4-[(3,4-dichlorophenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-[(3,4-dichlorophenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline
• 英文别名: N-(3,4-dichlorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine；N-(3,4-Dichlorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine；N-(3,4-dichlorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine
• 化学式: C₂₂H₂₄Cl₂N₄O₃
• 分子量: 463.364
• InChiKey: VSKQQUAAWOVMOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  68.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[(3,4-dichlorophenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline 、 丙烯酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以72%的产率得到4-[N-acryloyl-(3,4-dichlorophenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline
  参考文献：
  名称：

  Acrylamide Functional Group Incorporation Improves Drug-like Properties: An Example with EGFR Inhibitors

  摘要：

  We demonstrate that the acrylamide group can be used to improve the drug-like properties of potential drug candidates. In the EGFR inhibitor development, both the solubility and membrane permeability properties of compounds 6a and 7, each containing an acrylamide group, were substantially better than those of gefitinib (1) and AZD3759 (2), respectively. We demonstrated that incorporation of an acrylamide moiety could serve as a good strategy for improving drug-like properties.

  DOI：

  10.1021/acsmedchemlett.8b00270
• 作为产物：
  描述：

  7-甲氧基-6-(3-吗啉-4-基丙氧基)喹唑啉-4(3H)-酮 在 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 反应 10.0h， 生成 4-[(3,4-dichlorophenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline
  参考文献：
  名称：

  Acrylamide Functional Group Incorporation Improves Drug-like Properties: An Example with EGFR Inhibitors

  摘要：

  We demonstrate that the acrylamide group can be used to improve the drug-like properties of potential drug candidates. In the EGFR inhibitor development, both the solubility and membrane permeability properties of compounds 6a and 7, each containing an acrylamide group, were substantially better than those of gefitinib (1) and AZD3759 (2), respectively. We demonstrated that incorporation of an acrylamide moiety could serve as a good strategy for improving drug-like properties.

  DOI：

  10.1021/acsmedchemlett.8b00270

文献信息

• Design and Synthesis of Gefitinib Derivatives as Potential Drugs fo r Cancer Treatment: Antiproliferative Activity, Molecular Docking, and ADMET Prediction
  作者：Xiaoyan Ma、Min Shan、Yunlong Lu

  DOI：10.2174/1570180820666230810164118

  日期：2024.7

  main treatment. Gefitinib, the most widely studied targeted agent in non-small cell lung cancer, is an orally active tyrosine kinase inhibitor. However, gefitinib inevitably generates acquired drug resistance, leading to treatment failure. Objective: A new class of compounds containing 4-anilinoquinazoline lead structure was designed and synthesized by modifying the structure of gefitinib. These compounds

  背景：非小细胞肺癌是全球最常见的癌症之一，靶向化疗已成为主要治疗方法。吉非替尼是研究最广泛的非小细胞肺癌靶向药物，是一种口服活性酪氨酸激酶抑制剂。然而，吉非替尼不可避免地产生获得性耐药性，导致治疗失败。目的：通过修饰吉非替尼的结构，设计合成一类含有4-苯胺基喹唑啉先导结构的新化合物。这些化合物有望发挥更好的抗癌活性并更好地与EGFR-TK结构域结合，丰富4-苯胺基喹唑啉衍生物的结构并激发进一步的结构修饰。方法：使用 MTT 方法测定 9 种衍生物在三种癌细胞系（A549、PC9 和 HepG2）中的抗增殖活性。薛定谔预测了所有化合物的 ADMET 谱，并预测了化合物（5 和 6）与 EGFR 的结合亲和力。此外，还研究了这些化合物(3-6)诱导HepG2细胞凋亡的作用。结果：新合成的 4 种（3、5、6 和 9）种衍生物对 A549 的抗增殖活性优于吉非替尼（IC50 = 12.64 ± 3