1-acryloyl-3,5-bis(2-fluorobenzylidene)-4-piperidone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-acryloyl-3,5-bis(2-fluorobenzylidene)-4-piperidone
• 英文别名: 1-Acryloyl-3,5-bis(2-fluorobenzylidene)-4-piperidone；3,5-bis[(2-fluorophenyl)methylidene]-1-prop-2-enoylpiperidin-4-one
• 化学式: C₂₂H₁₇F₂NO₂
• 分子量: 365.379
• InChiKey: UAALLHXUCALBPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-acryloyl-3,5-bis(2-fluorobenzylidene)-4-piperidone 、 靛红 、 2-氨基-2-苯基乙酸 反应 0.5h， 以70%的产率得到4-(2-fluoro)-5-(phenyl)pyrrolo(spiro[2.3']oxindole)spiro[3.3"]-5"-(2-fluorophenylmethylidene)-1"-N-acrolylpiperidin-4"-one
  参考文献：
  名称：

  Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors

  摘要：

  Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 mu M, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 mu M, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.019
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 在 盐酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 生成 1-acryloyl-3,5-bis(2-fluorobenzylidene)-4-piperidone
  参考文献：
  名称：

  Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors

  摘要：

  Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 mu M, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 mu M, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.019

文献信息

• 3,5-Bis(2-fluorobenzylidene)-4-piperidone induce reactive oxygen species-mediated apoptosis in A549 cells
  作者：Guo-Yun Liu、Cong-Cong Jia、Pu-Ren Han、Jie Yang

  DOI：10.1007/s00044-017-2056-x

  日期：2018.1

  almost 13-fold cytotoxicity relative to curcumin against A549 cells. More importantly, 1d was more stable and more massive uptake than curcumin, which may be relationship to their cytotoxicity, apoptotic acitivity and reactive oxygen species generation. The generation of reactive oxygen species is associated with falling apart in the redox buffering system, and subsequently induces lipid peroxidation

  芳环的邻位上存在取代基有助于增强生物活性，从而突出了所谓的邻位效应。在本文中，我们合成了六个带有氟基团的单羰基姜黄素类似物，这些类似物赋予某些药物多种特性。然后，通过MTT分析评估针对A549和NCI-H460细胞的细胞毒性。结果表明，相对于姜黄素对A549细胞而言，1d表面上是一种重要的先导化合物，显示出几乎13倍的细胞毒性。更重要的是1d姜黄素比姜黄素更稳定，吸收更大，这可能与其姜黄素的细胞毒性，凋亡活性和活性氧的产生有关。活性氧的产生与氧化还原缓冲系统中的崩解有关，并随后引起脂质过氧化，线粒体膜电位的崩溃并最终导致细胞凋亡。这些数据表明邻位作用和将氟引入药物分子是提高单羰基姜黄素类似物的抗癌活性的成功策略。
• Anti-inflammatory activity of ortho-trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives in vitro and in vivo
  作者：Ziqing Wang、Wenwen Mu、Pengxiao Li、Guoyun Liu、Jie Yang

  DOI：10.1016/j.ejps.2021.105756

  日期：2021.5
• Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors
  作者：Yalda Kia、Hasnah Osman、Raju Suresh Kumar、Alireza Basiri、Vikneswaran Murugaiyah

  DOI：10.1016/j.bmcl.2014.02.019

  日期：2014.4

  Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 mu M, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 mu M, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes. (c) 2014 Elsevier Ltd. All rights reserved.