Chemistry:Hexestrol

From HandWiki
Short description: Chemical compound
Hexestrol
Hexestrol.svg
Clinical data
Trade namesSynestrol, Synoestrol, Estrifar, Estronal
Other namesHexoestrol; Hexanestrol; Hexanoestrol; Dihydrodiethylstilbestrol; Dihydrostilbestrol; 4,4'-(1,2-Diethylethylene)diphenol; NSC-9894
Routes of
administration		By mouth, intramuscular injection (as an ester)
Drug classNonsteroidal estrogen
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC18H22O2
Molar mass270.372 g·mol−1
3D model (JSmol)

Hexestrol, sold under the brand name Synestrol among others, is a nonsteroidal estrogen which was previously used for estrogen replacement therapy and in the treatment of certain hormone-dependent cancers as well as gynecological disorders but is mostly no longer marketed.[1][2][3][4] It has also been used in the form of esters such as hexestrol diacetate (brand name Sintestrol) and hexestrol dipropionate (brand name Hexanoestrol).[1][5] Hexestrol and its esters are taken by mouth, held under the tongue, or via injection into muscle.[5][6][7]

Medical uses

Hexestrol has been used in estrogen replacement therapy, for the treatment of breast cancer in women and prostate cancer in men, and for the treatment of certain gynecological disorders.[2]


Pharmacology

Pharmacodynamics

Hexestrol has approximately 302% and 234% of the affinity of estradiol for the estrogen receptors (ERs) ERα and ERβ, respectively.[8] The affinity of hexestrol for the ERs is said to be similar to or slightly higher than that of estradiol.[9] Along with diethylstilbestrol, hexestrol has been said to be one of the most potent estrogens known.[10] The total endometrial proliferation dose per cycle of different forms of hexestrol are 70 to 100 mg for oral hexestrol, 45 mg for sublingual hexestrol diacetate, and 25 mg for hexestrol dipropionate by intramuscular injection.[5] These doses are fairly similar to those of estradiol and its esters.[5] Hexestrol induces mammary gland development in rodents similarly to other estrogens.[11]

Nonsteroidal estrogens like diethylstilbestrol, which is closely related structurally to hexestrol, are known to have dramatically disproportionate estrogenic effects in the liver and on liver protein synthesis.[12]


Pharmacokinetics

Distribution of hexestrol radioactivity in blood and tissues after a subcutaneous injection of a physiological dose of tritium-labeled hexestrol in oil solution in five juvenile female goats.[13] Points are one animal each.[13] With the exception of skeletal muscle, tissues with a radioactivity concentration of less than 15% of that of the endometrium are not shown.[13] Hexestrol is concentrated in target tissues such as the uterus and vagina due to binding to estrogen receptors.[14]

The pharmacokinetics and distribution of hexestrol have been studied with intravenous injection of aqueous solution in women and with subcutaneous injection of oil solution in female goats and sheep.[15][13]

Chemistry

Hexestrol, also known as dihydrodiethylstilbestrol, is a synthetic nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol.[1][2] Esters of hexestrol include hexestrol diacetate, hexestrol dicaprylate, hexestrol diphosphate, and hexestrol dipropionate.[1]

History

Hexestrol was first described by Campbell, Dodds, and Lawson in 1938.[16][11][17][18] It was isolated from the demethylation products of anethole.[16][11][17][18]

Society and culture

Generic names

Hexestrol is the generic name of the drug and its INN.[1][2]

Brand names

Hexestrol has been marketed under a variety of brand names including Synestrol, Synoestrol, Estrifar, and Estronal, among others.[1][2]

Availability

Hexestrol has mostly been discontinued and remains available in only a handful of countries.[19][4] Esters of hexestrol which have been marketed include hexestrol diacetate, hexestrol dicaprylate, hexestrol diphosphate, and hexestrol dipropionate.[1]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 162–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA162. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. 6 December 2012. pp. 140–. ISBN 978-94-011-4439-1. https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA140. 
  3. ↑ Endocrine Toxicology, Second Edition. CRC Press. 12 March 1997. pp. 144–. ISBN 978-1-4398-1048-4. https://books.google.com/books?id=URc5JMoNirgC&pg=PA144. 
  4. ↑ 4.0 4.1 "Estradiol: Uses, Dosage & Side Effects". https://www.drugs.com/international/hexestrol.html. 
  5. ↑ 5.0 5.1 5.2 5.3 Ovarian Function and its Disorders: Diagnosis and Therapy. Springer Science & Business Media. 6 December 2012. pp. 83,85,145,310. ISBN 978-94-009-8195-9. https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA310. 
  6. ↑ Principles of Endocrine Pharmacology. Springer Science & Business Media. 6 December 2012. pp. 153–. ISBN 978-1-4684-5036-1. https://books.google.com/books?id=mTagBQAAQBAJ&pg=PA153. 
  7. ↑ Textbook of Pharmacology. S. Chand Publishing. 2012. pp. 348–. ISBN 978-81-219-4080-1. https://books.google.com/books?id=ZDJlDwAAQBAJ&pg=PA348. 
  8. ↑ "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology 138 (3): 863–870. March 1997. doi:10.1210/endo.138.3.4979. PMID 9048584. 
  9. ↑ "Physiological and pharmacological effects of estrogens in breast cancer". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 560 (4): 427–455. December 1979. doi:10.1016/0304-419x(79)90012-x. PMID 391285. 
  10. ↑ "Synthetic estrogens and the relation between their structure and their activity". Chemical Reviews 37 (3): 481–598. December 1945. doi:10.1021/cr60118a004. PMID 21013428. 
  11. ↑ 11.0 11.1 11.2 "Biological effects of the synthetic œstrogen hexœstrol". The Lancet 234 (6049): 312–313. 1939. doi:10.1016/S0140-6736(00)61997-9. ISSN 0140-6736. 
  12. ↑ "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric 8 (Suppl 1): 3–63. August 2005. doi:10.1080/13697130500148875. PMID 16112947. 
  13. ↑ 13.0 13.1 13.2 13.3 "Selective accumulation of tritium-labelled hexoestrol by the reproductive organs of immature female goats and sheep". The Biochemical Journal 72 (4): 673–682. August 1959. doi:10.1042/bj0720673. PMID 13828338. 
  14. ↑ "Mechanism of action of the female sex hormones". Annual Review of Biochemistry 41: 203–230. 1972. doi:10.1146/annurev.bi.41.070172.001223. PMID 4563437. 
  15. ↑ "Studies with tritium-labelled hexoestrol in advanced breast cancer. Comparison of tissue accumulation of hexoestrol with response to bilateral adrenalectomy and oophorectomy". Lancet 2 (7206): 796–798. October 1961. doi:10.1016/s0140-6736(61)91088-1. PMID 13893792. 
  16. ↑ 16.0 16.1 "Œstrogenic Activity of Anol; a Highly Active Phenol Isolated from the By-Products". Nature 142 (3608): 1121. 1938. doi:10.1038/1421121a0. ISSN 0028-0836. Bibcode: 1938Natur.142.1121C. 
  17. ↑ 17.0 17.1 Medicinal Chemistry. John Wiley & Sons. 1956. p. 40. https://books.google.com/books?id=bpXVAAAAMAAJ. 
  18. ↑ 18.0 18.1 "The nature of the oestrogenic substances produced during the demethylation of anethole". Proceedings of the Royal Society of London. Series B, Biological Sciences 128 (851): 253–262. 1940. doi:10.1098/rspb.1940.0009. ISSN 2053-9193. Bibcode: 1940RSPSB.128..253C. 
  19. ↑ "Micromdex". Merative. https://www.micromedexsolutions.com/. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Hexestrol&oldid=2971828"