Identification and synthesis of N-(thiophen-2-yl) benzamide derivatives as BRAFV600E inhibitors

Abstract

The V600E BRAF kinase mutation, which activates the downstream MAPK signaling pathway, commonly occurs in about 8% of all human malignancies and about 50% of all melanomas. In this study, we employed virtual screening and chemical synthesis to identify a series of N-(thiophen-2-yl) benzamide derivatives as potent BRAFV600E inhibitors.. Structure-activity relationship studies of these derivatives revealed that compounds b40 and b47 are the two most potent BRAFV600E inhibitors in this series.