6-chloro-11-methyl-11H-indolo[3,2-c]quinoline | 1449414-83-8

• 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: 6-chloro-11-methyl-11H-indolo[3,2-c]quinoline
• 英文别名: 6-Chloro-11-methylindolo[3,2-c]quinoline；6-chloro-11-methylindolo[3,2-c]quinoline
• CAS: 1449414-83-8
• 化学式: C₁₆H₁₁ClN₂
• 分子量: 266.73
• InChiKey: WFOUTVMCHPRXCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-chloro-11-methyl-11H-indolo[3,2-c]quinoline 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 1-(3-(11-methyl-11H-indolo[3,2-c]quinolin-6-ylamino)propyl)-3-phenylurea
  参考文献：
  名称：

  Synthesis and in vitro cytotoxic effect of 6-amino-substituted 11H- and 11Me-indolo[3,2-c]quinolines

  摘要：

  A series of 6-amino-11H- indolo[3,2-c]quinoline derivatives with various substituents on the quinoline ring were synthesized. A methyl group introduced to N-11 of the intermediate 4 to elaborate novel analog 7. The cytotoxic effect of these 6-amino-substituted 11H- and 11-methyl-indolo[3,2-c]quinoline derivatives in vitro were tested against MV4-11 (human leukemia), A549 (non-small cell lung cancer) and HCT116 (colon cancer) and BALB/3T3 (normal murine fibroblasts). All the N-11 methylated compounds significantly increased the cytotoxicity. Compound 7p was most active with the IC50 value of 0.052 mu M against the MV4-11 cell line, and also exhibited a selective activity against A549, HCT116 and BALB/3T3 cell line, with the respective IC50 values of 0.112, 0.007 and 0.083 mu M, which were higher or comparable to those of the anticancer drug doxorubicin HCl. The binding constants of 5g and 7h to salmon fish sperm DNA were also evaluated using UV-vis absorption spectroscopy, indicating intercalation binding with constants of 1.05 x 10(6) L/mol and 4.84 x 10(6) L/mol. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.038
• 作为产物：
  描述：

  靛红 在 sodium hydride 、 溶剂黄146 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 26.0h， 生成 6-chloro-11-methyl-11H-indolo[3,2-c]quinoline
  参考文献：
  名称：

  Regioselective N-Methylation of 6-Chloroindolo[3,2-c]quinolines and Their Amination Reactivity at the C-6 Position

  摘要：

  用 NaH-MeI 处理 6-氯吲哚并[3,2-c]喹啉 6 会导致 N-11 处发生甲基化，生成 8，而 6 与 MeI 反应并加热会生成相应的 5-甲基化喹啉鎓盐，其 SNAr 与水反应会顺利生成 5-甲基吲哚并[3,2-c]喹啉-6-酮 3b。C-6 处的胺化反应性依次为 6 > 11-甲基化的 8。

  DOI：

  10.1246/bcsj.20130063

文献信息

• インドロ［３，２−ｃ］キノリン誘導体、該誘導体の製造方法、ならびに該誘導体を含有する抗マラリア剤および抗がん剤
  申请人：国立大学法人 岡山大学

  公开号：JP2015063476A

  公开（公告）日：2015-04-09

  【課題】抗マラリア活性が高く（特にクロロキン抵抗性のマラリア原虫にも有効であり）かつ安全性の高い抗マラリア剤、および抗腫瘍活性が高くかつ非腫瘍細胞に対する毒性の低い抗がん剤を提供する。【解決手段】下記式（Ａ）で表わされることを特徴とするインドロ[3,2-c]キノリン誘導体（Ａ）またはその製薬学的に許容される塩を有効成分として含有することを特徴とする、抗マラリア剤および抗がん剤。式（Ａ）中、Ｒ1はハロゲン原子等の所定の置換基、Ｒ2はアミノアルキルアミノ基等の所定の置換基、Ｒ3はアルキル基、Ｒ4はハロゲン原子等の所定の置換基を表し、ｎは１〜４の整数、ｍは０〜４の整数である。【選択図】なし

  提供高抗疟活性（尤其对氯喹耐药疟原虫有效）且安全性高的抗疟药物，以及具有高抗肿瘤活性且对非肿瘤细胞毒性低的抗癌药物。具有以下式（A）所示的印度吲哚[3,2-c]喹啉衍生物（A）或其制药学上可接受的盐作为有效成分的抗疟药物和抗癌药物。在式（A）中，R1代表卤原子等特定的取代基，R2代表氨基烷基氨基等特定的取代基，R3代表烷基，R4代表卤原子等特定的取代基，n为1至4的整数，m为0至4的整数。【选择图】无
• Synthesis of indolo- and benzothieno[3,2-<i>c</i>]quinolines <i>via</i> POCl₃ mediated tandem cyclization of <i>o</i>-alkynylisocyanobenzenes derived from <i>o</i>-alkynyl-<i>N</i>-phenylformamides
  作者：Thikhamporn Uppalabat、Anyawan Tapdara、Onnicha Khaikate、Thanapat Worakul、Panida Surawatanawong、Pawaret Leowanawat、Darunee Soorukram、Vichai Reutrakul、Jatuporn Meesin、Chutima Kuhakarn

  DOI：10.1039/d2nj02791g

  日期：——

  A synthesis of indolo[3,2-c]quinolines and benzothieno[3,2-c]quinolines has been developed employing o-alkynyl-N-phenylformamide derivatives as the substrates. The reaction proceeded via a tandem process involving POCl3-assisted intramolecular cyclization of the firstly formed o-alkynylisocyanobenzenes, leading to the desired products in moderate to high yields. Furthermore, the reaction is efficient

  使用邻炔基-N-苯基甲酰胺衍生物作为底物，开发了吲哚并[3,2- c ]喹啉和苯并噻吩并[3,2- c ]喹啉的合成方法。该反应通过串联过程进行，包括 POCl 3辅助的分子内环化首先形成的邻炔基异氰基苯，以中等至高产率产生所需的产物。此外，该反应在克级上是有效的，并且通过胺化、Suzuzki-Miyaura 反应和 Heck 交叉偶联对产物进行了结构修饰。几种选定吲哚的光物理性质[3,2- c] 喹啉通过紫外可见和荧光光谱进行了研究，并使用时间相关的 DFT 计算进行了合理化。
• Synthesis, β-haematin inhibition, and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11
  作者：Ning Wang、Kathryn J. Wicht、Kento Imai、Ming-qi Wang、Tran Anh Ngoc、Ryo Kiguchi、Marcel Kaiser、Timothy J. Egan、Tsutomu Inokuchi

  DOI：10.1016/j.bmc.2014.03.030

  日期：2014.5

  A series of indolo[3,2-c]quinolines were synthesized by modifying the side chains of the omega-aminoalkylamines at the C6 position and introducing substituents at the C2 position, such as F, Cl, Br, Me, MeO and NO2, and a methyl group at the N11 position for an SAR study. The in vitro antiplasmodial activities of the derivative agents against two different strains (CQS: NF54 and CQR: K1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that compounds 6k and 6l containing the branched methyl groups of 3-aminopropylamino at C6 with a Cl atom at C2 exhibited a very low cytotoxicity with IC50 values above 4000 nM, high antimalarial activities with IC50 values of about 11 nM for CQS (NF54), IC50 values of about 17 nM for CQR (K1), and RI resistance indices of 1.6. Furthermore, the compounds were tested for beta-haematic inhibition, and QSAR revealed an interesting linear correlation between the biological activity of CQS (NF54) and three contributing factors, namely solubility, hydrophilic surface area, and beta-haematin inhibition for this series. In vivo testing of 6l showed a reduction in parasitaemia on day 4 with an activity of 38%. (C) 2014 Elsevier Ltd. All rights reserved.