6-(pyrimidin-4-yloxy)-1-naphthoic acid | 1017969-41-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(pyrimidin-4-yloxy)-1-naphthoic acid
• 英文别名: 6-(4-Pyrimidinyloxy)-1-naphthalenecarboxylic acid；6-pyrimidin-4-yloxynaphthalene-1-carboxylic acid
• CAS: 1017969-41-3
• 化学式: C₁₅H₁₀N₂O₃
• 分子量: 266.256
• InChiKey: WDTDEDPIUZKTAJ-UHFFFAOYSA-N

物化性质

• 沸点：
  513.4±25.0 °C(Predicted)
• 密度：
  1.378±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(pyrimidin-4-yloxy)-1-naphthoic acid 、 对氯苯胺 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以29%的产率得到N-(4-chlorophenyl)-6-(4-pyrimidinyloxy)-1-naphthalenecarboxamide
  参考文献：
  名称：

  Naphthamides as Novel and Potent Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: Design, Synthesis, and Evaluation

  摘要：

  A series of naphthyl-based compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptors. Investigations of structure-activity relationships led to the identification of a series of naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and of these several compounds possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48 demonstrated significant antitumor efficacy against established HT29 human colon adenocarcinoma xenografts implanted in athymic mice. A full account of the preparation, structure-activity relationships, pharmacokinetic properties, and pharmacology of analogues within this series is presented.

  DOI：

  10.1021/jm701097z
• 作为产物：
  描述：

  4-氯嘧啶 、 6-羟基-1-萘甲酸 在 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 以87%的产率得到6-(pyrimidin-4-yloxy)-1-naphthoic acid
  参考文献：
  名称：

  Naphthamides as Novel and Potent Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: Design, Synthesis, and Evaluation

  摘要：

  A series of naphthyl-based compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptors. Investigations of structure-activity relationships led to the identification of a series of naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and of these several compounds possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48 demonstrated significant antitumor efficacy against established HT29 human colon adenocarcinoma xenografts implanted in athymic mice. A full account of the preparation, structure-activity relationships, pharmacokinetic properties, and pharmacology of analogues within this series is presented.

  DOI：

  10.1021/jm701097z

文献信息

• Compounds and methods of use
  申请人：Potashman Michele

  公开号：US20090176774A1

  公开（公告）日：2009-07-09

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗HGF介导的疾病等疾病有效。该发明涵盖了新的化合物、类似物、前药和其药学上可接受的盐、制药组合物以及预防和治疗癌症等疾病和其他疾病或情况的方法。该发明还涉及制造这些化合物的过程以及在这些过程中有用的中间体。
• COMPOUNDS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：EP1713484A2

  公开（公告）日：2006-10-25
• US7435823B2
  申请人：——

  公开号：US7435823B2

  公开（公告）日：2008-10-14
• US8178557B2
  申请人：——

  公开号：US8178557B2

  公开（公告）日：2012-05-15
• [EN] COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSES ET LEURS PROCEDES D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2005070891A2

  公开（公告）日：2005-08-04

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutically compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.