868733-97-5Relevant articles and documents
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 selective and orally efficacious inhibitor of the met kinase superfamily
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.
, p. 1251 - 1254 (2009)
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 human gastric carcinoma xenograft model following oral administration. Because of its excellent in vivo efficacy and favorable pharmacokinetic and preclinical safety profiles, 10 has been advanced into phase I clinical trials.
