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  • Title: Discovery of novel type II c-Met inhibitors based on BMS-777607.
    Author: Zhang W, Ai J, Shi D, Peng X, Ji Y, Liu J, Geng M, Li Y.
    Journal: Eur J Med Chem; 2014 Jun 10; 80():254-66. PubMed ID: 24792774.
    Abstract:
    Twenty-two new analogs based on the structure of BMS-777607 were designed, synthesized, and evaluated to determine their biological activities. Compounds bearing a cyclic sulfonamide or α-chloropiperidone scaffold exhibited good activity, which may provide a new basis for further structural optimization. Quinoline-containing analogs exhibited better results than did their counterparts with an aminopyrimidine, aminopyridine, or pyrrolopyridine unit. Two analogs, 22d and 22e, stood out as the most potent c-Met inhibitors with IC50s of 0.9 and 1.7 nM, respectively. These two compounds were more potent than BMS-777607 in enzymatic inhibition and cell proliferation studies.
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