Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1, 2-dihydropyridine-3-carboxamide (BMS-777607), a …

…, J Dai, J Gullo-Brown, A Gupta, B Henley…

Index: Schroeder, Gretchen M.; An, Yongmi; Cai, Zhen-Wei; Chen, Xiao-Tao; Clark, Cheryl; Cornelius, Lyndon A. M.; Dai, Jun; Gullo-Brown, Johnni; Gupta, Ashok; Henley, Benjamin; Hunt, John T.; Jeyaseelan, Robert; Kamath, Amrita; Kim, Kyoung; Lippy, Jonathan; Lombardo, Louis J.; Manne, Veeraswamy; Oppenheimer, Simone; Sack, John S.; Schmidt, Robert J.; Shen, Guoxiang; Stefanski, Kevin; Tokarski, John S.; Trainor, George L.; Wautlet, Barri S.; Wei, Donna; Williams, David K.; Zhang, Yingru; Zhang, Yueping; Fargnoli, Joseph; Borzilleri, Robert M. Journal of Medicinal Chemistry, 2009 , vol. 52, # 5 p. 1251 - 1254

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Citation Number: 145

Abstract

Substituted N-(4-(2-aminopyridin-4-yloxy)-3-fluoro-phenyl)-1-(4-fluorophenyl)-2-oxo-1, 2- dihydropyridine-3-carboxamides were identified as potent and selective Met kinase inhibitors. Substitution of the pyridine 3-position gave improved enzyme potency, while substitution of the pyridone 4-position led to improved aqueous solubility and kinase selectivity. Analogue 10 demonstrated complete tumor stasis in a Met-dependent GTL-16 ...