Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase

  • J Med Chem. 2008 May 22;51(10):2879-82. doi: 10.1021/jm800043g.
Brian K Albrecht  1 ,  Jean-Christophe Harmange ,  David Bauer ,  Loren Berry ,  Christiane Bode ,  Alessandro A Boezio ,  April Chen ,  Deborah Choquette ,  Isabelle Dussault ,  Cary Fridrich ,  Satoko Hirai ,  Doug Hoffman ,  Jay F Larrow ,  Paula Kaplan-Lefko ,  Jasmine Lin ,  Julia Lohman ,  Alexander M Long ,  Jodi Moriguchi ,  Anne O'Connor ,  Michele H Potashman ,  Monica Reese ,  Karen Rex ,  Aaron Siegmund ,  Kavita Shah ,  Roman Shimanovich ,  Stephanie K Springer ,  Yohannes Teffera ,  Yajing Yang ,  Yihong Zhang ,  Steven F Bellon
Affiliations
PMID: 18426196 DOI: 10.1021/jm800043g
Abstract

Tumorigenesis is a multistep process in which oncogenes play a key role in tumor formation, growth, and maintenance. Met was discovered as an oncogene that is activated by its ligand, hepatocyte growth factor. Deregulated signaling in the c-Met pathway has been observed in multiple tumor types. Herein we report the discovery of potent and selective triazolopyridazine small molecules that inhibit c-Met activity.

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