2-[4-[3-(2-chloro-10H-phenothiazin-10-yl) propyl] piperazin-1-yl] acrylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 2-[4-[3-(2-chloro-10H-phenothiazin-10-yl) propyl] piperazin-1-yl] acrylate
• 英文别名: perphenazine acrylate；2-[4-[3-(2-Chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethyl prop-2-enoate
• 化学式: C₂₄H₂₈ClN₃O₂S
• 分子量: 458.024
• InChiKey: LQTSFONNOKHGBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  奋乃静 、 丙烯酰氯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 以77.7%的产率得到2-[4-[3-(2-chloro-10H-phenothiazin-10-yl) propyl] piperazin-1-yl] acrylate
  参考文献：
  名称：

  Molecular Design for Dual Modulation Effect of Amyloid Protein Aggregation

  摘要：

  Modulation of protein self-assembly has been a powerful strategy for controlling and understanding amyloid protein aggregation. Most modulators of amyloid aggregation only involve simple inhibition or acceleration. Here we report a new multivalent molecular motif, the polyethylenimineperphenazine (PEI-P) conjugate which has a dual accelerationinhibition modulation effect on amyloid beta (A beta) aggregation. Dose dependent results from Thioflavin T fluorescence assays, circular dichroism, and atomic force microscopy show that PEI-P conjugates accelerate formation of A beta prefibrillar intermediates and then inhibit A beta fibrillation. Furthermore, compared to perphenazine alone, PEI-P conjugates exhibit an enhanced inhibitory effect due to multivalency. Cell viability assays indicate that the PEI-P conjugates reduce the cytotoxicity of A beta aggregates in a dose-dependent manner. This new modulation strategy may shed light on controlling amyloid aggregation, which offers a general concept for designing new modulators.

  DOI：

  10.1021/jacs.5b01651

文献信息

• Molecular Design for Dual Modulation Effect of Amyloid Protein Aggregation
  作者：Lijuan Zhu、Yang Song、Pin-Nan Cheng、Jeffrey S. Moore

  DOI：10.1021/jacs.5b01651

  日期：2015.7.1

  Modulation of protein self-assembly has been a powerful strategy for controlling and understanding amyloid protein aggregation. Most modulators of amyloid aggregation only involve simple inhibition or acceleration. Here we report a new multivalent molecular motif, the polyethylenimineperphenazine (PEI-P) conjugate which has a dual accelerationinhibition modulation effect on amyloid beta (A beta) aggregation. Dose dependent results from Thioflavin T fluorescence assays, circular dichroism, and atomic force microscopy show that PEI-P conjugates accelerate formation of A beta prefibrillar intermediates and then inhibit A beta fibrillation. Furthermore, compared to perphenazine alone, PEI-P conjugates exhibit an enhanced inhibitory effect due to multivalency. Cell viability assays indicate that the PEI-P conjugates reduce the cytotoxicity of A beta aggregates in a dose-dependent manner. This new modulation strategy may shed light on controlling amyloid aggregation, which offers a general concept for designing new modulators.