(E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl)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-acryloyl-3-(3,4,5-trimethoxyphenyl)acrylamide
• 英文别名: (E)-N-prop-2-enoyl-3-(3,4,5-trimethoxyphenyl)prop-2-enamide
• 化学式: C₁₅H₁₇NO₅
• 分子量: 291.304
• InChiKey: VFFKBMBHXIQRTF-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (E)-3-(3,4,5-trimethoxyphenyl)acryloyl chloride 在 ammonium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醚 、 mineral oil 为溶剂， 反应 1.25h， 生成 (E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl)acrylamide
  参考文献：
  名称：

  哌隆明类似物的Senolytic活性：合成与生物学评价

  摘要：

  选择性清除衰老细胞（SCs）已成为治疗与年龄有关的疾病以及化学疗法和放射疗法引起的不良反应的潜在方法。通过基于细胞的表型筛选方法，我们最近确定了膳食中的天然产物哌隆定（PL）作为一种新型的抗衰老剂，是指可以选择性杀灭正常细胞或非衰老细胞的SC的小分子。为了建立PL类似物的结构-衰老活性关系，我们对PL的三甲氧基苯基和α，β-不饱和δ-戊内酰胺环进行了一系列结构修饰。我们表明三甲氧基苯基环上的修饰是很好的耐受性，而内酰胺环上的迈克尔受体对于senolytic活动至关重要。47 - 49具有增加的senolytic活性。这些含α-亚甲基的类似物在诱导WI-38 SC中产生ROS方面也比PL更有效。与PL相似，47 – 49降低了抗氧化蛋白1（OXR1）的蛋白水平，OXR1是一种重要的氧化应激反应蛋白，可调节细胞中多种抗氧化酶的表达。这项研究为发现用于治疗用途的镇静剂提供了有用的起点。

  DOI：

  10.1016/j.bmc.2018.06.013

文献信息

• 피페론구민과 그 유도체 및 그 합성방법
  申请人：Industry Academic Cooperation Foundation, Hallym University 한림대학교 산학협력단(220070195175) BRN ▼221-82-10284

  公开号：KR101633655B1

  公开（公告）日：2016-06-27

  3,4,5-트리메톡시시나믹산의 산 염화물과 다양한 아마이드/락탐 간의 직접적인 반응으로 피페론구민과 그 유도체들을 합성하였다. 또한, 이 화합물들에 대하여 LPS로 유도되는 RAW264.7 대식세포에서 항염증 효과를 평가하였다. 이 화합물들 중 최대 저해활성은 피페론구민 (91.3%)이 나타내었으나 세포독성이 있는 반면, α,β-불포화 부티로락탐 부위를 가진 화합물 3은 세포독성을 나타내지 않으면서 64.8%의 현저한 저해효과를 나타내었다. 이 연구 결과, 최소 3개의 탄소 사슬 길이의 α,β-불포화된 시나모일 기에 연결된 아마이드/락탐 부위가 세포독성 없이 강력한 항염증 활성을 나타내는 것으로 나타났다.

  通过3,4,5-三甲氧基肉桂酸的酸氯化物与各种酰胺/拉克坦之间的直接反应合成了皮肤素和其衍生物。此外，评估了这些化合物在LPS诱导的RAW264.7巨噬细胞中的抗炎作用。这些化合物中，最大的抑制活性由皮肤素（91.3%）表现出来，但具有细胞毒性，而具有α,β-不饱和丁酰胺部位的化合物3则没有细胞毒性，却表现出64.8%的显著抑制效果。研究结果表明，连接到α,β-不饱和肉桂酰基的酰胺/拉克坦部位的最短3个碳链长度显示出强大的抗炎活性，而没有细胞毒性。
• Synthesis and biological evaluation of piperlongumine derivatives as potent anti-inflammatory agents
  作者：Young Hwa Seo、Jin-Kyung Kim、Jong-Gab Jun

  DOI：10.1016/j.bmcl.2014.10.054

  日期：2014.12

  Piperlongumine (PL) and its derivatives were synthesized by the direct reaction between acid chloride of 3,4,5-trimethoxycinnamic acid and various amides/lactams. Later their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages. Of the piperlogs prepared in this study, the maximum (91%) inhibitory activity was observed with PL (IC50 = 3 mu M) but showed cytotoxicity whereas compound 3 (IC50 = 6 mu M) which possess alpha,beta-unsaturated gamma-butyrolactam moiety offered good level (65%) of activity with no cytotoxicity. This study revealed that amide/lactam moiety connected to cinnamoyl group with minimum 3 carbon chain length and alpha,beta-unsaturation is fruitful to show potent anti-inflammatory activity. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration
  作者：Marilia Valli、Wanessa Altei、Ricardo dos Santos、Emilio de Lucca Jr.、Marco Dessoy、Renan Pioli、Fernando Cotinguiba、Xavier Cachet、Sylvie Michel、Maysa Furlan、Luiz Dias、Adriano Andricopulo、Vanderlan Bolzani

  DOI：10.21577/0103-5053.20160303

  日期：——

  Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is described in the literature as selectively cytotoxic to several cancer cell lines. Inhibiting cell migration has gained considerable interest as an approach for discovering antimetastatic agents because this process is fundamental to metastasis. Piperlongumine, selected from cell-based assay screening of NuBBE Database, inhibited the migration of MDA-MB-231 breast cancer cells with an EC50 of 3.0 +/- 1.0 mu M by the Boyden chamber assay. A series of five analogous compounds based on the structure of piperlongumine were designed, synthesized and evaluated in cell migration and cytotoxicity assays. The analogue designed by molecular simplification ((E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl) acrylamide) was the most active of the series, with an EC50 of 1.5 +/- 1 mu M. Additionally, this compound was selectively cytotoxic, with a selectivity index (SI) of 4.4.
• Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation
  作者：Xingui Liu、Yingying Wang、Xuan Zhang、Zhengya Gao、Suping Zhang、Peizhong Shi、Xin Zhang、Lin Song、Howard Hendrickson、Daohong Zhou、Guangrong Zheng

  DOI：10.1016/j.bmc.2018.06.013

  日期：2018.8

  olefin with an exocyclic methylene at C2 render PL analogues 47–49 with increased senolytic activity. These α-methylene containing analogues are also more potent than PL in inducing ROS production in WI-38 SCs. Similar to PL, 47–49 reduce the protein levels of oxidation resistance 1 (OXR1), an important oxidative stress response protein that regulates the expression of a variety of antioxidant enzymes

  选择性清除衰老细胞（SCs）已成为治疗与年龄有关的疾病以及化学疗法和放射疗法引起的不良反应的潜在方法。通过基于细胞的表型筛选方法，我们最近确定了膳食中的天然产物哌隆定（PL）作为一种新型的抗衰老剂，是指可以选择性杀灭正常细胞或非衰老细胞的SC的小分子。为了建立PL类似物的结构-衰老活性关系，我们对PL的三甲氧基苯基和α，β-不饱和δ-戊内酰胺环进行了一系列结构修饰。我们表明三甲氧基苯基环上的修饰是很好的耐受性，而内酰胺环上的迈克尔受体对于senolytic活动至关重要。47 - 49具有增加的senolytic活性。这些含α-亚甲基的类似物在诱导WI-38 SC中产生ROS方面也比PL更有效。与PL相似，47 – 49降低了抗氧化蛋白1（OXR1）的蛋白水平，OXR1是一种重要的氧化应激反应蛋白，可调节细胞中多种抗氧化酶的表达。这项研究为发现用于治疗用途的镇静剂提供了有用的起点。