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The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a-b, 2a-v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC(50)=0.56-0.86 microM). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics. Copyright 2010 Elsevier Ltd. All rights reserved.

Citation

Hana Yu, Yunkyung Jung, Hwan Kim, Junghun Lee, Chang-Hyun Oh, Kyung Ho Yoo, Taebo Sim, Jung-Mi Hah. 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives: a novel type II Raf kinase inhibitors. Bioorganic & medicinal chemistry letters. 2010 Jun 15;20(12):3805-8

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PMID: 20466542

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