Synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors

As a class III receptor tyrosine kinase (RTK), FMS-like tyrosine kinase 3 (FLT3) is always overexpressed in many cases of acute leukemia. This paper studies the structure-based synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Encouragingly, compounds 15b, 16b, 24a, and 24c showed excellent biological activities in a low nanomolar range. In particular, compound 16b demonstrated significant inhibitory potency against FLT3-ITD (IC₅₀ = 5.60 nM) and better antiproliferative activity than quizartinib against MV4-11 cell line (IC₅₀ = 0.176 nM). It is indicated that compound 16b for the treatment of acute myeloid leukemia could be very promising.

Biological evaluation; FLT3 inhibitor; Internal tandem duplication; MV4-11.