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

被引：126

作者：

Albrecht, Brian K. ^{[1
]}

Harmange, Jean-Christophe ^{[1
]}

Bauer, David ^{[1
]}

Berry, Loren ^{[1
]}

Bode, Christiane ^{[1
]}

Boezio, Alessandro A. ^{[1
]}

Chen, April ^{[1
]}

Choquette, Deborah ^{[1
]}

Dussault, Isabelle ^{[2
]}

Fridrich, Cary ^{[1
]}

Hirai, Satoko ^{[1
]}

Hoffman, Doug ^{[2
]}

Larrow, Jay F. ^{[1
]}

Kaplan-Lefko, Paula ^{[2
]}

Lin, Jasmine ^{[1
]}

Lohman, Julia ^{[1
]}

Long, Alexander M. ^{[1
]}

Moriguchi, Jodi ^{[2
]}

O'Connor, Anne ^{[1
]}

Potashman, Michele H. ^{[1
]}

Reese, Monica ^{[2
]}

Rex, Karen ^{[2
]}

Siegmund, Aaron ^{[2
]}

Shah, Kavita ^{[1
]}

Shimanovich, Roman ^{[1
]}

Springer, Stephanie K. ^{[1
]}

Teffera, Yohannes ^{[1
]}

Yang, Yajing ^{[2
]}

Zhang, Yihong ^{[2
]}

Bellon, Steven F. ^{[1
]}

机构：

[1] Amgen Inc, Cambridge, MA 02139 USA

[2] Amgen Inc, Thousand Oaks, CA 91320 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 10期

关键词：

D O I：

10.1021/jm800043g

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 turner types. Herein we report the discovery of potent and selective triazolopyridazine small molecules that inhibit c-Met activity.

引用

页码：2879 / 2882

页数：4

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