4-(4-amino-2-fluorophenoxy)-3-((trimethylsilyl)ethynyl)pyridin-2-amine | 1132055-77-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-amino-2-fluorophenoxy)-3-((trimethylsilyl)ethynyl)pyridin-2-amine
• 英文别名: 4-(4-Amino-2-fluorophenoxy)-3-(2-trimethylsilylethynyl)pyridin-2-amine
• CAS: 1132055-77-6
• 化学式: C₁₆H₁₈FN₃OSi
• 分子量: 315.422
• InChiKey: RFCKWRSAFZIXFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.41
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  74.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-amino-2-fluorophenoxy)-3-((trimethylsilyl)ethynyl)pyridin-2-amine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以88%的产率得到4-(4-氨基-2-氟苯氧基)-3-乙炔基吡啶-2-胺
  参考文献：
  名称：

  Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors

  摘要：

  A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.

  DOI：

  10.1016/j.bmcl.2008.04.047
• 作为产物：
  描述：

  4-(2-fluoro-4-nitrophenoxy)-3-((trimethylsilyl)ethynyl)pyridin-2-amine 在 氯化铵 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 4-(4-amino-2-fluorophenoxy)-3-((trimethylsilyl)ethynyl)pyridin-2-amine
  参考文献：
  名称：

  Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors

  摘要：

  A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.

  DOI：

  10.1016/j.bmcl.2008.04.047

文献信息

• Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors
  作者：Zhen-Wei Cai、Donna Wei、Gretchen M. Schroeder、Lyndon A.M. Cornelius、Kyoung Kim、Xiao-Tao Chen、Robert J. Schmidt、David K. Williams、John S. Tokarski、Yongmi An、John S. Sack、Veeraswamy Manne、Amrita Kamath、Yueping Zhang、Punit Marathe、John T. Hunt、Louis J. Lombardo、Joseph Fargnoli、Robert M. Borzilleri

  DOI：10.1016/j.bmcl.2008.04.047

  日期：2008.6

  A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.
• 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.