2-fluoro-6-iodo-3-[2-(4-morpholinyl)ethoxy]benzonitrile | 796968-69-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-fluoro-6-iodo-3-[2-(4-morpholinyl)ethoxy]benzonitrile
• 英文别名: 2-fluoro-6-iodo-3-(2-morpholin-4-ylethoxy)benzonitrile
• CAS: 796968-69-9
• 化学式: C₁₃H₁₄FIN₂O₂
• 分子量: 376.169
• InChiKey: YIHJYTQXRKLURA-UHFFFAOYSA-N

物化性质

• 沸点：
  450.4±45.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-fluoro-6-iodo-3-[2-(4-morpholinyl)ethoxy]benzonitrile 在 四(三苯基膦)钯 sodium carbonate 、 一水合肼 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 21.0h， 生成 1-[4-[3-amino-7-(2-morpholin-4-ylethoxy)-1H-indazol-4-yl]phenyl]-3-(2-fluoro-5-methylphenyl)urea
  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-methoxybenzonitrile 在 三溴化硼 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 2-fluoro-6-iodo-3-[2-(4-morpholinyl)ethoxy]benzonitrile
  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。
• 3-Amino-benzo[<i>d</i>]isoxazoles as Novel Multitargeted Inhibitors of Receptor Tyrosine Kinases
  作者：Zhiqin Ji、Asma A. Ahmed、Daniel H. Albert、Jennifer J. Bouska、Peter F. Bousquet、George, A. Cunha、Gilbert Diaz、Keith B. Glaser、Jun Guo、Christopher M. Harris、Junling Li、Patrick A. Marcotte、Maria D. Moskey、Tetsuro Oie、Lori Pease、Nirupama B. Soni、Kent D. Stewart、Steven K. Davidsen、Michael R. Michaelides

  DOI：10.1021/jm701096v

  日期：2008.3.13

  A series of benzoisoxazoles and benzoisothiazoles have been synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs). Structure-activity relationship studies led to the identification of 3-amino benzo[d]isoxazoles, incorporating a N,N'-diphenyl urea moiety of the 4-position that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor families of RTKs. Within this series, orally bioavailable compounds possessing promising pharmacokinetic profiles were identified, and a number of compounds demonstrated in vivo efficacy in models of VEGF-stimulated vascular permeability and tumor growth. In particular, compound 50 exhibited an ED50 of 2.0 mg/kg in the VEGF-stimulated uterine edema model and 81% inhibition in the human fibrosarcoma (HT1080) tumor growth model when given orally at a dose of 10 mg/kg/day.
• US7297709B2
  申请人：——

  公开号：US7297709B2

  公开（公告）日：2007-11-20