N-(2-fluorophenyl)-N'-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]urea | 819056-63-8

• 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: N-(2-fluorophenyl)-N'-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]urea
• 英文别名: 1-(2-fluorophenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea；1-(2-fluorophenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea
• CAS: 819056-63-8
• 化学式: C₁₉H₂₂BFN₂O₃
• 分子量: 356.205
• InChiKey: JSVZHGYIWLYWRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-fluorophenyl)-N'-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]urea 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 生成 N-(6-(4-(3-(2-fluorophenyl)ureido)phenyl)pyridin-2-yl)acrylamide
  参考文献：
  名称：

  Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1 H -indazole-3-amine as multi-target RTKs inhibitors

  摘要：

  VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti proliferation against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, Tie-2, and EphB4. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.10.008
• 作为产物：
  描述：

  2-氟苯胺 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 N-(2-fluorophenyl)-N'-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]urea
  参考文献：
  名称：

  Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1 H -indazole-3-amine as multi-target RTKs inhibitors

  摘要：

  VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis. Herein, we designed and prepared three classes of multi-target inhibitors based on the extensive sequence homology along the kinase domain of angiogenic RTKs. Biological evaluation indicated that these multi-target inhibitors exhibited considerable potential as novel anti-angiogeneic and anticancer agents. Among them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most potent RTK inhibition and excellent selectivity. It also showed inhibition on viability of human umbilical vein endothelial cells and anti proliferation against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2, Tie-2, and EphB4. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.10.008

文献信息

• Linifanib – a multi-targeted receptor tyrosine kinase inhibitor and a low molecular weight gelator
  作者：Maria Marlow、Mohammed Al-Ameedee、Thomas Smith、Simon Wheeler、Michael J. Stocks

  DOI：10.1039/c5cc00454c

  日期：——

  Linifanib (1), a multi-targeted receptor tyrosine kinase inhibitor, self-assembles into a hydrogel in the presence of low amounts of solvent.

  Linifanib（1），一种多靶点受体酪氨酸激酶抑制剂，在存在少量溶剂的情况下自组装成水凝胶。
• Discovery of <i>N</i>-(4-(3-Amino-1<i>H</i>-indazol-4-yl)phenyl)-<i>N</i>‘-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-Aminoindazole-Based Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitor
  作者：Yujia Dai、Kresna Hartandi、Zhiqin Ji、Asma A. Ahmed、Daniel H. Albert、Joy L. Bauch、Jennifer J. Bouska、Peter F. Bousquet、George A. Cunha、Keith B. Glaser、Christopher M. Harris、Dean Hickman、Jun Guo、Junling Li、Patrick A. Marcotte、Kennan C. Marsh、Maria D. Moskey、Ruth L. Martin、Amanda M. Olson、Donald J. Osterling、Lori J. Pease、Niru B. Soni、Kent D. Stewart、Vincent S. Stoll、Paul Tapang、David R. Reuter、Steven K. Davidsen、Michael R. Michaelides

  DOI：10.1021/jm061280h

  日期：2007.4.1

  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.