ethyl 1-benzyl-4-phenyl-1,4-dihydroquinoline-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 1-benzyl-4-phenyl-1,4-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 1-benzyl-4-phenyl-1,4-dihydroquinolin-3-carboxylate；ethyl 1-benzyl-4-phenyl-4H-quinoline-3-carboxylate
• 化学式: C₂₅H₂₃NO₂
• 分子量: 369.463
• InChiKey: BPKCMUFJJQODNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-喹啉羧酸乙酯 在 copper(l) iodide 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 生成 ethyl 1-benzyl-4-phenyl-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Novel Structurally Varied N-Alkyl 1,4-Dihydropyridines as ABCB1 Inhibitors: Structure-Activity Relationships, Biological Activity and First Bioanalytical Evaluation

  摘要：

  一系列结构多样的N-烷基1,4-二氢吡啶和新型苯并环状衍生物作为1,4-二氢喹啉被鉴定为ABCB1抑制剂。讨论了结构-活性关系（SAR）。选定化合物的细胞毒性活性已被确定。首次在细胞模型中进行ABCB1底物特性生物分析。具有最高ABCB1抑制活性的化合物不是ABCB1的底物，且不被外排泵转运，从而为新的ABCB1抑制剂建立了谱系。

  DOI：

  10.2174/1573406411309040002

文献信息

• Novel Structurally Varied N-Alkyl 1,4-Dihydropyridines as ABCB1 Inhibitors: Structure-Activity Relationships, Biological Activity and First Bioanalytical Evaluation
  作者：Andreas Hilgeroth、Christiane Baumert、Claudius Coburger、Marianne Seifert、Soren Krawczyk、Cornelius Hempel、Felix Neubauer、Martin Krug、Josef Molnar、Hermann Lage

  DOI：10.2174/1573406411309040002

  日期：2013.4.1

  Series of structurally varied N-alkyl 1,4-dihydropyridines and novel benzo-annelated derivatives as 1,4- dihydroquinolines have been characterized as ABCB1 inhibitors. Structure-activity relationships (SARs) are discussed. Cytotoxic activities of selected compounds have been determined. A first bioanalysis of ABCB1 substrate properties has been carried out in a cell-based model. Compounds with highest ABCB1 inhibiting activities were no substrates of ABCB1 and not transported by the efflux pump, thus profiling the new ABCB1 inhibitors.

  一系列结构多样的N-烷基1,4-二氢吡啶和新型苯并环状衍生物作为1,4-二氢喹啉被鉴定为ABCB1抑制剂。讨论了结构-活性关系（SAR）。选定化合物的细胞毒性活性已被确定。首次在细胞模型中进行ABCB1底物特性生物分析。具有最高ABCB1抑制活性的化合物不是ABCB1的底物，且不被外排泵转运，从而为新的ABCB1抑制剂建立了谱系。
• Discovery of substituted 1,4-dihydroquinolines as novel class of ABCB1 modulators
  作者：Marc Hemmer、Sören Krawczyk、Ina Simon、Hermann Lage、Andreas Hilgeroth

  DOI：10.1016/j.bmc.2015.05.016

  日期：2015.8

  Transmembrane efflux pumps are one main cause for multidrug resistance (mdr) of cancer. One hopeful approach to combate the mdr has been the development of inhibitors of the efflux pump activity. A novel class of small-molecule inhibitors of the most important efflux pump ABCB1 (P-glycoprotein) has been discovered. Inhibitory activities are discussed in relation to substituent effects. Most active compounds have been evaluated in first bioanalytical studies to reverse the mdr of an anticancer drug. Cellular toxicity and ABCB1 substrate properties of the compounds were investigated. A cellular induction of relevant efflux pump protein expressions was not observed under inhibitor application, so that our compounds are perspective candidates for further preclinical studies. (C) 2015 Elsevier Ltd. All rights reserved.
• Discovery of substituted 1,4-dihydroquinolines as novel promising class of P-glycoprotein inhibitors: First structure–activity relationships and bioanalytical studies
  作者：Marc Hemmer、Sören Krawczyk、Ina Simon、Andreas Hilgeroth

  DOI：10.1016/j.bmcl.2015.05.018

  日期：2015.8

  Multidrug resistance (mdr) is the most important problem in the therapeutical treatment of cancer. One central problem in the resistance proceeding is the expression of transmembrane efflux pumps which transport drugs out of the cells. We developed novel substituted 1,4-dihydroquinolines as inhibitors of the transmembrane efflux pump P-glycoprotein. Structure-activity relationships are discussed for this first series. Promising active inhibitors have been identified and first bioanalytical studies have been carried out to address questions of cellular toxicity, P-gp substrate as well as mdr reversal properties. (C) 2015 Elsevier Ltd. All rights reserved.