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  • Title: Design, synthesis and biological activities of sorafenib derivatives as antitumor agents.
    Author: Yao J, He Z, Chen J, Sun W, Fang H, Xu W.
    Journal: Bioorg Med Chem Lett; 2012 Nov 01; 22(21):6549-53. PubMed ID: 23021967.
    Abstract:
    A series of novel sorafenib derivatives, 9a-w, was designed and synthesized in high yields using various substituted anilines, and their antiproliferative activities against HCT116, PC-3 and MDA-MB-231 cell lines were also evaluated and described. All compounds exhibited potent antiproliferative activity against HCT116 and PC-3 cells with IC(50)=2.8-52.0 and 2.2-45.6 μM; compounds 9p and 9q demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines, the cytotoxicity of compound 9r is more potent than that of sorafenib. Compounds (9g, 9p, 9q and 9r) were chosen for further evaluation of the anti-angiogenesis activity, and showed the inhibition of sprout formation from aortic ring ex vivo. The structures of all the newly synthesized compounds were determined by (1)H NMR, (13)C NMR and HRMS.
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