2-Anilino-4-(benzimidazol-2-yl)pyrimidines – A multikinase inhibitor scaffold with antiproliferative activity toward cancer cell lines

2-Anilino-4-(benzimidazol-2-yl)-pyrimidines, synthesized by reaction of a readily available benzimidazole-substituted enaminone with suitable arylguanidines, were shown to inhibit four cancer-related protein kinases (Aurora B, PLK1, FAK, and VEGF-R2). The most potent derivative exhibited antiproliferative activity for several cancer cell lines of the NCI in vitro cell line panel in submicromolar concentrations. Both the anilinopyrimidine structure and the substitution pattern at the aniline ring appear to be important for the protein kinase inhibitory activity.

Graphical abstractThe title compounds were developed as inhibitors of cancer-related protein kinases. The most potent congener exhibited antiproliferative activity toward cancer cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Title compounds were synthesized by reaction of an enaminone with arylguanidines. ► Title compounds inhibited Aurora B, FAK, PLK1, and VEGF-R2. ► The most potent derivative exhibited antiproliferative activity toward cancer cell lines.