Discovery of 1-[3-(1-Methyl-1 H-pyrazol-4-yl)-5-oxo-5 H-benzo [4, 5] cyclohepta [1, 2-b] pyridin-7-yl]-N-(pyridin-2-ylmethyl) methanesulfonamide (MK-8033): A Specific …

…, MH Daniels, SV Deshmukh, D Falcone…

Index: 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. Journal of Medicinal Chemistry, 2013 , vol. 56, # 6 p. 2294 - 2310

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Citation Number: 18

Abstract

This report documents the first example of a specific inhibitor of protein kinases with preferential binding to the activated kinase conformation: 5 H-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 ...