5,6-dihydro-2-methoxy-6-oxo-11H-indolo[3,2-c]quinoline | 649748-96-9

• 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
• 英文名称: 5,6-dihydro-2-methoxy-6-oxo-11H-indolo[3,2-c]quinoline
• 英文别名: 2-methoxy-5,11-dihydro-6H-indolo[3,2-c]quinolin-6-one
• CAS: 649748-96-9
• 化学式: C₁₆H₁₂N₂O₂
• 分子量: 264.283
• InChiKey: YRLDGIJJMDYYIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  57.88
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  5,6-dihydro-2-methoxy-6-oxo-11H-indolo[3,2-c]quinoline 在 三氯氧磷 作用下， 反应 8.0h， 生成 6-chloro-2-methoxy-11H-indolo[3,2-c]quinoline
  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：

  N-(4-methoxyphenyl)-1H-indole-3-carboxamide 在 potassium phosphate 、 palladium(II) trifluoroacetate 、 copper diacetate 、 三甲基乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以18 %的产率得到5,6-dihydro-2-methoxy-6-oxo-11H-indolo[3,2-c]quinoline
  参考文献：
  名称：

  钯催化 N-苯基-1H-吲哚-3-甲酰胺双 C-H 活化合成 5,11-二氢-6H-吲哚[3,2-c]喹啉-6-酮

  摘要：

  在本文中，我们报道了钯催化的N-苯基-1H-吲哚-3-甲酰胺的双C-H活化，用于合成5,11-二氢-6H-吲哚并[3,2- c ]喹啉-6个。最佳反应条件为：20 mol%的Pd(TFA) 2为催化剂，2.0当量的Cu(OAc) 2为氧化剂，1.0当量的K 3 PO 4为碱，3.0当量的PivOH为反应剂。添加剂 DMF/二恶烷 (1:9)。当在 120 °C 下进行 24 小时时，该反应可以以中等至优异的收率提供 19 种目标吲哚喹啉酮，包括N , N '-二甲基化和N , N '-未取代的产物，这些产物是通过报道的 C-H 活化无法获得的方法论。双C-H活化反应也适用于N-苯基-1H-吲哚-2-甲酰胺并形成相应的5,7-二氢-6H-吲哚[2,3- c ]喹啉-6-酮。基于对照实验和文献的数据，提出了一种合理的反应机制来解释这种转变。

  DOI：

  10.1002/jccs.202300325

文献信息

• Copper(I)-Catalyzed Nitrile-Addition/<i>N</i>-Arylation Ring-Closure Cascade: Synthesis of 5,11-Dihydro-6<i>H</i>-indolo[3,2-<i>c</i>]quinolin-6-ones as Potent Topoisomerase-I Inhibitors
  作者：Wen-Yun Hsueh、Ying-Shuan E. Lee、Min-Sian Huang、Chin-Hung Lai、Yu-Sheng Gao、Jo-Chu Lin、Yu-Fen Chen、Chih-Lin Chang、Shan-Yen Chou、Shyh-Fong Chen、Yann-Yu Lu、Lien-Hsiang Chang、Shu Fu Lin、Yu-Hsiang Lin、Pi-Chen Hsu、Win-Yin Wei、Ya-Chi Huang、Yi-Feng Kao、Li-Wei Teng、Hung-Huang Liu、Ying-Chou Chen、Ta-Tung Yuan、Ya-Wen Chan、Po-Hsun Huang、Yu-Ting Chao、Shin-Yi Huang、Bo-Han Jian、Hsin-Yi Huang、Sheng-Chuan Yang、Tzu-Hao Lo、Guan-Ru Huang、Shao-Yun Wang、Her-Sheng Lin、Shih-Hsien Chuang、Jiann-Jyh Huang

  DOI：10.1021/acs.jmedchem.0c00727

  日期：2021.2.11

  present a copper(I)-catalyzed nitrile-addition/N-arylation ring-closure cascade for the synthesis of 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones from 2-(2-bromophenyl)-N-(2-cyanophenyl)acetamides. Using CuBr and t-BuONa in dimethylformamide (DMF) as the optimal reaction conditions, the cascade reaction gave the target products, in high yields, with a good substrate scope. Application of the cascade reaction

  在本文中，我们提出了一种铜（I）催化的腈加成/ N-芳基化闭环级联反应，用于合成5,11-二氢-6 H-吲哚并[3,2 - c ]喹啉-6-酮。由2-（2-溴苯基）-N-（2-氰基苯基）乙酰胺。使用二甲基甲酰胺（DMF）中的CuBr和t- BuONa作为最佳反应条件，级联反应可高收率得到目标产物，并具有良好的底物范围。级联反应的应用已证明在生物碱异隐油菜素的简明总合成中。级联反应产物的进一步优化导致3-氯-5,12-双[2-（二甲基氨基）乙基] -5,12-二氢-6 H- [1,3]二氧杂环戊[4'，5' ：5,6] indolo [3,2- c] quinolin-6-one（2k），表现出特征性的DNA拓扑异构酶-I抑制作用机制，并具有强大的体外抗癌活性。化合物2k主动抑制ARC-111和SN-38耐药的HCT-116细胞，并在携带人HCT-116和SJCRH30异种移植物的小鼠中显示
• 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.
• Mulwad; Lohar, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2003, vol. 42, # 8, p. 1937 - 1942
  作者：Mulwad、Lohar

  DOI：——

  日期：——