10-aminopraziquantel | 948585-56-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 10-aminopraziquantel
• 英文别名: 10-amino-2-cyclohexanecarbonyl-1,2,3,6,7,11b-hexahydro-pyrazino[2,1-a]isoquinolin-4-one；10-amino-2-(cyclohexanecarbonyl)-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one
• CAS: 948585-56-6
• 化学式: C₁₉H₂₅N₃O₂
• 分子量: 327.426
• InChiKey: ASGIBDAQLLVVSZ-UHFFFAOYSA-N

物化性质

• 熔点：
  91-93 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  594.2±50.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  66.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  10-aminopraziquantel 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium nitrite 作用下， 生成 4-O-[2-(cyclohexanecarbonyl)-4-oxo-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-10-yl] 1-O-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl] butanedioate
  参考文献：
  名称：

  Praziquantel derivatives exhibit activity against both juvenile and adult Schistosoma japonicum

  摘要：

  A praziquantel analog 10-hydroxy praziquantel and eight praziquantel/peroxide conjugates were synthesized. The biological activity of these compounds was evaluated against juvenile and adult stages of Schistosoma japonicum. Unlike praziquantel, 10-hydroxy praziquantel exhibits activity against both juvenile and adult Schistosoma japonicumin. All hybrid compounds displayed modest to significant worm killing activity. The present study has important significance for the development of hybrid antischistosomal drugs. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.133
• 作为产物：
  描述：

  吡喹酮 在 硫酸 、 硝酸 、 tin(ll) chloride 作用下， 以 甲醇 为溶剂， 反应 26.0h， 生成 10-aminopraziquantel
  参考文献：
  名称：

  吡喹酮衍生物I：芳环的修饰。

  摘要：

  制备了有效的驱虫药吡喹酮的几种类似物，它们的芳环不同。评价这些类似物的生物学活性，并将其与已知类似物进行比较。环的胺化是可以容忍的，而其他变化则是不允许的。这些结果对血吸虫病药物开发具有重要意义。

  DOI：

  10.1016/j.bmcl.2007.05.063

文献信息

• Divergent Late‐Stage (Hetero)aryl C−H Amination by the Pyridinium Radical Cation
  作者：Won Seok Ham、Julius Hillenbrand、Jérôme Jacq、Christophe Genicot、Tobias Ritter

  DOI：10.1002/anie.201810262

  日期：2019.1.8

  (Hetero)arylamines constitute some of the most prevalent functional molecules, especially as pharmaceuticals. However, structurally complex aromatics currently cannot be converted into arylamines, so instead, each product isomer must be assembled through a multistep synthesis from simpler building blocks. Herein, we describe a late‐stage aryl C−H amination reaction for the synthesis of complex primary

  （杂）芳基胺构成一些最普遍的功能分子，尤其是作为药物。然而，结构复杂的芳族化合物目前不能转化为芳基胺，因此，必须通过更简单的结构单元通过多步合成来组装每种产物异构体。在本文中，我们描述了后期芳基CH胺化反应，用于合成其他反应无法直接进入的复杂伯芳基胺。我们通过机理分析显示了广泛的底物范围和反应的组成多样性的原因，并使之合理化，这使人们能够获得否则不容易获得的分子。
• Synthesis of fluorescent derivatives of praziquantel: cell-imaging and interaction with Schistosoma japonicum cercariae
  作者：Yunzhi Xie、Yibao Li、Yongquan Wu、Chunhua Liu、Xiaokang Li、Xun Li、Xiaolin Fan

  DOI：10.1039/c3ob41348a

  日期：——

  Schistosomiasis is one of the most burdensome of the neglected tropical diseases. Praziquantel is a recommended drug for treatment against all forms of schistosomiasis. To investigate the interaction between praziquantel and Schistosoma japonicum cercariae, two praziquantel derivatives (PZQ-2 and PZQ-3) and one praziquantel fluorescent derivative (PZQ-5) have been synthesized and characterized using nuclear magnetic resonance spectroscopy (NMR) and MS spectra. The cytotoxicity of PZQ-2, PZQ-3 and PZQ-5 was measured by performing the methyl thiazolyl tetrazolium (MTT) assay. The cell viability for them shows that the three compounds exhibit low cytotoxicity to HeLa cells. Cell imaging experiments demonstrate that PZQ-5 is biocompatible and cell-permeable, which indicates that PZQ-5 is suitable for studying their interaction. Confocal fluorescence microscopy revealed that PZQ-5 is mainly located at the cercarial tegument, which leads to the death of cercariae with the increase in time.

  血吸虫病是被忽视的热带疾病中最严重的疾病之一。吡喹酮是治疗各种血吸虫病的推荐药物。为了研究吡喹酮与日本血吸虫carcariae之间的相互作用，我们合成了两种吡喹酮衍生物（PZQ-2 和 PZQ-3）和一种吡喹酮荧光衍生物（PZQ-5），并利用核磁共振光谱（NMR）和质谱对其进行了表征。PZQ-2、PZQ-3 和 PZQ-5 的细胞毒性是通过甲基噻唑基四氮唑（MTT）试验测定的。细胞存活率表明，这三种化合物对 HeLa 细胞的细胞毒性较低。细胞成像实验表明，PZQ-5 具有生物相容性和细胞渗透性，这表明 PZQ-5 适合研究它们之间的相互作用。共聚焦荧光显微镜显示，PZQ-5 主要位于carcarial tegument，随着时间的延长，PZQ-5 会导致carcariae 死亡。
• Praziquantel derivatives exhibit activity against both juvenile and adult Schistosoma japonicum
  作者：Wen-wen Duan、Si-jie Qiu、Yue Zhao、Huan Sun、Chunhua Qiao、Chao-ming Xia

  DOI：10.1016/j.bmcl.2011.12.133

  日期：2012.2

  A praziquantel analog 10-hydroxy praziquantel and eight praziquantel/peroxide conjugates were synthesized. The biological activity of these compounds was evaluated against juvenile and adult stages of Schistosoma japonicum. Unlike praziquantel, 10-hydroxy praziquantel exhibits activity against both juvenile and adult Schistosoma japonicumin. All hybrid compounds displayed modest to significant worm killing activity. The present study has important significance for the development of hybrid antischistosomal drugs. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.
• Praziquantel derivatives I: Modification of the aromatic ring
  作者：Fiona Ronketti、A. Venkata Ramana、Xia Chao-Ming、Livia Pica-Mattoccia、Donato Cioli、Matthew H. Todd

  DOI：10.1016/j.bmcl.2007.05.063

  日期：2007.8

  Several analogues of the potent anthelmintic praziquantel were prepared with variation in the aromatic ring. The biological activity of these analogues was evaluated and compared against known analogues. Amination of the ring was tolerated while other variations were not. These results have important implications for drug development for schistosomiasis.

  制备了有效的驱虫药吡喹酮的几种类似物，它们的芳环不同。评价这些类似物的生物学活性，并将其与已知类似物进行比较。环的胺化是可以容忍的，而其他变化则是不允许的。这些结果对血吸虫病药物开发具有重要意义。