4-nitrophenyl 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenylcarbamate | 1000850-83-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-nitrophenyl 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenylcarbamate
• 英文别名: 4-Nitrophenyl 4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenylcarbamate；(4-nitrophenyl) N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]carbamate
• CAS: 1000850-83-8
• 化学式: C₂₄H₁₈FN₃O₇
• 分子量: 479.421
• InChiKey: HIFAHVREJNVRAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-苯基咪唑啉-2-酮 、 4-nitrophenyl 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenylcarbamate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.92h， 以32%的产率得到N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamide
  参考文献：
  名称：

  Structure-Based Design of Novel Class II c-Met Inhibitors: 1. Identification of Pyrazolone-Based Derivatives

  摘要：

  Deregulation of c-Met receptor tyrosine kinase activity leads to tumorigenesis and metastasis in animal models. More importantly, the identification of activating mutations in c-Met, as well as MET gene amplification in human cancers, points to c-Met as an important target for cancer therapy. We have previously described two classes of c-Met kinase inhibitors (class I and class II) that differ in their binding modes and selectivity profiles. The class II inhibitors tend to have activities on multiple kinases. Knowledge of the binding mode of these molecules in the c-Met protein led to the design and evaluation of several new class II c-Met inhibitors that utilize various 5-membered cyclic carboxamides to conformationally restrain key pharmacophoric groups within the molecule. These investigations resulted in the identification of a potent and novel class of pyrazolone c-Met inhibitors with good in vivo activity.

  DOI：

  10.1021/jm201330u
• 作为产物：
  描述：

  对硝基苯基氯甲酸酯 、 4-[(6,7-dimethoxyquinolin-4-yl)oxy]-3-fluoroaniline 在 N,N-二异丙基乙胺 作用下， 以 DCM 为溶剂， 生成 4-nitrophenyl 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenylcarbamate
  参考文献：
  名称：

  Inhibitors of protein tyrosine kinase activity

  摘要：

  这项发明涉及抑制蛋白酪氨酸激酶活性的化合物。具体而言，该发明涉及抑制生长因子受体蛋白酪氨酸激酶活性的化合物，导致受体信号传导的抑制，例如抑制VEGF受体信号传导和HGF受体信号传导。更具体地，该发明涉及用于抑制VEGF受体信号传导和HGF受体信号传导的化合物、组合物和方法。该发明还提供了用于治疗细胞增殖性疾病和病况的组合物和方法。

  公开号：

  US20080004273A1

文献信息

• Inhibitors of protein tyrosine kinase activity
  申请人：Raeppel Stephane

  公开号：US20080004273A1

  公开（公告）日：2008-01-03

  This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  这项发明涉及抑制蛋白酪氨酸激酶活性的化合物。具体而言，该发明涉及抑制生长因子受体蛋白酪氨酸激酶活性的化合物，导致受体信号传导的抑制，例如抑制VEGF受体信号传导和HGF受体信号传导。更具体地，该发明涉及用于抑制VEGF受体信号传导和HGF受体信号传导的化合物、组合物和方法。该发明还提供了用于治疗细胞增殖性疾病和病况的组合物和方法。
• [EN] INHIBITORS OF PROTEIN TYROSINE KINASE ACTIVITY<br/>[FR] INHIBITEURS DE L'ACTIVITÉ TYROSINE KINASE
  申请人：METHYLGENE INC

  公开号：WO2008035209A2

  公开（公告）日：2008-03-27

  (EN) The invention relates to quinoline and qumazoline derivatives that inhibit protein tyrosine kinase activity In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling The invention also provides compositions and methods for treating cell proliferative diseases and conditions(FR) L'invention concerne des composé inhibant l'activité tyrosine kinase. Plus particulièrement, l'invention concerne des composés inhibant l'activité tyrosine kinase de récepteurs de facteurs de croissance, ce qui provoque l'inhibition de la signalisation de récepteurs, et notamment l'inhibition de la signalisation des récepteurs de VEGF et de la signalisation des récepteurs de HGF. Plus particulièrement, l'invention concerne des composés, des compositions et des méthodes destinés à inhiber la signalisation des récepteurs de VEGF et la signalisation des récepteurs de HGF. L'invention se rapporte en outre à des compositions et des méthodes de traitement de maladies et de pathologies caractérisées par une prolifération cellulaire.
• Structure-Based Design of Novel Class II c-Met Inhibitors: 1. Identification of Pyrazolone-Based Derivatives
  作者：Mark H. Norman、Longbin Liu、Matthew Lee、Ning Xi、Ingrid Fellows、Noel D. D’Angelo、Celia Dominguez、Karen Rex、Steven F. Bellon、Tae-Seong Kim、Isabelle Dussault

  DOI：10.1021/jm201330u

  日期：2012.3.8

  Deregulation of c-Met receptor tyrosine kinase activity leads to tumorigenesis and metastasis in animal models. More importantly, the identification of activating mutations in c-Met, as well as MET gene amplification in human cancers, points to c-Met as an important target for cancer therapy. We have previously described two classes of c-Met kinase inhibitors (class I and class II) that differ in their binding modes and selectivity profiles. The class II inhibitors tend to have activities on multiple kinases. Knowledge of the binding mode of these molecules in the c-Met protein led to the design and evaluation of several new class II c-Met inhibitors that utilize various 5-membered cyclic carboxamides to conformationally restrain key pharmacophoric groups within the molecule. These investigations resulted in the identification of a potent and novel class of pyrazolone c-Met inhibitors with good in vivo activity.