Hispanopedia Wiki
Articulo de referencia

Methallenestril

Methallenestril ( International Nonproprietary Name "}]]}">INN Tooltip International Nonproprietary Name ) (brand names Cur-men , Ercostrol , Geklimon , Novestrine , Vallestril ...

Hispanopedia WikiContenido en espanolLectura gratuita

Methallenestril (INNTooltip International Nonproprietary Name) (brand names Cur-men, Ercostrol, Geklimon, Novestrine, Vallestril), also known as methallenoestril (BANTooltip British Approved Name) and as methallenestrol, as well as Horeau's acid,[1][2] is a syntheticnonsteroidal estrogen and a derivative of allenolic acid and allenestrol (specifically, a methylether of it) that was formerly used to treat menstrual issues but is now no longer marketed.[3][4][5][6] It is a seco-analogue of bisdehydrodoisynolic acid, and although methallenestril is potently estrogenic in rats, in humans it is only weakly so in comparison.[7]Vallestril was a brand of methallenestril issued by G. D. Searle & Company in the 1950s.[8] Methallenestril is taken by mouth.[9] By the oral route, a dose of 25 mg methallenestril is approximately equivalent to 1 mg diethylstilbestrol, 4 mg dienestrol, 20 mg hexestrol, 25 mg estrone, 2.5 mg conjugated estrogens, and 0.05 mg ethinylestradiol.[9]

Synthesis

The chemical synthesis has been described.[10][11] Unavailable methods:[12][13][14]

The Grignard reaction between 2-propionyl-6-methoxynaphthalene (promen) [2700-47-2] (1) and Ethyl 2-bromoisobutyrate [600-00-0] (2) occurs to give ethyl beta-ethyl-beta-hydroxy-6-methoxy-alpha,alpha-dimethylnaphthalene-2-propionate [85536-81-8] (3). Dehydration of the carbinol in aqueous lye may be accompanied by saponification of the ester (although not in the patented version) to give [60533-05-3] (4). Re-esterification with diazomethane gave (5). Catalytic hydrogenation of the olefin led to PC608080 (6). Saponification of the ester completed the synthesis of Methallenestril (7).

An alternative method is described in the patent that relies on 2-cyano-6-methoxynaphthalene (cyanonerolin) [67886-70-8]. The precursor to this is described in a Hoechst patent.[15]

See also

References

  1. ↑Heftmann E (1970). Steroid Biochemistry. Academic Press. p. 144. ISBN 978-0-12-336650-4.
  2. ↑Dodds EC (March 1949). "Synthetic oestrogens". The Journal of Pharmacy and Pharmacology. 1 (3): 137–147. doi:10.1111/j.2042-7158.1949.tb12391.x. PMID 18114509. S2CID 221921908.
  3. ↑Ganellin CR, Triggle DJ (21 November 1996). Dictionary of Pharmacological Agents. CRC Press. pp. 1295–. ISBN 978-0-412-46630-4.
  4. ↑Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 177–. ISBN 978-94-011-4439-1.
  5. ↑Thomas JA, Keenan EJ (1986). "Estrogens and Estrogenic Compounds". Principles of Endocrine Pharmacology. Springer Science & Business Media. p. 136. ISBN 978-1-4684-5036-1.
  6. ↑Herbai G, Ljunghall S (1983). "Normalization of hypercalcaemia of primary hyperparathyroidism by treatment with methallenestril, a synthetic oestrogen with low oestrogenicity". Urologia Internationalis. 38 (6): 371–373. doi:10.1159/000280925. PMID 6659184.
  7. ↑ Kirk RE, Othmer DF (1980). Enciclopedia de tecnología química . Wiley. pág. 670. ISBN  978-0-471-02065-3.
  8. ↑ Catálogo de registros de derechos de autor: Tercera serie . Vol. 17. Oficina de Derechos de Autor, Biblioteca del Congreso. Julio-diciembre de 1963. págs. 1984–.  
  9. 1 2 Swyer GI (abril de 1959). " Los estrógenos" . British Medical Journal . 1 (5128): 1029– 1031. doi : 10.1136/bmj.1.5128.1029 . PMC 1993181. PMID 13638626 .  
  10. ^ Wieland, P.; Miescher, K. (enero de 1948). "Abkömmlinge alquilierter β-Naphtyl-valeriansäuren. Über oestrogene Carbonsäuren XXVI" . Helvetica Chimica Acta . 31 (6): 1844–1854 . doi : 10.1002/hlca.19480310650 .
  11. ↑ Horeau Alain y Jacques Jean, patente estadounidense 2,547,123 (1951 a particular).
  12. ^ Gay, R. et al, Toro. Soc. Chim. Padre, 1955, 955.
  13. ↑ Jacques; Horeau Bulletin de la Société Chimique de France, 1948, p. 711.715.
  14. ^ Dubois, JC y col. Bulletin de la Société Chimique de France, 1967, p. 1827 – 1833.
  15. ^ Theodor Papenfuhs y Kurt Gengnagel, patente estadounidense 4.137.272 (1979 de Hoechst AG).