4-((((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)benzaldehyde | 1150591-57-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 4-((((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)benzaldehyde
• CAS: 1150591-57-3
• 化学式: C₂₃H₃₀O₆
• 分子量: 402.488
• InChiKey: PHFJVWDSBALRHH-BAJXCRMASA-N

物化性质

• 沸点：
  507.6±50.0 °C(predicted)
• 密度：
  1.24±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.22
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  63.22
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-((((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)benzaldehyde 、 N¹-(6-chloro-2-methoxyacridin-9-yl)ethane-1,2-diamine 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 以32%的产率得到N'-(6-chloro-2-methoxyacridin-9-yl)-N-[[4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxymethyl]phenyl]methyl]ethane-1,2-diamine
  参考文献：
  名称：

  Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis, preliminary SAR and comparison with acridine endoperoxide conjugates

  摘要：

  A novel series of semi-synthetic trioxaquines and synthetic trioxolaquines were prepared, in moderate to good yields. Antimalarial activity was evaluated against both the chloroquine-sensitive 3D7 and resistant K1 strain of Plasmodium falciparum and both series of compounds were shown to be active in the low nanomolar range. For comparison the corresponding 9-amino acridine analogues were also prepared and shown to have low nanomolar activity like their quinoline counterparts. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.013
• 作为产物：
  描述：

  10β-[[4-(hydroxymethyl)benzyl]oxy]dihydroartemisinin 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以100%的产率得到4-((((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)methyl)benzaldehyde
  参考文献：
  名称：

  Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis, preliminary SAR and comparison with acridine endoperoxide conjugates

  摘要：

  A novel series of semi-synthetic trioxaquines and synthetic trioxolaquines were prepared, in moderate to good yields. Antimalarial activity was evaluated against both the chloroquine-sensitive 3D7 and resistant K1 strain of Plasmodium falciparum and both series of compounds were shown to be active in the low nanomolar range. For comparison the corresponding 9-amino acridine analogues were also prepared and shown to have low nanomolar activity like their quinoline counterparts. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.013

文献信息

• Design and Evaluation of Primaquine-Artemisinin Hybrids as a Multistage Antimalarial Strategy
  作者：Rita Capela、Ghislain G. Cabal、Philip J. Rosenthal、Jiri Gut、Maria M. Mota、Rui Moreira、Francisca Lopes、Miguel Prudêncio

  DOI：10.1128/aac.05133-11

  日期：2011.10

  resistance. To that end, two hybrid molecules with covalently linked primaquine and artemisinin moieties were synthesized, and their effectiveness against the liver and blood stages of infection was compared in vitro and in vivo with those of the parent compounds. Both hybrids displayed enhanced in vitro activities, relative to those of the parent compounds, against Plasmodium berghei liver stages. Both

  人们普遍认为，抗击疟疾取决于制定抗击感染的新策略。被认为是根除所需的“灵丹妙药”不仅应该为所有疟原虫提供治疗。感染人类红细胞，但也应消除寄生虫的复制和休眠肝脏形式。此外，理想情况下，这些目标应该通过使用不同的作用机制来实现，以避免产生耐药性。为此，合成了两种具有共价连接的伯氨喹和青蒿素部分的杂合分子，并在体外和体内将它们对感染的肝脏和血液阶段的有效性与母体化合物进行了比较。相对于母体化合物，两种杂合体都显示出增强的体外活性，抗疟原虫肝脏阶段。两种化合物对培养的恶性疟原虫（50% 抑制浓度 [IC(50)]，约 10 nM）的效力与青蒿素差不多。当用于治疗鼠类伯氏疟原虫感染时，其中一种分子表现出比母体药效团的等摩尔混合物更好的功效，从而提高治愈率和存活率。这些结果揭示了一种基于作用于寄生虫生命周期不同阶段的分子的共价组合来设计和评估抗疟药的新方法。其中一种分子表现出比母体药效团的等摩尔混合物