Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities

By repurposing a typical dopamine D 1 /D 5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed.Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases.Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF 3 /EML4-ALK xenograft mice model.