1-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)ethanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)ethanone
• 英文别名: 1-[4-[(6,7-Dimethoxyquinazolin-4-yl)amino]phenyl]ethanone
• 化学式: C₁₈H₁₇N₃O₃
• 分子量: 323.351
• InChiKey: FHODFBPGUBHIJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-二甲氧基苯甲醛 、 1-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)ethanone 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以84%的产率得到
  参考文献：
  名称：

  喹唑啉查尔酮衍生物的新型杂种分子：体外细胞毒性活性的合成和研究

  摘要：

  背景：合成了一系列新的喹唑啉连接查尔酮缀合物，并对其体外细胞毒性进行了评估。 方法：喹唑啉-查尔酮衍生物（13a-r）是通过各种取代的苯甲醛（12a-r）与取代的1-（4-（3，4-二氢喹唑啉-4-基氨基）苯基）的克莱森-施密特缩合反应制得的NaOH水溶液中的乙酮（11a-b）。三种潜在的化合物13f，13g和13h对白血病表现出细胞毒性（GI50值为1.07、0.26和0.24 µM），非小肺（GI50值为2.05、1.32和0.23 µM），结肠（GI50值为0.54、0.34和0.34） µM）和乳腺癌（GI50值分别为2.17、1.84和0.22 µM）细胞系。 结果与结论：基于这些生物学结果，很明显，化合物13h有可能被单独或与作为潜在抗癌药的现有疗法组合进行进一步详细研究。

  DOI：

  10.2174/1570180814666171013162148
• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 12.0h， 生成 1-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)ethanone
  参考文献：
  名称：

  喹唑啉查尔酮衍生物的新型杂种分子：体外细胞毒性活性的合成和研究

  摘要：

  背景：合成了一系列新的喹唑啉连接查尔酮缀合物，并对其体外细胞毒性进行了评估。 方法：喹唑啉-查尔酮衍生物（13a-r）是通过各种取代的苯甲醛（12a-r）与取代的1-（4-（3，4-二氢喹唑啉-4-基氨基）苯基）的克莱森-施密特缩合反应制得的NaOH水溶液中的乙酮（11a-b）。三种潜在的化合物13f，13g和13h对白血病表现出细胞毒性（GI50值为1.07、0.26和0.24 µM），非小肺（GI50值为2.05、1.32和0.23 µM），结肠（GI50值为0.54、0.34和0.34） µM）和乳腺癌（GI50值分别为2.17、1.84和0.22 µM）细胞系。 结果与结论：基于这些生物学结果，很明显，化合物13h有可能被单独或与作为潜在抗癌药的现有疗法组合进行进一步详细研究。

  DOI：

  10.2174/1570180814666171013162148

文献信息

• 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。
• 4-Anilinequinazolines with adenosine-kiase inhibitor properties
  申请人：Franchini Gomes Kleber

  公开号：US20070060600A1

  公开（公告）日：2007-03-15

  The present invention relates to the use of 4-anilinoquinazoline derivatives as adenosine-kinase inhibitors. The present invention also relates to a method for protecting tissues and organs like heart, brain and kidneys affected by ischemia, and for treating heart insufficiency, myocardium infarct, arrhythmia, arterial hypertension, atherosclerosis, coronary artery restenosis after angioplasty, chronic renal insufficiency, cerebral vascular accident, and chronic inflanunatory diseases (e.g., rheumatoid arthritis). The present invention also relates to the compound 6,7-dimethoxy-4-(3′-N′,N′-dimethylaminoanilino)quinazoline, or a pharmaceutically acceptable salt thereof, pharmaceutical composition comprising it and use of such compound in the manufacture of a medicament for treating or preventing diseases or conditions that are benefited from the adenosine-kinase inhibition.

  本发明涉及使用4-苯胺基喹唑啉衍生物作为腺苷激酶抑制剂。本发明还涉及一种保护受缺血影响的心脏、脑和肾等组织和器官，并治疗心力衰竭、心肌梗塞、心律失常、动脉高血压、动脉粥样硬化、血管成形术后冠状动脉再狭窄、慢性肾功能不全、脑血管意外和慢性炎症性疾病（如类风湿性关节炎）的方法。本发明还涉及化合物6,7-二甲氧基-4-(3'-N',N'-二甲基氨基苯基)喹唑啉或其药学上可接受的盐、包含它的制药组合物以及使用该化合物制造治疗或预防从腺苷激酶抑制中受益的疾病或病情的药物的用途。
• 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.
• The combination of quinazoline and chalcone moieties leads to novel potent heterodimeric modulators of breast cancer resistance protein (BCRP/ABCG2)
  作者：Stefanie Kraege、Katja Stefan、Kapil Juvale、Thomas Ross、Thomas Willmes、Michael Wiese

  DOI：10.1016/j.ejmech.2016.03.067

  日期：2016.7

  During the last decade it has been found that chalcones and quinazolines are promising inhibitors of ABCG2. The combination of these two scaffolds offers a new class of heterocyclic compounds with potentially high inhibitory activity against ABCG2. For this purpose we investigated 22 different heterodimeric derivatives. In this series only methoxy groups were used as substituents as these had been proven superior for inhibitory activity of chalcones. All compounds were tested for their inhibitory activity, specificity and cytotoxicity. The most potent ABCG2 inhibitor in this series showed an IC50 value of 0.19 mu M. It possesses low cytotoxicity (GI(50) = 93 mu M), the ability to reverse MDR and is nearly selective toward ABCG2. Most compounds containing dimethoxy groups showed slight activity against ABCB1 too. Among these three compounds (17,19 and 24) showed even higher activity toward ABCB1 than ABCG2. All inhibitors were further screened for their effect on basal ATPase activity. Although the basal ATPase activity was partially stimulated, the compounds were not transported by ABCG2. Thus, quinazoline-chalcones are a new class of effective ABCG2 inhibitors. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents
  作者：Maiada M. Sadek、Rabah A. Serrya、Abdel-Hamid N. Kafafy、Marawan Ahmed、Feng Wang、Khaled A. M. Abouzid

  DOI：10.3109/14756366.2013.765417

  日期：2014.4.1

  Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 40 position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC50 equal to 2.09 and 1.94 mu M, respectively, and with IC50 equal to 3.98 and 1.04 mu M on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC50 range of 2.4 and 2.5 mu M, respectively.