(2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-benzylpenta-2,4-dienamide

• 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-benzylpenta-2,4-dienamide
• 英文别名: SCT-47；(2E,4E)-5-(1,3-benzodioxol-5-yl)-N-benzylpenta-2,4-dienamide
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: CMQXBFRIGCIICV-REZHQCRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 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-benzylpenta-2,4-dienamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以17%的产率得到(2E,4E)-N-benzyl-5-(3,4-dihydroxyphenyl)penta-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 草酰氯 、 三乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-benzylpenta-2,4-dienamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Piperic Acid Amides as Free Radical Scavengers and α-Glucosidase Inhibitors

  摘要：

  合成了一系列胡椒酸酰胺（4–24, 29, 30），并评估了它们对1,1-二苯基-2-苦苷肼（DPPH）自由基的清除活性及α-葡萄糖苷酶的抑制活性。在合成的化合物中，含有邻甲氧基苯酚、儿茶酚或5-羟基吲哚基团的酰胺11、13和15表现出强效的DPPH自由基清除活性（11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM）。酰胺10、18和23则展现出更高的α-葡萄糖苷酶抑制活性（10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM）。这些数据显示，结合胺的疏水性是α-葡萄糖苷酶抑制活性的一个重要决定因素。此外，酰胺13和15同时表现出强效的DPPH自由基清除活性和α-葡萄糖苷酶抑制活性（13: IC50 46 µM; 15: IC50 46 µM）。这是首次报告胡椒酸酰胺的DPPH自由基清除活性和α-葡萄糖苷酶抑制活性，并暗示这些酰胺可能作为开发具有抗氧化活性的新型α-葡萄糖苷酶抑制剂的先导化合物。

  DOI：

  10.1248/cpb.c14-00874

文献信息

• Mild, Metal-Free and Protection-Free Transamidation of N-Acyl-2-piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N-Acyl-2-piperidones
  作者：Muthuraman Subramani、Saravana Kumar Rajendran

  DOI：10.1002/ejoc.201900517

  日期：2019.6.16

  selective mild and metal‐free protocol for transamidation of N‐acyl piperidones to unprotected amino acids, amino alcohols and other aliphatic amines at short reaction times (30–45 min), with no additional base and at neat condition. Esterification of N‐acyl piperidones with aliphatic alcohols at 85 °C. Amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°.

  一种高选择性，温和且无金属的方案，可在短反应时间（30–45分钟）内将N-酰基哌啶酮转氨成未保护的氨基酸，氨基醇和其他脂肪族胺，且无其他碱且在纯净条件下进行。N酰基哌啶酮在85°C下用脂肪族醇酯化。酰胺键捻，τ= -20.39°和pyramidalization，χ Ñ = -11.73°。
• Synthesis and Biological Evaluation of Piperic Acid Amides as Free Radical Scavengers and α-Glucosidase Inhibitors
  作者：Koichi Takao、Takaki Miyashiro、Yoshiaki Sugita

  DOI：10.1248/cpb.c14-00874

  日期：——

  A series of piperic acid amides (4–24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM). The amides 10, 18 and 23 showed higher inhibitory activity of α-glucosidase (10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of α-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and α-glucosidase inhibitory activity (13: IC50 46 µM; 15: IC50 46 µM). This is the first report identifying the DPPH free radical scavenging and α-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel α-glucosidase inhibitors with antioxidant activity.

  合成了一系列胡椒酸酰胺（4–24, 29, 30），并评估了它们对1,1-二苯基-2-苦苷肼（DPPH）自由基的清除活性及α-葡萄糖苷酶的抑制活性。在合成的化合物中，含有邻甲氧基苯酚、儿茶酚或5-羟基吲哚基团的酰胺11、13和15表现出强效的DPPH自由基清除活性（11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM）。酰胺10、18和23则展现出更高的α-葡萄糖苷酶抑制活性（10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM）。这些数据显示，结合胺的疏水性是α-葡萄糖苷酶抑制活性的一个重要决定因素。此外，酰胺13和15同时表现出强效的DPPH自由基清除活性和α-葡萄糖苷酶抑制活性（13: IC50 46 µM; 15: IC50 46 µM）。这是首次报告胡椒酸酰胺的DPPH自由基清除活性和α-葡萄糖苷酶抑制活性，并暗示这些酰胺可能作为开发具有抗氧化活性的新型α-葡萄糖苷酶抑制剂的先导化合物。
• Amidic resonance not a barrier for transamidation of <i>N</i>-pivaloyl activated amides: catalyst, base and additive free conditions
  作者：Ida Angel Priya Samuel Rajan、Saravanakumar Rajendran

  DOI：10.1039/d3ob00418j

  日期：——

  stabilized N-pivaloyl activated amides is demonstrated in the absence of a catalyst, base and additive. Furthermore, C–N (1.374 Å) and CO (1.222 Å) bond lengths indicate the existence of amidic resonance; yet, transamidation is achieved at room temperature with alkyl amines in a short reaction time (0.5–2 h) with 60–97% yield. Amines bearing protic hydroxy and carboxylic acid groups were tolerated

  在没有催化剂、碱和添加剂的情况下证明了无扭曲（扭曲角 ( τ ) = 4.54°）和共振稳定的N-新戊酰活化酰胺的转酰胺基作用。此外，C–N (1.374 Å) 和 C O (1.222 Å) 键长表明存在酰胺共振；然而，转酰胺基反应是在室温下用烷基胺在短反应时间（0.5-2 小时）内实现的，产率为 60-97%。在反应条件下可以容忍带有质子羟基和羧酸基团的胺。因此，我们的研究结果表明N -新戊酰基激活的平面和共振稳定的酰胺对亲核加成具有足够的反应性。
• Efficient Modulation of γ-Aminobutyric Acid Type A Receptors by Piperine Derivatives
  作者：Angela Schöffmann、Laurin Wimmer、Daria Goldmann、Sophia Khom、Juliane Hintersteiner、Igor Baburin、Thomas Schwarz、Michael Hintersteininger、Peter Pakfeifer、Mouhssin Oufir、Matthias Hamburger、Thomas Erker、Gerhard F. Ecker、Marko D. Mihovilovic、Steffen Hering

  DOI：10.1021/jm5002277

  日期：2014.7.10

  Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates gamma-aminobutyric acid type A receptors (GABA(A)R). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABA(A)R by means of a two-microelectrode voltage-clamp technique. GABA(A)R were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABA(A)R. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABA(A) (maximal GABA-induced chloride current modulation (IGABA-max = 1673% +/- 146%, EC50 = 51.7 +/- 9.5 mu M), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 +/- 1.8 mu M, IGABA-max = 760% +/- 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABA(A)R modulators.
• Disruption of redox homeostasis with synchronized activation of apoptosis highlights the antifilarial efficacy of novel piperine derivatives: An in vitro mechanistic approach
  作者：Nikhilesh Joardar、Pradip Shit、Satyajit Halder、Utsab Debnath、Sudipto Saha、Anup Kumar Misra、Kuladip Jana、Santi P. Sinha Babu

  DOI：10.1016/j.freeradbiomed.2021.04.026

  日期：2021.6