3-bromo-9-chloroacridine | 35547-72-9

• 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: 3-bromo-9-chloroacridine
• 英文别名: 6-bromo-9-chloroacridine；3-bromo-9-chloro-acridine；3-Bromo-9-chloro-acridin；3-Brom-9-chlor-acridin；3-Brom-9-chloracridin
• CAS: 35547-72-9
• 化学式: C₁₃H₇BrClN
• 分子量: 292.562
• InChiKey: VALMAHPRLZLCAT-UHFFFAOYSA-N

物化性质

• 熔点：
  170-170.5 °C(Solv: benzene (71-43-2))
• 沸点：
  429.7±15.0 °C(Predicted)
• 密度：
  1.634±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-bromo-9-chloroacridine 在 四(三苯基膦)钯 、 碘 、 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 氯仿 为溶剂， 反应 10.17h， 生成 3-Iodo-9-methoxyacridine
  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-氯苯甲酸 在 copper(II) acetate monohydrate 、 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 11.0h， 生成 3-bromo-9-chloroacridine
  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

• Potential antitumor agents. 47. 3'-Methylamino analogs of amsacrine with in vivo solid tumor activity
  作者：Graham J. Atwell、Bruce C. Baguley、Graeme J. Finlay、Gordon W. Rewcastle、William A. Denny

  DOI：10.1021/jm00159a035

  日期：1986.9

  antileukemic agent amsacrine with a 3'-methylamino group provides a compound (3) with a broader spectrum of action, including in vivo activity against experimental solid tumors. The synthesis, physicochemical properties, and biological activity of a series of acridine-substituted analogues of 3 are described. The compounds show higher levels of DNA binding, water solubility, and in vivo solid tumor activity

  用3'-甲基氨基取代临床抗白血病药物氨苯磺酸的3'-甲氧基提供了具有更广谱作用的化合物（3），包括针对实验性实体瘤的体内活性。描述了一系列3的a啶取代的类似物的合成，理化性质和生物学活性。这些化合物显示出更高的DNA结合水平，水溶性和体内实体瘤活性（刘易斯肺癌），而其氨色林对应物更高。然而，a啶取代的结构-活性关系是不同的，其中3,5-二取代的3'-甲基氨基化合物显示出最高的活性（与4,5-二取代的氨ac碱类似物相比）。
• Potential antitumor agents. 52. Carbamate analogs of amsacrine with in vivo activity against multidrug-resistant P388 leukemia
  作者：Gordon W. Rewcastle、Bruce C. Baguley、Graham J. Atwell、William A. Denny

  DOI：10.1021/jm00392a009

  日期：1987.9

  provided increased activity against the multidrug-resistant P388/ADR leukemia subline in vivo. Since activity against such resistant tumors is of great clinical significance, a series of acridine-substituted carbamate derivatives were evaluated against both wild-type and ADR/resistant P388 leukemia and the Lewis lung solid tumor in vivo. Structure-activity relationships for all three tumor lines were similar

  对一系列与抗白血病药物氨苯磺酸有关的苯胺取代的9-苯胺基cr啶的研究表明，1'-氨基甲酸酯基团在体内对多药耐药的P388 / ADR白血病亚系提供增强的活性。由于针对这种抗药性肿瘤的活性具有重要的临床意义，因此在体内针对野生型和ADR /抗药性P388白血病以及Lewis肺实体瘤评估了一系列of啶取代的氨基甲酸酯衍生物。所有三个肿瘤细胞系的结构活性关系相似，其中3-卤代-5-甲基和3-卤代5-甲氧基化合物被证明是活性最高的。这种取代模式还提供了最高的DNA结合。此类化合物（尤其是3-氯-5-甲基和3-氯-5-甲氧基）对野生型P388和Lewis肺具有体内活性，其活性与先前开发的最佳氨水analogue类似物相当（治愈率超过50％） ，以及P388 / ADR活动。这项工作从根本上完成了amsacrine系列抗肿瘤药的开发。
• [EN] NOVEL ACRIDINE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'ACRIDINE
  申请人：PHARMINOX LTD

  公开号：WO2012042265A1

  公开（公告）日：2012-04-05

  The present invention relates to novel acridine derivatives of formula (I), or pharmaceutically acceptable salts thereof, which are inhibitors of the telomerase enzyme function. These compounds are useful for the treatment cellular proliferation disorders, such as cancer.

  本发明涉及式(I)的新型吖啶衍生物，或其药学上可接受的盐，这些衍生物是端粒酶酶功能的抑制剂。这些化合物对治疗细胞增殖紊乱如癌症等疾病有用。
• NOVEL FLUORESCENT DYES AND USES THEREOF
  申请人：Almac Sciences (Scotland) Limited

  公开号：EP1940965B1

  公开（公告）日：2014-03-26
• Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity
  作者：Graham J. Atwell、Gordon W. Rewcastle、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00387a012

  日期：1987.4

  Structure-activity relationships for a series of acridine-substituted 3'-N(CH3)2 derivatives of the clinical antileukemic drug amsacrine (1) are reported. The parent (unsubstituted) compound 3 has activity against the Lewis lung solid tumor that is superior to amsacrine (1), the new clinical amsacrine analogue 4, and the recently developed 3'-NHCH3 derivative 2. Although the compounds generally bind less well to DNA and are less dose potent in vivo than either their amsacrine (3'-OCH3) or 3'-NHCH3 analogues, they show very high levels of antitumor activity, with the 4-OCH3 derivative capable of effecting 100% cures of the Lewis lung solid tumor. The broad structure-activity relationships for acridine substitution more closely resemble those of the amsacrine than the 3'-NHCH3 series, with 4-substituted and 4,5-disubstituted compounds showing the highest activity.