97818-83-2Relevant articles and documents
Synthesis of Tamoxifen-Artemisinin and Estrogen-Artemisinin Hybrids Highly Potent Against Breast and Prostate Cancer
Fr?hlich, Tony,Mai, Christina,Bogautdinov, Roman P.,Morozkina, Svetlana N.,Shavva, Alexander G.,Friedrich, Oliver,Gilbert, Daniel F.,Tsogoeva, Svetlana B.
, p. 1473 - 1479 (2020/07/06)
In the search for new and effective treatments of breast and prostate cancer, a series of hybrid compounds based on tamoxifen, estrogens, and artemisinin were successfully synthesized and analyzed for their in vitro activities against human prostate (PC-3) and breast cancer (MCF-7) cell lines. Most of the hybrid compounds exhibit a strong anticancer activity against both cancer cell lines – for example, EC50 (PC-3) down to 1.07 μM, and EC50 (MCF-7) down to 2.08 μM – thus showing higher activities than their parent compounds 4-hydroxytamoxifen (afimoxifene, 7; EC50=75.1 (PC-3) and 19.3 μM (MCF-7)), dihydroartemisinin (2; EC50=263.6 (PC-3) and 49.3 μM (MCF-7)), and artesunic acid (3; EC50=195.1 (PC-3) and 32.0 μM (MCF-7)). The most potent compounds were the estrogen-artemisinin hybrids 27 and 28 (EC50=1.18 and 1.07 μM, respectively) against prostate cancer, and hybrid 23 (EC50=2.08 μM) against breast cancer. These findings demonstrate the high potential of hybridization of artemisinin and estrogens to further improve their anticancer activities and to produce synergistic effects between linked pharmacophores.
Aluminum Chloride Promoted Cross-Coupling of Trisubstituted Enol Phosphates with Organozinc Reagents En Route to the Stereoselective Synthesis of Tamoxifen and Its Analogues
Kotek, Vladislav,Polák, Peter,Dvo?áková, Hana,Tobrman, Tomá?
, p. 5037 - 5044 (2016/10/26)
A new method for the stereoselective cross-coupling reaction of arylzinc chlorides with trisubstituted enol phosphates is described. The developed method requires aluminum chloride as a promoter, and the reaction conditions tolerate various functional groups. The observed reactivity pattern of trisubstituted enol phosphates was used for the stereoselective preparation of tamoxifen and its analogues.
Reaction of pyrylium salts with nucleophiles. 23: Triarylethene derivatives containing an oxyalkyleneamino or oxyalkylene-N-pyridinium side chain
Stanciuc,Balaban
, p. 927 - 933 (2007/10/02)
A synthetic design was devised for preparing primary amines related to anticancer drugs clomiphene and tamoxifen on the basis of key intermediates with a phenolic group, to which a side chain (ω-aminoethoxy or ω- aminopropoxy) was attached. These compound
Highly Stereoselective Access to an (E)-Vinyl Bromide from an Aryl Ketone Leads to Short Syntheses of (Z)-Tamoxifen and Important Substituted Derivatives
Potter, Gerard A.,McCague, Raymond
, p. 6184 - 6187 (2007/10/02)
The enol triflate derived from a 1-(4-alkoxyphenyl)-2-phenyl-1-butanone is unstable, fragmenting to a vinyl cation that can be trapped by bromide ion.The E isomer of the vinyl bromide which is formed in preference (20:1) gave, upon palladium-catalyzed cou
Stereoselective Olefin Formation from the Dehydration of 1-(p-Alkoxyphenyl)-1,2-diphenylbutan-1-ols: Application to the Synthesis of Tamoxifen
McCague, Raymond
, p. 1011 - 1016 (2007/10/02)
Acid-catalysed dehydration of either diastereoisomer of a 1-(p-alkoxyphenyl)-1,2-diphenylbutan-1-ol gives mainly the Z isomer of the but-1-ene via a common carbenium ion intermediate that can be regenerated by protonation of the (Z)- or (E)-butene with fluorosulphonic acid.Highly stereoselective syn eliminations were achieved by treatment of the butan-1-ols with base and carbon disulphide but dehydrations using N,N,N-triethylammonio-N'-methoxycarbonylsulphamidate proceeded mainly via a carbenium ion.Aspects of the stereoselectivity of the reactions are discussed.The methods can be applied to give simple stereoselective syntheses of the anti-cancer drug tamoxifen.
Crossed Coupling of Functionalised Ketones by Low Valent Titanium (The McMurry Reaction): A New Stereoselective Synthesis of Tamoxifen
Coe, Paul L.,Scriven, Clare E.
, p. 475 - 478 (2007/10/02)
Low valent titanium-mediated crossed coupling of substitued benzophenones of the 4-XPhCOPh, where X = MeO, ClCH2CH2O, BrCH2CH2O, CF3C6H4O, HO, and Me2NCH2CH2O, with propiophenone affords the corresponding but-1-enes in high yield with a marked preponderance of the Z-isomer in most cases.Remarkably, when X = OH the E:Z ratio is 9:1.The value of this method is illustrated by simple syntheses of (Z)-1-phenyl>-1,2-diphenylbut-1-ene (Tamoxifen) a drug widely used in the treatment of eostrogen-dependent breast tumors.
The use of Octafluorotoluene and Pentafluoropyridine in the Synthesis of Pure Z and E Isomers of Derivatives of Tamoxifen -1-butene>
Jarman, Michael,McCague, Raymond
, p. 1342 - 1388 (2007/10/02)
Octafluorotoluene and pentafluoropyridine have been used in the synthesis of pure Z and E isomers of derivatives of the anticancer drug, tamoxifen (1).The isomeric ethers derived by reaction of these perfluoroarenes with an E/Z mixture of 1,2-diphenyl-1-(4-hydroxyphenyl)-1-butene (3) and (4) were easily separated.A process is described for conversion of the E/Z mixtures into one isomer.Cleavage of the ethers regenerated the phenol (3) or (4) of pure stereochemical configuration and the Z-isomer (3) was used for the synthesis of tamoxifen (1) and various monomeric and dimeric analogues.Other perfluoroarenes were less useful.A short synthesis involving early introduction of the perfluorotolyl group is also described.
