3-[2-(2-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione | 415696-70-7

• 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-(2-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione
• 英文别名: 3-(2-methoxyphenethyl)quinazoline-2,4(1H,3H)-dione；3-[2-(2-Methoxyphenyl)ethyl]quinazoline-2,4(1H,3H)-dione
• CAS: 415696-70-7
• 化学式: C₁₇H₁₆N₂O₃
• 分子量: 296.326
• InChiKey: MYDIDYUGSAVJRE-UHFFFAOYSA-N

物化性质

• 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-(2-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione 在 palladium 10% on activated carbon 、 氢气 、 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， 20.0 ℃ 、101.33 kPa 条件下， 反应 9.0h， 生成 N-hydroxy-4-((3-(2-methoxyphenethyl)-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)methyl)benzamide
  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-甲氧基苯乙胺 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-[2-(2-methoxyphenyl)ethyl]-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  Syntheses of Quinazoline-2,4-dione Alkaloids and Analogues from Mexican Zanthoxylum Species †

  摘要：

  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。

  DOI：

  10.3390/90700609

文献信息

• 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。
• 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.