3,9-二氯-5-甲基吖啶 | 88914-96-9

• 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
• 中文名称: 3,9-二氯-5-甲基吖啶
• 英文名称: 3,9-dichloro-5-methylacridine
• 英文别名: 4-Methyl-6,9-dichloroacridine；6,9-dichloro-4-methylacridine；3,9-dichloro-5-methyl-acridine；3,9-Dichlor-5-methyl-acridin
• CAS: 88914-96-9
• 化学式: C₁₄H₉Cl₂N
• 分子量: 262.138
• InChiKey: BUXFKVQAZPXFRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 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：

  3,9-二氯-5-甲基吖啶 在 3 A molecular sieve 、 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum

  摘要：

  A parallel synthetic strategy to the 9-aminoacridine scaffold of the classical anti-malarial drug quinacrine (2) is presented. The method features a new route to 9-chloroacridines that utilizes triflates of salicylic acid derivatives, which are commercially available in a variety of substitution patterns. The route allows ready variation of the two diversity elements present in this class of molecules: the tricyclic aromatic heterocyclic core, and the disubstituted diamine sidechain. In this study, a library of 175 compounds was designed, although only 93 of the final products had purities acceptable for screening. Impurity was generally due to incomplete removal of 9-acridones (18), a degradation product of the 9-chloroacridine synthetic intermediates. The library was screened against two strains of Plasmodium falciparum, including a model of the drug-resistant parasite, and six novel compounds were found to have IC50 values in the low nanomolar range. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.017
• 作为产物：
  描述：

  2,4-二氯苯甲酸 在 戊醇 、 铜 、 potassium carbonate 、 三氯氧磷 作用下， 生成 3,9-二氯-5-甲基吖啶
  参考文献：
  名称：

  New Compounds. 2-Arylamino-4-chlorobenzoic Acids and 9-Chloroacridines

  摘要：

  DOI：

  10.1021/ja01195a600

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。
• Formation and molecular structure of the novel acridine substituted uracil derivatiLves
  作者：Michio Kimura、Ichizo Okabayashi

  DOI：10.1002/jhet.5570230363

  日期：1986.5

  The reaction of enamine between 9-chloroacridines and 6-aminouracil derivatives gives the novel acridine substituted uracils, the structure of which has been determined by X-ray crystallography.

  烯胺在9-氯ac啶和6-氨基尿嘧啶衍生物之间的反应产生了新颖的a啶取代的尿嘧啶，其结构已经通过X射线晶体学确定。
• Acridine derivatives. III. Preparation and antitumor activity of the novel acridinyl-substituted uracils.
  作者：Michio KIMURA、Ichizo OKABAYASHI、Akira KATO

  DOI：10.1248/cpb.37.697

  日期：——

  In an investigation of a new class of deoxyribonucleic acid (DNA)-intercalating antitumor agents, novel acridinyl-substituted uracils have been synthesized and evaluated for activity against L1210 leukemia in vivo, and against bacteria and fungus. These compounds were prepared by the novel enamine reaction between 9-chloroacridines and 6-aminouracils. The positional effects of substituents on the acridine

  在对一类新型的插入脱氧核糖核酸（DNA）的抗肿瘤药物的研究中，合成了新的cri啶基取代的尿嘧啶，并评估了其在体内对L1210白血病以及对细菌和真菌的活性。这些化合物是通过9-氯ac啶和6-氨基尿嘧啶之间的新型烯胺反应制备的。取代基在the啶环上的位置效应表明，在the啶环的3或6位带有吸电子基团的化合物活性最高。
• 183. Structure and antimalarial activity. Part I. Some acridine derivatives
  作者：D. Muriel Hall、E. E. Turner

  DOI：10.1039/jr9450000694

  日期：——