(2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-phenylpenta-2,4-dienamide | 1087058-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-phenylpenta-2,4-dienamide
• 英文别名: N-Piperoylaniline；(2E,4E)-5-(1,3-benzodioxol-5-yl)-N-phenylpenta-2,4-dienamide
• CAS: 1087058-28-3
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: SDVNECXUKBRJNJ-REZHQCRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-phenylpenta-2,4-dienamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以12%的产率得到(2E,4E)-5-(3,4-dihydroxyphenyl)-N-phenylpenta-2,4-dienamide
  参考文献：
  名称：

  提高咖啡酸作为抗氧化剂和单胺氧化酶 B/儿茶酚-O-甲基转移酶抑制剂的性能

  摘要：

  增加的氧化应激 (OS) 和黑质纹状体多巴胺 (DA) 的消耗与帕金森病 (PD) 中观察到的神经变性密切相关。开发了基于咖啡酸（CA）的抗氧化剂，并筛选了它们对单胺氧化酶（MAOs）和儿茶酚O-甲基转移酶（COMT）的抑制活性。结果表明，额外双键的加入保持甚至增强了 CA 的抗氧化性能。α-CN 衍生物显示出与 CA ( 1 ) 相似的氧化还原电位 ( E p )，并以低 μM IC 50值抑制h MAO-B。此外，儿茶酚酰胺作为 MB-COMT 抑制剂，显示 IC 50低 μM 范围内的值。一般来说，CA 衍生物在浓度高达 10 μM 时表现出安全的细胞毒性特征。CA 衍生物诱导的活性氧 (ROS) 的形成可能是在较高浓度下观察到的细胞毒性作用的基础。10 μM 的儿茶酚酰胺3 – 6 , 8 – 11 可保护细胞免受氧化损伤。预计化合物3和8通过被动扩散穿过血脑屏障 (BBB)。总之，我们首次报道了可以恢复

  DOI：

  10.1016/j.ejmech.2022.114740
• 作为产物：
  描述：

  胡椒碱 在 乙醇 、 三乙胺 、 potassium hydroxide 作用下， 以 丙酮 为溶剂， 反应 0.5h， 生成 (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-phenylpenta-2,4-dienamide
  参考文献：
  名称：

  基于天然胡椒碱的脲和酰胺作为治疗乳腺癌的新型抗肿瘤剂

  摘要：

  摘要 在这项工作中，天然胡椒碱部分被用于开发两组基于胡椒碱的酰胺 ( 5a-i ) 和尿素 ( 8a-y ) 作为潜在的抗癌剂。针对三阴性乳腺癌 (TNBC) MDA-MB-231、卵巢 A2780CP 和肝细胞 HepG2 癌细胞系评估了抗癌作用。特别是，8q是针对 TNBC MDA-MB-231 细胞最有效的抗增殖类似物，其 IC 50等于 18.7 µM，优于胡椒碱 (IC 50  = 47.8 µM) 和 5-FU (IC 50  = 38.5 µM）。此外，通过以下途径研究了8q在 MDA-MB-231 细胞中的可能作用机制膜联蛋白 V-FITC 细胞凋亡测定和细胞周期分析。此外，计算机分析提出 VEGFR-2 作为胡椒碱衍生物的可能酶促靶标，然后探索了 VEGFR-2 活性位点 (PDB:4ASD) 内的结合相互作用。最后，进行体外VEGFR-2 抑制测定以验证计算机研究结果，其中8q显示出良好的

  DOI：

  10.1080/14756366.2021.1988944

文献信息

• Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities
  作者：Rattanaporn Wansri、Aye Chan Khine Lin、Jutharat Pengon、Sumalee Kamchonwongpaisan、Nitipol Srimongkolpithak、Roonglawan Rattanajak、Patcharin Wilasluck、Peerapon Deetanya、Kittikhun Wangkanont、Kowit Hengphasatporn、Yasuteru Shigeta、Jatupol Liangsakul、Aphinya Suroengrit、Siwaporn Boonyasuppayakorn、Taksina Chuanasa、Wanchai De-eknamkul、Supot Hannongbua、Thanyada Rungrotmongkol、Supakarn Chamni

  DOI：10.3390/molecules27092841

  日期：——

  phenyl piperamide 5 exhibited the most robust biological activities with no cytotoxicity against mammalian cell lines, Vero and Vero E6, as compared to the other compounds in this series. Its half-maximal inhibitory concentration (IC50) for antitrypanosomal activity against Trypanosoma brucei rhodesiense was 15.46 ± 3.09 μM, and its antimalarial activity against the 3D7 strain of Plasmodium falciparum

  Piper nigrum或黑胡椒产生胡椒碱，一种具有多种药理活性的生物碱。在本研究中，通过半合成方法制备了N-芳基酰胺胡椒碱类似物，包括胡椒碱 ( 1 ) 皂化生成胡椒酸 ( 2 ) ，然后酯化得到化合物3、4和5。检查了这些化合物的抗锥虫、抗疟和抗 SARS-CoV-2 主要蛋白酶活性。新型2,5-二甲氧基取代苯基哌酰胺5与该系列中的其他化合物相比，对哺乳动物细胞系 Vero 和 Vero E6 表现出最强大的生物活性，并且没有细胞毒性。其对布氏罗氏锥虫的抗锥虫活性的半数最大抑制浓度 (IC 50 ) 为15.46 ± 3.09 μM，对恶性疟原虫3D7 株的抗疟活性为 24.55 ± 1.91 μM，分别为四倍和五倍，比胡椒碱的活性。有趣的是，化合物5抑制 3C 样主蛋白酶 (3CL Pro ) 对抗 SARS-CoV-2 活性的 IC 50106.9 ± 1.2 μM，比芦丁的活性强
• Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors
  作者：Payare L. Sangwan、Jawahir L. Koul、Surrinder Koul、Mallepally V. Reddy、Niranjan Thota、Inshad A. Khan、Ashwani Kumar、Nitin P. Kalia、Ghulam N. Qazi

  DOI：10.1016/j.bmc.2008.09.042

  日期：2008.11

  Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid and verapamil. The inhibitory mechanism of the compounds was confirmed by efflux inhibition assay using ethidium bromide as NorA substrate. The present communication describes the synthesis, bioevaluation and structure related activity of these efflux pump inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.
• Design of novel monoamine oxidase-B inhibitors based on piperine scaffold: Structure-activity-toxicity, drug-likeness and efflux transport studies
  作者：Daniel Chavarria、Carlos Fernandes、Vera Silva、Catia Silva、Eva Gil-Martins、Pedro Soares、Tiago Silva、Renata Silva、Fernando Remião、Paulo J. Oliveira、Fernanda Borges

  DOI：10.1016/j.ejmech.2019.111770

  日期：2020.1

  Piperine has been associated with neuroprotective effects and monoamine oxidase (MAO) inhibition, thus being an attractive scaffold to develop new antiparkinsonian agents. Accordingly, we prepared a small library of piperine derivatives and screened the inhibitory activities towards human MAO isoforms (hMAO-A and hMAO-B). Structure-activity relationship (SAR) studies pointed out that the combination of alpha-cyano and benzyl ester groups increased both potency and selectivity towards hMAO-B. Kinetic experiments with compounds 7, 10 and 15 indicated a competitive hMAO-B inhibition mechanism. Compounds 15 and 16, at 10 mu M, caused a small but significant decrease in P-gp efflux activity in Caco-2 cells. Compound 15 stands out as the most potent piperine-based hMAO-B inhibitor (IC50 = 47.4 nM), displaying favourable drug-like properties and a broad safety window. Compound 15 is thus a suitable candidate for lead optimization and the development of multitarget-directed ligands. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Wahab, Aneela; Sultana, Amina; Khan, Khalid Mohammed, Journal of the Chemical Society of Pakistan, 2015, vol. 37, # 5, p. 1008 - 1014
  作者：Wahab, Aneela、Sultana, Amina、Khan, Khalid Mohammed、Sherwani, Sikandar K.、Perveen, Zeba、Taha, Muhammad、Karim, Aneela

  DOI：——

  日期：——
• Development of piperic acid-based monoamine oxidase inhibitors: Synthesis, structural characterization and biological evaluation
  作者：Daniel Chavarria、Fernando Cagide、Miguel Pinto、Lígia R. Gomes、John N. Low、Fernanda Borges

  DOI：10.1016/j.molstruc.2019.01.060

  日期：2019.4

  A series of piperic acid esters and amides were synthesized using a two-step strategy. Mass spectrometry and unidimensional (H-1 NMR, C-13 NMR, DEPT) and bidimensional (COSY, HSQC, HMBC) NMR methodologies were used to study the molecular structure of the final compounds, resulting in the assignment of all detected signals.Preliminary biological data of piperine and the derivatives thereof showed that piperic acid 2 and amides 3 and 4 did not display significant inhibitory activity at 10 tiM against both hMAO-A and hMAO-B. In contrast, the esters 5 and 6 displayed relevant hMAO inhibitory activities, with IC50 values for hMAO-B lower than piperine and within the nanomolar range (compound 1: IC50 = 1.05 ttM; compound 6: IC50 =169 nM; compound 5: IC50 =156 nM). Moreover, X-ray crystallographic analyses showed relevant differences between amides 3 and 4 and esters 5 and 6 constituting a valuable information to understand the ligand-target interactions.Additional studies are warranted for a systematic lead optimization process that can lead in the future to a more potent and selective hMAO-B inhibitor based on piperine scaffold. (C) 2019 Elsevier B.V. All rights reserved.