4-氯-6-乙氧基喹唑啉 | 155960-92-2

• 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-乙氧基喹唑啉
• 英文名称: 4-Chloro-6-ethoxy-quinazoline
• 英文别名: 4-Chloro-6-ethoxyquinazoline
• CAS: 155960-92-2
• 化学式: C₁₀H₉ClN₂O
• 分子量: 208.647
• InChiKey: GNWPZLGHHNOKML-UHFFFAOYSA-N

物化性质

• 沸点：
  334.7±22.0 °C(Predicted)
• 密度：
  1.284±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H320,H335

反应信息

• 作为反应物：
  描述：

  4-氯-6-乙氧基喹唑啉 、 3,4-亚甲二氧基苄胺 在 sodium carbonate 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 以44%的产率得到4-(3,4-Methylenedioxybenzyl)amino-6-ethoxyquinazoline
  参考文献：
  名称：

  Cyclic GMP Phosphodiesterase Inhibitors. 2. Requirement of 6-Substitution of Quinazoline Derivatives for Potent and Selective Inhibitory Activity

  摘要：

  We synthesized various 4-[[3,4-(methylenedioxy)benzyl]amino]quinazolines substituted at the 5-to 8-positions and evaluated their inhibitory activities toward cyclic GMP phosphodiesterase (cGMP-PDE) from porcine aorta, Monosubstitution at the 6-position was essential for the inhibitory activity, and the preferred substituents were compact and hydrophobic: methoxy (3b, IC50 = 0.23 mu M), methyl (3c, 0.10 mu M), chloro (3d, 0.019 mu M), thiomethyl (3f, 0.031 mu M), and cyano (3p, 0.090 mu M) groups. Compounds 3b-d,f,p lacked inhibitory activity toward other PDE isozymes (all IC50 values > 100 mu M), and their relaxing activities in porcine coronary arteries were well correlated with the inhibitory activities toward cGMP-PDE (r = 0.88, p < 0.05). One of these compounds, 3b, elevated the intracellular cGMP level in isolated porcine coronary arteries without causing any change in the cAMP level. We consider that this series of compounds dilates coronary arteries via potent and specific inhibition of cGMP-PDE,

  DOI：

  10.1021/jm00039a024
• 作为产物：
  描述：

  6-ethoxyquinazolin-4(3H)-one 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 生成 4-氯-6-乙氧基喹唑啉
  参考文献：
  名称：

  一类新型喹唑啉衍生物作为冠状病毒抑制剂的设计、合成及其构效关系

  摘要：

  临床上治疗冠状病毒感染的需求仍有很大未满足，迫切需要开发新型抗病毒药物。在这项工作中，针对我们内部化合物库的表型筛选鉴定了几种对HCoV-OC43 具有中等抗病毒活性的木豆碱衍生物。基于木豆碱的支架，采用支架跳跃策略设计了一系列喹唑啉衍生物。经过反复的结构优化活动，成功鉴定了几种具有有效抗病毒功效（EC50初步作用机制研究表明，此类喹唑啉衍生物在感染早期发挥作用。总的来说，这项工作提供了一种新型化学类型的冠状病毒抑制剂，它不仅可以用于进一步开发抗病毒药物，而且可以作为确定作用靶点的重要化学工具。

  DOI：

  10.1016/j.ejmech.2023.115831

文献信息

• Takase Yasutaka, Saeki Takao, Watanabe Nobuhisa, Adachi Hideyuki, Souda S+, J. Med. Chem, 37 (1994) N 13, S 2106-2111
  作者：Takase Yasutaka, Saeki Takao, Watanabe Nobuhisa, Adachi Hideyuki, Souda S+

  DOI：——

  日期：——
• Cyclic GMP Phosphodiesterase Inhibitors. 2. Requirement of 6-Substitution of Quinazoline Derivatives for Potent and Selective Inhibitory Activity
  作者：Yasutaka Takase、Takao Saeki、Nobuhisa Watanabe、Hideyuki Adachi、Shigeru Souda、Isao Saito

  DOI：10.1021/jm00039a024

  日期：1994.6

  We synthesized various 4-[[3,4-(methylenedioxy)benzyl]amino]quinazolines substituted at the 5-to 8-positions and evaluated their inhibitory activities toward cyclic GMP phosphodiesterase (cGMP-PDE) from porcine aorta, Monosubstitution at the 6-position was essential for the inhibitory activity, and the preferred substituents were compact and hydrophobic: methoxy (3b, IC50 = 0.23 mu M), methyl (3c, 0.10 mu M), chloro (3d, 0.019 mu M), thiomethyl (3f, 0.031 mu M), and cyano (3p, 0.090 mu M) groups. Compounds 3b-d,f,p lacked inhibitory activity toward other PDE isozymes (all IC50 values > 100 mu M), and their relaxing activities in porcine coronary arteries were well correlated with the inhibitory activities toward cGMP-PDE (r = 0.88, p < 0.05). One of these compounds, 3b, elevated the intracellular cGMP level in isolated porcine coronary arteries without causing any change in the cAMP level. We consider that this series of compounds dilates coronary arteries via potent and specific inhibition of cGMP-PDE,
• Design, synthesis, and structure-activity relationships of a novel class of quinazoline derivatives as coronavirus inhibitors
  作者：Shengchao Zhou、Kun Wang、Ziwei Hu、Tao Chen、Yao Dong、Rongmei Gao、Mengyuan Wu、Yuhuan Li、Xingyue Ji

  DOI：10.1016/j.ejmech.2023.115831

  日期：2023.12

  optimization campaign, several quinazoline derivatives with potent antiviral efficacy (EC50: ∼0.1 μM) and high selectivity (SI > 1000) were successfully identified. The preliminary mechanism of action study indicated that such quinazoline derivatives functioned at the early stage of infection. In aggregate, this work delivered a new chemical type of coronavirus inhibitors, which could be employed not only for

  临床上治疗冠状病毒感染的需求仍有很大未满足，迫切需要开发新型抗病毒药物。在这项工作中，针对我们内部化合物库的表型筛选鉴定了几种对HCoV-OC43 具有中等抗病毒活性的木豆碱衍生物。基于木豆碱的支架，采用支架跳跃策略设计了一系列喹唑啉衍生物。经过反复的结构优化活动，成功鉴定了几种具有有效抗病毒功效（EC50初步作用机制研究表明，此类喹唑啉衍生物在感染早期发挥作用。总的来说，这项工作提供了一种新型化学类型的冠状病毒抑制剂，它不仅可以用于进一步开发抗病毒药物，而且可以作为确定作用靶点的重要化学工具。