2-(4-(diethylamino)quinazolin-2-yl)-1H-indole-3-carbaldehyde

• 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: 2-(4-(diethylamino)quinazolin-2-yl)-1H-indole-3-carbaldehyde
• 英文别名: 2-[4-(diethylamino)quinazolin-2-yl]-1H-indole-3-carbaldehyde
• 化学式: C₂₁H₂₀N₄O
• 分子量: 344.416
• InChiKey: BMVLGQQAHWYJBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  bouchardatine 在 氯化亚砜 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 16.0h， 生成 2-(4-(diethylamino)quinazolin-2-yl)-1H-indole-3-carbaldehyde
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Bouchardatine Derivatives as Potential Adipogenesis/Lipogenesis Inhibitors for Antiobesity Treatment

  摘要：

  Our recent study has shown that the natural product bouchardatine (1) can reduce the triglyceride (TG) content in 3T3-L1 adipocytes (EC50 approximate to 25 mu M). Here, we synthesized two series of compounds by introducing amine side chains at the 5 or 8 position of 1 and evaluated the lipid-lowering activity of derivatives. It was found that some of the compounds had significant lipid-lowering effects, and the most active compound 3d showed better activity (EC50 = 0.017 mu M) than 2 (EC50 = 0.086 mu M), a compound reported by us. Further, the mechanism studies revealed that 3d blocked TG accumulation via activation of the LKB1-AMPK signaling pathway, efficiently down-regulating the expression of key regulators of adipogenesis/lipogenesis. Cell uptake assay and confocal imaging of 3d in cells indicated that compound 3d had favorable cell permeability. Our results suggest that 3d may be a promising agent for the treatment of obesity and related metabolic disorders.

  DOI：

  10.1021/acs.jmedchem.5b01566

文献信息

• Synthesis and Biological Evaluation of Novel Bouchardatine Derivatives as Potential Adipogenesis/Lipogenesis Inhibitors for Antiobesity Treatment
  作者：Yong Rao、Hong Liu、Lin Gao、Hong Yu、Tian-Miao Ou、Jia-Heng Tan、Shi-Liang Huang、Hong-Gen Wang、Ding Li、Lian-Quan Gu、Ji-Ming Ye、Zhi-Shu Huang

  DOI：10.1021/acs.jmedchem.5b01566

  日期：2015.12.10

  Our recent study has shown that the natural product bouchardatine (1) can reduce the triglyceride (TG) content in 3T3-L1 adipocytes (EC50 approximate to 25 mu M). Here, we synthesized two series of compounds by introducing amine side chains at the 5 or 8 position of 1 and evaluated the lipid-lowering activity of derivatives. It was found that some of the compounds had significant lipid-lowering effects, and the most active compound 3d showed better activity (EC50 = 0.017 mu M) than 2 (EC50 = 0.086 mu M), a compound reported by us. Further, the mechanism studies revealed that 3d blocked TG accumulation via activation of the LKB1-AMPK signaling pathway, efficiently down-regulating the expression of key regulators of adipogenesis/lipogenesis. Cell uptake assay and confocal imaging of 3d in cells indicated that compound 3d had favorable cell permeability. Our results suggest that 3d may be a promising agent for the treatment of obesity and related metabolic disorders.