173163-13-8Relevant articles and documents
Replacing the Z-phenyl ring in tamoxifen with a para-connected NCN pincer-Pt-Cl grouping by post-modification
Batema, Guido D.,Gossage, Robert A.,Guillena, Gabriela,Korstanje, Ties J.,Lutz, Martin,Rodríguez, Gema,van Klink, Gerard P. M.,van Koten, Gerard
, (2021)
Post-modification of a series of NCN-pincer platinum(II) complexes [PtX(NCN-R-4)] (NCN = [C6H2 (CH2NMe2)2-2,6]–, R = C(O)H, C(O)Me and C(O)Et), X = Cl– or Br–) at the para-position using the McMurry reaction was studied. The synthetic route towards two new [PtCl(NCN-R-4)] (R = C(O)Me and C(O)Et) complexes used above is likewise described. The utility and limitations of the McMurry reaction involving these pincer complexes was systematically evaluated. The predicted “homo-coupling” reaction of [PtBr(NCN-C(O)H-4)] led to the unexpected formation of 3,3′,5,5′-tetra[(dimethylamino)methyl]-4,4′-bis(platinum halide)-benzophenone (halide = Br or Cl), referred to hereafter as the bispincer-benzophenone complex 13. This material was further characterized using X-ray crystal structure determination. The applicability of the pincer complexes in the McMurry reaction is shown to open a route towards the synthesis of tamoxifen-type derivatives of which one phenyl ring of Tamoxifen itself is replaced by an NCN arylplatinum pincer fragment. The newly synthesized derivatives can be used as potential candidates in anti-cancer drug screening protocols. Two NCN-arylpincer platinum tamoxifen type derivatives, 5 and 6, were successfully synthesized and of 5 the separation of the diastereomeric E-/Z-forms was achieved. Compound 6, which is the pivaloyl protected NCN pincer platinum hydroxy-Tamoxifen derivative, was obtained as a mixture of E-/Z-isomers. The new derivatives were further analyzed and characterized with1H-,13C{1H}-and195Pt{1H}-NMR, IR, exact mass MS and elemental analysis.
Bis-arylidene oxindoles as anti-breast-cancer agents acting via the estrogen receptor
Pal, Abhishek,Ganguly, Anirban,Ghosh, Avijit,Yousuf, Md,Rathore, Bhowmira,Banerjee, Rajkumar,Adhikari, Susanta
supporting information, p. 727 - 732 (2014/05/06)
We report a new family of bis-arylidene oxindole derivatives that show highly selective estrogen receptor (ER)-mediated anticancer activity at low-nanomolar concentrations in ER-positive (ER+) breast cancer cells. In terms of cell growth inhibition, IC50 values for these compounds in ER+ breast cancer cells are two to three orders of magnitude lower than in ER-negative (ER-) breast cancer cells and non-cancer cells. In comparison with known bis-arylidene drugs, these compounds are at least three orders of magnitude more toxic than tamoxifen and 1.5-4-fold more toxic than 4-hydroxytamoxifen in ER+ MCF-7 cancer cells. These oxindoles inhibit ER transactivation, and their anticancer activities are inhibited in ER-depleted MCF-7 cells. Some of these nonsteroidal molecules also exhibit essential properties of selective ER down-regulation. From the development of two series of bis-arylidene oxindole-based compounds, we report a new series of anticancer agents for estrogen-responsive breast cancer. A trip to the ER: We developed oxindole derivatives that exhibit anticancer activity at low-nanomolar IC 50 concentrations (30-70 nM) against ER-positive breast cancer cells. Results of siRNA studies reveal that the anticancer effects of these molecules are mediated by the estrogen receptor (ER). These compounds also inhibit ER-mediated transactivation and exhibit selective ER modulating and down-regulating properties.
New highly stereoselective synthesis of (Z)-4-hydroxytamoxifen and (Z)-4-hydroxytoremifene via McMurry reaction
Gauthier, Sylvain,Mailhot, Josee,Labrie, Fernand
, p. 3890 - 3893 (2007/10/03)
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