Design and Synthesis of New Sulfonamides-Based Flt3 Inhibitors

Background: Flt3 is an oncogenic kinase involved in different leukemias. It is most prominently associated with acute myeloid leukemia (AML). Flt3-specific inhibitors have shown promising results in interfering with AML. Methods: The crystallographic structures of two inhibitors complexed within Flt3, namely, quizartinib and F6M, were used to guide the synthesis of new sulfonamide-based Flt3 inhibitors. Results: One of the prepared compounds showed low micromolar anti-Flt3 bioactivity, and interestingly, low micromolar bioactivity against the related oncogenic kinase VEGFR2. Conclusion: Sulfonamides were successfully used as privileged scaffolds for the synthesis of novel Flt3 inhibitors of micromolar potencies.