4-(4-aminophenyl)-7-[2-(1-pyrrolidinyl)ethoxy]-1H-indazol-3-amine | 796969-64-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 4-(4-aminophenyl)-7-[2-(1-pyrrolidinyl)ethoxy]-1H-indazol-3-amine
• 英文别名: 4-(4-aminophenyl)-7-(2-pyrrolidin-1-ylethoxy)-1H-indazol-3-amine
• CAS: 796969-64-7
• 化学式: C₁₉H₂₃N₅O
• 分子量: 337.425
• InChiKey: HQXLDFDWQUDHMG-UHFFFAOYSA-N

物化性质

• 沸点：
  629.1±55.0 °C(Predicted)
• 密度：
  1.291±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  93.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-aminophenyl)-7-[2-(1-pyrrolidinyl)ethoxy]-1H-indazol-3-amine 、 异氰酸间甲苯酯 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-(3-amino-7-(2-(pyrrolidin-1-yl)ethoxy)-1H-indazol-4-yl)phenyl)-3-m-tolylurea
  参考文献：
  名称：

  Discovery of N-(4-(3-Amino-1H-indazol-4-yl)phenyl)-N‘-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-Aminoindazole-Based Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitor

  摘要：

  In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models.

  DOI：

  10.1021/jm061280h
• 作为产物：
  描述：

  2-fluoro-6-iodo-3-methoxy-benzoic acid 在 四(三苯基膦)钯 ammonium hydroxide 、 氯化亚砜 、 三溴化硼 、 sodium carbonate 、 一水合肼 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 58.0h， 生成 4-(4-aminophenyl)-7-[2-(1-pyrrolidinyl)ethoxy]-1H-indazol-3-amine
  参考文献：
  名称：

  Discovery of N-(4-(3-Amino-1H-indazol-4-yl)phenyl)-N‘-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-Aminoindazole-Based Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitor

  摘要：

  In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models.

  DOI：

  10.1021/jm061280h

文献信息

• Indazole and benzisoxazole kinase inhibitors
  申请人：——

  公开号：US20040235892A1

  公开（公告）日：2004-11-25

  Compounds having the formula 1 are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有以下化学式的化合物对抑制蛋白酪氨酸激酶具有用处。本发明还公开了制备这些化合物的方法、含有这些化合物的组合物，以及使用这些化合物进行治疗的方法。
• Indazole, benzisoxazole, and benzisothiazole kinase inhibitors
  申请人：Dai Yujia

  公开号：US20050020603A1

  公开（公告）日：2005-01-27

  Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有公式的化合物对于抑制蛋白酪氨酸激酶很有用。本发明还揭示了制备这些化合物的方法，包含这些化合物的组合物以及使用这些化合物的治疗方法。
• INDAZOLE, BENZISOXAZOLE, AND BENZISOTHIAZOLE KINASE INHIBITORS
  申请人：Dai Yujia

  公开号：US20080076767A1

  公开（公告）日：2008-03-27

  Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有公式的化合物对于抑制蛋白酪氨酸激酶具有用处。本发明还公开了制备这些化合物的方法，含有这些化合物的组合物以及使用这些化合物的治疗方法。
• US7297709B2
  申请人：——

  公开号：US7297709B2

  公开（公告）日：2007-11-20
• US7598283B2
  申请人：——

  公开号：US7598283B2

  公开（公告）日：2009-10-06