[4-(Dimethylamino)phenyl][5-(3,4,5-trimethoxyphenyl)-1H-imidazol-2-yl]methanone | 1429621-88-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4-(Dimethylamino)phenyl][5-(3,4,5-trimethoxyphenyl)-1H-imidazol-2-yl]methanone
• 英文别名: [4-(dimethylamino)phenyl]-[5-(3,4,5-trimethoxyphenyl)-1H-imidazol-2-yl]methanone
• CAS: 1429621-88-4
• 化学式: C₂₁H₂₃N₃O₄
• 分子量: 381.431
• InChiKey: KWNVLLDBHNPVCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4,5-trimethoxyphenylglyoxal 、 (4-Dimethylamino-phenyl)-glyoxal 在 ammonium acetate 作用下， 以 乙醇 、 水 为溶剂， 生成 3,4,5-trimethoxyphenyl-(4-(3,4,5-trimethoxyphenyl)-1H-imidazol-2-yl)methanone 、 [4-(Dimethylamino)phenyl][5-(3,4,5-trimethoxyphenyl)-1H-imidazol-2-yl]methanone 、 (4-(dimethylamino)phenyl)(5-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)methanone 、 (4-(4-(dimethylamino)phenyl)-1H-imidazol-2-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Discovery of 4-Aryl-2-benzoyl-imidazoles as Tubulin Polymerization Inhibitor with Potent Antiproliferative Properties

  摘要：

  A series of 4-aryl-2-benzoyl-imidazoles were designed and synthesized based on our previously reported 2-aryl-4-benzoyl-imidazole (ABI) derivatives. The new structures reversed the aryl group and the benzoyl group of previous ABI structures and were named as reverse ABI (RABI) analogues. RABIs were evaluated for biological activity against eight cancer cell lines including multidrug-resistant cancer cell lines. In vitro assays indicated that several RABI compounds had excellent antiproliferative properties, with IC50 values in the low, nanomolar range. The average IC50 of the most active compound 12a is 14 nM. In addition, the mechanism of action of these new analogues was investigated by cell cycle analysis, tubulin polymerization assay, competitive mass spectrometry binding assay, and molecular docking studies. These studies confirmed that these new RABI analogues maintain their mechanisms of action by disrupting tubulin polymerization, similar to their parental ABI analogues.

  DOI：

  10.1021/jm4001117

文献信息

• Discovery of 4-Aryl-2-benzoyl-imidazoles as Tubulin Polymerization Inhibitor with Potent Antiproliferative Properties
  作者：Min Xiao、Sunjoo Ahn、Jin Wang、Jianjun Chen、Duane. D. Miller、James T Dalton、Wei Li

  DOI：10.1021/jm4001117

  日期：2013.4.25

  A series of 4-aryl-2-benzoyl-imidazoles were designed and synthesized based on our previously reported 2-aryl-4-benzoyl-imidazole (ABI) derivatives. The new structures reversed the aryl group and the benzoyl group of previous ABI structures and were named as reverse ABI (RABI) analogues. RABIs were evaluated for biological activity against eight cancer cell lines including multidrug-resistant cancer cell lines. In vitro assays indicated that several RABI compounds had excellent antiproliferative properties, with IC50 values in the low, nanomolar range. The average IC50 of the most active compound 12a is 14 nM. In addition, the mechanism of action of these new analogues was investigated by cell cycle analysis, tubulin polymerization assay, competitive mass spectrometry binding assay, and molecular docking studies. These studies confirmed that these new RABI analogues maintain their mechanisms of action by disrupting tubulin polymerization, similar to their parental ABI analogues.