δ4-Tibolone
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| Other names | Isotibolone; ORG-OM-38; Delta-4-Tibolone; 7α-Methylnorethisterone; 7α-Methyl-17α-ethynyl-19-nortestosterone; 17α-Ethynyl-17β-hydroxy-7α-methyl-4-estren-3-one |
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| Chemical and physical data | |
| Formula | C21H28O2 |
| Molar mass | 312.453 g·mol−1 |
| 3D model (JSmol) | |
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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
- ^ a b c 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.
- ^ 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.
- ^ John C Babcock & Campbell J Allan, U.S. patent 3,341,557 (1967 to Pharmacia and Upjohn Co).
- ^ NL 6406797 idem Jongh Hendrik Paul De, Nicolaas Pieter Van Vliet, U.S. patent 3,340,279 (1967 to Organon).
- ^ Lednicer, D. (2011). Steroid chemistry at a glance (1. publ ed.). Wiley. ISBN 9780470660843.
- ^ Lednicer, D., Mitscher, L. A. (1980). The organic chemistry of drug synthesis. 2. Wiley. ISBN 9780471043928.
- ^ Lednicer, D. (2009). Strategies for organic drug synthesis and design (2nd ed.). John Wiley & Sons. ISBN 9780470190395.
- ^ Lednicer, D., Mitscher, L. A. (1977). The organic chemistry of drug synthesis. 1. Wiley. ISBN 9780471521419.
- ^ Lednicer, D. (2015). Antineoplastic drugs: organic syntheses. John Wiley & Sons. Ltd. ISBN 9781118892572.
- ^ Richard Blye & Hyun K. Kim, U.S. patent 4,308,265 (1981 to Government of the United States of America).