6-[5-(3-trifluoromethyl phenylcarbamoyl)naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester | 890128-75-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-[5-(3-trifluoromethyl phenylcarbamoyl)naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester
• 英文别名: Ethyl 6-[5-[[3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyrimidine-4-carboxylate
• CAS: 890128-75-3
• 化学式: C₂₅H₁₈F₃N₃O₄
• 分子量: 481.431
• InChiKey: HSCHEEFSTGEALA-UHFFFAOYSA-N

物化性质

• 沸点：
  550.0±50.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-[5-(3-trifluoromethyl phenylcarbamoyl)naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 6-[5-(3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid lithium salt
  参考文献：
  名称：

  WO2007/31265

  摘要：

  公开号：
• 作为产物：
  描述：

  6-羟基-1-萘甲酸 在 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 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， 20.0~110.0 ℃ 、12.0 MPa 条件下， 反应 34.0h， 生成 6-[5-(3-trifluoromethyl phenylcarbamoyl)naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester
  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

• Pharmaceutical Compositions and Solid Forms
  申请人：BERGHAUSEN Joerg

  公开号：US20110112121A1

  公开（公告）日：2011-05-12

  The present invention relates to pharmaceutical compositions of 6-(6-hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide, to the use of 6-(6-hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide and compositions of 6-(6-hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide in therapeutic applications, especially indications with a dysregulation/overexpression of VEFG, (neo)-vascularisation and VEGF driven angiogenesis and to methods for manufacturing such compositions, the invention further relates to specific forms of 6-(6-hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide and to the manufacturing and use of such forms. The present invention also relates to a new process to produce 6-(6-hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide.

  本发明涉及6-(6-羟甲基嘧啶-4-氧基)-萘-1-羧酸(3-三氟甲基苯基)-酰胺的药物组合物，以及使用6-(6-羟甲基嘧啶-4-氧基)-萘-1-羧酸(3-三氟甲基苯基)-酰胺和6-(6-羟甲基嘧啶-4-氧基)-萘-1-羧酸(3-三氟甲基苯基)-酰胺的组合物在治疗应用中，尤其是在VEGF的失调/过度表达、(新生)血管生成和VEGF驱动的血管生成方面的适应症，并且涉及制造此类组合物的方法，本发明还涉及6-(6-羟甲基嘧啶-4-氧基)-萘-1-羧酸(3-三氟甲基苯基)-酰胺的特定形式以及制造和使用此类形式的方法。本发明还涉及一种生产6-(6-羟甲基嘧啶-4-氧基)-萘-1-羧酸(3-三氟甲基苯基)-酰胺的新工艺。
• WO2006/59234
  申请人：——

  公开号：——

  公开（公告）日：——
• BICYCLIC AMIDES AS KINASE INHIBITORS
  申请人：Novartis AG

  公开号：EP1794149A2

  公开（公告）日：2007-06-13
• COMBINATIONS COMPRISING A VEGF RECEPTOR INHIBITOR AND A PENETRATION ENHANCER
  申请人：Novartis AG

  公开号：EP1945217A2

  公开（公告）日：2008-07-23
• PHARMACEUTICAL COMPOSITIONS AND SOLID FORMS
  申请人：Novartis AG

  公开号：EP2451458A2

  公开（公告）日：2012-05-16