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ID: ALA1137237

Journal: Bioorg Med Chem Lett

Title: Identification of isothiazole-4-carboxamidines derivatives as a novel class of allosteric MEK1 inhibitors.

Authors: El Abdellaoui H, Varaprasad CV, Barawkar D, Chakravarty S, Maderna A, Tam R, Chen H, Allan M, Wu JZ, Appleby T, Yan S, Zhang W, Lang S, Yao N, Hamatake R, Hong Z.

Abstract: The development of potent, orally bioavailable, and selective series of 5-amino-3-hydroxy-N(1-hydroxypropane-2-yl)isothiazole-4-carboxamidine inhibitors of MEK1 and MEK-2 kinase is described. Optimization of the carboxamidine and the phenoxyaniline group led to the identification of 55 which gave good potency as in vitro MEK1 inhibitors, and good oral exposure in rat.

CiteXplore: 16934458

DOI: 10.1016/j.bmcl.2006.08.048