6-bromo-9-chloro-2-dimethylaminoacridine | 92433-00-6

• 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-9-chloro-2-dimethylaminoacridine
• 英文别名: 9-chloro-6-bromo-N,N-dimethylacridin-2-amine；9-Chlor-3-brom-7-dimethylamino-acridin；(6-bromo-9-chloro-acridin-2-yl)-dimethyl-amine；6-bromo-9-chloro-N,N-dimethylacridin-2-amine
• CAS: 92433-00-6
• 化学式: C₁₅H₁₂BrClN₂
• 分子量: 335.631
• InChiKey: FOSZNFAUWVMMIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  16.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-9-chloro-2-dimethylaminoacridine 在 四(三苯基膦)钯 、 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成 2-dimethylamino-9-methoxy-6-tributylstannylacridine
  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-bromo-2-(4-dimethylaminoanilino)benzoic acid 在 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 6.0h， 以12%的产率得到6-bromo-9-chloro-2-dimethylaminoacridine
  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

文献信息

• Development of radioiodinated acridine derivatives for in vivo imaging of prion deposits in the brain
  作者：Masao Kawasaki、Takeshi Fuchigami、Nobuya Kobashi、Takehiro Nakagaki、Kazunori Sano、Ryuichiro Atarashi、Sakura Yoshida、Mamoru Haratake、Noriyuki Nishida、Morio Nakayama

  DOI：10.1016/j.bmc.2016.12.020

  日期：2017.2

  Prion diseases are caused by deposition of abnormal prion protein aggregates (PrPsc) in the central nervous system. This study aimed to develop in vivo imaging probes that can detect cerebral PrPsc deposits. We synthesized several quinacrine-based acridine (AC) derivatives with 2,9-substitution and radioiodinated them. The AC derivatives were evaluated as prion-imaging probes using recombinant mouse prion protein (rMoPrP) aggregates and brain sections of mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice. The distribution of these compounds in mice was also evaluated. The 2-methoxy derivative [125112 exhibited the highest binding affinity for rMoPrP aggregates with an equilibrium dissociation constant (K-d) value of 43.4 nM. Fluorescence imaging with 2 showed clear signals at the thioflavin T (ThT)-positive amyloid deposits in the mBSE-infected mouse brain. Although a discrepancy was observed between the in vitro binding of AC derivatives to the aggregates and in vivo distribution of these compounds in the brain and we failed to identify prospective prion-imaging probes in this study, the AC derivatives may be considered a useful scaffold for the development of in vivo imaging probes. Further chemical modification of these AC derivatives may discover clinically applicable prion imaging probes. (C) 2016 Elsevier Ltd. All rights reserved.
• 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.