3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure–activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells.

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