caffeic acid phenethyl amide | 105955-01-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: caffeic acid phenethyl amide
• 英文别名: 3-(3,4-Dihydroxyphenyl)-N-(2-phenylethyl)prop-2-enamide
• CAS: 105955-01-9
• 化学式: C₁₇H₁₇NO₃
• 分子量: 283.327
• InChiKey: QOWABIXYAFJMQE-UHFFFAOYSA-N

物化性质

• 熔点：
  154-155 °C(Solv: benzene (71-43-2); hexane (110-54-3); ethanol (64-17-5))
• 沸点：
  575.5±50.0 °C(Predicted)
• 密度：
  1.248±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

制备方法与用途

KS370G 是一种口服活性降血糖和心血管保护剂，能够改善压力超负荷小鼠心脏的左心室肥大和功能，并且可以减轻肾梗阻性肾病的症状。

反应信息

• 作为反应物：
  描述：

  caffeic acid phenethyl amide 、 碘甲烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 (E)-3-(3,4-Dimethoxy-phenyl)-N-phenethyl-acrylamide
  参考文献：
  名称：

  CATECHOL-BASED DERIVATIVES FOR TREATING OR PREVENTING DIABETICS

  摘要：

  本发明提供了一种基于邻苯二酚的衍生物及其药用可接受的盐和溶剂化合物。一种用于预防或治疗糖尿病和缺血症的药物组合物，包括具有化学式(I)的基于邻苯二酚的衍生物和来自药用辅料、稀释剂和载体中选择的至少一种成分。

  公开号：

  US20090143397A1
• 作为产物：
  描述：

  咖啡酸 在 氯化亚砜 、 盐酸胍 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 caffeic acid phenethyl amide
  参考文献：
  名称：

  Antiproliferative, antiandrogenic and cytotoxic effects of novel caffeic acid derivatives in LNCaP human androgen-dependent prostate cancer cells

  摘要：

  Caffeic acid and its naturally occurring derivative caffeic acid phenethyl ester (CAPE) have antiproliferative and cytotoxic properties in a variety of cancer cell lines without displaying significant toxicity toward healthy cells, and are considered to be potential anticancer agents. However, little is known about their effects on prostate cancer cells. We synthesized and evaluated the effects of caffeic acid, CAPE (2) and 18 synthetic derivatives on cell viability and androgen-dependent cell proliferation, subcellular localisation and expression of androgen receptor (AR) and secretion of prostate-specific antigen (PSA) in LNCaP human hormone-dependent prostate cancer cells. Several synthetic derivatives of CAPE were strong, concentration-dependent cytotoxic agents in LNCaP cells with IC50 values in the 6.8-26.6 mu M range, potencies that were up to five-fold greater than that of CAPE (33.7 +/- 4.0 mu M). A number of caffeic acid derivatives were inhibitors of androgen-stimulated LNCaP cell proliferation with concomitant inhibition of DHT-stimulated PSA secretion. Compound 24 was the most cytotoxic and antiproliferative caffeic acid derivative (IC50 values of 6.8 +/- 0.3 and 2.4 +/- 0.8 mu M, respectively) inhibiting DHT-stimulated cell proliferation and PSA secretion statistically significantly at concentrations as low as 0.3 mu M. Exposure to DHT increased cytoplasmic and nuclear AR levels and co-treatment with increasing concentrations of compound 24 or CAPE (2), notably, further increased these levels. In conclusion, a number of synthetic derivatives of caffeic acid are potent inhibitors of androgen-dependent prostate cancer cell proliferation and viability, acting, at least in part, via an antiandrogenic mechanism that involves increased nuclear accumulation of (presumably inactive) AR. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.057

文献信息

• Synthesis of Caffeic Acid Phenethyl Ester Derivatives, and Their Cytoprotective and Neuritogenic Activities in PC12 Cells
  作者：Haiming Shi、Dongsheng Xie、Ruoling Yang、Yaqian Cheng

  DOI：10.1021/jf500464k

  日期：2014.6.4

  Twenty-one caffeic acid phenethyl ester (CAPE) derivatives were synthesized, and characterized by IR, HR-MS, 1H and 13C NMR analyses. All compounds were evaluated for their cytoprotective effects against H2O2-induced cytotoxicity and neuritogenic activities in the neurite outgrowth in PC12 cells. Compounds 1 and 20 exhibited stronger cytoprotective activities than their parent compound CAPE at 4 nM. Compounds

  合成了二十一种咖啡酸苯乙酯（CAPE）衍生物，并通过IR，HR-MS，1 H和13 C NMR分析对其进行了表征。评价了所有化合物对PC 12细胞中神经突生长中H 2 O 2诱导的细胞毒性和神经生成活性的细胞保护作用。化合物1和20在4 nM时比其母体化合物CAPE表现出更强的细胞保护活性。化合物1，4，12和13显示出潜在neuritogenic活动在为0.5nM，而化合物19和20在10 nM时引起神经突生长。这项研究的结果表明，CAPE及其衍生物可能是预防神经退行性疾病的潜在功能性食品成分。
• Synthesis and structure–activity relationship analysis of caffeic acid amides as selective matrix metalloproteinase inhibitors
  作者：Zhi-Hao Shi、Nian-Guang Li、Qian-Ping Shi、Hao Tang、Yu-Ping Tang、Wei Li、Lian Yin、Jian-Ping Yang、Jin-Ao Duan

  DOI：10.1016/j.bmcl.2013.01.027

  日期：2013.3

  Four series of acid amides were synthesized, and through measurement using a fluorogenic substrate assay with human recombinant MMP-1, MMP-2 and MMP-9, compound 3f showed considerable inhibitory activities against MMP-2, MMP-9 and the best selectivity over MMP-1. Preliminary structure–activity relationship analysis indicated that caffeic acid amides with electron-donating groups at para-position of

  合成了四个系列的酰胺，并通过使用荧光底物测定法与人重组MMP-1，MMP-2和MMP-9进行测量，化合物3f对MMP-2，MMP-9表现出相当大的抑制活性，并且选择性优于MMP-1。初步的结构-活性关系分析表明，在氨基苯基对位具有供电子基团的咖啡酰胺比具有吸电子基团的酰胺具有更好的抑制活性和选择性，并且在咖啡酰基中相邻的二羟基的存在非常多。对于MMP-2和MMP-9抑制活性很重要。
• Protective Effect of Caffeic Acid Derivatives on tert-Butyl Hydroperoxide-Induced Oxidative Hepato-Toxicity and Mitochondrial Dysfunction in HepG2 Cells
  作者：Tzung-Hsun Tsai、Chun-Hsien Yu、Yu-Ping Chang、Yu-Ting Lin、Ching-Jang Huang、Yueh-Hsiung Kuo、Po-Jung Tsai

  DOI：10.3390/molecules22050702

  日期：——

  Oxidative stress results in structural and functional abnormalities in the liver and is thought to be a crucial factor in liver diseases. The aim of this study was to investigate the cytoprotective and antioxidant effects of caffeic acid (CA) derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells. Nine CA derivatives were synthesized, including N-phenylethyl caffeamide (PECA), N-(3-florophen)methyl caffeamide (FMCA), N-(4-methoxy-phen)methyl caffeamide (MPMCA), N-heptyl caffeamide (HCA), N-octyl caffeamide (OCA), octyl caffeate (CAOE), phenpropyl caffeate (CAPPE), phenethyl caffeate (CAPE), and phenmethyl caffeate (CAPME). The results showed that CA and its derivatives significantly inhibited t-BHP-induced cell death of HepG2 cells. The rank order of potency of the CA derivatives for cytoprotection was CAOE > HCA > OCA > FMCA > CAPPE > CAPME > CAPE > PECA > MPMCA > CA. Their cytoprotective activity was associated with lipophilicity. The antioxidant effect of these compounds was supported by the reduction in the levels of thiobarbituric acid reactive substrates, a biomarker of lipid peroxidation, in HepG2 cells. Pre-treatment of CA derivatives significantly prevented the depletion of glutathione, the most important water-soluble antioxidant in hepatocytes. Pre-treatment of CA derivatives before t-BHP exposure maintained mitochondrial oxygen consumption rate and ATP content in the injured HepG2 cells. CA derivatives except OCA and HCA significantly suppressed t-BHP-induced hypoxia-inducible factor-1α (HIF-1α) protein level. In addition, all of these CA derivatives markedly increased the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation in the nucleus, indicating that their cytoprotection may be mediated by the activation of Nrf2. Our results suggest that CA derivatives might be a hepatoprotective agent against oxidative stress.

  氧化应激导致肝脏结构和功能异常，被认为是肝脏疾病的一个关键因素。本研究的目的是探讨咖啡酸（CA）衍生物在特丁基过氧化氢（t-BHP）诱导的肝HepG2细胞氧化应激中的细胞保护和抗氧化作用。合成了九种CA衍生物，包括N-苯乙基咖啡酰胺（PECA）、N-(3-氟苯)甲基咖啡酰胺（FMCA）、N-(4-甲氧基苯)甲基咖啡酰胺（MPMCA）、N-庚基咖啡酰胺（HCA）、N-辛基咖啡酰胺（OCA）、辛基咖啡酸酯（CAOE）、苯丙基咖啡酸酯（CAPPE）、苯乙基咖啡酸酯（CAPE）和苯甲基咖啡酸酯（CAPME）。结果显示，CA及其衍生物显著抑制了t-BHP诱导的HepG2细胞死亡。CA衍生物的细胞保护效力的排列顺序为CAOE > HCA > OCA > FMCA > CAPPE > CAPME > CAPE > PECA > MPMCA > CA。它们的细胞保护活性与脂溶性相关。这些化合物的抗氧化效果得到了支持，因为它们降低了HepG2细胞中硫代巴比妥酸反应底物的水平，这是脂质过氧化的生物标志物。CA衍生物的预处理显著防止了谷胱甘肽的耗竭，谷胱甘肽是肝细胞中最重要的水溶性抗氧化剂。CA衍生物在t-BHP暴露前的预处理保持了受损HepG2细胞的线粒体氧气消耗率和ATP含量。除OCA和HCA外，CA衍生物显著抑制了t-BHP诱导的缺氧诱导因子-1α（HIF-1α）蛋白水平。此外，所有这些CA衍生物显著增加了核因子红细胞2相关因子2（Nrf2）在细胞核中的积累，表明它们的细胞保护可能是通过激活Nrf2介导的。我们的结果表明，CA衍生物可能是对抗氧化应激的肝保护剂。
• Design, Synthesis of N-phenethyl Cinnamide Derivatives and Their Biological Activities for the Treatment of Alzheimer’s Disease: Antioxidant, Beta-amyloid Disaggregating and Rescue Effects on Memory Loss
  作者：Tian Chai、Xiao-Bo Zhao、Wei-Feng Wang、Yin Qiang、Xiao-Yun Zhang、Jun-Li Yang

  DOI：10.3390/molecules23102663

  日期：——

  Gx-50 is a bioactive compound for the treatment of Alzheimer’s disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (1–20) analogs have been designed and synthesized, and their molecular structures were determined based on nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis, as well as comparison with literature data. Compounds 1–20 were evaluated for their anti-AD potential by using DPPH radical scavenging assay for considering their anti-oxidant activity, thioflavin T (ThT) fluorescence assay for considering the inhibitory or disaggregate potency of Aβ, and transgenic Drosophila model assay for evaluating their rescue effect on memory loss. Finally, compound 13 was determined as a promising anti-AD candidate.

  Gx-50是一种用于治疗阿尔茨海默病（AD）的生物活性化合物，发现于花椒（Zanthoxylum bungeanum）中。为了寻找更强的抗AD活性化合物，设计和合成了20个gx-50（1-20）类似物，并通过核磁共振（NMR）和质谱分析（MS）以及与文献数据的比较确定了它们的分子结构。通过使用DPPH自由基清除实验评估化合物1-20的抗AD潜力，考虑其抗氧化活性；使用ThT荧光实验考虑其对Aβ的抑制或解聚作用；使用转基因果蝇模型实验评估其对记忆丧失的救助效果。最终，确定化合物13为有希望的抗AD候选化合物。
• Mining Plants for Bacterial Quorum Sensing Modulators
  作者：Shimrit David、Aviad Mandabi、Shaked Uzi、Asaph Aharoni、Michael M. Meijler

  DOI：10.1021/acschembio.7b00859

  日期：2018.1.19

  uses quorum sensing (QS) in order to regulate the transfer of DNA into the host plant genome, and this results in the induction of crown gall tumors. The deleterious results of these infections are widespread and affect many species of fruit and crops. In order to further our understanding of this process and to provide potential solutions, we evaluated a library of 3800 natural products from plant

  细菌植物病原体根癌农杆菌使用群体感应（QS）来调节DNA向宿主植物基因组中的转移，从而导致冠状胆囊肿瘤的诱导。这些感染的有害结果广泛存在，并影响许多种类的水果和农作物。为了进一步了解该过程并提供可能的解决方案，我们评估了一个来自植物的3800种天然产物的库，并确定了能够强烈调节植物与细菌相互作用的有效化合物。