867155-10-0Relevant academic research and scientific papers
Synthesis and SAR study of novel 3,3-diphenyl-1,3-dihydroindol-2-one derivatives as potent eIF2·GTP·Met-tRNAiMet ternary complex inhibitors
Denoyelle, Séverine,Chen, Ting,Yang, Hongwei,Chen, Limo,Zhang, Yingzhen,Halperin, José A.,Aktas, Bertal H.,Chorev, Michael
, p. 537 - 553 (2013/10/22)
The growing recognition of inhibition of translation initiation as a new and promising paradigm for mechanism-based anti-cancer therapeutics is driving the development of potent, specific, and druggable inhibitors. The 3,3-diaryloxindoles were recently reported as potential inhibitors of the eIF2·GTP·Met-tRNAiMet ternary complex assembly and 3-{5-tert-butyl-2-hydroxyphenyl}-3-phenyl-1,3-dihydro-2H-indol-2- one #1181 was identified as the prototypic agent of this chemotype. Herein, we report our continuous effort to further develop this chemotype by exploring the structural latitude toward different polar and hydrophobic substitutions. Many of the novel compounds are more potent than the parent compound in the dual luciferase ternary complex reporter assay, activate downstream effectors of reduced ternary complex abundance, and inhibit cancer cell proliferation in the low μM range. Moreover, some of these compounds are decorated with substituents that are known to endow favorable physicochemical properties and as such are good candidates for evaluation in animal models of human cancer.
Synthesis and antitumor effect in vitro and in vivo of substituted 1,3-dihydroindole-2-ones
Christensen, Mette K.,Erichsen, Kamille D.,Trojel-Hansen, Christina,Tj?rnelund, Jette,Nielsen, S?ren J.,Frydenvang, Karla,Johansen, Tommy N.,Nielsen, Birgitte,Sehested, Maxwell,Jensen, Peter B.,Ikaunieks, Martins,Zaichenko, Andrei,Loza, Einars,Kalvinsh, Ivars,Bj?rkling, Fredrik
supporting information; experimental part, p. 7140 - 7145 (2010/12/25)
Optimization of the anticancer activity for a class of compounds built on a 1,3-dihydroindole-2-one scaffold was performed. In comparison with recently published derivatives of oxyphenisatin the new analogues exhibited an equally potent antiproliferative activity in vitro and improved tolerability and activity in vivo. The best compounds from this series showed low nanomolar antiproliferative activity toward a series of cancer cell lines (compound (S)-38: IC50 of 0.48 and 2 nM in MCF-7 (breast) and PC3 (prostate), respectively) and potent antitumor effects in well tolerated doses in xenograft models. The racemic compound (RS)-38 showed complete tumor regression at a dose of 20 mg/kg administered iv on days 1 and 7 in a PC3 rat xenograft.
SUBSTITUTED 3-(4-HYDROXYPHENYL)-INDOLIN-2-ONE-COMPOUNDS
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Page/Page column 34, (2008/12/08)
The present application discloses substituted 3-(4-hydroxyphenyl)-indolin-2-one compounds(oxindole compounds) of the Formula (I) and the use of such compounds for the preparation of a medicament for the treatment of cancer in a mammal, in particular in hu
