97631-87-3Relevant academic research and scientific papers
Influence of the length and positioning of the antiestrogenic side chain of endoxifen and 4-hydroxytamoxifen on gene activation and growth of estrogen receptor positive cancer cells
Maximov, Philipp Y.,Fernandes, Daphne J.,McDaniel, Russell E.,Myers, Cynthia B.,Curpan, Ramona F.,Jordan, V. Craig
, p. 4569 - 4583 (2014/07/07)
Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains. Pharmacologic properties were documented in the MCF-7 cell line, and prolactin synthesis was assessed in GH3 rat pituitary tumor cells. The FR Z-isomers of 4OHT and endoxifen were equivalent to 4OHT and endoxifen. Other test compounds used possessed partial estrogenic activity. The E-isomers of FR 4OHT and endoxifen had no estrogenic activity at therapeutic serum concentrations. None of the newly synthesized compounds were able to down-regulate ER levels. Molecular modeling demonstrated that some compounds would each create a best fit with a novel agonist conformation of the ER. The results demonstrate modulation by the ER complex of cell replication or gene transcription in cancer.
Octafluorotoluene as a Reagent for the Selective Protection of Alcoholic and Phenolic Functions: Synthesis and Cleavage of Perfluorotolyl and other Perfluoroaryl Ethers of Steroids and Other Model Compounds
Jarman, Michael,McCague, Raymond
, p. 1301 - 1341 (2007/10/02)
Heptafluorotolyl derivatives of phenol, of the steroids oestrone, oestradiol , cholesterol, testosterone, cortisol and 4-hydroxyandrostene-3,17-dione, of the phenyl-substituted alcohols 1- and 2-phenylethanol and 3-phenylpropanol and of catechol were prepared by phase-transfer catalysed reactions with octafluorotoluene.Reaction with sodium methoxide in dimethylformamide regenerated the alcohol or phenolic functions, by a stepwise process involving replacement of fluorine substituents by methoxyl followed by aryl-oxygen cleavage.Phenols were regenerated more rapidly than alcohols and could be deprotected selectively.The perfluorotolyl group was stable under reducing and oxidising conditions and was compatible with Grignard reagents.Pentafluoropyridine similarly, and more rapidly gave perfluoropyridyl derivatives of oestradiol , which could similarly be cleaved with sodium methoxide.Hexafluorobenzene was relatively unreactive under phase transfer conditions and its derivatives with oestrone was cleaved only with difficulty.Perfluoro-o-xylene reacted with catechol to give dibenzodioxin derivatives from which catechol was regenerated using sodium methoxide.
