trans-3-(3,4,5-trimethoxyphenyl)acrylic acid 3-[(3-hydroxypropyl)methylamino]propyl ester | 870449-55-1

• 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-[(3-hydroxypropyl)methylamino]propyl ester
• 英文别名: 3-[3-hydroxypropyl(methyl)amino]propyl (E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate
• CAS: 870449-55-1
• 化学式: C₁₉H₂₉NO₆
• 分子量: 367.442
• InChiKey: DILFSNUIJCITLV-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  trans-3-(3,4,5-trimethoxyphenyl)acrylic acid 3-[(3-hydroxypropyl)methylamino]propyl ester 、 9-芴甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 49.0h， 以33%的产率得到(E)-3-(methyl(3-((3-(3,4,5-trimethoxyphenyl)acryloyl)oxy)propyl)amino)propyl 9H-fluorene-9-carboxylate
  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：

  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

文献信息

• Design and synthesis of aminoester heterodimers containing flavone or chromone moieties as modulators of P-glycoprotein-based multidrug resistance (MDR)
  作者：Silvia Dei、Maria Novella Romanelli、Dina Manetti、Niccolò Chiaramonte、Marcella Coronnello、Milena Salerno、Elisabetta Teodori

  DOI：10.1016/j.bmc.2017.11.016

  日期：2018.1

  to be critical for the interaction with the pump. This fact indicates that the presence of a flavone or chromone residue influences the SAR of these series of products, and that flexible molecules can find different productive binding modes with the P-gp recognition site. These results support the synthesis of new compounds that might be useful leads for the development of drugs to control P-gp-dependent

  在这项研究中，合成了一系列新的异二聚体。这些衍生物是Ñ，ñ -双（链烷醇）胺的芳基的酯或Ñ，ñ -带有甲氧基化的芳基残基与黄酮或色酮部分结合的双（乙氧基乙醇）胺芳基酯。研究了这些新化合物，以评估其对多药耐药性白血病细胞系的P-gp调节活性。一些新化合物显示出良好的MDR逆转活性。有趣的是，该系列新化合物不符合先前合成的带有不同芳族部分的类似物所概述的结构-活性关系（SAR）。对于本文所述的化合物，活性与不同的特征相关，尤其是垫片的特征，这对于与泵的相互作用似乎至关重要。这一事实表明，黄酮或色酮残基的存在会影响这些系列产品的SAR，而且柔性分子可以通过P-gp识别位点找到不同的生产性结合模式。这些结果支持了新化合物的合成，这可能是开发控制P-gp依赖性MDR的药物的有用线索。
• Dual P-Glycoprotein and CA XII Inhibitors: A New Strategy to Reverse the P-gp Mediated Multidrug Resistance (MDR) in Cancer Cells
  作者：Elisabetta Teodori、Laura Braconi、Silvia Bua、Andrea Lapucci、Gianluca Bartolucci、Dina Manetti、Maria Novella Romanelli、Silvia Dei、Claudiu T. Supuran、Marcella Coronnello

  DOI：10.3390/molecules25071748

  日期：——

  moiety to target CA XII. Many compounds displayed a dual activity against P-gp and CA XII being active in the Rhd 123 uptake test on K562/DOX cells and in the hCA XII inhibition test. On LoVo/DOX cells, that overexpress both P-gp and CA XII, some coumarin derivatives showed a high MDR reversal effect in Rhd 123 uptake and doxorubicin cytotoxicity enhancement tests. In particular, compounds 7 and 8 showed

  合成了一系列新的 N，N-双（烷醇）胺芳基二酯，并将其作为双重 P-糖蛋白 (P-gp) 和碳酸酐酶 XII 抑制剂 (CA XII) 进行研究。这些杂交体应该能够协同克服癌细胞中 P-gp 介导的多药耐药性 (MDR)。据报道，CA XII 可以调节 P-gp 的外排活性，因为 CA XII 抑制引起的 pH 降低导致 P-gp ATPase 活性显着降低。这里报道的新化合物具有 P-gp 和 CA XII 结合部分。这些杂交体包含在 P-糖蛋白配体中发现的 N,N-双（烷醇）胺二酯支架和香豆素或苯磺酰胺部分以靶向 CA XII。许多化合物显示出针对 P-gp 和 CA XII 的双重活性，在 K562/DOX 细胞的 Rhd 123 摄取测试和 hCA XII 抑制测试中具有活性。在同时过表达 P-gp 和 CA XII 的 LoVo/DOX 细胞上，一些香豆素衍生物在 Rhd 123
• 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.