trans-3-(3,4,5-trimethoxyphenyl)acrylic acid 3-bromopropyl ester | 870449-49-3

• 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: trans-3-(3,4,5-trimethoxyphenyl)acrylic acid 3-bromopropyl ester
• 英文别名: 3-bromopropyl (E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate
• CAS: 870449-49-3
• 化学式: C₁₅H₁₉BrO₅
• 分子量: 359.217
• InChiKey: RJWBDFDJEINDIJ-AATRIKPKSA-N

物化性质

• 沸点：
  462.6±45.0 °C(Predicted)
• 密度：
  1.337±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 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：

  trans-3-(3,4,5-trimethoxyphenyl)acrylic acid 3-bromopropyl ester 在 甲酸 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 trans-3-(3,4,5-trimethoxyphenyl)acrylic acid 3-[(3-hydroxypropyl)methylamino]propyl ester
  参考文献：
  名称：

  Multidrug resistance (MDR) reversers: High activity and efficacy in a series of asymmetrical N,N-bis(alkanol)amine aryl esters

  摘要：

  As a continuation of our research on potent and efficacious P-gp-dependent multidrug resistance (MDR) reversers, several new N,N-bis(alkanol)amine aryl esters were designed and synthesized, varying the aromatic moieties or the length of the methylenic chain. The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay, where most of the new compounds were shown to be active. In particular the asymmetrical compounds, characterized by two linkers of different length, generally showed fairly high activities as MDR reversers. Some selected compounds (isomers 15-17) were further studied by evaluating their doxorubicin cytotoxicity enhancement (reversal fold, RF) on the K562/DOX cell line. The results of both pharmacological assays indicate that compounds 16 (GDE6) and 17 (GDE19) could be interesting leads for the development of new P-gp dependent MDR modulators. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.084
• 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 trans-3-(3,4,5-trimethoxyphenyl)acrylic acid 3-bromopropyl 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
• New Dual P-Glycoprotein (P-gp) and Human Carbonic Anhydrase XII (hCA XII) Inhibitors as Multidrug Resistance (MDR) Reversers in Cancer Cells
  作者：Laura Braconi、Elisabetta Teodori、Chiara Riganti、Marcella Coronnello、Alessio Nocentini、Gianluca Bartolucci、Marco Pallecchi、Marialessandra Contino、Dina Manetti、Maria Novella Romanelli、Claudiu T. Supuran、Silvia Dei

  DOI：10.1021/acs.jmedchem.2c01175

  日期：2022.11.10

  continuing search of dual P-gp and hCA XII inhibitors, we synthesized and studied new N,N-bis(alkanol)amine aryl diester derivatives characterized by the presence of a coumarin group. These hybrids contain both P-gp and hCA XII binding groups to synergistically overcome the P-gp-mediated multidrug resistance (MDR) in cancer cells expressing both P-gp and hCA XII. Indeed, hCA XII modulates the efflux activity

  在持续寻找双重 P-gp 和 hCA XII 抑制剂的过程中，我们合成并研究了新的N、N-双（链烷醇）胺芳基二酯衍生物，其特征在于存在香豆素基团。这些杂交体包含 P-gp 和 hCA XII 结合基团，以协同克服表达 P-gp 和 hCA XII 的癌细胞中 P-gp 介导的多药耐药性 (MDR)。实际上，hCA XII 调节 P-gp 的外排活性，抑制 hCA XII 会降低细胞内 pH，从而降低 P-gp 的 ATP 酶活性。所有化合物均对 P-gp 和 hCA XII 蛋白单独显示出抑制活性，其中许多化合物在过表达 P-gp 和 hCA XII 的 HT29/DOX 和 A549/DOX 细胞中表现出协同作用，比 K562/仅过表达 P-gp 的 DOX 细胞。化合物5和14被鉴定为有前途的化学增敏剂，用于选择性抑制过度表达 P-gp 和 hCA XII 的 MDR 癌细胞。
• Structure−Activity Relationships Studies in a Series of <i>N</i>,<i>N</i>-Bis(alkanol)amine Aryl Esters as P-Glycoprotein (Pgp) Dependent Multidrug Resistance (MDR) Inhibitors
  作者：Cecilia Martelli、Marcella Coronnello、Silvia Dei、Dina Manetti、Francesca Orlandi、Serena Scapecchi、Maria Novella Romanelli、Milena Salerno、Enrico Mini、Elisabetta Teodori

  DOI：10.1021/jm9016174

  日期：2010.2.25

  As a continuation Or a previous research, a series of N,N-bis(alkanol)amine aryl esters, as Pgp-dependent MDR inhibitors, was; designed and synthesized. The aromatic ester portions are suitably modulated, and new aryl rings (Ar-1 and Ar-2) were combined with trans-3-(3,4,5-trimethoxyphenyl)-vinyl, 3,4,5-trimethoxybenzyl and anthracene moieties that were present in the most potent previously Studied compounds. The new compounds showed I wide range of potencies and efficacies Oil doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Selected compounds (5, 6, 8, 9, and 21) were further Studied, evaluating their action on doxorubicin cytotoxicity potentiation oil K562 cells; they significantly enhanced doxorubicin cytotoxicity oil K562/DOX cells, confirming the results obtained with pirarubicin. Compound 9 Shows file Most promising properties as it was able to nearly completely reverse Pgp-dependent pirarubicin extrusion at nanomolar closes and increased the cytotoxicity of doxorubicin with a reversal fold (RF) of 19.1 at 3 mu M dose.
• Exploratory Chemistry toward the Identification of a New Class of Multidrug Resistance Reverters Inspired by Pervilleine and Verapamil Models
  作者：Elisabetta Teodori、Silvia Dei、Arlette Garnier-Suillerot、Fulvio Gualtieri、Dina Manetti、Cecilia Martelli、Maria Novella Romanelli、Serena Scapecchi、Paiwan Sudwan、Milena Salerno

  DOI：10.1021/jm050542x

  日期：2005.11.1

  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.
• Multidrug resistance (MDR) reversers: High activity and efficacy in a series of asymmetrical N,N-bis(alkanol)amine aryl esters
  作者：Silvia Dei、Marcella Coronnello、Elisa Floriddia、Gianluca Bartolucci、Cristina Bellucci、Luca Guandalini、Dina Manetti、Maria Novella Romanelli、Milena Salerno、Ivan Bello、Enrico Mini、Elisabetta Teodori

  DOI：10.1016/j.ejmech.2014.09.084

  日期：2014.11

  As a continuation of our research on potent and efficacious P-gp-dependent multidrug resistance (MDR) reversers, several new N,N-bis(alkanol)amine aryl esters were designed and synthesized, varying the aromatic moieties or the length of the methylenic chain. The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay, where most of the new compounds were shown to be active. In particular the asymmetrical compounds, characterized by two linkers of different length, generally showed fairly high activities as MDR reversers. Some selected compounds (isomers 15-17) were further studied by evaluating their doxorubicin cytotoxicity enhancement (reversal fold, RF) on the K562/DOX cell line. The results of both pharmacological assays indicate that compounds 16 (GDE6) and 17 (GDE19) could be interesting leads for the development of new P-gp dependent MDR modulators. (C) 2014 Elsevier Masson SAS. All rights reserved.