An amino-indazole scaffold with spectrum selective kinase inhibition of FLT3, PDGFRα and kit

Here we describe the synthesis and characterization of a number of 3-amino-1H-indazol-6-yl-benzamides that were designed to target the ‘DFG-out’ conformation of the kinase activation loop. Several compounds such as 4 and 11 exhibit single-digit nanomolar EC50s against FLT3, c-Kit and the gatekeeper T674M mutant of PDGFRα.

Graphical abstractHere we describe the synthesis and characterization of a number of 3-amino-1H-indazol-6-yl-benzamides that were designed to target the ‘DFG-out’ conformation of the kinase activation loop. Several compounds such as 4 and 11 exhibit single-digit nanomolar EC50s against FLT3, c-Kit and the gatekeeper T674M mutant of PDGFRα.Figure optionsDownload full-size imageDownload as PowerPoint slide