Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors.

Basic Information

ID: ALA1158562

Journal: Bioorg Med Chem Lett

Title: Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors.

Authors: Williams DK, Chen XT, Tarby C, Kaltenbach R, Cai ZW, Tokarski JS, An Y, Sack JS, Wautlet B, Gullo-Brown J, Henley BJ, Jeyaseelan R, Kellar K, Manne V, Trainor GL, Lombardo LJ, Fargnoli J, Borzilleri RM.

Abstract: Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model.

CiteXplore: 20382527

DOI: 10.1016/j.bmcl.2010.01.042

Patent ID: