1151801-90-9Relevant articles and documents
Synthesis and biological evaluation of new [1,2,4]triazolo[4,3-a]pyridine derivatives as potential c-Met inhibitors
Zhao, Junjun,Fang, Lei,Zhang, Xiaobing,Liang, Yan,Gou, Shaohua
, p. 3483 - 3493 (2016)
A series of [1,2,4]triazolo[4,3-a]pyrazine derivatives (4a–4i) were designed, synthesized and evaluated for their c-Met kinase inhibition and antitumor activity against SNU5 gastric cell line in vitro. Among these compounds, 4d was found to show the highest activity against c-Met and high selectivity against the tumor cells which are believed to be dependent on the c-Met oncogene amplification, because 4d selectively inhibited c-Met while had no effect on other 59 kinases. In vivo efficacy study on human gastric (MKN-45) and human non-small cell lung (NCI-H1993) tumor xenograft in nude mouse demonstrated that 4d·CH3SO3H had a better inhibiting activity than SGX-523 in a dose-dependent manner. When tested in mice, compound 4d·CH3SO3H was found to have biological half-lives and plasma exposure values higher than those of JNJ-38877605, and its long-term toxicity and acute toxicity turned out to be acceptable, all of which indicates that 4d·CH3SO3H is a desirable drug candidate.
Discovery of potent and selective 8-fluorotriazolopyridine c-met inhibitors
Peterson, Emily A.,Teffera, Yohannes,Albrecht, Brian K.,Bauer, David,Bellon, Steven F.,Boezio, Alessandro,Boezio, Christiane,Broome, Martin A.,Choquette, Deborah,Copeland, Katrina W.,Dussault, Isabelle,Lewis, Richard,Lin, Min-Hwa Jasmine,Lohman, Julia,Liu, Jingzhou,Potashman, Michele,Rex, Karen,Shimanovich, Roman,Whittington, Douglas A.,Vaida, Karina R.,Harmange, Jean-Christophe
, p. 2417 - 2430 (2015/03/30)
The overexpression of c-Met and/or hepatocyte growth factor (HGF), the amplification of the MET gene, and mutations in the c-Met kinase domain can activate signaling pathways that contribute to cancer progression by enabling tumor cell proliferation, survival, invasion, and metastasis. Herein, we report the discovery of 8-fluorotriazolopyridines as inhibitors of c-Met activity. Optimization of the 8-fluorotriazolopyridine scaffold through the combination of structure-based drug design, SAR studies, and metabolite identification provided potent (cellular IC50 a mouse liver pharmacodynamic model.
6 - SUBSTITUTED 3 - (QUINOLIN- 6 - YLTHIO) - [1,2,4] TRIAZOLO [4, 3 -A] PYRADINES AS TYROSINE KINASE
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Page/Page column 78; 79, (2013/03/28)
The invention relates to compounds of formula (I) and salts thereof: Formula (I) wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).