1001917-62-9Relevant articles and documents
ANTIVIRAL PYRIDOPYRAZINEDIONE COMPOUNDS
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Paragraph 0587-0588, (2020/04/09)
The invention provides compounds of Formula (I) as described herein, along with pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and methods to use these compounds, salts and compositions for treating viral infections, particularly infections caused by herpesviruses.
Discovery of 1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5] cyclohepta[1,2-b]pyridin-7-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide (MK-8033): A specific c-Met/Ron dual kinase inhibitor with preferential affinity for the activated state of c-Met
Northrup, Alan B.,Katcher, Matthew H.,Altman, Michael D.,Chenard, Melissa,Daniels, Matthew H.,Deshmukh, Sujal V.,Falcone, Danielle,Guerin, David J.,Hatch, Harold,Li, Chaomin,Lu, Wei,Lutterbach, Bart,Allison, Timothy J.,Patel, Sangita B.,Reilly, John F.,Reutershan, Michael,Rickert, Keith W.,Rosenstein, Craig,Soisson, Stephen M.,Szewczak, Alexander A.,Walker, Deborah,Wilson, Kevin,Young, Jonathan R.,Pan, Bo-Sheng,Dinsmore, Christopher J.
, p. 2294 - 2310 (2013/06/04)
This report documents the first example of a specific inhibitor of protein kinases with preferential binding to the activated kinase conformation: 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one 11r (MK-8033), a dual c-Met/Ron inhibitor under investigation as a treatment for cancer. The design of 11r was based on the desire to reduce time-dependent inhibition of CYP3A4 (TDI) by members of this structural class. A novel two-step protocol for the synthesis of benzylic sulfonamides was developed to access 11r and analogues. We provide a rationale for the observed selectivity based on X-ray crystallographic evidence and discuss selectivity trends with additional examples. Importantly, 11r provides full inhibition of tumor growth in a c-Met amplified (GTL-16) subcutaneous tumor xenograft model and may have an advantage over inactive form kinase inhibitors due to equal potency against a panel of oncogenic activating mutations of c-Met in contrast to c-Met inhibitors without preferential binding to the active kinase conformation.