We report the discovery of an imidazopyridine series of IRAK1/4/pan-FLT3 kinase inhibitors. Optimization of this series has produced compound 31 which displays potent and selective inhibition of IRAK1, IRAK4, FLT3, and all mutant forms of FLT3, as well as good in vitro ADME and pharmacokinetic properties. In a mouse xenograft model of AML, 31 produces survival prolongation equal to that of Gilteritinib, the leading marketed FLT3 inhibitor currently used to treat AML.
© 2024 The Authors. Published by American Chemical Society.