2-chloro-N-(3-ethynylphenyl)-6,7-dimethoxyquinazoline-4-amine | 1403933-69-6

• 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: 2-chloro-N-(3-ethynylphenyl)-6,7-dimethoxyquinazoline-4-amine
• 英文别名: 2-chloro-4-(3-ethynylanilino)-6,7-dimethoxyquinazoline；2-chloro-N-(3-ethynylphenyl)-6,7-dimethoxyquinazolin-4-amine
• CAS: 1403933-69-6
• 化学式: C₁₈H₁₄ClN₃O₂
• 分子量: 339.781
• InChiKey: TTXPPSWOWRTMRA-UHFFFAOYSA-N

物化性质

• 沸点：
  464.4±45.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(3-ethynylphenyl)-6,7-dimethoxyquinazoline-4-amine 在 potassium fluoride 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 以30%的产率得到2-fluoro-4-(3-ethynylanilino)-6,7-dimethoxyquinazoline
  参考文献：
  名称：

  2-氟代喹唑啉环类化合物及其制备方法和药 用用途

  摘要：

  本发明属有机化学及药物合成领域，具体涉及2‑氟代喹唑啉环类化合物及其制备方法和药用用途，所述化合物通过2‑氯代、2‑溴代或者2‑碘代喹唑啉衍生物的经卤交换反应制备获得；该类化合物具有显著的受体酪氨酸激酶抑制活性，可用于制备治疗肿瘤以及EGFR高表达相关疾病的治疗药物。

  公开号：

  CN104230826B
• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 、 3-氨基苯乙炔 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 2.0h， 以94%的产率得到2-chloro-N-(3-ethynylphenyl)-6,7-dimethoxyquinazoline-4-amine
  参考文献：
  名称：

  ARYL AMINE SUBSTITUTED PYRIMIDINE AND QUINAZOLINE AND THEIR USE AS ANTICANER DRUGS

  摘要：

  基于厄洛替尼（一种EGFR抑制剂）骨架合成了一系列单取代和双取代的喹唑啉和嘧啶衍生物，并评估了它们对肝细胞癌和人类肺腺癌的生物活性。

  公开号：

  US20140080848A1

文献信息

• Development of erlotinib derivatives as CIP2A-ablating agents independent of EGFR activity
  作者：Kuen-Feng Chen、Kuan-Chuan Pao、Jung-Chen Su、Yi-Chieh Chou、Chun-Yu Liu、Hui-Ju Chen、Jui-Wen Huang、InKi Kim、Chung-Wai Shiau

  DOI：10.1016/j.bmc.2012.08.039

  日期：2012.10

  Cancerous inhibitor of PP2A (CIP2A) is a novel human oncoprotein that inhibits PP2A, contributing to tumor aggressiveness in various cancers. Several studies have shown that downregulation of CIP2A by small molecules reduces PP2A-dependent phosphorylation of Akt and induces cell death. Here, a series of mono- and di-substituted quinazoline and pyrimidine derivatives based on the skeleton of erlotinib (an EGFR inhibitor) were synthesized and their bioactivities against hepatocellular carcinoma were evaluated. The di-substituted quinazoline and pyrimidine derivatives were more potent inhibitors of cancer-cell proliferation than the mono-substituted derivatives. In particular, compound 1 with chloride at position 2 of quinazoline was as potent as erlotinib in inducing cell death but no inhibition for EGFR activity. Further assays confirmed a correlation between cell death, and CIP2A and Akt inhibition by these derivatives. Among all the derivatives, compounds 19 and 22 showed the most potent antiproliferative activities and the strongest inhibition of CIP2A and p-Akt expression. (C) 2012 Elsevier Ltd. All rights reserved.
• ARYL AMINE SUBSTITUTED PYRIMIDINE AND QUINAZOLINE AND THEIR USE AS ANTICANCER DRUGS
  申请人：National Yang-Ming University

  公开号：US20150246891A1

  公开（公告）日：2015-09-03

  A series of mono- and di-substituted quinazoline and pyrimidine derivatives based on the skeleton of erlotinib (an EGFR inhibitor) were synthesized and their bioactivities against hepatocellular carcinoma and human lung adenocarcinoma were evaluated.
• US9394261B2
  申请人：——

  公开号：US9394261B2

  公开（公告）日：2016-07-19
• ARYL AMINE SUBSTITUTED PYRIMIDINE AND QUINAZOLINE AND THEIR USE AS ANTICANER DRUGS
  申请人：National Taiwan University

  公开号：US20140080848A1

  公开（公告）日：2014-03-20

  A series of mono- and di-substituted quinazoline and pyrimidine derivatives based on the skeleton of erlotinib (an EGFR inhibitor) were synthesized and their bioactivities against hepatocellular carcinoma and human lung adenocarcinoma were evaluated.

  基于厄洛替尼（一种EGFR抑制剂）骨架合成了一系列单取代和双取代的喹唑啉和嘧啶衍生物，并评估了它们对肝细胞癌和人类肺腺癌的生物活性。
• 2-氟代喹唑啉环类化合物及其制备方法和药 用用途
  申请人：复旦大学

  公开号：CN104230826B

  公开（公告）日：2017-03-29

  本发明属有机化学及药物合成领域，具体涉及2‑氟代喹唑啉环类化合物及其制备方法和药用用途，所述化合物通过2‑氯代、2‑溴代或者2‑碘代喹唑啉衍生物的经卤交换反应制备获得；该类化合物具有显著的受体酪氨酸激酶抑制活性，可用于制备治疗肿瘤以及EGFR高表达相关疾病的治疗药物。