(E)-3,4,5-三甲氧基肉桂酰二乙胺 | 701954-63-4

• 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
• 中文名称: (E)-3,4,5-三甲氧基肉桂酰二乙胺
• 英文名称: (E)-N,N-diethyl-3-(3,4,5-trimethoxyphenyl)acrylamide
• 英文别名: (E)-N,N-diethyl-3-(3,4,5-trimethoxyphenyl)prop-2-enamide
• CAS: 701954-63-4
• 化学式: C₁₆H₂₃NO₄
• 分子量: 293.363
• InChiKey: AVHBHSSFLFWJCY-CMDGGOBGSA-N

物化性质

• 熔点：
  132-134 °C
• 沸点：
  461.3±45.0 °C(Predicted)
• 密度：
  1.075±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3,4,5-三甲氧基肉桂酰二乙胺 在 sodium hypochlorite 、 四丁基氟化铵 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 trans-N,N-diethyl-3-(3-hydroxy-4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydroisoxazole-4-carboxamide
  参考文献：
  名称：

  1,3-Dipolar cycloaddition route to novel isoxazole-type derivatives related to combretastatin A-4

  摘要：

  A series of compounds related to combretastatin A-4, containing a five-membered heterocyclic ring interposed between the two phenyl groups have been Prepared. Synthetic approach involves 1,3-dipolar cycloaddition of various 3,4,5-trimethoxyphenyl units with an in situ generated nitrile oxide from a suitable aldoxime using sodium hypochlorite. Depending oil the nature of the dipolarophile, 3,5-diarylisoxazole derivatives obtained along with the 3,4-regioisomeric isomers. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.03.020
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 在 吡啶 、 草酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.33h， 生成 (E)-3,4,5-三甲氧基肉桂酰二乙胺
  参考文献：
  名称：

  肉桂醛衍生物作为细菌细胞分裂蛋白FtsZ抑制剂的设计，合成和抗菌活性

  摘要：

  为了发现潜在的抗细菌耐药性增强剂，设计，合成和评估了新型肉桂醛衍生物作为FtsZ抑制剂，使用肉汤微稀释法评估了其对九种重要病原体的抗菌活性，以及​​它们对四种代表性菌株的细胞分裂抑制活性。在体外抗菌活性中，新合成的化合物一般对金黄色葡萄球菌ATCC25923显示出比其他化合物更好的功效。特别是化合物3，8和10发挥了优于所有参比药物的活性。在细胞分裂抑制活性中，所有化合物均显示出与其体外抗菌活性相同的趋势，与其他菌株相比，其对金黄色葡萄球菌ATCC25923的活性更好。此外，化合物3，6，7和8中显示强效的细胞分裂的抑制活性具有低于1微克/毫升，超过256倍更好所有参考药物的MIC值。

  DOI：

  10.1016/j.ejmech.2015.04.048

文献信息

• Design, Antileishmanial Activity, and QSAR Studies of a Series of Piplartine Analogues
  作者：Flávio R. Nóbrega、Larisse V. Silva、Carlos da Silva M. Bezerra Filho、Tamires C. Lima、Yunierkis P. Castillo、Daniel P. Bezerra、Tatjana K. Souza Lima、Damião P. de Sousa

  DOI：10.1155/2019/4785756

  日期：2019.1.8

  Most compounds were found to be active against L. amazonensis. Among 32 assayed derivatives, compound (E)-(−)-bornyl 3-(3,4,5-trimethoxyphenyl)-acrylate exhibited the most potent antileishmanial activity (IC50 = 0.007 ± 0.008 μM, SI > 10), followed by benzyl 3,4,5-trimethoxybenzoate (IC50 = 0.025 ± 0.009 μM, SI > 3.205) and (E)-furfuryl 3-(3,4,5-trimethoxyphenyl)-acrylate (IC50 = 0.029 ± 0.007 μM, SI > 2

  Piplartine 是一种存在于不同 Piper 物种中的烷酰胺，具有多种生物活性，包括抗寄生虫特性。因此，本研究的目的是评估一系列 32 种合成的 piplartine 类似物对抗 Leishmania amazonensis 前鞭毛体形式，并建立这些化合物的构效关系和 3D-QSAR。使用MTT方法确定化合物的抗利什曼病作用。大多数化合物被发现对 L. amazonensis 有活性。在 32 种测定的衍生物中，化合物 (E)-(-)-冰片基 3-(3,4,5-三甲氧基苯基)-丙烯酸酯表现出最有效的抗利什曼原虫活性（IC50 = 0.007 ± 0.008 μM，SI > 10），其次是苄基3,4,5-三甲氧基苯甲酸酯 (IC50 = 0.025 ± 0.009 μM, SI > 3.205) 和 (E)-糠基 3-(3,4,5-三甲氧基苯基)-丙烯酸酯 (IC50 = 0.029 ±
• Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma
  作者：Flávio da Nóbrega、Ozlem Ozdemir、Sheila Nascimento Sousa、Joice Barboza、Hasan Turkez、Damião de Sousa

  DOI：10.3390/molecules23061382

  日期：——

  Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.

  Piplartine (1) 是一种从胡椒属植物中提取的醇胺，具有多种药理特性，包括抗肿瘤活性。为了提高其活性，研究人员通过酯化和酰胺化合成了一系列基于1的类似物，这些类似物以3,4,5-三甲氧基肉桂酸为起始材料。在研究过程中，3-(3,4,5-三甲氧基苯基)丙烯酸酯和3-(3,4,5-三甲氧基苯基)丙烯酰胺分别保留在酯和酰胺中。同时，研究了功能性变化，结果显示侧链中两个芳香环的存在对增加对U87MG细胞系的细胞毒性活性至关重要，例如化合物(E)-苯甲基3-(3,4,5-三甲氧基苯基)丙烯酸酯 (10) 是一种表现出强细胞毒性并且活性水平与阳性对照紫杉醇相似的酯。化合物10对U87MG细胞系的存活率具有明显的浓度依赖性抑制作用，并伴随有凋亡和氧化过程，显示出良好的潜力以改变主要分子通路以防止肿瘤发展。此外，该化合物具有良好的生物利用度，并且对人类血细胞表现出非基因毒性和非细胞毒性。总之，本研究的结果表明，化合物10是一个有前景的药物，有可能应用于抗击与氧化应激相关的疾病，并作为开发用于治疗胶质母细胞瘤的新药的原型。
• Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation
  作者：Julia Kaffy、Renée Pontikis、Danièle Carrez、Alain Croisy、Claude Monneret、Jean-Claude Florent

  DOI：10.1016/j.bmc.2006.02.001

  日期：2006.6

  Novel combretastatin analogues bearing various five-membered heterocycles with consecutive oxygen and nitrogen atoms, in place of the olefinic bridge of CA4, have been synthesized (isoxazole, isoxazoline, oxadiazole, etc). These compounds have been evaluated for cytotoxicity and their ability to inhibit the tubulin assembly. On the basis of the relative position of the aromatic A- and B-rings on the heterocyclic moiety, they could be split in two classes, the alpha,gamma- or alpha,beta-diaryl heterocyclic derivatives. In the first series, the 3,5-diaryloxadiazole 9a displayed comparable antitubulin activity to that of CA4, but was devoid of cytotoxic effects. Among the alpha,beta-diaryl heterocyclic derivatives, the 4,5-diarylisoxazole 35 exhibited greater antitubulin activity than that of CA4 (0.75 vs 1.2 mu M), but modest antiproliferative activity. These data showed that minor alteration in the chemical structure of the heterocyclic ring and its relative orientation with regard to the two phenyl rings of CA4 could dramatically influence the tubulin binding properties. (c) 2006 Elsevier Ltd. All rights reserved.
• US4335054A
  申请人：——

  公开号：US4335054A

  公开（公告）日：1982-06-15
• Design, synthesis and antibacterial activity of cinnamaldehyde derivatives as inhibitors of the bacterial cell division protein FtsZ
  作者：Xin Li、Juzheng Sheng、Guihua Huang、Ruixin Ma、Fengxin Yin、Di Song、Can Zhao、Shutao Ma

  DOI：10.1016/j.ejmech.2015.04.048

  日期：2015.6

  exerted superior or comparable activity to all the reference drugs. In the cell division inhibitory activity, all the compounds showed the same trend as their in vitro antibacterial activity, exhibiting better activity against S. aureus ATCC25923 than the other strains. Additionally, compounds 3, 6, 7 and 8 displayed potent cell division inhibitory activity with an MIC value of below 1 μg/mL, over 256-fold

  为了发现潜在的抗细菌耐药性增强剂，设计，合成和评估了新型肉桂醛衍生物作为FtsZ抑制剂，使用肉汤微稀释法评估了其对九种重要病原体的抗菌活性，以及​​它们对四种代表性菌株的细胞分裂抑制活性。在体外抗菌活性中，新合成的化合物一般对金黄色葡萄球菌ATCC25923显示出比其他化合物更好的功效。特别是化合物3，8和10发挥了优于所有参比药物的活性。在细胞分裂抑制活性中，所有化合物均显示出与其体外抗菌活性相同的趋势，与其他菌株相比，其对金黄色葡萄球菌ATCC25923的活性更好。此外，化合物3，6，7和8中显示强效的细胞分裂的抑制活性具有低于1微克/毫升，超过256倍更好所有参考药物的MIC值。