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

ABSTRACT

ß-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 ß-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)-ß-carboline, 7e exhibited potent activity (IC(50)=1.62 µM), showing the potential for further investigation as a lead compound.