(E)-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)pyrrolidin-2-one | 1415686-59-7

• 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)-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)pyrrolidin-2-one
• 英文别名: (E)-1-(3-(3,4,5-Trimethoxyphenyl)acryloyl)pyrrolidin-2-one；1-[(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoyl]pyrrolidin-2-one
• CAS: 1415686-59-7
• 化学式: C₁₆H₁₉NO₅
• 分子量: 305.331
• InChiKey: YLCDYVPFKMKRKE-VOTSOKGWSA-N

物化性质

• 沸点：
  490.2±45.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl (E)-3-(3,4,5-trimethoxyphenyl)acrylate 在 水 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 14.75h， 生成 (E)-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)pyrrolidin-2-one
  参考文献：
  名称：

  作为有效醛糖还原酶抑制剂 (ARI) 的新 piplartine 类似物的合成和生物学评价

  摘要：

  作为我们致力于从天然来源开发抗糖尿病药物的继续努力，从胡椒中分离出了哌拉汀，并发现它可以抑制重组人 ALR2，IC 50为 160 μM。为了提高功效，通过修饰这种天然产物先导物的苯乙烯基/芳香族和杂环官能团，合成了一系列类似物。对所有衍生物的ALR2抑制活性进行了测试，结果表明，哌拉汀与吲哚衍生物迈克尔加成制备的加合物3c 、 3e和2j表现出有效的ARI活性，而其他化合物则表现出不同程度的抑制作用。这些活性化合物还能够防止山梨醇在人红细胞中积聚。

  DOI：

  10.1016/j.ejmech.2012.09.014

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.
• Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents
  作者：Shoujiao Peng、Baoxin Zhang、Xianke Meng、Juan Yao、Jianguo Fang

  DOI：10.1021/acs.jmedchem.5b00410

  日期：2015.7.9

  The cellular antioxidant system plays key roles in blocking or retarding the pathogenesis of adult neurodegenerative disorders as elevated oxidative stress has been implicated in the pathophysiology of such diseases. Molecules with the ability in enhancing the antioxidant defense thus are promising candidates as neuroprotective agents. We reported herein the synthesis of piperlongumine analogues and evaluation of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced neuronal cell oxidative damage in the neuron-like PC12 cells. The structure-activity relationship was delineated after the cytotoxicity and protection screening. Two compounds (4 and 5) displayed low cytotoxicity and confer potent protection of PC12 cells from the oxidative injury via upregulation of a panel of cellular antioxidant molecules. Genetically silencing the transcription factor Nrf2, a master regulator of the cellular stress responses, suppresses the cytoprotection, indicating the critical involvement of Nrf2 for the cellular action of compounds 4 and 5 in PC12 cells.
• Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)
  作者：Vidadala Ramasubba Rao、Puppala Muthenna、Gundeti Shankaraiah、Chandrasekhar Akileshwari、Kothapalli Hari Babu、Ganji Suresh、Katragadda Suresh Babu、Rotte Sateesh Chandra Kumar、Kothakonda Rajendra Prasad、Potharaju Ashok Yadav、J. Mark Petrash、Geereddy Bhanuprakash Reddy、Janaswamy Madhusudana Rao

  DOI：10.1016/j.ejmech.2012.09.014

  日期：2012.11

  As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC50 of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead

  作为我们致力于从天然来源开发抗糖尿病药物的继续努力，从胡椒中分离出了哌拉汀，并发现它可以抑制重组人 ALR2，IC 50为 160 μM。为了提高功效，通过修饰这种天然产物先导物的苯乙烯基/芳香族和杂环官能团，合成了一系列类似物。对所有衍生物的ALR2抑制活性进行了测试，结果表明，哌拉汀与吲哚衍生物迈克尔加成制备的加合物3c 、 3e和2j表现出有效的ARI活性，而其他化合物则表现出不同程度的抑制作用。这些活性化合物还能够防止山梨醇在人红细胞中积聚。