methyl 11-chloro-5-methyl-5H-indolo[2,3-b]quinoline-2-carboxylate | 1421349-28-1

• 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: methyl 11-chloro-5-methyl-5H-indolo[2,3-b]quinoline-2-carboxylate
• 英文别名: Methyl 11-chloro-5-methyl-5h-indolo[2,3-b]quinoline-2-carboxylate；methyl 11-chloro-5-methylindolo[2,3-b]quinoline-2-carboxylate
• CAS: 1421349-28-1
• 化学式: C₁₈H₁₃ClN₂O₂
• 分子量: 324.766
• InChiKey: FMHTUAOJPRPWAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 11-chloro-5-methyl-5H-indolo[2,3-b]quinoline-2-carboxylate 以 四氢呋喃 为溶剂， 生成 methyl 5-methyl-11-(3-(3-phenylureido)propylamino)-5H-indolo[2,3-b]quinoline-2-carboxylate
  参考文献：
  名称：

  Synthesis and antimalarial testing of neocryptolepine analogues: Addition of ester function in SAR study of 2,11-disubstituted indolo[2,3-b]quinolines

  摘要：

  This report describes the synthesis, and in vitro and in vivo antimalarial evaluations of certain ester-modified neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives. The modifications were carried out by introducing ester groups at the C2 and/or C9 position on the neocryptolepine core and the terminal amino group of the 3-aminopropylamine substituents at the C11 position with a urea/thiourea unit. The antiplasmodial activities of our derivative agents against two different strains (CQS: NF54, and CQR: R1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that the ester modified neocryptolepine derivatives have higher antiplasmodial activities against both strains and a low cytotoxic activity against normal cells. The best results were achieved by compounds 9c and 12b against the NF54 strain with the IC50/SI value as 2.27 nM/361 and 1.81 nM/321, respectively. While against R1 strain, all the tested compounds showed higher activity than the well-known antimalarial drug chloroquine. Furthermore, the compounds were tested for beta-haematin inhibition and 12 were found to be more active than chloroquine (IC50 = 18 mu M). Structure activity relationship studies exposed an interesting linear correlation between polar surface area of the molecule and beta-haematin inhibition for this series. In vivo testing of compounds 7 and 8a against NF54 strain on Plasmodium berghei female mice showed that the introduction of the ester group increased the antiplasmodial activity of the neocryptolepine core substantially. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.072
• 作为产物：
  描述：

  吲哚 在 1,4-二甲基哌嗪 、 吡啶 、 N-氯代丁二酰亚胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二苯醚 、 甲苯 为溶剂， 反应 5.0h， 生成 methyl 11-chloro-5-methyl-5H-indolo[2,3-b]quinoline-2-carboxylate
  参考文献：
  名称：

  11-氨基烷基氨基取代的5 H-吲哚并[2,3-b]喹啉的体外抗增殖活性；通过安装酯取代基改善新隐油菜素的活性

  摘要：

  摘要该研究文章描述了酯基对5-甲基-5 H-吲哚并[2,3- b ]喹啉（新隐油菜籽）衍生物的SAR研究中体外抗增殖活性的影响。从吲哚-3-羧酸酯和N开始合成C-2和/或C-9酯取代的新隐油松-带有酯基的甲基苯胺。在这些酯取代的新隐油松上，在C-11处进一步连接了多个氨基烷基氨基取代基，并通过改变C-11处的取代基以及A和/或D中酯基的位置进行了体外抗增殖测定新隐油环的环。结果表明，通过在C-9位引入酯取代基可以改善药物的抗增殖活性。其中，11-（3-氨基丙基氨基）-5-甲基-5 H-吲哚并[2,3 - b ]喹啉-9-羧酸酯（8b）是最有效的IC 50试剂。0.044μM对人白血病MV4-11细胞株的抗 还描述了药剂在癌细胞系和正常细胞系之间的选择性细胞毒性。二甲基11-（3-氨基丙基氨基）-5-甲基-5 H-吲哚并[2,3 - b ]喹啉-2,9-二羧酸盐（9a）对人结肠癌细胞系HCT

  DOI：

  10.1007/s00044-012-0443-x

文献信息

• Improved Synthesis and Reaction of 11-Chloroneocryptolepines, Strategic Scaffold for Antimalaria Agent, and Their 6-Methyl Congener from Indole-3-carboxylate
  作者：Li Wang、Wen-Jie Lu、Tomohito Odawara、Ryuhei Misumi、Zhen-Wu Mei、Wei Peng、Ibrahim El-Tantawy El-Sayed、Tsutomu Inokuchi

  DOI：10.1002/jhet.1617

  日期：2014.7

  Various 11‐chloro‐5‐methyl‐5H‐indolo[2,3‐b]quinolines (neocryptolepines) with different substituents on the quinoline ring, key intermediates for antimalaria agents, are prepared from the substituted N‐methylanilines, easily accessible by the N‐methylation of anilines, and indole‐3‐carboxylate as a counterpart. This protocol is benign in terms of the reduced number of steps to reach the target, compared

  由取代的N-甲基苯胺制备喹啉环上具有不同取代基的各种11-氯-5-甲基-5 H-吲哚并[2,3- b ]喹啉（新隐油松），它们是抗疟疾药物的关键中间体，可通过以下方法容易地获得苯胺的N-甲基化，以及吲哚-3-羧酸盐的对应物。与使用苯胺的已知方法相比，该方案在减少到达目标的步骤数方面是良性的，并且产品易于纯化。或者，他们的6-甲基同源物由N制备2-芳基氨基吲哚-3-羧酸吲哚部分的甲基化，然后连续环化和氯化。在C11位置的亲核取代反应中，发现11-Chloroneocryptolepines比其6-甲基同类物更具反应性。