2-chloro-N-(4-chloro-3-(trifluoromethyl)phenyl)pyrimidin-4-amine | 1403933-75-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-N-(4-chloro-3-(trifluoromethyl)phenyl)pyrimidin-4-amine
• 英文别名: 2-chloro-N-[4-chloro-3-(trifluoromethyl)phenyl]pyrimidin-4-amine
• CAS: 1403933-75-4
• 化学式: C₁₁H₆Cl₂F₃N₃
• 分子量: 308.09
• InChiKey: FMFXJFCIWRRLPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(4-chloro-3-(trifluoromethyl)phenyl)pyrimidin-4-amine 、 2-氯-5-氨基三氟甲苯 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 8.5h， 以5%的产率得到N²,N⁴-bis(4-chloro-3-(trifluoromethyl)phenyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Development of erlotinib derivatives as CIP2A-ablating agents independent of EGFR activity

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2012.08.039
• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 、 2-氯-5-氨基三氟甲苯 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 8.5h， 以3%的产率得到2-chloro-N-(4-chloro-3-(trifluoromethyl)phenyl)pyrimidin-4-amine
  参考文献：
  名称：

  Development of erlotinib derivatives as CIP2A-ablating agents independent of EGFR activity

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2012.08.039

文献信息

• 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。
• 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
• 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.