(E)-3-(1H-indol-3-yl)-2-(1H-indole-3-carbonyl)acrylonitrile | 1391815-84-1

• 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: (E)-3-(1H-indol-3-yl)-2-(1H-indole-3-carbonyl)acrylonitrile
• 英文别名: (E)-2-(1H-indole-3-carbonyl)-3-(1H-indol-3-yl)prop-2-enenitrile
• CAS: 1391815-84-1
• 化学式: C₂₀H₁₃N₃O
• 分子量: 311.343
• InChiKey: KAIHDMDITCAQCA-UKTHLTGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-3-(1H-indol-3-yl)-2-(1H-indole-3-carbonyl)acrylonitrile 、 硫酸二甲酯 在 PEG-600 作用下， 反应 1.0h， 以90%的产率得到
  参考文献：
  名称：

  Simple and efficient Knoevenagel synthesis of (E)-2-((1H-indol-3-yl)methylene)-3-oxoindolylnitrile catalysed by PPh3

  摘要：

  研究发现，三苯基膦（TPP）是一种高效催化剂，可用于吲哚-3-羧基醛 1（a-e）及其 N-取代衍生物 4（a-e）与活性亚甲基化合物（即 3-氰乙酰基吲哚 (2)）的克诺文纳格尔缩合反应，分别生成新型取代烯烃 3（a-e）和 5（a-e）。后者在 PEG-600 存在下与二甲基亚砜反应，得到相应的 N，Nl 二甲基衍生物 6(a-e)。

  DOI：

  10.1007/s12039-011-0136-x
• 作为产物：
  描述：

  吲哚 在 哌啶 作用下， 以 乙醇-D1 、 乙酸酐 为溶剂， 反应 2.08h， 生成 (E)-3-(1H-indol-3-yl)-2-(1H-indole-3-carbonyl)acrylonitrile
  参考文献：
  名称：

  Focused library development of 2-phenylacrylamides as broad spectrum cytotoxic agents

  摘要：

  With our lead compound (E)-3-(4-chlorophenyl)-2-(1H-pyrrole-2-carbonyl)acrylonitrile (1) inducing 50% growth inhibition of 11 cancer cell lines at 27-61 mu M, potency enhancements were rapidly established through the synthesis of a series of focused compound libraries. Six highly focused libraries (46 compounds in total) were synthesised. Each library allowed the identification of a new lead compound, viz Library A identified (E)-3-(pentafluorophenyl)-2-(1H-pyrrole-2-carbonyl) acrylonitrile (11) and (E)-3-(1H-indol-3-yl)-2-(1H-pyrrole-2-carbonyl) acrylonitrile (13) as inhibitors with improved cytotoxicity. Synthesis of discrete libraries of amidoacrylamide analogues (Ar-C=C(CN)-A(sic)Ar-C=C(CN)-C(=O)NH)-Ar) resulted in a series of analogues significantly more potent that the lead, 1. Three furan three analogues: (E)-3-(5-chlorofuran-2-yl)-2-cyano-N-(4-methoxybenzyl)acrylamide (33), (E)-3-(5-bromofuran-2-yl)-2-cyano-N-(4-methoxybenzyl) acrylamide (34) and (E)-2-cyano-3-(furan-3-yl)-N-(4-methoxybenzyl)acrylamide (37) returned broad spectrum growth inhibition (GI(50) values of 5-16 mu M). Replacement of the furan moiety with simple aromatics gave an additional three analogues: (E)-2-cyano-N-(4-methoxybenzyl)-3-phenylacrylamide (39), (E)-3-(4-chlorophenyl)-2-cyano-N-(4-methoxybenzyl) acrylamide (41) and (E)-2-cyano-N-(4-methoxyphenyl)-3-(naphthalen-1-yl)acrylamide (45) with GI(50) values of 7-24 mu M. The final library retained the aromatic substituents but introduced a 3,4-dichlorbenzylamine moiety to afford the 1-naphthyl substituted 52, which was the most potent broad spectrum cytotoxic analogue produced here in with an average GI(50) = 8.6 mu M. This represents a fivefold potency enhancement relative to 1 and a new cytotoxic scaffold suitable for further development. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.10.003

文献信息

• Synthesis and antiproliferative activity of 2,4-bis(indol-3-yl)pyrrole derivatives: Marine Nortopsentin analogs
  作者：Mohamed Rdwan、Osama alrugaie、waleed monem、Mohammad Alfaifi、Serag Eldin Elbehairi

  DOI：10.21608/ejchem.2021.84060.4117

  日期：2021.7.25

  Abstract In this study, a series of nortopsentin analogs (2,4-bis(indol-3-yl)pyrrole derivatives) were designed, synthesized, and tested for their in vitro cytotoxic activity against three cell lines: human prostate adenocarcinoma (PC-3), human ovary adenocarcinoma (SKOV3), and human Dukes' type B colorectal adenocarcinoma (LS-174T). Compounds 5a, 5e, 5h, 5j, and 5k had stronger antiproliferative activity against SKOV3, compound 5h and 5b against LS-174T, and compound 5e against PC-3 than the known doxorubicin drug. As a result, this work provides the framework for further research into 2,4-bis(indol-3-yl)pyrrole derivatives as antiproliferative drugs.

  摘要：在本研究中，设计、合成了一系列去甲前丁类似物（2,4-双（吲哚-3-基）吡咯衍生物），并测试了其对三种细胞系的体外细胞毒活性：人前列腺腺癌（PC- 3)、人卵巢腺癌(SKOV3)和人Dukes B型结直肠腺癌(LS-174T)。与已知的阿霉素药物相比，化合物5a、5e、5h、5j和5k对SKOV3具有更强的抗增殖活性，化合物5h和5b对LS-174T具有更强的抗增殖活性，化合物5e对PC-3具有更强的抗增殖活性。因此，这项工作为进一步研究 2,4-双(吲哚-3-基)吡咯衍生物作为抗增殖药物提供了框架。
• Focused library development of 2-phenylacrylamides as broad spectrum cytotoxic agents
  作者：Mark Tarleton、Lauren Dyson、Jayne Gilbert、Jennette A. Sakoff、Adam McCluskey

  DOI：10.1016/j.bmc.2012.10.003

  日期：2013.1

  With our lead compound (E)-3-(4-chlorophenyl)-2-(1H-pyrrole-2-carbonyl)acrylonitrile (1) inducing 50% growth inhibition of 11 cancer cell lines at 27-61 mu M, potency enhancements were rapidly established through the synthesis of a series of focused compound libraries. Six highly focused libraries (46 compounds in total) were synthesised. Each library allowed the identification of a new lead compound, viz Library A identified (E)-3-(pentafluorophenyl)-2-(1H-pyrrole-2-carbonyl) acrylonitrile (11) and (E)-3-(1H-indol-3-yl)-2-(1H-pyrrole-2-carbonyl) acrylonitrile (13) as inhibitors with improved cytotoxicity. Synthesis of discrete libraries of amidoacrylamide analogues (Ar-C=C(CN)-A(sic)Ar-C=C(CN)-C(=O)NH)-Ar) resulted in a series of analogues significantly more potent that the lead, 1. Three furan three analogues: (E)-3-(5-chlorofuran-2-yl)-2-cyano-N-(4-methoxybenzyl)acrylamide (33), (E)-3-(5-bromofuran-2-yl)-2-cyano-N-(4-methoxybenzyl) acrylamide (34) and (E)-2-cyano-3-(furan-3-yl)-N-(4-methoxybenzyl)acrylamide (37) returned broad spectrum growth inhibition (GI(50) values of 5-16 mu M). Replacement of the furan moiety with simple aromatics gave an additional three analogues: (E)-2-cyano-N-(4-methoxybenzyl)-3-phenylacrylamide (39), (E)-3-(4-chlorophenyl)-2-cyano-N-(4-methoxybenzyl) acrylamide (41) and (E)-2-cyano-N-(4-methoxyphenyl)-3-(naphthalen-1-yl)acrylamide (45) with GI(50) values of 7-24 mu M. The final library retained the aromatic substituents but introduced a 3,4-dichlorbenzylamine moiety to afford the 1-naphthyl substituted 52, which was the most potent broad spectrum cytotoxic analogue produced here in with an average GI(50) = 8.6 mu M. This represents a fivefold potency enhancement relative to 1 and a new cytotoxic scaffold suitable for further development. (C) 2012 Published by Elsevier Ltd.
• Simple and efficient Knoevenagel synthesis of (E)-2-((1H-indol-3-yl)methylene)-3-oxoindolylnitrile catalysed by PPh3
  作者：M VENKATANARAYANA、P K DUBEY

  DOI：10.1007/s12039-011-0136-x

  日期：2011.9

  Triphenylphosphine (TPP) is found to be an efficient catalyst for the Knoevenagel condensation of indole-3-carboxyaldehydes 1(a–e) and their N-substituted derivatives 4(a–e) with the active methylene compound, i.e., 3-cyanoacetylindole (2), affording novel substituted olefins 3(a–e) and 5(a–e) respectively. The latter products reacted with DMS in the presence of PEG-600 to afford the corresponding N, Nl dimethylated derivatives 6(a–e).

  研究发现，三苯基膦（TPP）是一种高效催化剂，可用于吲哚-3-羧基醛 1（a-e）及其 N-取代衍生物 4（a-e）与活性亚甲基化合物（即 3-氰乙酰基吲哚 (2)）的克诺文纳格尔缩合反应，分别生成新型取代烯烃 3（a-e）和 5（a-e）。后者在 PEG-600 存在下与二甲基亚砜反应，得到相应的 N，Nl 二甲基衍生物 6(a-e)。