(E)-N-(4-chlorobenzyl)-3-phenyl-acrylamide | 1019771-77-7

• 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-(4-chlorobenzyl)-3-phenyl-acrylamide
• 英文别名: (E)-N-(4-chlorobenzyl)-3-phenylacrylamide；N-(4-chlorobenzyl)-3-phenylprop-2-enamide；N-(4-chlorobenzyl)cinnamamide；(2E)-N-(4-chlorobenzyl)-3-phenyl-2-propenamide；(E)-N-[(4-chlorophenyl)methyl]-3-phenylprop-2-enamide
• CAS: 1019771-77-7
• 化学式: C₁₆H₁₄ClNO
• 分子量: 271.746
• InChiKey: XIYOPZUQIZTXJD-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (E)-N-(4-chlorobenzyl)-3-phenyl-acrylamide 、 三氟甲磺酸 以 氯仿 为溶剂， 反应 3.0h， 以61%的产率得到肉桂酰胺
  参考文献：
  名称：

  The triflic acid-mediated cyclisation of N-benzyl-cinnamamides

  摘要：

  N-Benzyl-cinnamamides cyclise with triflic acid to form 5-aryl-benzazepinones and/or cinnamamides. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.11.035
• 作为产物：
  描述：

  肉桂酸 在 三乙胺 作用下， 以 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (E)-N-(4-chlorobenzyl)-3-phenyl-acrylamide
  参考文献：
  名称：

  The triflic acid-mediated cyclisation of N-benzyl-cinnamamides

  摘要：

  N-Benzyl-cinnamamides cyclise with triflic acid to form 5-aryl-benzazepinones and/or cinnamamides. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2012.11.035

文献信息

• Efficient Synthesis of New <i>N</i>-Benzyl- or <i>N</i>-(2-Furylmethyl)cinnamamides Promoted by the ‘Green’ Catalyst Boric Acid, and Their Spectral Analysis
  作者：Vladimir Kouznetsov、José Barajas、Leonor Méndez、Elena Stashenko

  DOI：10.1055/s-2008-1032039

  日期：2008.2

  New N-benzyl- or N-(2-furylmethyl)cinnamamides were prepared in good to excellent yields by amidation reactions between cinnamic acid and benzylamines or (2-furylmethyl)amine in the presence of 5 mol% boric acid. All the cinnamamides were characterized by IR and 1H and 13C NMR spectroscopy.

  在 5 mol% 硼酸存在下，通过肉桂酸与苄胺或 (2-呋喃甲基) 胺之间的酰胺化反应，以良好至优异的产率制备了新的 N-苄基-或 N-(2-呋喃甲基)肉桂酰胺。所有肉桂酰胺均通过 IR、1H 和 13C NMR 光谱进行表征。
• Antifungal Activity of N-(4-Halobenzyl)amides against Candida spp. and Molecular Modeling Studies
  作者：Yunierkis Perez-Castillo、Ricardo Carneiro Montes、Cecília Rocha da Silva、João Batista de Andrade Neto、Celidarque da Silva Dias、Allana Brunna Sucupira Duarte、Hélio Vitoriano Nobre Júnior、Damião Pergentino de Sousa

  DOI：10.3390/ijms23010419

  日期：——

  Fungal infections remain a high-incidence worldwide health problem that is aggravated by limited therapeutic options and the emergence of drug-resistant strains. Cinnamic and benzoic acid amides have previously shown bioactivity against different species belonging to the Candida genus. Here, 20 cinnamic and benzoic acid amides were synthesized and tested for inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019. Five compounds inhibited the Candida strains tested, with compound 16 (MIC = 7.8 µg/mL) producing stronger antifungal activity than fluconazole (MIC = 16 µg/mL) against C. krusei ATCC 14243. It was also tested against eight Candida strains, including five clinical strains resistant to fluconazole, and showed an inhibitory effect against all strains tested (MIC = 85.3–341.3 µg/mL). The MIC value against C. krusei ATCC 6258 was 85.3 mcg/mL, while against C. krusei ATCC 14243, it was 10.9 times smaller. This strain had greater sensitivity to the antifungal action of compound 16. The inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019 was also achieved by compounds 2, 9, 12, 14 and 15. Computational experiments combining target fishing, molecular docking and molecular dynamics simulations were performed to study the potential mechanism of action of compound 16 against C. krusei. From these, a multi-target mechanism of action is proposed for this compound that involves proteins related to critical cellular processes such as the redox balance, kinases-mediated signaling, protein folding and cell wall synthesis. The modeling results might guide future experiments focusing on the wet-lab investigation of the mechanism of action of this series of compounds, as well as on the optimization of their inhibitory potency.

  真菌感染仍然是全球高发的健康问题，由于治疗选择有限和药物耐药菌株的出现而加剧。曾经显示出对属于念珠菌属不同物种具有生物活性的肉桂酸和苯甲酸酰胺。在这里，合成了20种肉桂酸和苯甲酸酰胺，并对C. krusei ATCC 14243和C. parapsilosis ATCC 22019的抑制进行了测试。五种化合物抑制了测试的念珠菌菌株，其中化合物16（MIC = 7.8 µg/mL）对C. krusei ATCC 14243的抗真菌活性比氟康唑（MIC = 16 µg/mL）更强。它还被测试对抗包括五种对氟康唑耐药的临床菌株在内的八种念珠菌菌株，显示出对所有测试菌株的抑制作用（MIC = 85.3-341.3 µg/mL）。对C. krusei ATCC 6258的MIC值为85.3 mcg/mL，而对C. krusei ATCC 14243的MIC值则小了10.9倍。这株菌株对化合物16的抗真菌作用更为敏感。化合物2、9、12、14和15也能抑制C. krusei ATCC 14243和C. parapsilosis ATCC 22019的生长。进行了结合靶点预测、分子对接和分子动力学模拟的计算实验，以研究化合物16对C. krusei的潜在作用机制。从这些实验中，提出了这种化合物的多靶点作用机制，涉及与关键细胞过程相关的蛋白质，如氧化还原平衡、激酶介导的信号传导、蛋白质折叠和细胞壁合成。建模结果可能指导未来的实验，重点研究这一系列化合物的作用机制的湿实验调查，以及优化它们的抑制效力。
• Synthetic derivatives of natural cinnamic acids as potential anti‐colorectal cancer agents
  作者：Federica Falbo、Sandra Gemma、Adrian Koch、Sarah Mazzotta、Gabriele Carullo、Anna Ramunno、Stefania Butini、Regine Schneider‐Stock、Giuseppe Campiani、Francesca Aiello

  DOI：10.1111/cbdd.14415

  日期：2024.1

  particular, 9f overcame the resistance of HT29 cells, which have a mutant p53 and BRAF. Furthermore, 9f, amide of piperonilic acid with the 3,4-dichlorobenzyl substituent upregulated p21, which is involved in cell cycle arrest as well as in apoptosis induction. Cinnamic acid derivatives might be potential anticancer compounds, useful for the development of promising anti-CRC agents.

  肉桂酸及其衍生物代表了药理学工具开发的有吸引力的构建模块。一系列胡椒酰基和肉桂酰基酰胺 ( 6-9 af ) 已被合成，并针对多种结直肠癌 (CRC) 细胞进行了检测，目的是寻找有前景的抗癌药物。在所有二十四个合成分子中， 7a 、 7e-f 、 9c和9f显示出最好的抗增殖活性。在 FACS 分析和蛋白质印迹中，在结肠肿瘤细胞系 HCT116、SW480、LoVo 和 HT29 中观察到诱导的 G1 细胞周期停滞和凋亡细胞死亡的增加，但在非肿瘤细胞系 HCEC 中未观察到。特别是， 9f克服了具有突变p53和BRAF的HT29细胞的耐药性。此外，带有 3,4-二氯苄基取代基的胡椒酸酰胺9f上调 p21，其参与细胞周期停滞以及细胞凋亡诱导。肉桂酸衍生物可能是潜在的抗癌化合物，可用于开发有前景的抗结直肠癌药物。
• The triflic acid-mediated cyclisation of N-benzylcinnamanilides
  作者：Frank D. King、Stephen Caddick

  DOI：10.1016/j.tet.2013.07.075

  日期：2013.10

  N-Benzylcinnamanilides cyclise with triflic acid to form 1-benzyl-4-aryl-2,4-dihydro-1H-quinolin-2-ones and 2,5-diaryl-benzazepin-3-ones. The product ratio is determined by the preferred orientation of the amide and by the electronics of the substituents. With ortho-substituted anilides, N-debenzylation also occurs to give 4-aryl-2,4-dihydro-1H-quinoline-2-ones. (C) 2013 Elsevier Ltd. All rights reserved.
• Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole
  作者：Li Dai、Chengxu Zang、Shujuan Tian、Wei Liu、Shanlun Tan、Zhan Cai、Tingjunhong Ni、Maomao An、Ran Li、Yue Gao、Dazhi Zhang、Yuanying Jiang

  DOI：10.1016/j.bmcl.2014.11.022

  日期：2015.1

  A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 mu g/ml, decreased the MIC80 of fluconazole from 128.0 mu g/ml to 1.0-0.5 mu g/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides. (C) 2014 Elsevier Ltd. All rights reserved.