Design, Synthesis and Biological Evaluation of Quinoxalin-2(1H)-one Derivatives as EGFR Tyrosine Kinase Inhibitors

With the successful use of gefitinib and erlotinib in clinic, some potent EGFR tyrosine kinase receptor inhibitors have gained widespread concern in the treatment of ovarian or non-small-cell lung cancer. However, the emergence of EGFR-activating mutations resist to the drugs, there is an impending need to design new inhibitor targeted EGFR. Furthermore, the understanding of mutual effect between EGFR and drug has been available, it has become a hot spot for the research of anticancer drugs. We have designed and synthesized a series of 6-methoxy-7-(3-morpholinopropoxy)-1-(2- phenoxyethyl)-quinoxalin-2(1H)-one derivatives as novel EGFR inhibitors. Most of the compounds have showed inhibitory activity toward EGFR kinase. This work has demonstrated it is possible to construct a new type of EGFR protein kinase inhibitor using a designin strategy.