3-[2'-(4'-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione | 847238-29-3

• 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: 3-[2'-(4'-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione
• 英文别名: 3-(4-methoxyphenethyl)quinazoline-2,4(1H,3H)-dione；3-(4-methoxyphenethyl)-1H,3H-quinazoline-2,4-dione；3-(4-methoxyphenethyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline；3-[2-(4-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione
• CAS: 847238-29-3
• 化学式: C₁₇H₁₆N₂O₃
• 分子量: 296.326
• InChiKey: JQKXTXKAKUQQRR-UHFFFAOYSA-N

物化性质

• 熔点：
  224-228 °C(Solv: ethanol (64-17-5))
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-[2'-(4'-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione 在 sodium hydride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成
  参考文献：
  名称：

  Quinazolin-2,4-dione-Based Hydroxamic Acids as Selective Histone Deacetylase-6 Inhibitors for Treatment of Non-Small Cell Lung Cancer

  摘要：

  We designed and synthesized quinazolin-2,4-dione-based hydroxamic acids to serve as selective competitive inhibitors of histone deacetylase-6 (HDAC6). The most potent and selective compound, 3d (IC50, 4 nM, HDAC6; IC50 > 10 mu M, HDAC1), substantially increased acetylation of alpha-tubulin instead of histones in the lung cancer cell line, LL2. Paclitaxel in combination with 3d had a synergistic anticancer effect on reduction of programmed death-ligand 1 expression in LL/2 cells. When given orally, 3d was mainly found to locate in the liver and lungs, at a concentration 18- to 70-fold greater, respectively, than in plasma. As an orally active HDAC6 inhibitor, 3d (20 mg/kg) potentiated paclitaxel antitumor activity (percentage tumor growth inhibition, 67.5%) in a xenograft syngeneic non-small cell lung cancer mouse model.

  DOI：

  10.1021/acs.jmedchem.8b01590
• 作为产物：
  描述：

  2-溴苯基氨基甲酸甲酯 在 palladium diacetate 、 caesium carbonate 、 正丁基二(1-金刚烷基)膦 作用下， 以 1,4-二氧六环 、 水 为溶剂， 80.0 ℃ 、1.0 MPa 条件下， 反应 18.0h， 生成 3-[2'-(4'-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  钯催化杂环合成中将异氰化物与二氧化碳结合：通过三组分反应的N 3-取代的喹唑啉-2,4（1 H，3 H）-二酮

  摘要：

  我们报告了2-溴苯胺，二氧化碳和异氰酸酯的钯催化三组分反应。这两种容易获得的C 1-反应物的组合，在动力学和热力学稳定性方面具有巨大差异，是过渡金属催化领域前所未有的。通过这种一锅三组分反应，以完全的区域选择性和化学选择性的方式以中等至高收率获得了N 3-取代的喹唑啉-2,4（1 H，3 H）-二酮。我们的方法很容易让芳烃和氮的变化所需杂环的3取代模式。不同API的形式综合说明了其实际适用性。此外，该方法还允许通过使用13 CO 2方便且选择性地进行13 C标记。这被示出为[2- 13 C] -2,4-二氯-6,7-二甲氧基合成，连续数的API的关键中间体。

  DOI：

  10.1021/acscatal.7b01503

文献信息

• Facile One-Pot Synthesis of Quinazoline-2,4-dione Derivatives and Application to Naturally Occurring Alkaloids from Zanthoxylum Arborescens
  作者：Xin Li、Yong-Rok Lee

  DOI：10.5012/bkcs.2011.32.6.2121

  日期：2011.6.20

  method that canefficiently provide quinazoline-2,4-dione derivatives. Wereport herein a convenient one-pot synthesis of quinazoline-2,4-dione derivatives. We also report on the synthesis of thenaturally occurring alkaloids 2 and 3. Results and DiscussionA two-step reaction for the synthesis of quinazoline-2,4-dione derivatives starting from isatoic anhydride and amineshas already been described.

  仍然需要一种更方便、更高效的合成方法，可以有效地提供喹唑啉-2,4-二酮衍生物。本文报道了一种方便的一锅法合成喹唑啉-2,4-二酮衍生物。我们还报告了天然存在的生物碱 2 和 3 的合成。结果和讨论已经描述了从靛红酸酐和胺开始合成喹唑啉-2,4-二酮衍生物的两步反应。
• Syntheses of Quinazoline-2,4-dione Alkaloids and Analogues from Mexican Zanthoxylum Species †
  作者：I. Rivero、K. Espinoza、R. Somanathan

  DOI：10.3390/90700609

  日期：——

  Quinazolinone and quinazolinedione derivatives are of considerable interest due to their wide array of pharmacological properties. In this paper we report the synthesis of ten quinazolinediones. The previous isolation of two of these compounds, namely 1-methyl-3-(2'-phenylethyl)-1H,3H-quinazoline-2,4-dione and 1-methyl-3-[2'-(4'- methoxyphenyl)ethyl]-lH,3H-quinazoline-2,4-dione, from the seed husks of Mexican Zanthoxylum species has been reported

  喹唑啉酮和喹唑啉二酮衍生物因其广泛的药理性质而受到广泛关注。在本文中，我们报告了十种喹唑啉二酮的合成。此前已经报道了其中两个化合物，即1-甲基-3-(2'-苯乙基)-1H,3H-喹唑啉-2,4-二酮和1-甲基-3-[2'-(4'-甲氧基苯基)乙基]-1H,3H-喹唑啉-2,4-二酮，来自墨西哥刺柠檬种子的种皮。
• One‐pot Syntheses of Some New 2,4(1 <i>H</i> ,3 <i>H</i> )‐quinazolinedione Derivatives in the Absence of Catalyst
  作者：Ali Asghar Mohammadi

  DOI：10.1002/jhet.2778

  日期：2017.5

  A facile, rapid and one‐pot procedure for the synthesis of some new 2,4(1H,3H)‐quinazolinediones is described. The method involves the one‐pot condensation of isatoic anhydride, primary amine and carbonyl diimidazole (CDI) in the absence of organic or inorganic catalyst. It affords the corresponding product in high yield.

  描述了一种合成一些新的2,4（1 H，3 H）-喹唑啉二酮的简便，快速，单罐方法。该方法涉及在不存在有机或无机催化剂的情况下，对等酸酐，伯胺和羰基二咪唑（CDI）进行单锅缩合。它以高收率提供了相应的产品。
• Quinazolin-2,4-dione-Based Hydroxamic Acids as Selective Histone Deacetylase-6 Inhibitors for Treatment of Non-Small Cell Lung Cancer
  作者：Chao-Wu Yu、Pei-Yun Hung、Hui-Ting Yang、Yi-Hsun Ho、Hsing-Yi Lai、Yi-Sheng Cheng、Ji-Wang Chern

  DOI：10.1021/acs.jmedchem.8b01590

  日期：2019.1.24

  We designed and synthesized quinazolin-2,4-dione-based hydroxamic acids to serve as selective competitive inhibitors of histone deacetylase-6 (HDAC6). The most potent and selective compound, 3d (IC50, 4 nM, HDAC6; IC50 > 10 mu M, HDAC1), substantially increased acetylation of alpha-tubulin instead of histones in the lung cancer cell line, LL2. Paclitaxel in combination with 3d had a synergistic anticancer effect on reduction of programmed death-ligand 1 expression in LL/2 cells. When given orally, 3d was mainly found to locate in the liver and lungs, at a concentration 18- to 70-fold greater, respectively, than in plasma. As an orally active HDAC6 inhibitor, 3d (20 mg/kg) potentiated paclitaxel antitumor activity (percentage tumor growth inhibition, 67.5%) in a xenograft syngeneic non-small cell lung cancer mouse model.
• Combining Isocyanides with Carbon Dioxide in Palladium-Catalyzed Heterocycle Synthesis: <i>N</i>3-Substituted Quinazoline-2,4(1<i>H</i>,3<i>H</i>)-diones via a Three-Component Reaction
  作者：Pieter Mampuys、Helfried Neumann、Sergey Sergeyev、Romano V. A. Orru、Haijun Jiao、Anke Spannenberg、Bert U. W. Maes、Matthias Beller

  DOI：10.1021/acscatal.7b01503

  日期：2017.8.4

  We report a Pd-catalyzed three-component reaction of 2-bromoanilines, carbon dioxide, and isocyanides. The combination of these two readily available C1-reactants, featuring a huge difference in kinetic and thermodynamic stability, is hitherto unprecedented in transition-metal catalysis. With this one-pot three-component reaction, N3-substituted quinazoline-2,4(1H,3H)-diones are obtained in moderate

  我们报告了2-溴苯胺，二氧化碳和异氰酸酯的钯催化三组分反应。这两种容易获得的C 1-反应物的组合，在动力学和热力学稳定性方面具有巨大差异，是过渡金属催化领域前所未有的。通过这种一锅三组分反应，以完全的区域选择性和化学选择性的方式以中等至高收率获得了N 3-取代的喹唑啉-2,4（1 H，3 H）-二酮。我们的方法很容易让芳烃和氮的变化所需杂环的3取代模式。不同API的形式综合说明了其实际适用性。此外，该方法还允许通过使用13 CO 2方便且选择性地进行13 C标记。这被示出为[2- 13 C] -2,4-二氯-6,7-二甲氧基合成，连续数的API的关键中间体。