4-氯-7-氟-6-甲氧基喹唑啉 | 159768-48-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-氯-7-氟-6-甲氧基喹唑啉
• 英文名称: 4-chloro-7-fluoro-6-methoxyquinazoline
• CAS: 159768-48-6
• 化学式: C₉H₆ClFN₂O
• mdl: MFCD08234562
• 分子量: 212.611
• InChiKey: XVFCYYAFOCEJSI-UHFFFAOYSA-N

物化性质

• 沸点：
  333.0±37.0 °C(Predicted)
• 密度：
  1.415±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-氯-7-氟-6-甲氧基喹唑啉 在 吡啶 、 ammonium cerium(IV) nitrate 、 sodium hexamethyldisilazane 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙腈 、 叔丁醇 为溶剂， 反应 26.25h， 生成 2-chloro-5-({6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-yl}amino)benzo-1,4-quinone
  参考文献：
  名称：

  2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as Covalent-Binding, Irreversible Inhibitors of the Kinase Domain of Vascular Endothelial Growth Factor Receptor-2

  摘要：

  A series of 2-(quinazolin-4-ylamino)-[1,4] benzoquinone derivatives that function as potent covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2 (VEGFR-2) has been prepared by ceric ammonium nitrate oxidation of substituted (2,5-dimethoxyphenyl)(6,7-disubstituted-quinazolin-4-yl)amines and by displacement of the chlorine atom of substituted 2-chloro-5-(6,7-disubstituted-quinazolin-4-ylamino)-[1,41benzoquinones with various amines, anilines, phenols, and alcohols. Enzyme studies were conducted in the absence and presence of glutathione and plasma. Several of the compounds inhibit VEGF-stimulated autophosphorylation in intact cells. Kinetic experiments were performed to study the reactivity of selected inhibitors toward glutathione. Reactivities correlated with LUMO energies calculated as averages of those of individual conformers weighted by the Boltzmann distribution. These results and molecular modeling were used to rationalize the biological observations. The compounds behave as non-ATP-competitive inhibitors. Unequivocal evidence, from mass spectral studies, indicates that these inhibitors form a covalent interaction with Cys-1045. One member of this series displays antitumor activity in an in vivo model.

  DOI：

  10.1021/jm050559f
• 作为产物：
  描述：

  4-氟-5-甲氧基-2-硝基苯甲酸甲酯 在 palladium on activated charcoal 氯化亚砜 、 氢气 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 22.0h， 生成 4-氯-7-氟-6-甲氧基喹唑啉
  参考文献：
  名称：

  Facile synthesis of 7-amino anilinoquinazolines via direct amination of the quinazoline core

  摘要：

  The facile preparation of 4-(3-chloro-4-fluoroanilino)-6-alkoxy-7-aminoquinazolines from their corresponding 7-triflate and 7-fluoro precursors are highlighted. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.08.123

文献信息

• Quinazoline derivatives
  申请人：Zeneca Limited

  公开号：US05580870A1

  公开（公告）日：1996-12-03

  The invention concerns quinazoline derivatives of the formula I ##STR1## wherein m is 1, 2 or 3 and each R.sup.1 includes hydroxy, amino, ureido, hydroxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy and (1-3C)alkylenedioxy; and Q is a 9- or 10-membered bicyclic heterocyclic moiety containing one or two nitrogen heteroatoms and optionally containing a further heteroatom selected from nitrogen, oxygen and sulphur, or Q is a 9- or 10-membered bicyclic aryl moiety which heterocyclic or aryl moiety may optionally bear one or two substituents selected from halogeno, hydroxy, oxo, amino, nitro, carbamoyl, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di-[(1-4C)alkyl]amino and (2-4C)alkanoylamino; or a pharmaceutically-acceptable salt thereof; processes for their preparation; pharmaceutical compositions containing them; and the use of the receptor tyrosine kinase inhibitory properties of the compounds in the treatment of cancer.

  该发明涉及式I的喹唑啉衍生物##STR1##其中m为1、2或3，每个R.sup.1包括羟基、氨基、脲基、羟氨基、三氟甲氧基、(1-4C)烷基、(1-4C)烷氧基和(1-3C)烷二氧基；Q是含有一个或两个氮杂原子并且可选地含有进一步来自氮、氧和硫的杂原子的9-或10-成员双环杂环基，或Q是含有一个或两个卤素、羟基、酮基、氨基、硝基、氨甲酰基、(1-4C)烷基、(1-4C)烷氧基、(1-4C)烷基氨基、二-[(1-4C)烷基]氨基和(2-4C)烷酰氨基中的一种或两种取代基的9-或10-成员双环芳基基，或其药学上可接受的盐；它们的制备方法；含有它们的制剂；以及利用化合物的受体酪氨酸激酶抑制性能在癌症治疗中的应用。
• Quinone Substituted Quinazoline and Quinoline Kinase Inhibitors
  申请人：Floyd Jr Brawner Middleton

  公开号：US20070299092A1

  公开（公告）日：2007-12-27

  The present invention provides for compounds with the general formula: A compound of formula (1) having the structure (1) wherein Z is a radical selected from the group (a), (b), or (c) as well as methods and compositions containing these compounds useful for treatment of diseases that are characterized, at least in part, by excessive, abnormal, or inappropriate angiogenesis. These disease states, include but are not limited to, cancer, diabetic retinopathy, macular degeneration and rheumatoid arthritis. These compounds inhibit angiogenesis by inhibiting a tyrosine kinase receptor enzyme, specifically KDR, and binding to the KDR in an irreversible manner.

  本发明提供了一般式为：具有结构式（1）的化合物，其中Z是从（a）、（b）或（c）组中选择的基团，以及包含这些化合物的方法和组合物，用于治疗至少部分特征为过度、异常或不适当血管生成的疾病。这些疾病状态包括但不限于癌症、糖尿病视网膜病变、黄斑变性和类风湿性关节炎。这些化合物通过抑制酪氨酸激酶受体酶，特别是KDR，并以不可逆的方式与KDR结合来抑制血管生成。
• [EN] QUINONE SUBSTITUTED QUINAZOLINE AND QUINOLINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE QUINAZOLINE ET QUINOLINE KINASE A SUBSTITUTION QUINONE
  申请人：WYETH CORP

  公开号：WO2005115145A3

  公开（公告）日：2006-02-23
• WO2020163193A5
  申请人：——

  公开号：WO2020163193A5

  公开（公告）日：2023-02-09
• Quinazoline derivatives and their use as anti-cancer agents
  申请人：Syngenta Limited

  公开号：EP0635498B1

  公开（公告）日：2001-04-18