(E)-N-(3,4-dimethoxyphenethyl)-3-(3,4,5-trimethoxyphenyl)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-(3,4-dimethoxyphenethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide
• 英文别名: (E)-N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(3,4,5-trimethoxyphenyl)prop-2-enamide
• 化学式: C₂₂H₂₇NO₆
• 分子量: 401.459
• InChiKey: YJVKOFLUBFQEDK-VQHVLOKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  75.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-N-(3,4-dimethoxyphenethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide 在 1-butyl-3-methylimidazolium hexafluorophosphate 、 三氯氧磷 作用下， 反应 24.0h， 以86%的产率得到6,7-dimethoxy-1-(3,4,5-trimethoxystyryl)-3,4-dihydroisoquinoline hexafluorophosphate
  参考文献：
  名称：

  Bischler–Napieralski反应过程中意外的PF6阴离子复分解：3,4-二氢异喹啉六氟磷酸盐及其四氢异喹啉相关生物碱的合成

  摘要：

  抽象的 一系列N-苯乙基肉桂酰胺经过Bischler-Napieralski反应，以提供各种1-styryl-3,4-dihydroisoquinolines。我们注意到，当反应在常规溶剂条件下进行时，所需产物不稳定。但是，当[bmim] PF 6用作反应介质时，Bischler-Napieralski反应的性质促进了该离子液体与二氢异喹啉核心之间异常的原位离子交换，从而导致所需的1-苯乙烯基-苯乙烯的稳定化。 3,4-二氢异喹啉，可将其分离为六氟磷酸盐。最后，一锅还原/还原甲基化过程提供了N-甲基衍生物，证明我们的发现可以是合成四氢异喹啉碱生物碱的一种有效且有用的策略。 一系列N-苯乙基肉桂酰胺经过Bischler-Napieralski反应，以提供各种1-styryl-3,4-dihydroisoquinolines。我们注意到，当反应在常规溶剂条件下进行时，所需产物不稳定。但是，当[bmim]

  DOI：

  10.1055/s-0037-1610684
• 作为产物：
  描述：

  3,4,5-三甲氧基肉桂酸 在 4-二甲氨基吡啶 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 生成 (E)-N-(3,4-dimethoxyphenethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide
  参考文献：
  名称：

  Synthesis and Identification of Small Molecules that Potently Induce Apoptosis in Melanoma Cells through G1 Cell Cycle Arrest

  摘要：

  Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms that melanocytes possess to protect cells from DNA damage often confer resistance to drugs that derive their toxicity from S or M phase arrest. Described herein is the synthesis of a combinatorial library of potential proapoptotic agents and the subsequent identification of a class of small molecules (triphenyl methylamides, TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell cycle. Several of these TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC50 similar to 0.5 mu M), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs were found to dramatically reduce the level of active nuclear factor kappa-B (NF kappa B) in the cell; NF kappa B is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. Compounds that reduce the level of NF kappa B and arrest cells in the G1 phase of the cell cycle can provide insights into the biology of melanoma and may be effective antimelanoma agents.

  DOI：

  10.1021/ja042913p

文献信息

• Synthesis of zanthoxylamide protoalkaloids and their in silico ADME-Tox screening and in vivo toxicity assessment in zebrafish embryos
  作者：Carlos E. Puerto Galvis、Vladimir V. Kouznetsov

  DOI：10.1016/j.ejps.2018.10.028

  日期：2019.1

  the synthesis of a series of 29 substituted N-phenylethyl cinnamamides through the direct amidation of a variety of cinnamic acids with a broad range of phenylethylamines promoted by tris-(2,2,2-trifluoroethyl) borate (B(OCH2CF3)3) in excellent yields and under mild reaction conditions. Then, the toxicological profile of the prepared compounds was studied through in silico computational methods, analyzing

  受到花椒酰胺原生物碱简单且引人入胜的结构的启发：阿米酰胺，卢比烯酰胺，雷莫拉明，卢比明和花青素；分离自花椒属植物。我们报告了一系列29种取代的N-苯基乙基肉桂酰胺的合成，该合成是通过将各种肉桂酸与由广泛的三（2,2,2-三氟乙基）硼酸酯（B（OCH 2 CF 3）3）以优异的收率和温和的反应条件。然后，通过计算机研究了所制备化合物的毒理学特征。计算方法，分析了八种毒性风险（肝毒性，致突变性，致癌性，致瘤性，免疫毒性，细胞毒性，刺激性和生殖效应）和两个毒性目标（AOFA和PGH1），而对斑马鱼胚胎的急性毒性（96 hpf-LC 50，50）在本研究中还确定了％致死浓度）。根据毒性测试的结果，我们得出的结论是，zanthoxylamide原生物碱可以归为轻度毒性化合物，LC 50值为217μM，可以理解其对活生物体的毒性以及对环境的潜在影响。
• Design, synthesis and biological evaluation of (E)-3-(3,4,5-trimethoxyphenyl) acrylic acid (TMCA) amide derivatives as anticonvulsant and sedative agents
  作者：Zefeng Zhao、Yajun Bai、Xufei Chen、Shaoping Wu、Xirui He、Yujun Bai、Ying Sun、Xiaohui Zheng

  DOI：10.1007/s00044-018-2228-3

  日期：2018.12

  article, a novel series of (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (TMCA) amide derivatives 1-18 were designed and synthesized by a facile and one-pot step, which were achieved with good yields using 1-hydroxybenzotriazole (HOBT) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as activation system. All the synthesized derivatives were biologically evaluated for their anticonvulsant

  本文设计了一系列新颖的（E）-3-（3,4,5-三甲氧基苯基）丙烯酸（TMCA）酰胺衍生物1-18，并通过简单的一锅法步骤合成了使用1-羟基苯并三唑（HOBT）和1-（3-二甲基氨基丙基）-3-乙基碳二亚胺盐酸盐（EDCI）作为活化体系可得到良好的收率。分别使用最大电击（MES）模型，sc-戊烯四唑（PTZ）模型，戊巴比妥钠诱发的睡眠模型和运动功能测试，对所有合成衍生物的抗惊厥，镇静活性和神经毒性进行了生物学评估。其中，化合物4、9和16在初步评估中表现出良好的抗惊厥活性。此外，化合物4是随后测试中最有效的抗惊厥药和镇静剂，而化合物4的低毒性阈值则保持警惕。在随后的测试中，化合物9和16还具有明显的抗惊厥活性，且毒性较弱。分子建模实验还预测了获得的活性分子与GABA转移蛋白的良好结合相互作用。因此，可以得出结论，合成的衍生物4、9和16将代表有用的先导化合物，用于进一步研究抗惊厥药和镇静剂。
• Lead Optimization Studies of Cinnamic Amide EP2 Antagonists
  作者：Thota Ganesh、Jianxiong Jiang、Myung-Soon Yang、Ray Dingledine

  DOI：10.1021/jm5000672

  日期：2014.5.22

  Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (similar to 10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role.
• Synthesis and antihyperglycemic activity of novel N-acyl-2-arylethylamines and N-acyl-3-coumarylamines
  作者：Atma P. Dwivedi、Shailesh Kumar、Vandana Varshney、Amar B. Singh、Arvind K. Srivastava、Devi P. Sahu

  DOI：10.1016/j.bmcl.2008.03.003

  日期：2008.4

  A series of novel N-acyl-2-arylethylamines and N-acyl-3-coumarylamines were synthesized and evaluated for their anti-hyperglycemic activity. Compounds 3g and 6d exhibited lowering of postprandial plasma glucose by 30.7%, 23.3% in SLM and 25.6%, 25.4% in STZ models respectively which is significant compared to metformin and glybenclamide. Other compounds exhibited moderate to good activity ranging from 19.5% to 32.8% in SLM and 3.26% to 25.4% in STZ models. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and Identification of Small Molecules that Potently Induce Apoptosis in Melanoma Cells through G1 Cell Cycle Arrest
  作者：Robin S. Dothager、Karson S. Putt、Brittany J. Allen、Benjamin J. Leslie、Vitaliy Nesterenko、Paul J. Hergenrother

  DOI：10.1021/ja042913p

  日期：2005.6.1

  Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms that melanocytes possess to protect cells from DNA damage often confer resistance to drugs that derive their toxicity from S or M phase arrest. Described herein is the synthesis of a combinatorial library of potential proapoptotic agents and the subsequent identification of a class of small molecules (triphenyl methylamides, TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell cycle. Several of these TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC50 similar to 0.5 mu M), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs were found to dramatically reduce the level of active nuclear factor kappa-B (NF kappa B) in the cell; NF kappa B is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. Compounds that reduce the level of NF kappa B and arrest cells in the G1 phase of the cell cycle can provide insights into the biology of melanoma and may be effective antimelanoma agents.