2-cyano-N-hexyl-3-(3-hydroxy-4-methoxyphenyl)acrylamide

• 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: 2-cyano-N-hexyl-3-(3-hydroxy-4-methoxyphenyl)acrylamide
• 英文别名: (E)-2-cyano-N-hexyl-3-(3-hydroxy-4-methoxyphenyl)prop-2-enamide
• 化学式: C₁₇H₂₂N₂O₃
• 分子量: 302.373
• InChiKey: KCDHXWJPBWBAGR-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  正己胺 在 哌啶 作用下， 生成 2-cyano-N-hexyl-3-(3-hydroxy-4-methoxyphenyl)acrylamide
  参考文献：
  名称：

  Knoevenagel缩合反应的绿色化学方法：乙醇，水和无溶剂（干磨）方法的比较

  摘要：

  我们报告了使用三种不同的方法对Knoevenagel与各种取代的苯甲醛（17个实例）和氰基酰胺（3个实例）进行缩合的比较研究：（a）传统的乙醇回流；（b）水回流；（c）无溶剂条件。当以无溶剂方式进行反应时，这些反应几乎毫无例外地进行得更快，更干净并且产率更高。此外，我们的无溶剂方法允许使用硝基苯甲醛，而传统方法和水基方法均无法产生所需的产品。

  DOI：

  10.1016/s0040-4039(02)00480-x

文献信息

• Green chemistry approaches to the Knoevenagel condensation: comparison of ethanol, water and solvent free (dry grind) approaches
  作者：Adam McCluskey、Philip J. Robinson、Tim Hill、Janet L. Scott、J.Kate Edwards

  DOI：10.1016/s0040-4039(02)00480-x

  日期：2002.4

  We report a comparative study of the Knoevenagel condensation with a variety of substituted benzaldehydes (17 examples) and cyanoamides (3 examples), using three different methodologies: (a) traditional ethanol reflux; (b) water reflux; and (c) solvent free conditions. Almost without exception these reactions proceeded faster, more cleanly and in higher yields when the reactions were conducted in a

  我们报告了使用三种不同的方法对Knoevenagel与各种取代的苯甲醛（17个实例）和氰基酰胺（3个实例）进行缩合的比较研究：（a）传统的乙醇回流；（b）水回流；（c）无溶剂条件。当以无溶剂方式进行反应时，这些反应几乎毫无例外地进行得更快，更干净并且产率更高。此外，我们的无溶剂方法允许使用硝基苯甲醛，而传统方法和水基方法均无法产生所需的产品。
• Small Molecule Inhibitors of Dynamin I GTPase Activity:  Development of Dimeric Tyrphostins
  作者：Timothy Hill、Luke R. Odell、Jennifer K. Edwards、Mark E. Graham、Andrew B. McGeachie、Jenny Rusak、Annie Quan、Ruben Abagyan、Janet L. Scott、Phillip J. Robinson、Adam McCluskey

  DOI：10.1021/jm040208l

  日期：2005.12.1

  Dynamin I is a GTPase enzyme required for endocytosis and is an excellent target for the design of potential endocytosis inhibitors. Screening of a library of tyrphostins, in our laboratory, against the GTPase activity of dynamin I gave rise to a mu M potent lead, 2-cyano-3-(3,4-dihydroxyphenyl)thioacrylamide (1, IC50 70 mu M). Our initial investigations suggested that only the dimeric form of 1 displayed dynamin I GTPase inhibitory activity. Subsequent synthetic iterations were based on dimeric analogues and afforded a number of small molecules, low mu M potent, inhibitors of dynamin I GTPase, in particular, symmetrical analogues with a minimum of two free phenolic -OHs: catechol-acrylamide (9) (IC50 = 5.1 +/- 0.6 mu M), its 3,4,5-trihydroxy congener (10) (IC50 = 1.7 +/- 0.2 mu M), and the corresponding 3-methyl ether (11) (IC50 = 9 3 mu M). Increasing the length of the central alkyl spacer from ethyl to propyl (22-24) afforded essentially identical activity with IC50'S of 1.7 0.2, 1.7 0.2, and 5 +/- 1 mu M, respectively. No decrease in activity was noted until the introduction of a hexyl spacer. Our studies highlight the requirement for two free amido NHs with neither the mono-N-methyl (86) nor the bis-N-methyl (87) analogues inhibiting dynamin I GTPase. A similar effect was noted for the removal of the nitrile moieties. However, modest potency was observed with the corresponding ester analogues of 9-11: ethyl ester (90), propyl ester (91), and butyl ester (92), with IC50'S of 42 3, 38 2, and 61 2 mu M, respectively. Our studies reveal the most potent and promising dynamin I GTPase inhibitor in this series as (22), which is also known as BisT.