4-[(2,3,4-三甲氧基苯基)甲基]-1-哌嗪羧酸乙酯 | 53531-01-4

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-[(2,3,4-三甲氧基苯基)甲基]-1-哌嗪羧酸乙酯
• 中文别名: 曲美他嗪N-羧酸乙酯
• 英文名称: Ethyl 4-(2,3,4-trimethoxybenzyl)piperazine-1-carboxylate
• 英文别名: ethyl 4-[(2,3,4-trimethoxyphenyl)methyl]piperazine-1-carboxylate
• CAS: 53531-01-4
• 化学式: C₁₇H₂₆N₂O₅
• mdl: MFCD10039170
• 分子量: 338.404
• InChiKey: RPRSCQFIVQGRJO-UHFFFAOYSA-N

物化性质

• 沸点：
  426.1±45.0 °C(Predicted)
• 密度：
  1.154±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  6

制备方法与用途

应用中，杂质的研究是药品研发的重要内容之一。这项研究涉及选择合适的分析方法，准确分辨和测定杂质的含量，并结合药学、毒理及临床研究的结果来确定合理限度。这一过程贯穿于药品研发的整个阶段。

在药品临床使用过程中，不良反应不仅与药物本身的药理活性有关，还与其中的杂质相关。例如，在青霉素等抗生素中，多聚物等高分子杂质是引起过敏的主要原因。因此，规范地进行杂质研究，并将其控制在一个安全、合理的范围内，直接关系到上市药品的质量和安全性。

在曲美他嗪的研发过程中，杂质H可以用于制定研发标准。而在开展曲美他嗪仿制药研发时，需要对已上市的同品种产品的质量进行全面研究，分析其杂质种类及含量，特别是曲美他嗪杂质H，并与在研产品进行详细的质量对比，以此为基础制订出在研产品的杂质限度，包括曲美他嗪杂质H的具体限度。

反应信息

• 作为反应物：
  描述：

  4-[(2,3,4-三甲氧基苯基)甲基]-1-哌嗪羧酸乙酯 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 2.5h， 生成 曲美他嗪
  参考文献：
  名称：

  Flavonoid-Related Modulators of Multidrug Resistance:  Synthesis, Pharmacological Activity, and Structure−Activity Relationships

  摘要：

  A series of 28 flavonoid derivatives containing a N-benzylpiperazine chain have been synthesized and tested for their ability to modulate multidrug resistance (MDR) in vitro. At 5 mu M, most compounds potentiated doxorubicin cytotoxicity on resistant K562/DOX cells. They were also able to increase the intracellular accumulation of JC-1, a fluorescent molecule recently described as a probe of P-glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. As in other studies, lipophilicity was shown to influence MDR-modulating activity but was not the only determinant. Diverse di- and trimethoxy substitutions on N-benzyl were examined and found to affect the activity differently. The most active compounds had a 2,3,4-trimethoxybenzylpiperazine chain attached to either a flavone or a flavanone moiety (13, 19, 33, and 37) and were found to be more potent; than verapamil.

  DOI：

  10.1021/jm981064b
• 作为产物：
  描述：

  N-哌嗪甲酸乙酯 、 2,3,4-三甲氧基苯甲醛 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 反应 16.0h， 生成 4-[(2,3,4-三甲氧基苯基)甲基]-1-哌嗪羧酸乙酯
  参考文献：
  名称：

  Flavonoid-Related Modulators of Multidrug Resistance:  Synthesis, Pharmacological Activity, and Structure−Activity Relationships

  摘要：

  A series of 28 flavonoid derivatives containing a N-benzylpiperazine chain have been synthesized and tested for their ability to modulate multidrug resistance (MDR) in vitro. At 5 mu M, most compounds potentiated doxorubicin cytotoxicity on resistant K562/DOX cells. They were also able to increase the intracellular accumulation of JC-1, a fluorescent molecule recently described as a probe of P-glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. As in other studies, lipophilicity was shown to influence MDR-modulating activity but was not the only determinant. Diverse di- and trimethoxy substitutions on N-benzyl were examined and found to affect the activity differently. The most active compounds had a 2,3,4-trimethoxybenzylpiperazine chain attached to either a flavone or a flavanone moiety (13, 19, 33, and 37) and were found to be more potent; than verapamil.

  DOI：

  10.1021/jm981064b