3-(3,4-dihydroxyphenyl)-N-{4-[3-(3,4-dihydroxyphenyl)acryloylamino]butyl}acrylamide | 60422-23-3

• 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: 3-(3,4-dihydroxyphenyl)-N-{4-[3-(3,4-dihydroxyphenyl)acryloylamino]butyl}acrylamide
• 英文别名: Dicaffeoylputrescine；(E)-3-(3,4-dihydroxyphenyl)-N-[4-[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]butyl]prop-2-enamide
• CAS: 60422-23-3
• 化学式: C₂₂H₂₄N₂O₆
• 分子量: 412.442
• InChiKey: WKIWXOKCKNMLIX-NXZHAISVSA-N

物化性质

• 沸点：
  831.8±65.0 °C(Predicted)
• 密度：
  1.357±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  139
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  TRANS-咖啡酸 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 氯仿 、 丙酮 为溶剂， 反应 8.0h， 生成 3-(3,4-dihydroxyphenyl)-N-{4-[3-(3,4-dihydroxyphenyl)acryloylamino]butyl}acrylamide
  参考文献：
  名称：

  Small Molecule Inhibitors of Dynamin I GTPase Activity:  Development of Dimeric Tyrphostins

  摘要：

  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.

  DOI：

  10.1021/jm040208l

文献信息

• Amide derivatives and 5-lipoxygenase inhibitors containing the same as an active ingredient
  申请人：TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION

  公开号：EP0157420A2

  公开（公告）日：1985-10-09

  According to the invention, there are provided novel amide derivatives and 5-lipoxygenase inhibitors containing the same as an effective ingredient. The above-mentioned compounds of the invention have been demonstrated to possess 5-lipoxygenase-inhibiting activities. These compounds can inhibit the production of leucotrienes such as LTC4 and LTD4 which are allergy-inducing factors by inhibiting the activity of 5-lipoxygenase. Accordingly, the amide derivatives can be used as 5-lipoxygenase inhibitors effective for allergic asthma, allergic rhinitis and the like.

  根据本发明，提供了新型酰胺衍生物和以酰胺衍生物为有效成分的 5-脂氧合酶抑制剂。 上述本发明化合物已被证实具有 5-脂氧合酶抑制活性。 这些化合物可以通过抑制 5-脂氧合酶的活性来抑制白三烯（如 LTC4 和 LTD4）的产生，而白三烯是过敏诱因。 因此，酰胺衍生物可用作 5-脂氧合酶抑制剂，对过敏性哮喘、过敏性鼻炎等有效。
• US4673684A
  申请人：——

  公开号：US4673684A

  公开（公告）日：1987-06-16
• [EN] POLYAMINE ANALOG PRODUCING YEASTS<br/>[FR] LEVURES PRODUISANT DES ANALOGUES DE POLYAMINE
  申请人：CHRYSEA LTD

  公开号：WO2021083869A1

  公开（公告）日：2021-05-06

  The invention relates to production of polyamine analogs in yeast cells that are capable of producing at least one polyamine. The yeast cells also comprise a 4-coumarate:CoA ligase encoding gene, at least one polyamine N-acyltransferase gene and at least one polyamine synthase encoding gene but lacks a polyamine oxidase encoding gene or comprises a disrupted polyamine oxidase encoding gene. The yeast cells are capable of producing mono- and/or multi-substituted N-acylated polyamines.
• 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.