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Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase. 2008
Brian K Albrecht, and
Jean-Christophe Harmange, and
David Bauer, and
Loren Berry, and
Christiane Bode, and
Alessandro A Boezio, and
April Chen, and
Deborah Choquette, and
Isabelle Dussault, and
Cary Fridrich, and
Satoko Hirai, and
Doug Hoffman, and
Jay F Larrow, and
Paula Kaplan-Lefko, and
Jasmine Lin, and
Julia Lohman, and
Alexander M Long, and
Jodi Moriguchi, and
Anne O'Connor, and
Michele H Potashman, and
Monica Reese, and
Karen Rex, and
Aaron Siegmund, and
Kavita Shah, and
Roman Shimanovich, and
Stephanie K Springer, and
Yohannes Teffera, and
Yajing Yang, and
Yihong Zhang, and
Steven F Bellon
Amgen Inc., Cambridge, MA 02139, USA. brian.albrecht@amgen.com
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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