Fms-like tyrosine kinase 3 (FLT3) is widely expressed and often mutated in acute myeloid leukemia (AML), which makes it an important target for the treatment of AML. The structure-based synthesis and biological evaluation of 5,6-dihydrobenzo[h]quinazoline derivatives as FLT3 inhibitors has been studied in this paper. III-1a, III-1c, III-2a, III-2c and III-4a displayed comparable inhibitory potency against FLT3-ITD and showed remarkable antiproliferative activities against MV4-11.