3-(2-amino-4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl)prop-2-yn-1-ol | 868736-81-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(2-amino-4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl)prop-2-yn-1-ol
• 英文别名: 3-[2-Amino-4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl]prop-2-yn-1-ol
• CAS: 868736-81-6
• 化学式: C₁₄H₁₀FN₃O₄
• 分子量: 303.25
• InChiKey: BZFAEHKFORRWQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(2-amino-4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl)prop-2-yn-1-ol 在 氯化铵 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 3-(2-amino-4-(4-amino-2-fluorophenoxy)pyridin-3-yl)prop-2-yn-1-ol
  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-iodopyridin-2-amine 、 2-丙炔-1-醇 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.42h， 以81%的产率得到3-(2-amino-4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl)prop-2-yn-1-ol
  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

• Monocyclic heterocycles as kinase inhibitors
  申请人：Borzilleri M. Robert

  公开号：US20050245530A1

  公开（公告）日：2005-11-03

  The present invention is directed to compounds having the formula and methods for using them for the treatment of cancer.

  本发明涉及具有以下公式化合物的用途以及使用它们治疗癌症的方法。
• MONOCYCLIC HETEROCYCLES AS KINASE INHIBITORS
  申请人：Borzilleri Robert M.

  公开号：US20090054436A1

  公开（公告）日：2009-02-26

  The present invention is directed to compounds having the formula and methods for using them for the treatment of cancer.

  本发明涉及具有以下结构式的化合物及其用于癌症治疗的方法。
• 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.
• US7459562B2
  申请人：——

  公开号：US7459562B2

  公开（公告）日：2008-12-02
• US7714138B2
  申请人：——

  公开号：US7714138B2

  公开（公告）日：2010-05-11