10282-51-6Relevant academic research and scientific papers
Modular Continuous Flow Synthesis of Imatinib and Analogues
Fu, Wai Chung,Jamison, Timothy F.
supporting information, p. 6112 - 6116 (2019/08/26)
A modular continuous flow synthesis of imatinib and analogues is reported. Structurally diverse imatinib analogues are rapidly generated using three readily available building blocks via a flow hydration/chemoselective C-N coupling sequence. The newly developed continuous flow hydration and amidation modules each exhibit a broad scope with good to excellent yields. Overall, the method described does not require solvent switches, in-line purifications, or packed-bed apparatuses due to the judicious manipulation of flow setups and solvent mixtures.
New Indole Tubulin Assembly Inhibitors Cause Stable Arrest of Mitotic Progression, Enhanced Stimulation of Natural Killer Cell Cytotoxic Activity, and Repression of Hedgehog-Dependent Cancer
La Regina, Giuseppe,Bai, Ruoli,Coluccia, Antonio,Famiglini, Valeria,Pelliccia, Sveva,Passacantilli, Sara,Mazzoccoli, Carmela,Ruggieri, Vitalba,Verrico, Annalisa,Miele, Andrea,Monti, Ludovica,Nalli, Marianna,Alfonsi, Romina,Di Marcotullio, Lucia,Gulino, Alberto,Ricci, Biancamaria,Soriani, Alessandra,Santoni, Angela,Caraglia, Michele,Porto, Stefania,Da Pozzo, Eleonora,Martini, Claudia,Brancale, Andrea,Marinelli, Luciana,Novellino, Ettore,Vultaggio, Stefania,Varasi, Mario,Mercurio, Ciro,Bigogno, Chiara,Dondio, Giulio,Hamel, Ernest,Lavia, Patrizia,Silvestri, Romano
, p. 5789 - 5807 (2015/08/24)
We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of the indole and with halogen or methoxy substituent(s) at positions 4-7. Compounds 33 and 44 strongly inhibited the growth of the P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES and Messa/Dx5. At 10 nM, 33 and 44 stimulated the cytotoxic activity of NK cells. At 20-50 nM, 33 and 44 arrested >80% of HeLa cells in the G2/M phase of the cell cycle, with stable arrest of mitotic progression. Cell cycle arrest was followed by cell death. Indoles 33, 44, and 81 showed strong inhibition of the SAG-induced Hedgehog signaling activation in NIH3T3 Shh-Light II cells with IC50 values of 19, 72, and 38 nM, respectively. Compounds of this class potently inhibited tubulin polymerization and cancer cell growth, including stimulation of natural killer cell cytotoxic activity and repression of Hedgehog-dependent cancer.
