Triphenylchloroethylene Explained

Triphenylchloroethylene (TPCE; brand names Gynosone, Oestrogyl), or triphenylchlorethylene, also known as chlorotriphenylethylene or as phenylstilbene chloride, is a synthetic nonsteroidal estrogen of the triphenylethylene group that was marketed in the 1940s for the treatment of menopausal symptoms, vaginal atrophy, lactation suppression, and all other estrogen-indicated conditions.^{[1] [2] [3]}

The estrogenic effects of triphenylethylene, the parent compound of triphenylchloroethylene, were discovered in 1937.^[4] Triphenylchloroethylene was first reported in 1938 and was found to have 20 to 100 times the estrogenic activity of the relatively weak triphenylethylene, a potentiation of effect that was afforded by its halogen substituent.^[5] The drug has a relatively long duration of action when administered via subcutaneous injection but a duration similar to that of diethylstilbestrol or estradiol benzoate when administered orally.^{[6] [7]} Along with diethylstilbestrol and triphenylmethylethylene, triphenylchloroethylene was studied in 1944 by Sir Alexander Haddow for the treatment of breast cancer and was found to be significantly effective, and this is historically notable in that it was the first time that high-dose estrogens were found to be effective in the treatment of breast cancer.^{[8] [9]}

Chlorotrianisene, or tri-p-anisylchloroethylene (TACE), is a potent marketed estrogen and a derivative of triphenylchloroethylene in which each of the three phenyl rings has been substituted with a 4-methoxy group.^{[5] [10]} Estrobin, or DBE, is a related, never-marketed estrogen in which there is a bromine in place of the chlorine and two of the three phenyl rings have ethoxy groups. Broparestrol, or BDPE is a marketed selective estrogen receptor modulator (SERM) that has a bromine in place of the chlorine of triphenylchloroethylene and a 4-ethyl group on one of the phenyl rings. The SERM clomifene is also a derivative of triphenylchloroethylene.^[11]

See also

• Triphenylbromoethylene
• Triphenyliodoethylene

Notes and References

1. Book: Negwer M, Scharnow HG . Organic-chemical drugs and their synonyms: (an international survey). 2001. Wiley-VCH. 978-3-527-30247-5. 1861–1862. C20H15Cl 18084-97-4 Chlorotriphenylethene = Triphenylchloroethylene = Phenylstilbene chloride = 1,1',1"-(1-Chloro-1-ethenyl-2-ylidene)tris[benzene] (•) S Gynosone, Oestrogyl, Phenylstilbene chloride U Synthetic estrogen.
2. Emmens CW . Halogen-substituted oestrogens related to triphenylethylene . The Journal of Endocrinology . 5 . 3 . 170–173 . July 1947 . 20259249 . 10.1677/joe.0.0050170 .
3. "Gynosone" A New Synthetic Oestrogen . Proc R Soc Med. 39. 11. Sep 1946 . Advertisement . 2181944.
4. Book: Li JJ . Genesis of Statins . Triumph of the Heart: The Story of Statins. https://books.google.com/books?id=-GPl1PA5EgMC&pg=PA33. 3 April 2009. Oxford University Press, USA. 978-0-19-532357-3. 33–.
5. Solmssen UV . Synthetic estrogens and the relation between their structure and their activity . Chemical Reviews . 37 . 3 . 481–598 . December 1945 . 21013428 . 10.1021/cr60118a004 .
6. Book: Jordon VC, Koch R, Lieberman ME . Structure-Activity Relationships of Nonsteroidal Estrogens and Antiestrogens . Jordan VC . Estrogen/antiestrogen Action and Breast Cancer Therapy. https://books.google.com/books?id=7WmLZfGXST0C&pg=PA23. 1986. University of Wisconsin Press. 978-0-299-10480-1. 23–.
7. Book: Maximov PY, McDaniel RE, Jordan VC . Discovery and Pharmacology of Nonsteroidal Estrogens and Antiestrogens . Tamoxifen: Pioneering Medicine in Breast Cancer. https://books.google.com/books?id=p-W5BAAAQBAJ&pg=PA4. 23 July 2013. Springer Science & Business Media. 978-3-0348-0664-0. 4–.
8. Book: Lewis-Wambi J, Jordan VC . Diethylstilbestrol: A Tragedy in Reproductive Endocrinology But a Pioneering Cancer Treatment . Jordan VC . Estrogen Action, Selective Estrogen Receptor Modulators and Women's Health: Progress and Promise. https://books.google.com/books?id=ZM26CgAAQBAJ&pg=PA42. 27 May 2013. World Scientific. 978-1-84816-959-3. 42–.
9. Book: Wagener DJ . The history of the hormonal treatment of cancer . The History of Oncology. https://books.google.com/books?id=53fmwacXu44C&pg=PA189. 13 July 2009. Bohn Stafleu van Loghum. 978-90-313-6143-4. 189–.
10. Book: Lisi F . Adjunctions to Clomiphene Citrate . Allahbadia G . Contemporary Perspectives on Assisted Reproductive Technology. https://books.google.com/books?id=Zx-lRwGFU4gC&pg=PA18. 2006. Elsevier India. 978-81-8147-782-8. 18–.
11. Book: Shoham Z, Howles CM . Drugs used for ovarian stimulation: Clomiphene citrate, aromatase inhibitors, metformin, gonadotropins, gonadotropin-releasing hormone analogs and recombinant gonadotropins . Gardner DK, Weissman A, Howles CM, Shoham Z . Textbook of Assisted Reproductive Techniques Fourth Edition: Volume 2: Clinical Perspectives. https://books.google.com/books?id=Ap1_AwAAQBAJ&pg=PA51. 27 June 2012. CRC Press. 978-1-84184-972-0. 51–.