tert-butyl 3-((tert-butyldimethylsilyloxy)methyl)-4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylcarbamate | 868736-56-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl 3-((tert-butyldimethylsilyloxy)methyl)-4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylcarbamate
• 英文别名: tert-butyl N-[3-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]carbamate
• CAS: 868736-56-5
• 化学式: C₂₃H₃₂FN₃O₆Si
• 分子量: 493.607
• InChiKey: WJAPQFFTBJKLKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.79
• 重原子数：
  34
• 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：
  116
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  tert-butyl (4-(2-fluoro-4-nitrophenoxy)-3-(hydroxymethyl)pyridin-2-yl)carbamate 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以102 mg的产率得到tert-butyl 3-((tert-butyldimethylsilyloxy)methyl)-4-(2-fluoro-4-nitrophenoxy)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

• Discovery of <i>N</i>-(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
  作者：Gretchen M. Schroeder、Yongmi An、Zhen-Wei Cai、Xiao-Tao Chen、Cheryl Clark、Lyndon A. M. Cornelius、Jun Dai、Johnni Gullo-Brown、Ashok Gupta、Benjamin Henley、John T. Hunt、Robert Jeyaseelan、Amrita Kamath、Kyoung Kim、Jonathan Lippy、Louis J. Lombardo、Veeraswamy Manne、Simone Oppenheimer、John S. Sack、Robert J. Schmidt、Guoxiang Shen、Kevin Stefanski、John S. Tokarski、George L. Trainor、Barri S. Wautlet、Donna Wei、David K. Williams、Yingru Zhang、Yueping Zhang、Joseph Fargnoli、Robert M. Borzilleri

  DOI：10.1021/jm801586s

  日期：2009.3.12

  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.