Synthesis and inhibitory activity of 4-alkynyl and 4-alkenylquinazolines: Identification of new scaffolds for potent EGFR tyrosine kinase inhibitors

The present study identified several 4-alkynyl and 4-alkenylquinazolines that serve as novel and potent EGFR tyrosine kinase inhibitors. The IC50 values of these compounds are in the nanomolar range. In addition, the 4-(4-phenylbut-1-yn/en-yl)quinazolines provided scaffolds for potent enzyme inhibition. Chiral discrimination was observed to occur in one of the 4-alkynylquinazoline derivatives with the (R)-isomer being more than 150 times as potent as the (S)-isomer.

Novel chemotypes for EGFR TK inhibitors with IC50 values in the nM range were reported.Figure optionsDownload as PowerPoint slide