Synthesis and biological evaluation of 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-substituted-phenoxy)pyrimidines as dual EGFR/ErbB-2 kinase inhibitors

A series of 4,6-disubstituted pyrimidines derivatives were designed and synthesized as dual EGFR/ErbB-2 inhibitors. 4-[3-Chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-acrylamidophenoxy)pyrimidine and 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-{3-[6-(4-amino)pyrimidinyl]amino)phenoxy}pyrimidine had the best biological activities in vitro. Docking simulation was performed to explore the binding model of these compounds with EGFR.