5-羟基-2-(4-甲基-哌嗪-1-羰基)-色烯-4-酮 | 546093-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 5-羟基-2-(4-甲基-哌嗪-1-羰基)-色烯-4-酮
• 英文名称: MH-11
• 英文别名: 5-Hydroxy-2-(4-methyl-piperazine-1-carbonyl)-chromen-4-one；5-hydroxy-2-(4-methylpiperazine-1-carbonyl)chromen-4-one
• CAS: 546093-05-4
• 化学式: C₁₅H₁₆N₂O₄
• 分子量: 288.303
• InChiKey: IQWFMMMDLDKSJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为产物：
  描述：

  2,6-二羟基苯乙酮 在 氢溴酸 、 sodium ethanolate 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 44.0h， 生成 5-羟基-2-(4-甲基-哌嗪-1-羰基)-色烯-4-酮
  参考文献：
  名称：

  Modulation of P-Glycoprotein-Mediated Multidrug Resistance by Flavonoid Derivatives and Analogues

  摘要：

  Flavonoid derivatives were synthesized and tested for their ability to modulate P-glycoprotein (Pgp)-mediated multidrug resistance (MDR) in vitro. These compounds belong to various flavonoid subclasses, namely: chromones, azaisoflavones, and aurones. Among the investigated compounds, three showed potent reversing activity. 2-(4-Methylpiperazin-1-ylcarbonyl)-5-hydroxychromone (4a), 5,7-dimethoxy-3-phenyl-4-quinolone (5), and 4,6-dimethoxyaurone (6) potentiated daunorubicin cytotoxicity on resistant K562 cells. They were also able to increase the intracellular accumulation of rhodamine-123, a fluorescent molecule which acts as a probe of P-glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. The most active compound, 5-hydroxy-2-(4-methylpiperazin-1-ylcarbonyl)chromone (4a) was found to be a powerful reversal agent, more potent than cyclosporin A, used as the reference molecule. No effect was observed on MRP transport nor on cell proliferation. Little apoptosis was induced on K562S cells with 4a compared to K562R, probably due to the extrusion of the compound by Pgp.

  DOI：

  10.1021/jm021099i

文献信息

• Modulation of P-Glycoprotein-Mediated Multidrug Resistance by Flavonoid Derivatives and Analogues
  作者：Mohamed Hadjeri、Magali Barbier、Xavier Ronot、Anne-Marie Mariotte、Ahcène Boumendjel、Jean Boutonnat

  DOI：10.1021/jm021099i

  日期：2003.5.1

  Flavonoid derivatives were synthesized and tested for their ability to modulate P-glycoprotein (Pgp)-mediated multidrug resistance (MDR) in vitro. These compounds belong to various flavonoid subclasses, namely: chromones, azaisoflavones, and aurones. Among the investigated compounds, three showed potent reversing activity. 2-(4-Methylpiperazin-1-ylcarbonyl)-5-hydroxychromone (4a), 5,7-dimethoxy-3-phenyl-4-quinolone (5), and 4,6-dimethoxyaurone (6) potentiated daunorubicin cytotoxicity on resistant K562 cells. They were also able to increase the intracellular accumulation of rhodamine-123, a fluorescent molecule which acts as a probe of P-glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. The most active compound, 5-hydroxy-2-(4-methylpiperazin-1-ylcarbonyl)chromone (4a) was found to be a powerful reversal agent, more potent than cyclosporin A, used as the reference molecule. No effect was observed on MRP transport nor on cell proliferation. Little apoptosis was induced on K562S cells with 4a compared to K562R, probably due to the extrusion of the compound by Pgp.