Knowledge-based design of 7-azaindoles as selective B-Raf inhibitors

The synthesis of a 7-azaindole series of novel, potent B-Raf kinase inhibitors using knowledge-based design was carried out. Compound 6h exhibits not only excellent potency in both the enzyme assay (IC50 = 2.5 nM) and the cellular assay (IC50 = 63 nM), but also has an outstanding selectivity profile against other kinases.

Graphical abstractWe have identified the title compound 6h as a novel, potent, and selective B-Raf kinase inhibitor using knowledge-based design.Figure optionsDownload full-size imageDownload as PowerPoint slide