Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia

Profiling of the
kinase-binding capabilities of an aminopyrimidine
analogue detected in a cellular screen of the St. Jude small-molecule
collection led to the identification of a novel series of FMS-like
tyrosine kinase 3 (FLT3) inhibitors. Structure–activity relationship
studies led to the development of compounds exhibiting good potency
against MV4-11 and MOLM13 acute myelogenous leukemia cells driven
by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological
profiling demonstrated that compound 5e shows characteristics
suitable for further preclinical development.