N-(3-chlorophenyl)-N'-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]urea | 796967-52-7

• 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-(3-chlorophenyl)-N'-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]urea
• 英文别名: 1-(3-Chlorophenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea；1-(3-chlorophenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea
• CAS: 796967-52-7
• 化学式: C₁₉H₂₂BClN₂O₃
• 分子量: 372.659
• InChiKey: HLWYXXVYRFMXAQ-UHFFFAOYSA-N

物化性质

• 沸点：
  423.3±30.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.28
• 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：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-chlorophenyl)-N'-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]urea 在 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 0.5h， 生成 N-(5-(4-(3-(3-chlorophenyl)ureido)phenyl)pyridin-2-yl)acrylamide
  参考文献：
  名称：

  Discovery of novel anti-angiogenesis agents. Part 7: Multitarget inhibitors of VEGFR-2, TIE-2 and EphB4

  摘要：

  Herein, we embarked on a structural optimization campaign aiming at the discovery of second generation anti-angiogenesis agents with our previously reported BPS-7 as lead compound. A library of 27 compounds has been afforded based on the highly conserved ATP-binding pocket of VEGFR-2, Tie-2, and EphB4. Several title compounds exhibited simultaneous inhibitory effects against three angiogenic RTKs. These compounds with a 'triplet' inhibition profile have been identified as novel anti-angiogenic and anticancer agents. The representative VDAU11 displayed prominent anti-angiogenic and anticancer potency and could be considered as a candidate for further optimization. These results indicate that N(pyridin-2-yl)acrylamide could serve as a novel hinge-binding group of triple inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.10.030
• 作为产物：
  描述：

  3-氯苯胺 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 N-(3-chlorophenyl)-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

• Thienopyridine urea inhibitors of KDR kinase
  作者：H. Robin Heyman、Robin R. Frey、Peter F. Bousquet、George A. Cunha、Maria D. Moskey、Asma A. Ahmed、Niru B. Soni、Patrick A. Marcotte、Lori J. Pease、Keith B. Glaser、Melinda Yates、Jennifer J. Bouska、Daniel H. Albert、Candace L. Black-Schaefer、Peter J. Dandliker、Kent D. Stewart、Paul Rafferty、Steven K. Davidsen、Michael R. Michaelides、Michael L. Curtin

  DOI：10.1016/j.bmcl.2006.12.015

  日期：2007.3

  A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.
• 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.
• Discovery of novel anti-angiogenesis agents. Part 7: Multitarget inhibitors of VEGFR-2, TIE-2 and EphB4
  作者：Chuansheng Li、Yuanyuan Shan、Ying Sun、Ru Si、Liyuan Liang、Xiaoyan Pan、Binghe Wang、Jie Zhang

  DOI：10.1016/j.ejmech.2017.10.030

  日期：2017.12

  Herein, we embarked on a structural optimization campaign aiming at the discovery of second generation anti-angiogenesis agents with our previously reported BPS-7 as lead compound. A library of 27 compounds has been afforded based on the highly conserved ATP-binding pocket of VEGFR-2, Tie-2, and EphB4. Several title compounds exhibited simultaneous inhibitory effects against three angiogenic RTKs. These compounds with a 'triplet' inhibition profile have been identified as novel anti-angiogenic and anticancer agents. The representative VDAU11 displayed prominent anti-angiogenic and anticancer potency and could be considered as a candidate for further optimization. These results indicate that N(pyridin-2-yl)acrylamide could serve as a novel hinge-binding group of triple inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1 H -indazole-3-amine as multi-target RTKs inhibitors
  作者：Ying Sun、Yuanyuan Shan、Chuansheng Li、Ru Si、Xiaoyan Pan、Binghe Wang、Jie Zhang

  DOI：10.1016/j.ejmech.2017.10.008

  日期：2017.12

  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.