Design and synthesis of N-(4-aminopyridin-2-yl)amides as B-RafV600E inhibitors. Issue 12 (15th June 2016) - Li, Xiaokai
Graphical abstract: Abstract: B-Raf V600E was an effective target for the treatment of human cancers. Based on a pan-Raf inhibitor TAK-632, a series of N -(4-aminopyridin-2-yl)amide derivatives were designed as novel B-Raf V600E inhibitors. Detailed structure–activity studies of the compounds revealed that most of the compounds displayed potent enzymatic activity against B-Raf V600E, and good selectivity over B-Raf WT . One of the most promising compound4l exhibited potent inhibitory activity with an IC50 value of 38 nM for B-raf V600E, and displayed antiproliferative activities against colo205 and HT29 cells with IC50 values of 0.136 and 0.094 μM, respectively. It also displayed good selectivity on both enzymatic and cellular assays over B-Raf WT . These inhibitors may serve as lead compounds for further developing novel B-Raf V600E inhibitors as anticancer drugs.