6-(6-amino-pyrimidin-4-yloxy)naphthalene-1-carboxylic acid(4-fluoro-3-trifluoromethyl phenyl)amide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(6-amino-pyrimidin-4-yloxy)naphthalene-1-carboxylic acid(4-fluoro-3-trifluoromethyl phenyl)amide
• 英文别名: 6-(6-aminopyrimidin-4-yl)oxy-N-[4-fluoro-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide
• 化学式: C₂₂H₁₄F₄N₄O₂
• 分子量: 442.372
• InChiKey: HJFDTNBKNJFDQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  90.1
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  6-羟基-1-萘甲酸 在 4-二甲氨基吡啶 、 sodium azide 、 palladium 10% on activated carbon 、 1-丙基磷酸酐 、 三乙胺 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 5.67h， 生成 6-(6-amino-pyrimidin-4-yloxy)naphthalene-1-carboxylic acid(4-fluoro-3-trifluoromethyl phenyl)amide
  参考文献：
  名称：

  A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis

  摘要：

  This paper describes the identification of 6-(pyrimidin-4-yloxy)-naphthalene-1-carboxamides as a new class of potent and selective human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitors. In biochemical and cellular assays, the compounds exhibit single-digit nanomolar potency toward VEGFR2. Compounds of this series show good exposure in rodents when dosed orally. They potently inhibit VEGF-driven angiogenesis in a chamber model and rodent tumor models at daily doses of less than 3 mg/kg by targeting the tumor vasculature as demonstrated by ELISA for TIE-2 in lysates or by immunohistochemical analysis. This novel series of compounds shows a potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role.

  DOI：

  10.1021/acs.jmedchem.5b01582

文献信息

• WO2007/31265
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2006/59234
  申请人：——

  公开号：——

  公开（公告）日：——
• COMBINATIONS COMPRISING A VEGF RECEPTOR INHIBITOR AND A PENETRATION ENHANCER
  申请人：Novartis AG

  公开号：EP1945217B1

  公开（公告）日：2012-05-02
• Combinations Comprising a Vegf Receptor Inhibitor
  申请人：Billich Andreas

  公开号：US20080306058A1

  公开（公告）日：2008-12-11

  A composition comprising a VEGF receptor inhibitor and a penetration enhancer and uses thereof.
• Combinations Comprising a VEGF Receptor Inhibitor
  申请人：BILLICH Andreas

  公开号：US20120172386A1

  公开（公告）日：2012-07-05

  A composition comprising a VEGF receptor inhibitor and a penetration enhancer and uses thereof.