ethyl (2E)-2-benzoyl-3-(1H-indol-3-yl)acrylate | 1334479-29-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl (2E)-2-benzoyl-3-(1H-indol-3-yl)acrylate
• 英文别名: ethyl (E)-2-benzoyl-3-(1H-indol-3-yl)prop-2-enoate
• CAS: 1334479-29-6
• 化学式: C₂₀H₁₇NO₃
• 分子量: 319.36
• InChiKey: XRVLZDSTDGUYBL-SFQUDFHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-氯乙基)吗啉 、 ethyl (2E)-2-benzoyl-3-(1H-indol-3-yl)acrylate 在 potassium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 以40%的产率得到ethyl 3-(1-(2-morpholinoethyl)-1H-indol-3-yl)-2-(phenylcarbonyl)prop-2-enoate
  参考文献：
  名称：

  Homology modeling in tandem with 3D-QSAR analyses: A computational approach to depict the agonist binding site of the human CB2 receptor

  摘要：

  CB2 receptor belongs to the large family of G-protein coupled receptors (GPCRs) controlling a wide variety of signal transduction. The recent crystallographic determination of human beta 2 adrenoreceptor and its high sequence similarity with human CB2 receptor (hCB2) prompted us to compute a theoretical model of hCB2 based also on beta 2 adrenoreceptor coordinates. This model has been employed to perform docking and molecular dynamic simulations on WIN-55,212-2 (CB2 agonist commonly used in binding experiments), in order to identify the putative CB2 receptor agonist binding site, followed by molecular docking studies on a series of indol-3-yl-tetramethylcyclopropyl ketone derivatives, a novel class of potent CB2 agonists. Successively, docking-based Comparative Molecular Fields Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies were also performed. The CoMSIA model resulted to be the more predictive, showing r(ncv)(2) = 0.96, r(cv)(2) = 0.713, SEE = 0.193, F = 125.223, and r(pred)(2) = 0.78. The obtained 3D-QSAR models allowed us to derive more complete guidelines for the design of new analogues with improved potency so as to synthesize new indoles showing high CB2 affinity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.07.023
• 作为产物：
  描述：

  吲哚 在 苯甲酰氯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 ethyl (2E)-2-benzoyl-3-(1H-indol-3-yl)acrylate
  参考文献：
  名称：

  通过亚胺盐与活性亚甲基试剂的原位缩合非常规立体选择性一锅合成Knoevenagel型吲哚

  摘要：

  描述了一种简单的一锅法，用于立体选择性合成Knoevenagel型吲哚。该方法基于在三乙胺存在下吲哚亚胺盐（已充分表征其中的四种）与无环对称和不对称活性亚甲基试剂的原位反应。总的来说，总产量是中等至良好。讨论了影响立体选择性的一些相关反应参数和空间效应。

  DOI：

  10.1016/j.tet.2013.10.086

文献信息

• Unconventional Knoevenagel-type indoles: Synthesis and cell-based studies for the identification of pro-apoptotic agents
  作者：Andrea Spallarossa、Chiara Caneva、Matteo Caviglia、Silvana Alfei、Stefania Butini、Giuseppe Campiani、Sandra Gemma、Margherita Brindisi、Daniela M. Zisterer、Sandra A. Bright、Clive D. Williams、Emmanuele Crespan、Giovanni Maga、Giuseppina Sanna、Ilenia Delogu、Gabriella Collu、Roberta Loddo

  DOI：10.1016/j.ejmech.2015.08.009

  日期：2015.9

  A new series of indole-based analogues were recently identified as potential anticancer agents. The Knoevenagel-type indoles herein presented were prepared via a one-pot condensation of iminium salts with active methylene reagents and were isolated as single geometric isomers. Biological evaluation in different cell-based assays revealed an antiproliferative activity for some analogues already in the nanomolar range against leukaemia, breast. and renal cancer cell lines. To explain these effects, the most promising analogues of the series were engaged in further cell-based studies. Compounds 5e, I, p and 6a, b highlighted a pro-apoptotic potential being able to induce apoptosis in HL60, K562 and MCF-7 cell lines in a dose and time-dependent manner. The ability of these compounds to arrest cell cycle at the G2/M phase inspired the immunofluorescence studies which allowed us to identify tubulin as a potential target for compounds 5l and 6b. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Unconventional stereoselective one-pot synthesis of Knoevenagel-type indoles via in situ condensation of iminium salts with active methylene reagents
  作者：Angelo Ranise、Francesco Lucchesini、Matteo Caviglia、Silvana Alfei、Andrea Spallarossa、Chiara Caneva

  DOI：10.1016/j.tet.2013.10.086

  日期：2013.12

  Knoevenagel-type indoles is described. The method is based on the in situ reaction of indole iminium salts (four of them are fully characterized) with acyclic symmetrical and unsymmetrical active methylene reagents in the presence of triethylamine. In general, the overall yields are moderate to good. Some of relevant reaction parameters and steric effects affecting stereoselectivity are discussed.

  描述了一种简单的一锅法，用于立体选择性合成Knoevenagel型吲哚。该方法基于在三乙胺存在下吲哚亚胺盐（已充分表征其中的四种）与无环对称和不对称活性亚甲基试剂的原位反应。总的来说，总产量是中等至良好。讨论了影响立体选择性的一些相关反应参数和空间效应。
• Homology modeling in tandem with 3D-QSAR analyses: A computational approach to depict the agonist binding site of the human CB2 receptor
  作者：Elena Cichero、Alessia Ligresti、Marco Allarà、Vincenzo di Marzo、Zelda Lazzati、Pasqualina D’Ursi、Anna Marabotti、Luciano Milanesi、Andrea Spallarossa、Angelo Ranise、Paola Fossa

  DOI：10.1016/j.ejmech.2011.07.023

  日期：2011.9

  CB2 receptor belongs to the large family of G-protein coupled receptors (GPCRs) controlling a wide variety of signal transduction. The recent crystallographic determination of human beta 2 adrenoreceptor and its high sequence similarity with human CB2 receptor (hCB2) prompted us to compute a theoretical model of hCB2 based also on beta 2 adrenoreceptor coordinates. This model has been employed to perform docking and molecular dynamic simulations on WIN-55,212-2 (CB2 agonist commonly used in binding experiments), in order to identify the putative CB2 receptor agonist binding site, followed by molecular docking studies on a series of indol-3-yl-tetramethylcyclopropyl ketone derivatives, a novel class of potent CB2 agonists. Successively, docking-based Comparative Molecular Fields Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies were also performed. The CoMSIA model resulted to be the more predictive, showing r(ncv)(2) = 0.96, r(cv)(2) = 0.713, SEE = 0.193, F = 125.223, and r(pred)(2) = 0.78. The obtained 3D-QSAR models allowed us to derive more complete guidelines for the design of new analogues with improved potency so as to synthesize new indoles showing high CB2 affinity. (C) 2011 Elsevier Masson SAS. All rights reserved.