2-(cyclohexanecarbonyl)-9,10-dimethoxy-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one | 220399-14-4

• 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: 2-(cyclohexanecarbonyl)-9,10-dimethoxy-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one
• 英文别名: 9,10-Dimethoxy-2-cyclohexylcarbonyl-1,3,4,6,7,11b-hexahydro-2 h-pyrazino[2,1-a]isoquinolin-4-one；2-(cyclohexanecarbonyl)-9,10-dimethoxy-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one
• CAS: 220399-14-4
• 化学式: C₂₁H₂₈N₂O₄
• 分子量: 372.464
• InChiKey: ARHAPKSNAJRFLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6,7-二甲氧基-3,4-二氢异喹啉 在 吡啶 、 氢气 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 41.0h， 生成 2-(cyclohexanecarbonyl)-9,10-dimethoxy-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one
  参考文献：
  名称：

  Synthesis of new praziquantel analogues: Potential candidates for the treatment of schistosomiasis

  摘要：

  An efficient synthesis of antischistosomal drug praziquantel and analogues was achieved and the synthetic route designed was to afford structurally diverse analogues for better structure-activity relationship understanding. Total of nineteen PZQ analogues with structural variations at amide, piperazine and aromatic moieties have been synthesized and fully characterized. Among all the new analogues tested for antischistosomal activity, one dimethoxy tetrahydroisoquinoline analogue and two tetrahydro-beta-carboline analogues exhibited moderate activity against adult Schistosoma mansoni. Tetrahydro-beta-carboline analogues showed moderate activity whereas the presence of p-trifluoromethylbenzoyl and p-toluenesulphonyl moieties resulted in complete suppression of antischistosomal activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.108

文献信息

• MCR Synthesis of Praziquantel Derivatives
  作者：Haixia Liu、Samia William、Eberhardt Herdtweck、Sanaa Botros、Alexander Dömling

  DOI：10.1111/j.1747-0285.2011.01288.x

  日期：2012.4

  Schistosomiasis, a high volume neglected tropical disease affecting more than 200 million people worldwide, can only be effectively treated by the tetrahydroisoquinoline drug praziquantel (PZQ). Herein, we describe an efficient approach to access PZQ derivatives by the Ugi 4‐component reaction followed by the Pictet–Spengler reaction in a two‐step, one‐pot procedure. 30 novel PZQ derivatives are described

  血吸虫病是一种影响全球 2 亿多人的大量被忽视的热带疾病，只能通过四氢异喹啉药物吡喹酮 (PZQ) 进行有效治疗。在此，我们描述了一种通过 Ugi 4 组分反应和 Pictet-Spengler 反应在两步单锅程序中获得 PZQ 衍生物的有效方法。基于 Ugi 4 组分反应描述了 30 种新型 PZQ 衍生物，并讨论了一种新型衍生物的 X 射线结构，与 PZQ 相比，揭示了不同的构象。基于体外曼氏血吸虫蠕虫活力测定，已经确定了几种在活性上与药物 PZQ 相当的类似物。
• Synthesis of new praziquantel analogues: Potential candidates for the treatment of schistosomiasis
  作者：Partha Sarathi Sadhu、Singam Naveen Kumar、Malapaka Chandrasekharam、Livia Pica-Mattoccia、Donato Cioli、Vaidya Jayathirtha Rao

  DOI：10.1016/j.bmcl.2011.11.108

  日期：2012.1

  An efficient synthesis of antischistosomal drug praziquantel and analogues was achieved and the synthetic route designed was to afford structurally diverse analogues for better structure-activity relationship understanding. Total of nineteen PZQ analogues with structural variations at amide, piperazine and aromatic moieties have been synthesized and fully characterized. Among all the new analogues tested for antischistosomal activity, one dimethoxy tetrahydroisoquinoline analogue and two tetrahydro-beta-carboline analogues exhibited moderate activity against adult Schistosoma mansoni. Tetrahydro-beta-carboline analogues showed moderate activity whereas the presence of p-trifluoromethylbenzoyl and p-toluenesulphonyl moieties resulted in complete suppression of antischistosomal activity. (C) 2011 Elsevier Ltd. All rights reserved.