Δ4-Tibolone

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Wikipedia

Δ4-Tibolone
Clinical data
Other namesIsotibolone; ORG-OM-38; Delta-4-Tibolone; 7α-Methylnorethisterone; 7α-Methyl-17α-ethynyl-19-nortestosterone; 17α-Ethynyl-17β-hydroxy-7α-methyl-4-estren-3-one
Identifiers
  • (7R,8R,9S,10R,13S,14S,17R)-17-Ethynyl-17-hydroxy-7,13-dimethyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC21H28O2
Molar mass312.453 g·mol−1
3D model (JSmol)
  • C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@@H]3[C@@H]1[C@@H]4CC[C@]([C@]4(CC3)C)(C#C)O
  • InChI=1S/C21H28O2/c1-4-21(23)10-8-18-19-13(2)11-14-12-15(22)5-6-16(14)17(19)7-9-20(18,21)3/h1,12-13,16-19,23H,5-11H2,2-3H3/t13-,16+,17-,18+,19-,20+,21+/m1/s1
  • Key:WAOKMNBZWBGYIK-KIURNNQRSA-N

δ4-Tibolone (developmental code name ORG-OM-38), also known as isotibolone or as 7α-methylnorethisterone or as 7α-methyl-17α-ethynyl-19-nortestosterone, is a synthetic androgen and progestin which was never marketed.[1][2] The compound is a major active metabolite of tibolone, which itself is a prodrug of δ4-tibolone along with 3α-hydroxytibolone and 3β-hydroxytibolone (which, in contrast to δ4-tibolone, are estrogens).[1] Tibolone and δ4-tibolone are thought to be responsible for the androgenic and progestogenic activity of tibolone, while 3α-hydroxytibolone and 3β-hydroxytibolone are thought to be responsible for its estrogenic activity.[1]

Synthesis

Isotibolone, mibolerone, bolasterone, and calusterone all appear in the same patent file.[3] The specific entry for the synthesis of isotibolone is Example 31. Note that these agents were all produced by Upjohn whereas Tibolone is the subject of an Organon patent.[4]

The organic synthesis of these agents related to isotibolone are summarized in textbooks published by Daniel Lednicer (& Lester Mitscher):[5][6][7][8][9]

The enanthate ester of isotibolone was also prepared in a separate patent.[10]

See also

References

  1. 1 2 3 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. S2CID 24616324.
  2. ↑ Escande A, Servant N, Rabenoelina F, Auzou G, Kloosterboer H, Cavaillès V, Balaguer P, Maudelonde T (2009). "Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites". J. Steroid Biochem. Mol. Biol. 116 (1–2): 8–14. doi:10.1016/j.jsbmb.2009.03.008. PMID 19464167. S2CID 18346113.
  3. ↑ John C Babcock & Campbell J Allan, U.S. patent 3,341,557 (1967 to Pharmacia and Upjohn Co).
  4. ↑ NL 6406797 idem Jongh Hendrik Paul De, Nicolaas Pieter Van Vliet, U.S. patent 3,340,279 (1967 to Organon).
  5. ↑ Lednicer, D. (2011). Steroid chemistry at a glance (1. publ ed.). Wiley. ISBN 9780470660843.
  6. ↑ Lednicer, D., Mitscher, L. A. (1980). The organic chemistry of drug synthesis. 2. Wiley. ISBN 9780471043928.
  7. ↑ Lednicer, D. (2009). Strategies for organic drug synthesis and design (2nd ed.). John Wiley & Sons. ISBN 9780470190395.
  8. ↑ Lednicer, D., Mitscher, L. A. (1977). The organic chemistry of drug synthesis. 1. Wiley. ISBN 9780471521419.
  9. ↑ Lednicer, D. (2015). Antineoplastic drugs: organic syntheses. John Wiley & Sons. Ltd. ISBN 9781118892572.
  10. ↑ Richard Blye & Hyun K. Kim, U.S. patent 4,308,265 (1981 to Government of the United States of America).