69967-79-9Relevant academic research and scientific papers
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.
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
Synthesis of cis- and trans-tamoxifen
Al-Hassan, Mohammed I.
, p. 1247 - 1252 (2007/10/02)
The synthesis of cis-tamoxifen, non antiestrogenic tetrasubstituted olefin, was achieved via carboalumination of diphenylacetylene as a key step.Conversion to the antiestrogenic trans-tamoxifen was achieved by facile cis-trans isomerization of the corresponding phenol by acid or catalysts.
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.
1,1,2-Triphenylbut-1-enes: Relationship between Structure, Estradiol Receptor Affinity, and Mammary Tumor Inhibiting Properties
Schneider, Martin R.,Angerer, Erwin von,Schoenenberger, Helmut,Michel, Ralf Th.,Fortmeyer, H. P.
, p. 1070 - 1077 (2007/10/02)
1,1,2-Triphenylbut-1-enes, which are substituted with acetoxy groups on one, two, or three aromatic rings in the para and/or meta positions, were synthesized.The identity of the occurring E and Z isomers were established by 1H NMR spectroscopy.A study on structure-activity relationships was carried out with regard to estradiol receptor affinity and to inhibiting effects on the growth of a postmenopausal human mammary carcinoma implanted in nude mice.The para-substituted compounds generally exhibited a higher receptor affinity and a better antitumor activity than the corresponding meta-substituted ones.The E isomers were superior to the respective Z isomers in those two properties.The tumor-inhibiting effect of the mono-and disubstituted compounds was better than that of the trisubstituted ones.Except for the trisubstituted compounds, they all showed a good correlation between estradiol receptor affinity and antitumor activity.One of the compounds was also tested on the 9,10-dimethylbenzanthracene-induced, hormone-dependent mammary carcinoma of the Spraque-Dawley rat, and the results corresponded to those obtained in the xenograft tumor.
