2,2'-dichloro-N-methyl-5'-nitroacetanilide | 449760-68-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,2'-dichloro-N-methyl-5'-nitroacetanilide
• 英文别名: 2-chloro-N-(2-chloro-5-nitrophenyl)-N-methylacetamide
• CAS: 449760-68-3
• 化学式: C₉H₈Cl₂N₂O₃
• 分子量: 263.08
• InChiKey: IMXHPIVHUMZFRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2'-dichloro-N-methyl-5'-nitroacetanilide 以 硝基甲烷 、 丙酮 为溶剂， 反应 76.0h， 生成 4-[2'-(chloromethyl)phenethyl]-1-methyl-7-nitro-3,4-dihydro-1H-quinoxalin-2-one
  参考文献：
  名称：

  Synthesis of quinoxaline derivatives from substituted acetanilides through intramolecular quaternization reactions

  摘要：

  对2-二烷基氨基-2′-卤烷基和2-氯-2′-(二烷基氨基)乙酰苯胺环化为喹喏啉衍生物的反应进行了详细研究。根据取代基和实验条件，这些反应通过分子内芳香族亲核或脂肪族亲核取代反应进行，分别生成3-氧喹喏啉盐，或者在消除烷基氯之后生成喹喏啉-2-酮。还描述了一些关于芳基卤化物与三氟氨基化物的分子内季铵化的新案例。

  DOI：

  10.1039/b109725c
• 作为产物：
  描述：

  toluene-4-sulfonic acid-(2-chloro-N-methyl-5-nitro-anilide) 以 丙酮 为溶剂， 反应 3.0h， 生成 2,2'-dichloro-N-methyl-5'-nitroacetanilide
  参考文献：
  名称：

  Synthesis of quinoxaline derivatives from substituted acetanilides through intramolecular quaternization reactions

  摘要：

  对2-二烷基氨基-2′-卤烷基和2-氯-2′-(二烷基氨基)乙酰苯胺环化为喹喏啉衍生物的反应进行了详细研究。根据取代基和实验条件，这些反应通过分子内芳香族亲核或脂肪族亲核取代反应进行，分别生成3-氧喹喏啉盐，或者在消除烷基氯之后生成喹喏啉-2-酮。还描述了一些关于芳基卤化物与三氟氨基化物的分子内季铵化的新案例。

  DOI：

  10.1039/b109725c

文献信息

• A Quinoxaline Derivative as a Potent Chemotherapeutic Agent, Alone or in Combination with Benznidazole, against Trypanosoma cruzi
  作者：Jean Henrique da Silva Rodrigues、Tânia Ueda-Nakamura、Arlene Gonçalves Corrêa、Diego Pereira Sangi、Celso Vataru Nakamura

  DOI：10.1371/journal.pone.0085706

  日期：——

  Background Chagas’ disease is a condition caused by the protozoan Trypanosoma cruzi that affects millions of people, mainly in Latin America where it is considered endemic. The chemotherapy for Chagas disease remains a problem; the standard treatment currently relies on a single drug, benznidazole, which unfortunately induces several side effects and it is not successful in the cure of most of the chronic patients. In order to improve the drug armamentarium against Chagas’ disease, in the present study we describe the synthesis of the compound 3-chloro-7-methoxy-2-(methylsulfonyl) quinoxaline (quinoxaline 4) and its activity, alone or in combination with benznidazole, against Trypanosoma cruzi in vitro. Methodology/Principal Findings Quinoxaline 4 was found to be strongly active against Trypanosoma cruzi Y strain and more effective against the proliferative forms. The cytotoxicity against LLCMK2 cells provided selective indices above one for all of the parasite forms. The drug induced very low hemolysis, but its anti-protozoan activity was partially inhibited when mouse blood was added in the experiment against trypomastigotes, an effect that was specifically related to blood cells. A synergistic effect between quinoxaline 4 and benznidazole was observed against epimastigotes and trypomastigotes, accompanied by an antagonistic interaction against LLCMK2 cells. Quinoxaline 4 induced several ultrastructural alterations, including formations of vesicular bodies, profiles of reticulum endoplasmic surrounding organelles and disorganization of Golgi complex. These alterations were also companied by cell volume reduction and maintenance of cell membrane integrity of treated-parasites. Conclusion/Significance Our results demonstrated that quinoxaline 4, alone or in combination with benznidazole, has promising effects against all the main forms of T. cruzi. The compound at low concentrations induced several ultrastructural alterations and led the parasite to an autophagic-like cell death. Taken together these results may support the further development of a combination therapy as an alternative more effective in Chagas’ disease treatment.

  背景 查加斯病是由原生动物克氏锥虫（Trypanosoma cruzi）引起的一种疾病，影响数百万人，主要集中在拉丁美洲，被认为是地方性疾病。查加斯病的化疗仍然是一个问题；目前的标准治疗依赖于一种单一药物苯尼达唑，但不幸的是，它会引起多种副作用，并且对大多数慢性患者的治愈效果不佳。为了改善对查加斯病的药物武器库，本研究描述了化合物3-氯-7-甲氧基-2-(甲基磺酰基)喹喔啉（喹喔啉4）的合成及其在体外对克氏锥虫的活性，单独使用或与苯尼达唑联合使用。 方法/主要发现 喹喔啉4对克氏锥虫Y株表现出强烈活性，并对增殖形态的效果更为显著。对LLCMK2细胞的细胞毒性显示出所有寄生虫形态的选择性指数均大于1。该药物诱导的溶血非常低，但在针对锥虫时，加入小鼠血液后其抗原生动物活性部分受到抑制，这一效应与血液细胞特定相关。观察到喹喔啉4与苯尼达唑在对表慢性虫及锥虫时表现出协同效应，同时在LLCMK2细胞上则表现出拮抗作用。喹喔啉4诱导了多种超微结构改变，包括囊泡体的形成、环状内质网包围细胞器的轮廓以及高尔基体的解构。这些改变也伴随着细胞体积缩小和处理寄生虫细胞膜完整性的维持。 结论/重要性 我们的结果表明，喹喔啉4无论单独使用还是与苯尼达唑联用，对T. cruzi的所有主要形态均具有良好的效果。该化合物在低浓度下诱导了多种超微结构改变，并导致寄生虫发生类似自噬的细胞死亡。综合这些结果可能支持进一步开发作为查加斯病治疗的更有效替代方案的联合疗法。
• Synthesis of quinoxaline derivatives from substituted acetanilides through intramolecular quaternization reactions
  作者：Sonia de Castro、Roberto Chicharro、Vicente J. Arán

  DOI：10.1039/b109725c

  日期：2002.3.8

  The cyclization of 2-dialkylamino-2′-halogeno- and 2-chloro-2′-(dialkylamino)acetanilides to quinoxaline derivatives has been studied in detail. These reactions proceed, respectively, through intramolecular aromatic nucleophilic or aliphatic nucleophilic substitution reactions and depending on the substituents and the experimental conditions, they lead to 3-oxoquinoxalinium salts or, after an alkyl chloride elimination, to quinoxalin-2-ones. Some new cases of the little known intramolecular quaternization of tertiary amines with aryl halides are described.

  对2-二烷基氨基-2′-卤烷基和2-氯-2′-(二烷基氨基)乙酰苯胺环化为喹喏啉衍生物的反应进行了详细研究。根据取代基和实验条件，这些反应通过分子内芳香族亲核或脂肪族亲核取代反应进行，分别生成3-氧喹喏啉盐，或者在消除烷基氯之后生成喹喏啉-2-酮。还描述了一些关于芳基卤化物与三氟氨基化物的分子内季铵化的新案例。