1-(4-chloro-3-trifluoromethyl-phenyl)-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-urea | 1258961-70-4

• 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: 1-(4-chloro-3-trifluoromethyl-phenyl)-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-urea
• 英文别名: 1-(4-Chloro-3-trifluoromethyl-phenyl)-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-urea；1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea
• CAS: 1258961-70-4
• 化学式: C₂₀H₂₁BClF₃N₂O₃
• 分子量: 440.658
• InChiKey: HHMQOEKHTVHWFM-UHFFFAOYSA-N

物化性质

• 沸点：
  439.1±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-amino-pyrimidin-4-yl)-3-iodo-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester 、 1-(4-chloro-3-trifluoromethyl-phenyl)-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-urea 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 、 lithium chloride 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 以30%的产率得到2-(2-amino-pyrimidin-4-yl)-3-{3-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureido]-phenyl}-1-methyl-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIMIDINYLPYRROLOPYRIDINONE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  [FR] DÉRIVÉS DE PYRIMIDINYLPYRROLOPYRIDINONE SUBSTITUÉS, PROCÉDÉ POUR LEUR PRÉPARATION ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE

  摘要：

  公开了规范中定义的式（I）的嘧啶基吡咯吡啶酮衍生物及其药学上可接受的盐，其制备方法以及包含它们的药物组合物；本发明的化合物可能在治疗中对与蛋白激酶活性失调有关的疾病，如癌症，具有用处。

  公开号：

  WO2010145998A1
• 作为产物：
  描述：

  3-氨基苯硼酸 在 magnesium sulfate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.33h， 生成 1-(4-chloro-3-trifluoromethyl-phenyl)-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-urea
  参考文献：
  名称：

  Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach

  摘要：

  Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.045

文献信息

• SUBSTITUTED PYRIMIDINYLPYRROLOPYRIDINONE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
  申请人：Marchionni Chiara

  公开号：US20120178770A1

  公开（公告）日：2012-07-12

  Pyrimidinylpyrrolopyridinone derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

  本发明公开了式（I）中定义的嘧啶基吡咯吡啶酮衍生物及其药学上可接受的盐，以及制备它们的方法和包含它们的制药组合物；该发明的化合物可能在治疗与蛋白激酶活性失调有关的疾病，如癌症中有用。
• Substituted pyrimidinylpyrrolopyridinone derivatives, process for their preparation and their use as kinase inhibitors
  申请人：Marchionni Chiara

  公开号：US08969366B2

  公开（公告）日：2015-03-03

  Pyrimidinylpyrrolopyridinone derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

  本发明揭示了式（I）中定义的嘧啶基吡咯吡啶酮衍生物及其药学上可接受的盐，其制备过程和包含它们的制药组合物；本发明的化合物可能在治疗与蛋白激酶活性失调有关的疾病，如癌症方面有用。
• Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach
  作者：Yuanyuan Shan、Hongping Gao、Xiaowei Shao、Jinfeng Wang、Xiaoyan Pan、Jie Zhang

  DOI：10.1016/j.ejmech.2015.08.045

  日期：2015.10

  Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization. (C) 2015 Elsevier Masson SAS. All rights reserved.
• [EN] SUBSTITUTED PYRIMIDINYLPYRROLOPYRIDINONE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIMIDINYLPYRROLOPYRIDINONE SUBSTITUÉS, PROCÉDÉ POUR LEUR PRÉPARATION ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE
  申请人：NERVIANO MEDICAL SCIENCES SRL

  公开号：WO2010145998A1

  公开（公告）日：2010-12-23

  Pyrimidinylpyrrolopyridinone derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

  公开了规范中定义的式（I）的嘧啶基吡咯吡啶酮衍生物及其药学上可接受的盐，其制备方法以及包含它们的药物组合物；本发明的化合物可能在治疗中对与蛋白激酶活性失调有关的疾病，如癌症，具有用处。