69967-80-2Relevant articles and documents
Identification of a new tamoxifen-xanthene hybrid as pro-apoptotic anticancer agent
Catanzaro, Elena,Seghetti, Francesca,Calcabrini, Cinzia,Rampa, Angela,Gobbi, Silvia,Sestili, Piero,Turrini, Eleonora,Maffei, Francesca,Hrelia, Patrizia,Bisi, Alessandra,Belluti, Federica,Fimognari, Carmela
, p. 538 - 549 (2019/02/24)
Breast cancer is the most diagnosed type of cancer among women for which an exhaustive cure has not been discovered yet. Nowadays, tamoxifen still represents the gold standard for breast cancer therapy; it acts on both estrogen receptor-positive and estrogen receptor-negative breast cancers. Unfortunately, its toxicity and the related chemoresistance undermine its antitumor potential. In this paper, new tamoxifen-based derivatives with a rigid structural motif in their structure were designed, synthesized, and evaluated to assess their antitumor behavior. All the tested compounds affected estrogen receptor-positive tumor (MCF-7) cell growth, even with different extents, among which, the most active ones proved also to induce mitochondria-mediated apoptosis through activation of PARP cleavage, decrease in Bax/Bcl-2 ratio and increase in Bim gene expression levels. Here we found that the compound 1, carrying a rigid xanthene core, turned out to be the most promising of the set showing an activity profile comparable to that of tamoxifen. Furthermore, a more favorable genotoxic profile than tamoxifen made compound 1 a promising candidate for further studies.
Divergent Synthetic Access to E- and Z-Stereodefined All-Carbon-Substituted Olefin Scaffolds: Application to Parallel Synthesis of (E)- and (Z)-Tamoxifens
Ashida, Yuichiro,Honda, Atsushi,Sato, Yuka,Nakatsuji, Hidefumi,Tanabe, Yoo
, p. 73 - 89 (2017/02/10)
A highly substrate-general synthesis of all-carbon-substituted E- and Z-stereodefined olefins is performed. The method comprises two sets of parallel and stereocomplementary preparations of (E)- and (Z)-α,β-unsaturated esters involving two robust and distinctive reactions: 1) stereocomplementary enol tosylations using readily available TsCl/diamine/(LiCl) base reagents, and 2) stereoretentive Negishi cross-coupling using the catalysts [Pd(dppe)Cl2] (for E) and [Pd(dppb)Cl2] (for Z). The present parallel approach is categorized as both type I (convergent approach: 16 examples, 56–87 % yield) and type II (divergent approach: 18 examples, 70–95 % yield). The obtained (E)- and (Z)-α,β-unsaturated ester scaffolds are successfully transformed into various E- and Z-stereodefined known and novel olefins (8×2 derivatization arrays). As a demonstration, application to the parallel synthesis of both (E)- and (Z)-tamoxifens, a representative motif of all-carbon-substituted olefins, is accomplished in a total of eight steps with an overall yield of 58 % (average 93 %) and 57 % (average 93 %), respectively.
Synthesis, spectroscopic characterization, and molecular structure of triphenyl butene derivatives containing a cyclopentadienyl iron unit
Han, Junru,Li, Guanglei,Wang, Tao
, p. 374 - 379 (2013/01/13)
Three hydroxyl substituted triphenyl butene compounds (PHB) and their derivatives containing a cyclopentadienyl iron (PHB-Fc) unit were efficiently synthesized. The synthesis involved the McMurry cross-coupling reaction of appropriate ketones and the nucleophilic aromatic substitution (SNAr) reaction of (η6-chlorobenzene) (η5- cyclopentadienyl) iron hexafluorophosphate (Fc-Cl). The target compounds were characterized by IR, 1H NMR, 13C NMR, and MS. Their photophysical processes were investigated by UV-Vis absorption and fluorescence emission spectra in acetonitrile. The geometric structure was optimized based on the density functional theory at the B3LYP level. Theoretical results reveal that electron transfer occurred from the HOMO to the LUMO in PHB-Fc. The change in electron distribution subsequently led to the improved second-order optical susceptibility of PHB-Fc.
Tamoxifen stimulates calcium entry into human platelets
Dobrydneva, Yuliya,Weatherman, Ross V.,Trebley, Joseph P.,Morrell, Melinda M.,Fitzgerald, Megan C.,Fichandler, Craig E.,Chatterjie, Nithiananda,Blackmore, Peter F.
, p. 380 - 390 (2008/03/12)
The anti-estrogenic drug tamoxifen, which is used therapeutically for treatment and prevention of breast cancer, can lead to the development of thrombosis. We found that tamoxifen rapidly increased intracellular free calcium [Ca]i in human platelets from
Identification of new triarylethylene oxyalkanoic acid analogues as bone selective estrogen mimetics
Rubin, Valeria N,Ruenitz, Peter C,Boudinot,Boyd, Jason L
, p. 1579 - 1587 (2007/10/03)
Previously, the estrogen receptor (ER) ligand 4-[1-(p-hydroxyphenyl)-2-phenylethyl]phenoxyacetic acid (5) was found to have differential bone loss suppressive effects in the ovariectomized (OVX) rat approaching those of selective ER modulators (SERMs) suc
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.
Stereospecific Synthesis of (Z)-Tamoxifen via Carbometalation of Alkynylsilanes
Miller, R. Bryan,Al-Hassan, Mohammed I.
, p. 2121 - 2123 (2007/10/02)
A sterospecific synthesis of (Z)-tamoxifen, a tetrasubstituted alkene with antiestrogenic activity, is described.The key reaction that establishes the olefin stereochemistry is a carbometalation of phenyl(trimethylsilyl)acetylene with diethylaluminum chloride-titanocene dichloride.A key intermediate that would lead to (E)-tamoxifen was also prepared in an analogous stereospecific manner.
