Identification of 2-acylaminothiophene-3-carboxamides as potent inhibitors of FLT3.

Raymond J Patch, Christian A Baumann, Jian Liu, Alan C Gibbs, Heidi Ott, Jennifer Lattanze, Mark R Player

Index: Bioorg. Med. Chem. Lett. 16 , 3282-3286

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Abstract

A series of 2-acylaminothiophene-3-carboxamides has been identified which exhibit potent inhibitory activity against the FLT3 tyrosine kinase. Compound 44 inhibits the isolated enzyme (IC50 = 0.027 microM) and blocks the proliferation of MV4-11 cells (IC50 = 0.41 microM). Structure-activity relationship studies within this series are described in the context of a proposed binding model within the ATP binding site of the enzyme.