(E)-N-(4-bromophenyl)-3-(3,4-dihydroxyphenyl)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-(4-bromophenyl)-3-(3,4-dihydroxyphenyl)acrylamide
• 英文别名: (E)-N-(4-bromophenyl)-3-(3,4-dihydroxyphenyl)prop-2-enamide
• 化学式: C₁₅H₁₂BrNO₃
• 分子量: 334.169
• InChiKey: ALPZTNNLEIYSMJ-KRXBUXKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  咖啡酸 、 4-溴苯胺 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到(E)-N-(4-bromophenyl)-3-(3,4-dihydroxyphenyl)acrylamide
  参考文献：
  名称：

  Synthesis, structure and structure–activity relationship analysis of caffeic acid amides as potential antimicrobials

  摘要：

  A series of caffeic acid amides 1-23 were synthesized and nine of which (13-17, 19-21 and 23) were reported for the first time. The chemical structures of these compounds were confirmed by means of H-1 NMR, ESI MS and elemental analyses. Compound 15 was determined by single-crystal X-ray diffraction analysis. All of the compounds were assayed for antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT method. Compounds 10-12, 15, 18 and 21 showed considerable antibacterial activities against B.subtilis with MICs of 795, 625, 389, 118, 312 and 155 mu g/mL, respectively. Structure-activity relationship analysts disclosed that caffeic acid amilides with electron-donating groups at p-position of benzene ring have better inhibitory activities.

  DOI：

  10.1016/j.ejmech.2010.01.066

文献信息

• Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design, Synthesis and In-Vitro Biological Evaluation
  作者：Shahira M. Ezzat、Heba El Sayed Teba、Inas G. Shahin、Ahmed M. Hafez、Aliaa M. Kamal、Nora M. Aborehab

  DOI：10.3390/molecules27196724

  日期：——

  A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and evaluation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage.

  药物研究的一个重要目标是提高疗效和降低毒性。因此，使用天然活性成分作为前体将提高安全性和生物活性。尽管咖啡酸和阿魏酸具有多种药理活性，但由于它们的生物利用度低、消除速度快，因此临床应用有限。因此，我们制备了这两种酸的半合成化合物，并将其作为抗癌剂进行筛选。在这项研究中，CA 和 FA 对 Caco-2 细胞显示出非常强的抗癌活性。因此，研究人员针对同一细胞系测试了 18 种衍生物。在确定选择性指数时，选出了四种有效的候选化合物，其中化合物 10 显示出较高的安全系数。化合物 10 代表了一种新的支架，对 Caco-2 细胞具有显著的细胞毒性活性。细胞周期分析和细胞凋亡评估显示，衍生物 10、7、11、15 和 14 中细胞凋亡晚期的比例最高。
• 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.
• Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents
  作者：Chia-Cheng Hung、Wei-Jen Tsai、Li-Ming Yang Kuo、Yao-Haur Kuo

  DOI：10.1016/j.bmc.2004.11.055

  日期：2005.3.1

  A series of amides of caffeic acid were synthesized and evaluated for their anti-platelet and anti-oxidative activities. N-(2-Bromo-phenyl)-3-(3,4-dihydroxy-phenyl)-acrylamide (12) and N-(3-Bromo-phenyl)-3-(3,4-dihydroxy-phenyl)-acrylamide (13) exhibited potent inhibitory activity (IC50 = 5.8 and 6.7 muM, respectively) against arachidonic acid-induced (AA) platelet aggregation, comparable with invalid caffeic acid. Most of the synthesized caffeic acid anifides exhibited the promising anti-platelet aggregation in AA-induced assay and anti-oxidative activities. This study also exhibited that caffeic anilides displayed more potent anti-oxidative activity in the radical scavenging activity assay than trolox and vitamin E. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis, structure and structure–activity relationship analysis of caffeic acid amides as potential antimicrobials
  作者：Jie Fu、Kui Cheng、Zhi-ming Zhang、Rui-qin Fang、Hai-liang Zhu

  DOI：10.1016/j.ejmech.2010.01.066

  日期：2010.6

  A series of caffeic acid amides 1-23 were synthesized and nine of which (13-17, 19-21 and 23) were reported for the first time. The chemical structures of these compounds were confirmed by means of H-1 NMR, ESI MS and elemental analyses. Compound 15 was determined by single-crystal X-ray diffraction analysis. All of the compounds were assayed for antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT method. Compounds 10-12, 15, 18 and 21 showed considerable antibacterial activities against B.subtilis with MICs of 795, 625, 389, 118, 312 and 155 mu g/mL, respectively. Structure-activity relationship analysts disclosed that caffeic acid amilides with electron-donating groups at p-position of benzene ring have better inhibitory activities.