(E)-N-(3-aminopropyl)-3-(4-hydroxy-3-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: (E)-N-(3-aminopropyl)-3-(4-hydroxy-3-methoxyphenyl)acrylamide
• 英文别名: (E)-N-(3-aminopropyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enamide
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: ZPCGUQAJQKIIFB-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  84.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-N-(3-aminopropyl)-3-(4-hydroxy-3-methoxyphenyl)acrylamide 、 3-amino-5,7-dimethyltricyclo[3.3.1.1^3,7]decane-1-carboxylic acid hydrochloride 在 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.17h， 以52%的产率得到(E)-3-amino-N-(3-(3-(4-hydroxy-3-methoxyphenyl)acrylamido)propyl)-5,7-dimethyladamantane-1-carboxamide
  参考文献：
  名称：

  Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease

  摘要：

  N-methyl-D-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trigger neurotoxic events mediated by amyloid beta peptide (A beta) and oxidative stress. In this study, we applied a multifunctional approach by conjugating memantine to ferulic acid, which is known to protect the brain from A beta neurotoxicity and neuronal death caused by ROS. The most interesting compound (7) behaved, like memantine, as a voltage-dependent antagonist of NMDAR (IC50 = 6.9 mu M). In addition, at 10 mu M concentration, 7 exerted antioxidant properties both directly and indirectly through the activation of the Nrf-2 pathway in SH-SY5Y cells. At the same concentration, differently from the parent compounds memantine and ferulic acid alone, it was able to modulate A beta production, as revealed by the observed increase of the non-amyloidogenic sAPP alpha in H4-SW cells. These findings suggest that compound 7 may represent a promising tool for investigating NMDAR-mediated neurotoxic events involving A beta burden and oxidative damage. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.011
• 作为产物：
  描述：

  tert-butyl (E)-(3-(3-(4-hydroxy-3-methoxyphenyl)acrylamido)propyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 (E)-N-(3-aminopropyl)-3-(4-hydroxy-3-methoxyphenyl)acrylamide
  参考文献：
  名称：

  新型抗阿尔茨海默氏症酚-脂酰杂化物：合成，物理化学表征和生物学评估。

  摘要：

  迄今为止，达到单一靶标的药物不足以治疗神经退行性疾病，例如阿尔茨海默氏病或​​帕金森氏病。能够与参与这些疾病进展的不同途径相互作用的多靶点配体的发展，对药物化学家提出了巨大的挑战。在这种情况下，我们在这里报告通过链接策略获得的酚-脂酰杂化物（SV1-13）的合成和生物学评估，以利用由于单一成分的抗氧化剂部分和抗淀粉样蛋白特性而产生的协同效应存在于杂化分子中。生物学结果表明，SV5和SV10在分化的SH-SY5Y细胞中对Aβ1-42诱导的神经毒性具有最佳的保护活性。SV9和SV10由于具有抵抗过氧化氢对SHSY-5Y处理的细胞造成的损害的能力，因此具有出色的抗氧化性能。Hovewer SV5具有适度的抗氧化剂和良好的神经保护活性，是进行进一步实验的最佳人选，因为它还可以产生稳定的模拟液和血浆液。

  DOI：

  10.1016/j.ejmech.2019.111880

文献信息

• Improving the Adjuvanticity of Small Molecule Immune Potentiators Using Covalently Linked NF-κB Modulators
  作者：Flora W. Kimani、Saikat Manna、Brittany Moser、Jingjing Shen、Naorem Nihesh、Aaron P. Esser-Kahn

  DOI：10.1021/acsmedchemlett.1c00267

  日期：2021.9.9

  we report the design and synthesis of novel imidazoquinolinone-NF-κB immunomodulator dimers. Employing in vitro assays, we screened a select library of synthesized dimers and selected viable candidates for further in vivo experiments. With ovalbumin as a model antigen, we vaccinated mice and demonstrated that these dimers reduce the systemic toxicity associated with SMIPs to baseline levels while simultaneously

  小分子免疫增强剂 (SMIP)，例如激活 Toll 样受体 (TLR) 7/8 的咪唑喹啉酮衍生物，具有作为疫苗佐剂和抗肿瘤剂的巨大潜力。然而，这些分子具有高生物利用度，由于佐剂毒性导致不可接受的全身炎症水平，从而极大地限制了它们的使用。为了应对这一挑战，我们在这里报告了新型咪唑喹啉酮-NF-κB 免疫调节剂二聚体的设计和合成。采用体外检测，我们筛选了合成二聚体的精选文库，并选择了可行的候选物用于进一步的体内试验实验。使用卵清蛋白作为模型抗原，我们给小鼠接种疫苗并证明这些二聚体将与 SMIP 相关的全身毒性降低到基线水平，同时保持疫苗制剂的佐剂性。此外，我们表明选择的二聚体提高了 CT26 小鼠结肠癌肿瘤模型的疗效，同时引起最小的佐剂毒性。
• Solid-phase synthesis and antibacterial activity of hydroxycinnamic acid amides and analogues against methicillin-resistant Staphylococcus aureus and vancomycin-resistant S. aureus
  作者：Boon-ek Yingyongnarongkul、Nuttapon Apiratikul、Nuntana Aroonrerk、Apichart Suksamrarn

  DOI：10.1016/j.bmcl.2006.08.062

  日期：2006.11

  A library of hydroxycinnamic acid amides (HCAAs) and analogues were synthesized using solid-phase synthesis technique. These compounds were screened for antibacterial against methicillin-resistant Staphylococcus aureus (MRSA) (11 strains) and vancomycin-resistant S. aureus (VRSA) (4 strains). Dihydrocaffeoyl analogues showed activity against VRSA which were better than the reference drugs, vancomycin and oxacillin. These compounds also exhibited antibacterial activity against MRSA, which were more potent than oxacillin. (c) 2006 Elsevier Ltd. All rights reserved.
• Merging memantine and ferulic acid to probe connections between NMDA receptors, oxidative stress and amyloid-β peptide in Alzheimer's disease
  作者：Michela Rosini、Elena Simoni、Roberta Caporaso、Filippo Basagni、Michele Catanzaro、Izuddin F. Abu、Francesca Fagiani、Federica Fusco、Sara Masuzzo、Diego Albani、Cristina Lanni、Ian R. Mellor、Anna Minarini

  DOI：10.1016/j.ejmech.2019.07.011

  日期：2019.10

  N-methyl-D-aspartate receptors (NMDAR) are critically involved in the pathogenesis of Alzheimer's disease (AD). Acting as an open-channel blocker, the anti-AD drug memantine preferentially targets NMDAR overactivation, which has been proposed to trigger neurotoxic events mediated by amyloid beta peptide (A beta) and oxidative stress. In this study, we applied a multifunctional approach by conjugating memantine to ferulic acid, which is known to protect the brain from A beta neurotoxicity and neuronal death caused by ROS. The most interesting compound (7) behaved, like memantine, as a voltage-dependent antagonist of NMDAR (IC50 = 6.9 mu M). In addition, at 10 mu M concentration, 7 exerted antioxidant properties both directly and indirectly through the activation of the Nrf-2 pathway in SH-SY5Y cells. At the same concentration, differently from the parent compounds memantine and ferulic acid alone, it was able to modulate A beta production, as revealed by the observed increase of the non-amyloidogenic sAPP alpha in H4-SW cells. These findings suggest that compound 7 may represent a promising tool for investigating NMDAR-mediated neurotoxic events involving A beta burden and oxidative damage. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Novel anti-Alzheimer phenol-lipoyl hybrids: Synthesis, physico-chemical characterization, and biological evaluation
  作者：Aikaterini Pagoni、Lisa Marinelli、Antonio Di Stefano、Michele Ciulla、Hasan Turkez、Adil Mardinoglu、Stamatia Vassiliou、Ivana Cacciatore

  DOI：10.1016/j.ejmech.2019.111880

  日期：2020.1

  challenge for medicinal chemists. In this context, we report here the synthesis and biological evaluation of phenol-lipoyl hybrids (SV1-13), obtained via a linking strategy, to take advantage of the synergistic effect due to the antioxidant portions and anti-amyloid properties of the single constituents present in the hybrid molecule. Biological results showed that SV5 and SV10 possessed the best protective

  迄今为止，达到单一靶标的药物不足以治疗神经退行性疾病，例如阿尔茨海默氏病或​​帕金森氏病。能够与参与这些疾病进展的不同途径相互作用的多靶点配体的发展，对药物化学家提出了巨大的挑战。在这种情况下，我们在这里报告通过链接策略获得的酚-脂酰杂化物（SV1-13）的合成和生物学评估，以利用由于单一成分的抗氧化剂部分和抗淀粉样蛋白特性而产生的协同效应存在于杂化分子中。生物学结果表明，SV5和SV10在分化的SH-SY5Y细胞中对Aβ1-42诱导的神经毒性具有最佳的保护活性。SV9和SV10由于具有抵抗过氧化氢对SHSY-5Y处理的细胞造成的损害的能力，因此具有出色的抗氧化性能。Hovewer SV5具有适度的抗氧化剂和良好的神经保护活性，是进行进一步实验的最佳人选，因为它还可以产生稳定的模拟液和血浆液。