(E)-2-cyano-N-[(4-methoxyphenyl)methyl]-3-naphthalen-2-ylprop-2-enamide | 1415976-06-5

• 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-cyano-N-[(4-methoxyphenyl)methyl]-3-naphthalen-2-ylprop-2-enamide
• CAS: 1415976-06-5
• 化学式: C₂₂H₁₈N₂O₂
• 分子量: 342.397
• InChiKey: BBVMYKDIJPAINY-DEDYPNTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-甲氧基苄胺 在 哌啶 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 0.5h， 生成 (E)-2-cyano-N-[(4-methoxyphenyl)methyl]-3-naphthalen-2-ylprop-2-enamide
  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

• 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.