Overcoming the FLT3-ITD mutant has been a promising drug design strategy for treating acute myeloid leukemia (AML). Herein, we discovered a novel FLT3 inhibitor <b>17</b>, which displayed potent inhibitory activity against the FLT3-ITD mutant (IC<sub>50</sub> = 0.8 nM) and achieved good selectivity over c-KIT kinase (over 500-fold). Compound <b>17</b> selectively inhibited the proliferation of FLT3-ITD-positive AML cell lines MV4-11 (IC<sub>50</sub> = 23.5 nM) and MOLM-13 (IC<sub>50</sub> = 35.5 nM) and exhibited potent inhibitory effects against associated acquired resistance mutations. In cellular mechanism studies, compound <b>17</b> strongly inhibited FLT3-mediated signaling pathways and induced apoptosis by arresting the cell cycle in the sub-G1 phase. In in vivo studies, compound <b>17</b> demonstrated a good bioavailability (73.6%) and significantly suppressed tumor growth in MV4-11 (10 mg/kg, TGI 93.4%) and MOLM-13 (20 mg/kg, TGI 98.0%) xenograft models without exhibiting obvious toxicity. These results suggested that compound <b>17</b> may be a promising drug candidate for treating FLT3-ITD-positive AML.