FLT3 and acute myeloid leukemia: These findings are substantiated inanother of our studies, which found that trisubstituted purine derivativesare potent FLT3 inhibitors that selectively block the proliferationof AML cell lines harboring FLT3-ITD mutations.12 In order to identify potent and selective FLT3 inhibitors,we focused on synthesizing heterocyclic mimics of the purine basebearing similar substitution patterns as the parent purine derivatives.We designed trisubstituted derivatives containing various heterocycliccores (Figure 1B) andthen evaluated their inhibitory effects on FLT3 kinase in vitro andin vivo.