3-(6,7-dimethoxy-4-morpholinoquinazolin-2-yl)-N,N-dimethylbenzamide

• 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-(6,7-dimethoxy-4-morpholinoquinazolin-2-yl)-N,N-dimethylbenzamide
• 英文别名: 3-(6,7-dimethoxy-4-morpholin-4-ylquinazolin-2-yl)-N,N-dimethylbenzamide
• 化学式: C₂₃H₂₆N₄O₄
• 分子量: 422.484
• InChiKey: ZBQYLLPVKDIKDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 反应 4.5h， 生成 3-(6,7-dimethoxy-4-morpholinoquinazolin-2-yl)-N,N-dimethylbenzamide
  参考文献：
  名称：

  Synthesis and antitumor activities evaluation of m-(4-morpholinoquinazolin-2-yl)benzamides in vitro and in vivo

  摘要：

  In the present study, a series of m-(4-morpholinoquinazolin-2-yl)benzamides were designed, synthesized and characterized. The antiproliferative activities of the synthesized compounds were evaluated against two human cell lines (HCF-116 and MCF-7). Compounds with IC50 values below 4 mu M were further evaluated against U-87 MG and A549 cell lines. Among these evaluated compounds, compound T10 displayed a remarkable antiproliferative effect in vitro. The hoechst staining assay showed that compound T10 caused morphological changes. The cell cycle and apoptosis assay further indicated that compound T10 can arrest HCT-116 cells in G2/M and G0/G1 phase and induce apoptosis. PI3K enzyme assays indicated that compounds 17 and T10 selectively inhibit PI3K alpha. A Western bolt assay further suggested that compound T10 can block the PI3K/Akt/mTOR pathway. Moreover, compound T10 inhibited tumor growth on a mice S180 homograft model. These findings directly identify m-(4-morpholinoquinazolin-2-yl)benzamide derivatives as novel anticancer agents. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.037

文献信息

• Synthesis and antitumor activities evaluation of m-(4-morpholinoquinazolin-2-yl)benzamides in vitro and in vivo
  作者：Xiao-Meng Wang、Min-Hang Xin、Jing Xu、Bo-Rui Kang、Yan Li、She-Min Lu、San-Qi Zhang

  DOI：10.1016/j.ejmech.2015.04.037

  日期：2015.5

  In the present study, a series of m-(4-morpholinoquinazolin-2-yl)benzamides were designed, synthesized and characterized. The antiproliferative activities of the synthesized compounds were evaluated against two human cell lines (HCF-116 and MCF-7). Compounds with IC50 values below 4 mu M were further evaluated against U-87 MG and A549 cell lines. Among these evaluated compounds, compound T10 displayed a remarkable antiproliferative effect in vitro. The hoechst staining assay showed that compound T10 caused morphological changes. The cell cycle and apoptosis assay further indicated that compound T10 can arrest HCT-116 cells in G2/M and G0/G1 phase and induce apoptosis. PI3K enzyme assays indicated that compounds 17 and T10 selectively inhibit PI3K alpha. A Western bolt assay further suggested that compound T10 can block the PI3K/Akt/mTOR pathway. Moreover, compound T10 inhibited tumor growth on a mice S180 homograft model. These findings directly identify m-(4-morpholinoquinazolin-2-yl)benzamide derivatives as novel anticancer agents. (C) 2015 Elsevier Masson SAS. All rights reserved.