tert-butyl 4-(4-amino-2-fluorophenoxy)-3-((tert-butyldimethylsilyloxy)-methyl)pyridin-2-ylcarbamate | 868736-57-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl 4-(4-amino-2-fluorophenoxy)-3-((tert-butyldimethylsilyloxy)-methyl)pyridin-2-ylcarbamate
• 英文别名: tert-butyl N-[4-(4-amino-2-fluorophenoxy)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]pyridin-2-yl]carbamate
• CAS: 868736-57-6
• 化学式: C₂₃H₃₄FN₃O₄Si
• 分子量: 463.625
• InChiKey: ZDTHFCFCHWYINB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.46
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  95.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-氟苯基)-2-氧代-1,2-二氢吡啶-3-羧酸 、 tert-butyl 4-(4-amino-2-fluorophenoxy)-3-((tert-butyldimethylsilyloxy)-methyl)pyridin-2-ylcarbamate 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 tert-butyl 3-((tert-butyldimethylsilyloxy)methyl)-4-(2-fluoro-4-(1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)pyridin-2-ylcarbamate
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm801586s
• 作为产物：
  描述：

  tert-butyl 3-((tert-butyldimethylsilyloxy)methyl)-4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylcarbamate 在 氯化铵 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 tert-butyl 4-(4-amino-2-fluorophenoxy)-3-((tert-butyldimethylsilyloxy)-methyl)pyridin-2-ylcarbamate
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm801586s

文献信息

• MET kinase inhibitors
  申请人：Borzilleri M. Robert

  公开号：US20070078140A1

  公开（公告）日：2007-04-05

  The present invention is directed to compounds having the formula I or II: including salts thereof, and methods for using them for the treatment of cancer.

  本发明涉及具有以下化学式I或II的化合物：包括其盐，并且使用它们用于治疗癌症的方法。