(E)-2-(1H-indole-3-carbonyl)-3-(4-methoxyphenyl)acrylonitrile | 1415975-82-4

• 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: (E)-2-(1H-indole-3-carbonyl)-3-(4-methoxyphenyl)acrylonitrile
• 英文别名: (E)-2-(1H-indole-3-carbonyl)-3-(4-methoxyphenyl)prop-2-enenitrile
• CAS: 1415975-82-4
• 化学式: C₁₉H₁₄N₂O₂
• 分子量: 302.332
• InChiKey: SCDWZYALKZZCIW-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  65.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-2-(1H-indole-3-carbonyl)-3-(4-methoxyphenyl)acrylonitrile 、 trans-ethyl 4-mercapto-2-butenoate 在 三乙胺 作用下， 生成 (3R,4S,5R)-[4-cyano-4-(1H-indole-3-carbonyl)-5-(4-methoxyphenyl)tetrahydrothiophen-3-yl]acetic acid ethyl ester
  参考文献：
  名称：

  Asymmetric synthesis of 3-substituted indole derivatives containing tetrahydrothiophene via cascade sulfa-Michael/Michael additions catalyzed by a chiral squaramide catalyst

  摘要：

  The organocatalyzed enantioselective cascade sulfa-Michael/Michael addition reaction of (E)-3-mercapto-2-butenoic acid esters to (E)-3-aryl-2-(indol-3-ylcarbonyl)acrylonitriles has been developed. This process was promoted by a chiral squaramide catalyst to afford chiral 3-substituted indole derivatives containing tetrahydrothiophene with three contiguous stereocenters in excellent diastereoselectivities (up to >20:1 dr) with moderate to good yields and enantioselectivities (up to 93%, 89% ee). (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2014.10.012
• 作为产物：
  描述：

  吲哚 在 哌啶 作用下， 以 乙醇 、 乙酸酐 为溶剂， 反应 2.08h， 生成 (E)-2-(1H-indole-3-carbonyl)-3-(4-methoxyphenyl)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

• Novel cyanochalcones as potential anticancer agents: apoptosis, cell cycle arrest, DNA binding, and molecular docking studies
  作者：Mohamed A. Ragheb、Hanan E. Abdelrashid、Emad M. Elzayat、Ismail A. Abdelhamid、Marwa H. Soliman

  DOI：10.1080/07391102.2024.2316764

  日期：——

  In the light of anticancer drug discovery and development, a new series of cyanochalcones incorporating indole moiety (5a-g) were efficiently synthesized and characterized by different spectral ana...

  根据抗癌药物的发现和开发，有效合成了一系列含有吲哚部分（5a-g）的新氰基查耳酮，并通过不同的光谱分析对其进行了表征。
• 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.
• Asymmetric synthesis of 3-substituted indole derivatives containing tetrahydrothiophene via cascade sulfa-Michael/Michael additions catalyzed by a chiral squaramide catalyst
  作者：Ying-He Li、Bo-Liang Zhao、Yu Gao、Da-Ming Du

  DOI：10.1016/j.tetasy.2014.10.012

  日期：2014.12

  The organocatalyzed enantioselective cascade sulfa-Michael/Michael addition reaction of (E)-3-mercapto-2-butenoic acid esters to (E)-3-aryl-2-(indol-3-ylcarbonyl)acrylonitriles has been developed. This process was promoted by a chiral squaramide catalyst to afford chiral 3-substituted indole derivatives containing tetrahydrothiophene with three contiguous stereocenters in excellent diastereoselectivities (up to >20:1 dr) with moderate to good yields and enantioselectivities (up to 93%, 89% ee). (C) 2014 Elsevier Ltd. All rights reserved.