4-(4-((2-fluoro-5-(trifluoromethyl)phenyl)aminocarbonylamino)phenoxy)phenylene-1,2-diamine | 433225-94-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(4-((2-fluoro-5-(trifluoromethyl)phenyl)aminocarbonylamino)phenoxy)phenylene-1,2-diamine
• 英文别名: 1-[4-(3,4-Diaminophenoxy)phenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea
• CAS: 433225-94-6
• 化学式: C₂₀H₁₆F₄N₄O₂
• 分子量: 420.366
• InChiKey: PDXZFXDFASXJMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  102
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(4-((2-fluoro-5-(trifluoromethyl)phenyl)aminocarbonylamino)phenoxy)phenylene-1,2-diamine 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-(6-{4-[3-(2-fluoro-5-trifluoromethyl-phenyl)-ureido]-phenoxy}-1H-benzoimidazol-2-yl)-2-(4-methyl-piperazin-1-yl)-acetamide
  参考文献：
  名称：

  Discovery of Novel Benzimidazoles as Potent Inhibitors of TIE-2 and VEGFR-2 Tyrosine Kinase Receptors

  摘要：

  We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the NI nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the NI nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity.

  DOI：

  10.1021/jm0611051
• 作为产物：
  描述：

  3,4'-二氨基-4-硝基二苯醚 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 72.0h， 生成 4-(4-((2-fluoro-5-(trifluoromethyl)phenyl)aminocarbonylamino)phenoxy)phenylene-1,2-diamine
  参考文献：
  名称：

  Discovery of Novel Benzimidazoles as Potent Inhibitors of TIE-2 and VEGFR-2 Tyrosine Kinase Receptors

  摘要：

  We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the NI nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the NI nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity.

  DOI：

  10.1021/jm0611051

文献信息

• Chemical compounds
  申请人：——

  公开号：US20040082583A1

  公开（公告）日：2004-04-29

  Benzimidazole derivatives, which are useful as TIE-2 and/or VEGFR2 inhibitors are described herein. The described invention also includes methods of making such benzimidazole derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

  本文描述了作为TIE-2和/或VEGFR2抑制剂有用的苯并咪唑衍生物。所述发明还包括制备这种苯并咪唑衍生物的方法，以及在治疗过度增殖性疾病中使用它们的方法。
• SOLUBLE EPOXIDE HYDROLASE INHIBITORS
  申请人：Gless, JR. Richard D.

  公开号：US20090023731A1

  公开（公告）日：2009-01-22

  Disclosed are urea and thiourea compounds and compositions that inhibit soluble epoxide hydrolase (sEH), methods for preparing the compounds and compositions, and methods for treating patients with such compounds and compositions. The compounds, compositions, and methods are useful for treating a variety of sEH mediated diseases, including hypertensive, cardiovascular, inflammatory, and diabetic-related diseases.

  本发明涉及一种抑制可溶性环氧水解酶（sEH）的尿素和硫脲化合物及其组合物和组合物的制备方法，以及使用这些化合物和组合物治疗患者的方法。这些化合物、组合物和方法对于治疗各种sEH介导的疾病，包括高血压、心血管、炎症和糖尿病相关疾病非常有用。
• CHEMICAL COMPOUNDS
  申请人：Cheung Mui

  公开号：US20070249600A1

  公开（公告）日：2007-10-25

  Benzimidazole derivatives, which are useful as TIE-2 and/or VEGFR2 inhibitors are described herein. The described invention also includes methods of making such benzimidazole derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

  本文描述了作为TIE-2和/或VEGFR2抑制剂有用的苯并咪唑衍生物。所述发明还包括制备这种苯并咪唑衍生物的方法，以及在治疗过度增生性疾病中使用它们的方法。
• BENZIMIDAZOLE DERIVATIVES USEFUL AS TIE-2 AND/OR VEGFR-2 INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1341771A2

  公开（公告）日：2003-09-10
• US7238813B2
  申请人：——

  公开号：US7238813B2

  公开（公告）日：2007-07-03