxyprogesterone derivatives as hormonal contraceptives from the market (though medroxyprogesterone acetate, cyproterone acetate, and chlormadinone acetate have continued to be used).[4][8] According to Hughes et al., "It is still doubtful how much relevance these findings have for humans as the dog mammary gland seems to be the only one which can be directly maintained by progestogens."[7][10] Subsequent research revealed species differences between dogs and humans and established that there is no similar risk in humans.[11]

Society and culture

Generic names

Anagestone acetate is the generic name of the drug and its USAN.[1] It is also known by its developmental code name ORF-1658.[1]

Brand names

Anagestone acetate was marketed under the brand names Anatropin and Neo-Novum, the latter in combination with the estrogen mestranol.[1]

Availability

Anagestone acetate was withdrawn from the market and is no longer available.[4][7][9]

See also

References

  1. 1 2 3 4 5 6 7 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 85–. ISBN 978-1-4757-2085-3.
  2. ↑ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 322–. ISBN 978-0-8155-1856-3.
  3. 1 2 A. Labhart (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 571–. ISBN 978-3-642-96158-8.
  4. 1 2 3 4 5 6 7 Christian Streffer; H. Bolt; D. Follesdal; P. Hall; J.G. Hengstler; P. Jacob; D. Oughton; K. Prieß; E. Rehbinder; E. Swaton (11 November 2013). Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation. Springer Science & Business Media. pp. 135–. ISBN 978-3-662-08422-9.
  5. ↑ Ian S. Fraser (1998). Estrogens and Progestogens in Clinical Practice. Churchill Livingstone. p. 281. ISBN 978-0-443-04706-0. Progestational activity depends on the presence of a 3-keto group in ring A of the steroid skeleton. Most of the progestogens used today do indeed carry such a group in their original molecules. However, the 3-keto group is initially missing in the case of desogestrel and norgestimate. They are prodrugs which undergo metabolic conversion to active 3-keto derivatives in the body.
  6. ↑ McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK (May 2008). "Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay". J. Steroid Biochem. Mol. Biol. 110 (1–2): 39–47. doi:10.1016/j.jsbmb.2007.10.008. PMID 18395441. Prodrugs (lack 3-keto): Ethylestrenol, Lynestrenol, Ethynodiol, Allylestrenol, Norgestimate
  7. 1 2 3 4 5 6 C.H. Lingeman (6 December 2012). Carcinogenic Hormones. Springer Science & Business Media. pp. 149–. ISBN 978-3-642-81267-5.
  8. 1 2 V. H. T. James; J. R. Pasqualini (22 October 2013). Hormonal Steroids: Proceedings of the Fifth International Congress on Hormonal Steroids. Elsevier Science. pp. 7–. ISBN 978-1-4831-5895-2.
  9. 1 2 Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments. United Nations Publications. 1983. pp. 25–. ISBN 978-92-1-130230-1.
  10. ↑ A. Hughes; S. H. Hasan; G. W. Oertel; H. E. Voss; F. Bahner; F. Neumann; H. Steinbeck; K.-J. Gräf; J. Brotherton; H. J. Horn; R. K. Wagner (27 November 2013). Androgens II and Antiandrogens / Androgene II und Antiandrogene. Springer Science & Business Media. pp. 531–. ISBN 978-3-642-80859-3.
  11. ↑ Benno Clemens Runnebaum; Thomas Rabe; Ludwig Kiesel (6 December 2012). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 134–135. ISBN 978-3-642-73790-9.
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