Discovery\nof IRAK1/4/pan-FLT3 Kinase Inhibitors as\nTreatments for Acute Myeloid Leukemia

We report the discovery of an imidazopyridine series\nof IRAK1/4/pan-FLT3\nkinase inhibitors. Optimization of this series has produced compound <b>31</b> which displays potent and selective inhibition of IRAK1,\nIRAK4, FLT3, and all mutant forms of FLT3, as well as good in vitro\nADME and pharmacokinetic properties. In a mouse xenograft model of\nAML, <b>31</b> produces survival prolongation equal to that\nof Gilteritinib, the leading marketed FLT3 inhibitor currently used\nto treat AML.