6-bromo-2-methoxy-9-(4-(diethyl-1-methyl)-N-butyl)aminoacridine | 95433-79-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-bromo-2-methoxy-9-(4-(diethyl-1-methyl)-N-butyl)aminoacridine
• 英文别名: 3-Brom-9-<(4-diethylamino-1-methyl-butyl)-amino>-7-methoxy-acridin；N⁴,N⁴-diethyl-N¹-(6-bromo-2-methoxy-acridin-9-yl)-1-methyl-butanediyldiamine；N⁴,N⁴-Diaethyl-N¹-(6-brom-2-methoxy-acridin-9-yl)-1-methyl-butandiyldiamin；4-N-(6-bromo-2-methoxyacridin-9-yl)-1-N,1-N-diethylpentane-1,4-diamine
• CAS: 95433-79-7
• 化学式: C₂₃H₃₀BrN₃O
• 分子量: 444.415
• InChiKey: GWOHACDAYAXYDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  37.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-bromo-2-methoxy-9-(4-(diethyl-1-methyl)-N-butyl)aminoacridine 在 四(三苯基膦)钯 、 碘 、 三乙胺 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 4.17h， 生成 2-methoxy-9-(4-(diethyl-1-methyl)-N-butyl)amino-6-iodo acridine
  参考文献：
  名称：

  Synthesis and biological evaluation of radioiodinated quinacrine-based derivatives for SPECT imaging of Aβ plaques

  摘要：

  The aim of the present study was to characterize the binding property of quinacrine-based acridine derivatives for A beta plaques and to evaluate this series of compounds as A beta imaging probes. Quinacrine clearly stained A beta plaques in the brain sections of A beta deposition model transgenic mice (Tg2576 mice). Similarly, the quinacrine analog, 2-methoxy-9-(4-(dimethyl-1-methyl) -N-butyl) amino-6-iodo acridine (5), labeled A beta plaques in the brain slices of Tg2576 mice. In addition, [I-125]5 showed modest affinity for A beta(1-42) aggregates with a K-d value of 48 nM. Biodistribution studies using normal mice demonstrated that [I-125]5 displayed poor initial brain uptake. Next, I-125-labeled acridines without aliphatic amino groups were synthesized and characterized. Similar to quinacrine and 5, these compounds could detect A beta plaques in the brain sections of Tg2576 mice. It should be noted that the acridines showed much higher binding affinity for A beta aggregates and greater in vivo blood brain barrier permeability than [I-125]5. Among them, 13 (6-Iodo-2-methoxy-9-methylaminoacridine) and 25 (2,9-Dimethoxy-6-iodo acridine) exhibited high affinity for the A beta aggregates with K-i values of 14 and 29 nM, respectively. In the in vivo studies, [I-125]13 and [I-125]25 showed excellent initial brain uptake (3.0 and 4.4% dose/g, respectively, at 2 min) with fast washout from the brain (0.33 and 0.37% dose/g, respectively, at 60 min). These acridine derivatives are demonstrated to be promising SPECT imaging probes for amyloid in the living brain. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.12.020
• 作为产物：
  描述：

  4-溴-2-氯甲苯 在 硝酸 、 potassium acetate 、 铜 、 potassium carbonate 、 汞 、 三氯氧磷 、 苯酚 作用下， 生成 6-bromo-2-methoxy-9-(4-(diethyl-1-methyl)-N-butyl)aminoacridine
  参考文献：
  名称：

  Magidson et al., Zhurnal Obshchei Khimii, 1938, vol. 8, p. 56,62

  摘要：

  DOI：

文献信息

• DE553072
  申请人：——

  公开号：——

  公开（公告）日：——
• Basically substituted amino-acridine derivatives
  申请人：WINTHROP CHEM CO INC

  公开号：US02113357A1

  公开（公告）日：1938-04-05
• Magidson et al., Zhurnal Obshchei Khimii, 1938, vol. 8, p. 56,62
  作者：Magidson et al.

  DOI：——

  日期：——
• Synthesis and biological evaluation of radioiodinated quinacrine-based derivatives for SPECT imaging of Aβ plaques
  作者：Takeshi Fuchigami、Nobuya Kobashi、Mamoru Haratake、Masao Kawasaki、Morio Nakayama

  DOI：10.1016/j.ejmech.2012.12.020

  日期：2013.2

  The aim of the present study was to characterize the binding property of quinacrine-based acridine derivatives for A beta plaques and to evaluate this series of compounds as A beta imaging probes. Quinacrine clearly stained A beta plaques in the brain sections of A beta deposition model transgenic mice (Tg2576 mice). Similarly, the quinacrine analog, 2-methoxy-9-(4-(dimethyl-1-methyl) -N-butyl) amino-6-iodo acridine (5), labeled A beta plaques in the brain slices of Tg2576 mice. In addition, [I-125]5 showed modest affinity for A beta(1-42) aggregates with a K-d value of 48 nM. Biodistribution studies using normal mice demonstrated that [I-125]5 displayed poor initial brain uptake. Next, I-125-labeled acridines without aliphatic amino groups were synthesized and characterized. Similar to quinacrine and 5, these compounds could detect A beta plaques in the brain sections of Tg2576 mice. It should be noted that the acridines showed much higher binding affinity for A beta aggregates and greater in vivo blood brain barrier permeability than [I-125]5. Among them, 13 (6-Iodo-2-methoxy-9-methylaminoacridine) and 25 (2,9-Dimethoxy-6-iodo acridine) exhibited high affinity for the A beta aggregates with K-i values of 14 and 29 nM, respectively. In the in vivo studies, [I-125]13 and [I-125]25 showed excellent initial brain uptake (3.0 and 4.4% dose/g, respectively, at 2 min) with fast washout from the brain (0.33 and 0.37% dose/g, respectively, at 60 min). These acridine derivatives are demonstrated to be promising SPECT imaging probes for amyloid in the living brain. (C) 2013 Elsevier Masson SAS. All rights reserved.