9-chloro-5-methoxy-3-nitroacridine | 1744-99-6

• 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: 9-chloro-5-methoxy-3-nitroacridine
• 英文别名: 9-chloro-5-methoxy-3-nitro-acridine
• CAS: 1744-99-6
• 化学式: C₁₄H₉ClN₂O₃
• 分子量: 288.69
• InChiKey: GDGUIIZNYIXNDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-chloro-5-methoxy-3-nitroacridine 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Shapovalov, V. A.; Novotny, L.; Gaidukevich, A. N., Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 2283 - 2285

  摘要：

  DOI：
• 作为产物：
  描述：

  邻甲氧基苯胺 在 铜 、 potassium carbonate 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 9-chloro-5-methoxy-3-nitroacridine
  参考文献：
  名称：

  Design, synthesis and evaluation of acridine derivatives as multi-target Src and MEK kinase inhibitors for anti-tumor treatment

  摘要：

  Clinical studies have shown enhanced anticancer effects of combined inhibition of Src and MEK kinases. Development of multi-target drugs against Src and MEK is of potential therapeutic advantage against cancers. As a follow-up of our previous studies, and by using molecular docking method, we designed and synthesized a new series of 9-anilinoacridines containing phenyl-urea moieties as potential novel dual Src and MEK inhibitors. The anti-proliferative assays against K562 and HepG-2 tumor cells showed that most of the derivatives displayed good cytotoxicity in vitro. In particular, kinase inhibition assays showed that compound 8m inhibited Src (59.67%) and MEK (43.23%) at 10 mu M, and displayed moderate inhibitory activity against ERK and AKT, the downstream effectors of both Src and MEK. Moreover, compound 8m was found to induce K562 cells apoptosis. Structure-activity relationships of these derivatives were analyzed. Our study suggested that acridine scaffold, particularly compound 8m, is of potential interest for developing novel multi-target Src and MEK kinase inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.011

文献信息

• Synthesis of Monomeric and Dimeric Acridine Compounds as Potential Therapeutics in Alzheimer and Prion Diseases
  作者：René Csuk、Alexander Barthel、Christian Raschke、Ralph Kluge、Dieter Ströhl、Lothar Trieschmann、Gerald Böhm

  DOI：10.1002/ardp.200900065

  日期：2009.12

  spacered dimeric acridine compounds was prepared. Their ability to interrupt the protein association of prion‐ and Alzheimer‐specific proteins and Ab peptides was explored using a fast screening system based on FACS analysis. The bis‐acridines displayed a higher activity than the corresponding monomers. Among these derivatives, best results were obtained with the 2,4‐dimethoxy‐6‐nitro compound 7h for

  从取代的 9-氯吖啶开始，制备了一系列奎纳克林和间隔二聚吖啶化合物。使用基于 FACS 分析的快速筛选系统探索了它们中断朊病毒和阿尔茨海默特异蛋白与 Ab 肽的蛋白质结合的能力。双吖啶比相应的单体表现出更高的活性。在这些衍生物中，Aβ-肽的 2,4-二甲氧基-6-硝基化合物 7h 和 PrP 的 2-甲氧基-6-硝基化合物 7f 获得了最好的结果。
• Synthesis and Antitumor Activity of 9-Anilino, Phenylhydrazino, and Sulphonamido Analogs of 2- or 4-Methoxy-6-nitroacridines
  作者：H. I. El-Subbagh、A. H. Abadi、H. A. Al-Khamees

  DOI：10.1002/ardp.19973300903

  日期：——

  Synthesis of several new 9‐anilino, phenylhydrazino, and sulphonamido analogs of 2‐ or 4‐methoxy‐6‐nitroacridine derivatives is described. The prepared compounds were tested for their in vitro antitumor activity against 60 human tumor cell lines by the National Cancer Institute (NCI) and showed a potential anticancer activity. Compounds 9‐(phenylhydrazino)‐2‐methoxy‐6‐nitroacridine (8a) and 9‐(4‐c

  描述了几种新的 9-苯胺基、苯肼基和 2-或 4-甲氧基-6-硝基吖啶衍生物的磺酰氨基类似物的合成。美国国家癌症研究所 (NCI) 测试了制备的化合物对 60 种人类肿瘤细胞系的体外抗肿瘤活性，并显示出潜在的抗癌活性。化合物9-(苯肼)-2-甲氧基-6-硝基吖啶(8a)和9-(4-氯苯肼)-4-甲氧基-6-硝基吖啶(9b)在全面板(MG-MID)中表现出广谱抗肿瘤活性中值生长抑制 (GI50) 分别为 16.1 和 10.9 μM，总生长抑制 (TGI) 分别为 66.7 和 37.9 μM。同时，化合物15a和15b对白血病细胞系表现出中等选择性。作为探索其抗肿瘤活性作用方式的试验，评估了 6-硝基吖啶类似物对主要细胞周期控制蛋白 cdc2 激酶和 cdc25 磷酸酶的抑制作用，这些蛋白可能是抗有丝分裂效力的可能分子靶标。没有一种测试化合物证明通过这种抗有丝分裂的作用方式发挥其活性。
• Convenient access to substituted acridines by a Buchwald–Hartwig amination
  作者：René Csuk、Alexander Barthel、Christian Raschke

  DOI：10.1016/j.tet.2004.05.013

  日期：2004.6

  A convenient, high yield procedure for the synthesis of anthranilic acids carrying a variety of different substituents as well as their straightforward transformation into the corresponding 9-chloroacridines could be established by using modified Buchwald-Hartwig amination conditions. (C) 2004 Elsevier Ltd. All rights reserved.