(E)-3-(3,4,5-Trimethoxy-phenyl)-acrylic acid 6-chloro-hexyl ester | 870449-52-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3,4,5-Trimethoxy-phenyl)-acrylic acid 6-chloro-hexyl ester
• 英文别名: 6-chlorohexyl (E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate
• CAS: 870449-52-8
• 化学式: C₁₈H₂₅ClO₅
• 分子量: 356.846
• InChiKey: AYLVZGADFNEJJT-CMDGGOBGSA-N

物化性质

• 沸点：
  478.4±45.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-3-(3,4,5-Trimethoxy-phenyl)-acrylic acid 6-chloro-hexyl ester 在 甲酸 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 9.0h， 生成 6-[6-hydroxyhexyl(methyl)amino]hexyl (E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate
  参考文献：
  名称：

  Exploratory Chemistry toward the Identification of a New Class of Multidrug Resistance Reverters Inspired by Pervilleine and Verapamil Models

  摘要：

  On the basis of the present knowledge of the substrate recognition site of ABC transporter proteins and inspired by the structures of verapamil and pervilleine A, a new class of Pgp-mediated multidrug resistance (MDR) reverters has been designed and synthesized. The new compounds are flexible molecules carrying one or two basic nitrogen atoms flanked, at properly modulated distance, by two aromatic moieties. Most of the molecules studied possess MDR inhibitory activity on anthracycline-resistant erythroleukemia K 562 cells, showing a potency that is higher than that of the reference compound verapamil and, in a few cases (7, 12, 13, 17, 20, 22, 28), is in the high nanomolar range. These compounds may be useful leads to develop new MDR reverting agents. In fact, the chemical structure of the class is fairly simple and can be implemented in a variety of ways that will allow the synthesis of new compounds that might be useful leads for the development of drugs to control Pgp-dependent MDR.

  DOI：

  10.1021/jm050542x
• 作为产物：
  描述：

  3,4,5-三甲氧基肉桂酸 在 氯化亚砜 作用下， 以 氯仿 、 苯 为溶剂， 生成 (E)-3-(3,4,5-Trimethoxy-phenyl)-acrylic acid 6-chloro-hexyl ester
  参考文献：
  名称：

  Exploratory Chemistry toward the Identification of a New Class of Multidrug Resistance Reverters Inspired by Pervilleine and Verapamil Models

  摘要：

  On the basis of the present knowledge of the substrate recognition site of ABC transporter proteins and inspired by the structures of verapamil and pervilleine A, a new class of Pgp-mediated multidrug resistance (MDR) reverters has been designed and synthesized. The new compounds are flexible molecules carrying one or two basic nitrogen atoms flanked, at properly modulated distance, by two aromatic moieties. Most of the molecules studied possess MDR inhibitory activity on anthracycline-resistant erythroleukemia K 562 cells, showing a potency that is higher than that of the reference compound verapamil and, in a few cases (7, 12, 13, 17, 20, 22, 28), is in the high nanomolar range. These compounds may be useful leads to develop new MDR reverting agents. In fact, the chemical structure of the class is fairly simple and can be implemented in a variety of ways that will allow the synthesis of new compounds that might be useful leads for the development of drugs to control Pgp-dependent MDR.

  DOI：

  10.1021/jm050542x

文献信息

• Modulation of the spacer in N,N-bis(alkanol)amine aryl ester heterodimers led to the discovery of a series of highly potent P-glycoprotein-based multidrug resistance (MDR) modulators
  作者：Silvia Dei、Laura Braconi、Alfonso Trezza、Marta Menicatti、Marialessandra Contino、Marcella Coronnello、Niccolò Chiaramonte、Dina Manetti、Maria Grazia Perrone、Maria Novella Romanelli、Chatchanok Udomtanakunchai、Nicola Antonio Colabufo、Gianluca Bartolucci、Ottavia Spiga、Milena Salerno、Elisabetta Teodori

  DOI：10.1016/j.ejmech.2019.03.054

  日期：2019.6

  In this study, a new series of N,N-bis(alkanol)amine aryl ester heterodimers was synthesized and studied. The new compounds were designed based on the structures of our previous arylamine ester derivatives endowed with high P-gp-dependent multidrug resistance reversing activity on a multidrug-resistant leukemia cell line. All new compounds were active in the pirarubicin uptake assay on the doxorubicin–resistant

  在这项研究中，一个新的系列的N，N- -双（链烷醇）胺芳基酯的异源二聚体的合成和研究。根据我们先前的芳胺酯衍生物的结构设计新化合物，该衍生物具有对多药耐药性白血病细胞系具有高P-gp依赖性多药耐药性逆转活性。所有新化合物在耐阿霉素的红白血病K562细胞（K562 / DOX）的吡柔比星摄取测定中均具有活性。带有由10个亚甲基组成的连接基的化合物无论芳族基团如何组合，都表现出空前的高逆转活性。对接由得到的结果，在硅片这项研究支持了通过生物学测试获得的数据，一项致力于建立磷酸盐缓冲溶液（PBS）和人血浆中化学稳定性的研究表明，只有少数化合物在人血浆基质中表现出明显的降解。十种选定的非水解性衍生物能够抑制K562 / DOX细胞上P-gp介导的若丹明-123流出，对它们在其他细胞系上的表观通透性和ATP消耗的评估表明该化合物可以表现为明确或不明确运输的底物。还分析了这些化合物对转运蛋白乳腺癌抗性