4-氯-6-(4-氟苯基)-喹唑啉 | 1003025-51-1

• 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-6-(4-氟苯基)-喹唑啉
• 英文名称: 4-chloro-6-(4-fluorophenyl)quinazoline
• CAS: 1003025-51-1
• 化学式: C₁₄H₈ClFN₂
• 分子量: 258.682
• InChiKey: CBQNSXJGOYCSOL-UHFFFAOYSA-N

物化性质

• 沸点：
  393.9±32.0 °C(Predicted)
• 密度：
  1.351±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯-6-(4-氟苯基)-喹唑啉 、 丙基溴化镁 在 iron(III)-acetylacetonate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以43%的产率得到6-(4-fluoro-phenyl)-4-propyl-quinazoline
  参考文献：
  名称：

  WO2008/9077

  摘要：

  公开号：
• 作为产物：
  描述：

  6-溴-4-羟基喹唑啉 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 8.0h， 生成 4-氯-6-(4-氟苯基)-喹唑啉
  参考文献：
  名称：

  4-（卤代苯胺基）-6-溴喹唑啉及其6-（4-氟苯基）取代衍生物作为表皮生长因子受体酪氨酸激酶的潜在抑制剂的合成及体外细胞毒性

  摘要：

  评估了一系列2-未取代和2-（4-氯苯基）-取代的4-苯胺基-6-溴喹唑啉及其6-（4-氟苯基）-取代的衍生物对MCF-7和HeLa细胞的体外细胞毒性。2-未取代的4-苯胺基-6-溴喹唑啉缺乏活性，而发现它们的大多数2-（4-氯苯基）取代的衍生物对HeLa细胞显示出显着的细胞毒性和选择性。与吉非替尼相比，用2-氟苯基取代2-未取代的4-苯胺基喹唑啉的溴导致对HeLa细胞的优异活性。除了3-氯苯胺基衍生物以外，在2-（4-氯苯基）取代的衍生物中存在4-氟苯基导致对HeLa细胞的细胞毒性增加。活性最高的化合物3g，3l和4l 被发现对表皮生长因子受体酪氨酸激酶（EGFR-TK）表现出中度至显着的抑制作用。EGFR分子对接模型表明这些化合物与EGFR区域结合良好。

  DOI：

  10.3390/ph10040087

文献信息

• 4,6-DI- AND 2,4,6-TRISUBSTITUTED QUINAZOLINE DERIVATIVES USEFUL FOR TREATING VIRAL INFECTIONS
  申请人：Gao Ling-Jie

  公开号：US20090285782A1

  公开（公告）日：2009-11-19

  This invention provides quinazoline derivatives represented by the structural formula: (I); wherein: R 2 is hydrogen, NR′R″, C 1-7 alkyl, arylC 1-7 alkyl or C 3-10 cycloalkyl; R 4 is amino, C 1-7 alkyl, C 2-7 alkenyl, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted C 1-7 alkyl or C 3-10 cycloalkyl-C 1-7 alkyl; R 5 is hydrogen or C 1-7 alkyl, or R 5 and R 4 together with the nitrogen atom to which they are attached form a heterocyclic ring; Y is a single bond, C 1-7 alkylene, C 2-7 alkenylene or C 2-7 alkynylene; R 6 is halogen, heteroaryl or aryl; R′ and R″ are each independently hydrogen, C 1-7 alkyl-carbonyl or C 1-7 alkyl; provided that R 4 is not phenyl substituted with morpholino when R 2 is H and R 5 is H, and provided that when NR 4 R 5 is piperazinyl, said NR 4 R 5 is either non-substituted or substituted with methyl or acetyl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-N-oxide, a solvate or a pro-drug thereof, for the treatment of viral infections.

  该发明提供了由结构式(I)表示的喹唑啉衍生物；其中：R2是氢、NR′R″、C1-7烷基、芳基C1-7烷基或C3-10环烷基；R4是氨基、C1-7烷基、C2-7烯基、C3-10环烷基、C3-10环烯基、芳基、杂环、芳基烷基、杂环取代的C1-7烷基或C3-10环烷基-C1-7烷基；R5是氢或C1-7烷基，或者R5和R4与它们所连接的氮原子一起形成杂环环；Y是单键、C1-7烷基、C2-7烯基或C2-7炔基；R6是卤素、杂环芳基或芳基；R′和R″各自独立地是氢、C1-7烷基-羰基或C1-7烷基；前提是当R2为H且R5为H时，R4不是取代有吗啡啶基的苯基；当NR4R5是哌嗪基时，所述的NR4R5要么未取代，要么被甲基或乙酰基取代；其药学上可接受的加合物、立体异构体、单烯氮或双烯氮、溶剂化合物或前药，用于治疗病毒感染。
• 4,6-DI- AND 2,4,6-TRISUBSTITUTED QUINAZOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS USEFUL FOR TREATING VIRAL INFECTIONS
  申请人：Gao Ling-Jie

  公开号：US20100143299A1

  公开（公告）日：2010-06-10

  This invention provides the treatment of viral infections with a 4,6-disubstituted or 2,4,6-trisubstituted quinazoline derivative represented by the structural formula [(I)] wherein: R 2 is selected from the group consisting of hydrogen, NR′R″ and C 1-7 alkyl; —A is selected from the group consisting of a bond, O, S(O) n , C 1-7 alkylene, C 2-7 alkenylene and C 2-7 alkynylene; R 4 is selected from the group consisting of C 1-7 alkyl, C 2-7 alkenyl, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted alkyl and cycloalkyl-alkyl; —Y is selected from the group consisting of a single bond, C 1-7 alkylene, C 2-7 alkenylene, and C 2-7 alkynylene; n is 0, 1 or 2; and R 6 is selected from the group consisting of halogen, heteroaryl and aryl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-Λ/-oxide, a solvate or a pro-drug thereof.

  本发明提供了一种使用4,6-二取代或2,4,6-三取代喹唑啉衍生物的治疗病毒感染的方法，其结构式表示为[(I)]，其中：R2选自氢、NR′R″和C1-7烷基的组；—A选自键、O、S(O)n、C1-7烷基、C2-7烯基和C2-7炔基的组；R4选自C1-7烷基、C2-7烯基、C3-10环烷基、C3-10环烯基、芳基、杂环、芳基烷基、杂环取代烷基和环烷基-烷基的组；—Y选自单键、C1-7烷基、C2-7烯基和C2-7炔基的组；n为0、1或2；R6选自卤素、杂芳基和芳基的组；以及其药学上可接受的加合物盐、立体异构体、单-或双-Λ/-氧化物、溶剂化合物或前药。
• 4,6-di- and 2,4,6-trisubstituted quinazoline derivatives and pharmaceutical compositions useful for treating viral infections
  申请人：Gao Ling-Jie

  公开号：US08673929B2

  公开（公告）日：2014-03-18

  This invention provides the treatment of viral infections with a 4,6-disubstituted or 2,4,6-trisubstituted quinazoline derivative represented by the structural formula [(I)] wherein: R2 is selected from the group consisting of hydrogen, NR′R″ and C1-7 alkyl; —A is selected from the group consisting of a bond, O, S(O)n, C1-7 alkylene, C2-7 alkenylene and C2-7 alkynylene; R4 is selected from the group consisting of C1-7 alkyl, C2-7 alkenyl, C3-10cycloalkyl, C3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted alkyl and cycloalkyl-alkyl; —Y is selected from the group consisting of a single bond, C1-7 alkylene, C2-7 alkenylene, and C2-7 alkynylene; n is 0, 1 or 2; and R6 is selected from the group consisting of halogen, heteroaryl and aryl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-Λ/-oxide, a solvate or a pro-drug thereof.

  本发明提供了一种使用4,6-二取代或2,4,6-三取代的喹唑啉衍生物[(I)]的治疗病毒感染的方法，其中：R2选自氢、NR′R″和C1-7烷基组成的群；-A选自键合、O、S（O）n、C1-7烷基、C2-7烯基和C2-7炔基组成的群；R4选自C1-7烷基、C2-7烯基、C3-10环烷基、C3-10环烯基、芳基、杂环、芳基烷基、杂环取代烷基和环烷基烷基组成的群；-Y选自单键、C1-7烷基、C2-7烯基和C2-7炔基组成的群；n为0、1或2；R6选自卤素、杂芳基和芳基组成的群；以及其药学上可接受的加成盐、立体异构体、单Λ/-氧化物、双Λ/-氧化物、溶剂化合物或前药。
• 4,6-di- and 2,4,6-trisubstituted quinazoline derivatives useful for treating viral infections
  申请人：Gao Ling-Jie

  公开号：US09259426B2

  公开（公告）日：2016-02-16

  This invention provides quinazoline derivatives represented by the structural formula: (I); wherein: R2 is hydrogen, NR′R″, C1-7 alkyl, arylC1-7 alkyl or C3-10 cycloalkyl; R4 is amino, C1-7 alkyl, C2-7 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted C1-7 alkyl or C3-10 cycloalkyl-C1-7 alkyl; R5 is hydrogen or C1-7 alkyl, or R5 and R4 together with the nitrogen atom to which they are attached form a heterocyclic ring; Y is a single bond, C1-7 alkylene, C2-7 alkenylene or C2-7 alkynylene; R6 is halogen, heteroaryl or aryl; R′ and R″ are each independently hydrogen, C1-7 alkyl-carbonyl or C1-7 alkyl; provided that R4 is not phenyl substituted with morpholino when R2 is H and R5 is H, and provided that when NR4R5 is piperazinyl, said NR4R5 is either non-substituted or substituted with methyl or acetyl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-N-oxide, a solvate or a pro-drug thereof, for the treatment of viral infections.

  本发明提供了由结构式（I）表示的喹唑啉衍生物；其中：R2为氢、NR′R″、C1-7烷基、芳基C1-7烷基或C3-10环烷基；R4为氨基、C1-7烷基、C2-7烯基、C3-10环烷基、C3-10环烯基、芳基、杂环、芳基烷基、杂环取代的C1-7烷基或C3-10环烷基-C1-7烷基；R5为氢或C1-7烷基，或R5与R4一起与它们所连接的氮原子形成杂环环；Y为单键、C1-7亚烷基、C2-7烯基或C2-7炔基；R6为卤素、杂环芳基或芳基；R′和R″各自独立地为氢、C1-7烷基-羰基或C1-7烷基；前提是当R2为H且R5为H时，R4不是取代了吗啡啉的苯基，且当NR4R5为哌嗪基时，所述的NR4R5要么是非取代的，要么是取代了甲基或乙酰基的；其中所述的衍生物是药学上可接受的加合盐、立体异构体、单一或二重N-氧化物、溶剂合物或前药，用于治疗病毒感染。
• WO2008/9078
  申请人：——

  公开号：——

  公开（公告）日：——