Design, synthesis and antitumor activities of novel bis-aryl ureas derivatives as Raf kinase inhibitors.

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Zhan W, Li Y, Huang W, Zhao Y, Yao Z, Yu S, Yuan S, Jiang F, Yao S, Li S

Design, synthesis and antitumor activities of novel bis-aryl ureas derivatives as Raf kinase inhibitors.

Bioorg Med Chem. 2012 Jul 15;20(14):4323-9. doi: 10.1016/j.bmc.2012.05.051. Epub 2012 May 30.

PubMed ID

22721924 [ View in PubMed

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Abstract

A series of novel bis-aryl ureas containing trifluoromethyl imidazolyl group targeting Raf kinase were designed and synthesized based on the lead compound of Sorafenib. All the prepared compounds were evaluated for their in vitro antiproliferative activities against three human cancer cell lines including MDA-MB-231 (breast), BGC-823 (gastric), and SMMC-7721 (liver). Several compounds from the series exhibited excellent antitumor activities against all three tested cancer lines. Further their inhibitory activities against Raf kinase were investigated, and three compounds (11c, 11d, and 11p) demonstrated better activities than contrast drug Sorafenib. Especially compound 11c was found to be a potent and selective Raf kinase inhibitor and could be considered as a candidate compound for further development.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Sorafenib	RAF proto-oncogene serine/threonine-protein kinase	IC 50 (nM)	24.3	N/A	N/A	Details