Potent and selective EGFR inhibitors based on 5-aryl-7H-pyrrolopyrimidin-4-amines.

The epidermal growth factor receptor represents an important target in cancer therapy, and low molecular weight inhibitors based on quinazolines have reached the marked. Herein we report on a new scaffold, 5-aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines, and show that when employing (S)-phenylglycinol as C-4 substituent, potent inhibitors can be made. The two most active inhibitors have suitable druglike properties, were equipotent with Erlotinib in Ba/F3 cell studies, and showed lower cross reactivity than Erlotinib in a panel of 50 kinases.