6,7-dimethoxy-N-(4-(trifluoromethoxy)phenyl)quinazolin-4-amine

• 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: 6,7-dimethoxy-N-(4-(trifluoromethoxy)phenyl)quinazolin-4-amine
• 英文别名: HI-P219；4-(4'-trifluoromethyloxyphenyl)-amino-6,7-dimethxyquinazoline；6,7-dimethoxy-N-[4-(trifluoromethoxy)phenyl]quinazolin-4-amine
• 化学式: C₁₇H₁₄F₃N₃O₃
• 分子量: 365.312
• InChiKey: GPEUBQWVLAIIPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  对三氟甲氧基苯胺 、 4-氯-6,7-二甲氧基喹唑啉 以 异丙醇 为溶剂， 以62%的产率得到6,7-dimethoxy-N-(4-(trifluoromethoxy)phenyl)quinazolin-4-amine
  参考文献：
  名称：

  Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis

  摘要：

  一系列新型的4-苯胺基喹唑啉类似物DW（1-10）在人类乳腺癌（BT-20）和人类结肠癌（CRC）细胞系（HCT116、HT29和SW620）中进行了抗癌功效评估。化合物DW-8在结肠癌细胞系HCT116、HT29和SW620中表现出最高的抗癌功效和选择性，其IC50值分别为8.50±2.53 µM、5.80±0.92 µM和6.15±0.37 µM，而非癌性结肠细胞系CRL1459的IC50为14.05±0.37 µM。DW-8在与载体培养的结肠癌细胞中的选择性指数大于2倍。我们进一步确定了DW-8在SW620结肠癌细胞中诱导细胞死亡的机制。DW-8（10和30 µM）通过（1）在G2期引起细胞周期停滞；（2）激活内源性凋亡途径，表现为caspase-9和执行者caspase-3和7的激活；（3）核碎裂和（4）增加活性氧化物种（ROS）水平来诱导凋亡。总的来说，我们的结果表明DW-8可能是开发治疗CRC的新型化合物的合适先导。

  DOI：

  10.3390/molecules26154417

文献信息

• Synthesis, biological evaluation and molecular modelling studies of 4-anilinoquinazoline derivatives as protein kinase inhibitors
  作者：Digambar Kumar Waiker、Chandrabose Karthikeyan、Vasanthanathan Poongavanam、Jacob Kongsted、Olivier Lozach、Laurent Meijer、Piyush Trivedi

  DOI：10.1016/j.bmc.2014.01.044

  日期：2014.3

  A series of novel 4-anilinoquinazoline derivatives (3a-3j) has been synthesized and evaluated as potential inhibitors for protein kinases implicated in Alzheimer's disease. Among all the synthesized compounds, compound 3e (N-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine) exhibited the most potent inhibitory activity against CLK1 and GSK-3 alpha/beta kinase with IC50 values of 1.5 mu M and 3 mu M, respectively. Docking studies were performed to elucidate the binding mode of the compounds to the active site of CLK1 and GSK-3 beta. The results of our study suggest that compound 3e may serve as a valuable template for the design and development of dual inhibitors of CLK1 and GSK-3 alpha/beta enzymes with potential therapeutic application in Alzheimer's disease. (C) 2014 Elsevier Ltd. All rights reserved.
• US6358962B2
  申请人：——

  公开号：US6358962B2

  公开（公告）日：2002-03-19
• Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis
  作者：Rabin Neupane、Saloni Malla、Mariam Sami Abou-Dahech、Swapnaa Balaji、Shikha Kumari、Digambar Kumar Waiker、N. S. Hari Narayana Moorthy、Piyush Trivedi、Charles R. Ashby、Chandrabose Karthikeyan、Amit K. Tiwari

  DOI：10.3390/molecules26154417

  日期：——

  A novel series of 4-anilinoquinazoline analogues, DW (1–10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

  一系列新型的4-苯胺基喹唑啉类似物DW（1-10）在人类乳腺癌（BT-20）和人类结肠癌（CRC）细胞系（HCT116、HT29和SW620）中进行了抗癌功效评估。化合物DW-8在结肠癌细胞系HCT116、HT29和SW620中表现出最高的抗癌功效和选择性，其IC50值分别为8.50±2.53 µM、5.80±0.92 µM和6.15±0.37 µM，而非癌性结肠细胞系CRL1459的IC50为14.05±0.37 µM。DW-8在与载体培养的结肠癌细胞中的选择性指数大于2倍。我们进一步确定了DW-8在SW620结肠癌细胞中诱导细胞死亡的机制。DW-8（10和30 µM）通过（1）在G2期引起细胞周期停滞；（2）激活内源性凋亡途径，表现为caspase-9和执行者caspase-3和7的激活；（3）核碎裂和（4）增加活性氧化物种（ROS）水平来诱导凋亡。总的来说，我们的结果表明DW-8可能是开发治疗CRC的新型化合物的合适先导。