Design, synthesis and biological evaluation of β-carboline derivatives as novel inhibitors targeting B-Raf kinase

β-Carboline family of compounds is a large group of alkaloids widely distributed in nature and exhibits broad-spectrum anti-tumor activities. We designed and synthesized two series of novel 1-carboxamide- and 6-sulfonamide-substituted β-carboline derivatives 7a–p and 12a–b, and their wild type B-Raf kinase inhibitory activities were described. Most compounds showed moderate to excellent inhibitory activities. Among them, 1-carboxamide-6-(N-(3-(dimethylamino)propyl)-sulfamoyl)-β-carboline, 7e exhibited potent activity (IC50 = 1.62 μM), showing the potential for further investigation as a lead compound.

Graphical abstractTwo series of novel 1-carboxamide and 6-sulfonamide substituted β-carboline derivatives 7a–o, 12a–b were designed and synthesized and their wild type B-Raf kinase inhibitory activities were described. Compound 1-carboxamide-6-(N-(3-(dimethylamino)propyl)sulfamoyl)-β-carboline, 7e exhibited potent activity (IC50 = 1.62 μM), showing the potential for further investigation as a lead compound.Figure optionsDownload full-size imageDownload as PowerPoint slide