1001500-53-3Relevant academic research and scientific papers
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.
Design, synthesis, and evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase (InhA) for the treatment of tuberculosis
?ink, Roman,Sosi?, Izidor,?ivec, Matej,Fernandez-Menendez, Raquel,Turk, Samo,Pajk, Stane,Alvarez-Gomez, Daniel,Lopez-Roman, Eva Maria,Gonzales-Cortez, Carolina,Rullas-Triconado, Joaquin,Angulo-Barturen, Inigo,Barros, David,Ballell-Pages, Lluís,Young, Robert J.,Encinas, Lourdes,Gobec, Stanislav
, p. 613 - 624 (2015)
Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.
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
AMINOPYRAZOLE TRIAZOLOTHIADIAZOLE INHIBITORS OF C-MET PROTEIN KINASE
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Page/Page column 26, (2010/12/26)
The present invention relates to compounds of formula (I), which is useful in the inhibition of c-Met protein kinase. The invention also provides pharmaceutically acceptable compositions comprising compounds of formula (I) and methods of using the compositions in the treatment of proliferative disorders
