1001500-53-3Relevant articles and documents
Discovery of Potent, Selective Triazolothiadiazole-Containing c-Met Inhibitors
Aronov, Alex M.,Boucher, Diane,Deininger, David D.,Ford, Pamella J.,Giroux, Simon,Lauffer, David J.,Li, Pan,Liang, Jianglin,McGinty, Kira,Moody, Cameron S.,Ronkin, Steven,Swett, Rebecca,Tang, Qing,Waal, Nathan
, p. 955 - 960 (2021)
Herein, we report a novel series of highly potent and selective triazolothiadiazole c-Met inhibitors. Starting with molecule 5, we have applied structure-based drug design principles to identify the triazolothiadiazole ring system. We successfully replaced the metabolically unstable phenolic moiety with a quinoline group. Further optimization around the 5,6 bicyclic moiety led to the identification of 21. Compound 21 suffered from PDE3 selectivity issues and subsequent, structurally informed design led to the discovery of compound 23. Compound 23 has exquisite kinase selectivity, excellent potency, favorable ADME profile, and showed dose-dependent antitumor efficacy in a SNU-5 gastric cancer xenograft model.
8 - SUBSTITUTED 2 -AMINO - [1,2,4] TRIAZOLO [1, 5 -A] PYRAZINES AS SYK TRYROSINE KINASE INHIBITORS AND GCN2 SERIN KINASE INHIBITORS
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Page/Page column 107; 108, (2013/09/12)
Compounds of the formula I in which R1, R2 and R4 have the meanings indicated in Claim 1, are inhibitors of Syk, and can be employed, inter alia, for the treatment of cancer, rheumatoid arthritis and / or systemic lupus
