N-benzyl-N-(11-oxo-5,11-dihydrobenzo[4,5]imidazo[1,2-b]isoquinolin-6-yl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-benzyl-N-(11-oxo-5,11-dihydrobenzo[4,5]imidazo[1,2-b]isoquinolin-6-yl)benzamide
• 英文别名: N-(11-oxo-5H-benzimidazolo[1,2-b]isoquinolin-6-yl)-N-phenylbenzamide
• 化学式: C₂₈H₁₉N₃O₂
• 分子量: 429.478
• InChiKey: AFUFKRNJVOKTHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 N-benzyl-N-(11-oxo-5,11-dihydrobenzo[4,5]imidazo[1,2-b]isoquinolin-6-yl)benzamide
  参考文献：
  名称：

  Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells

  摘要：

  Colorectal cancer (CRC) is one of the most frequent, malignant gastrointestinal tumors, and strategies and effectiveness of current therapy are limited. A series of benzimidazole-isoquinolinone derivatives (BIDs) was synthesized and screened to identify novel scaffolds for CRC. Of the compounds evaluated, 7g exhibited the most promising anti-cancer properties. Employing two CRC cell lines, SW620 and HT29, 7g was found to suppress growth and proliferation of the cell lines at a concentration of similar to 20 mu M. Treatment followed an increase in G(2)/M cell cycle arrest, which was attributed to cyclin B1 and cyclin-dependent kinase 1 (CDK1) signaling deficiencies with simultaneous enhancement in p21 and p53 activity. In addition, mitochondrial-mediated apoptosis was induced in CRC cells. Interestingly, 7g decreased phosphorylated AKT, mTOR and 4E-BP1 levels, while promoting the expression/stability of PTEN. Since PTEN controls input into the PI3K/AKT/mTOR pathway, antiproliferative effects can be attributed to PTEN-mediated tumor suppression. Collectively, these results suggest that BIDs exert antitumor activity in CRC by impairing PI3K/AKT/mTOR signaling. Against a small kinase panel, 7g exhibited low affinity at 5 mu M suggesting anticancer properties likely stem through a non-kinase mechanism. Because of the novelty of BIDs, the structure can serve as a lead scaffold to design new CRC therapies.

  DOI：

  10.1016/j.bmc.2018.06.010

文献信息

• An Efficient and Facile Method for the Synthesis of Benzimidazoisoquinoline Derivatives via a Multicomponent Reaction
  作者：Wen-Li Liao、Shi-Qiang Li、Jun Wang、Zhi-Yu Zhang、Zhi-Wei Yang、Di Xu、Chuan Xu、Hai-Tao Lan、Zhong-Zhu Chen、Zhi-Gang Xu

  DOI：10.1021/acscombsci.5b00145

  日期：2016.1.11

  Two series of benzimidazoisoquinoline and fused benzimidazoisoquinoline-benzimidazole derivatives have been synthesized using an efficient one-pot procedure. This process involves an intramolecular nucleophilic substitution reaction and provides facile access to two series of complexes and potentially interesting biologically active scaffolds.
• Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells
  作者：Liu-Jun He、Dong-Lin Yang、Shi-Qiang Li、Ya-Jun Zhang、Yan Tang、Jie Lei、Brendan Frett、Hui-kuan Lin、Hong-yu Li、Zhong-Zhu Chen、Zhi-Gang Xu

  DOI：10.1016/j.bmc.2018.06.010

  日期：2018.8

  Colorectal cancer (CRC) is one of the most frequent, malignant gastrointestinal tumors, and strategies and effectiveness of current therapy are limited. A series of benzimidazole-isoquinolinone derivatives (BIDs) was synthesized and screened to identify novel scaffolds for CRC. Of the compounds evaluated, 7g exhibited the most promising anti-cancer properties. Employing two CRC cell lines, SW620 and HT29, 7g was found to suppress growth and proliferation of the cell lines at a concentration of similar to 20 mu M. Treatment followed an increase in G(2)/M cell cycle arrest, which was attributed to cyclin B1 and cyclin-dependent kinase 1 (CDK1) signaling deficiencies with simultaneous enhancement in p21 and p53 activity. In addition, mitochondrial-mediated apoptosis was induced in CRC cells. Interestingly, 7g decreased phosphorylated AKT, mTOR and 4E-BP1 levels, while promoting the expression/stability of PTEN. Since PTEN controls input into the PI3K/AKT/mTOR pathway, antiproliferative effects can be attributed to PTEN-mediated tumor suppression. Collectively, these results suggest that BIDs exert antitumor activity in CRC by impairing PI3K/AKT/mTOR signaling. Against a small kinase panel, 7g exhibited low affinity at 5 mu M suggesting anticancer properties likely stem through a non-kinase mechanism. Because of the novelty of BIDs, the structure can serve as a lead scaffold to design new CRC therapies.