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.

中文翻译：

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的发现ñ - （4-（2-氨基-3-氯吡啶-4-基氧基）-3-氟苯基）-4-乙氧基-1-（4-氟苯基）-2-氧代-1,2-二氢吡啶-3-羧酰胺（BMS-777607），Met激酶超家族的选择性和口服有效抑制剂

取代的N-（4-（2-氨基吡啶-4-基氧基）-3-氟-苯基）-1-（4-氟苯基）-2-氧代-1,2-二氢吡啶-3-羧酰胺被确定为有效的和选择性的Met激酶抑制剂。取代吡啶3位可提高酶的效力，而取代吡啶酮4位可提高水溶性和激酶选择性。类似物10在口服给药后在Met依赖性GTL-16人胃癌异种移植模型中显示出完全的肿瘤停滞。由于其出色的体内功效以及良好的药代动力学和临床前安全性，已将10种药物进入了I期临床试验。