2-chloro-5,11-dihydro-6H-indolo[3,2-c]quinolin-6-one | 483995-48-8

• 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: 2-chloro-5,11-dihydro-6H-indolo[3,2-c]quinolin-6-one
• 英文别名: 2-chloro-11H-indolo[3,2-c]quinolin-6-ol；2-chloro-5,11-dihydroindolo[3,2-c]quinolin-6-one
• CAS: 483995-48-8
• 化学式: C₁₅H₉ClN₂O
• 分子量: 268.702
• InChiKey: JBWNGLUFOQPPBL-UHFFFAOYSA-N

物化性质

• 熔点：
  >360 °C
• 沸点：
  426.4±28.0 °C(Predicted)
• 密度：
  1.468±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-chloro-5,11-dihydro-6H-indolo[3,2-c]quinolin-6-one 在 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 生成 1-(3-(2-chloro-11H-indolo[3,2-c]quinolin-6-ylamino)propyl)-3-phenylurea
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2014.03.030
• 作为产物：
  描述：

  6-chloro-4-(N'-cyclohexylidenehydrazino)quinolin-2(1H)-one 在 palladium on activated charcoal 作用下， 以 二苯醚 为溶剂， 反应 3.5h， 以82%的产率得到2-chloro-5,11-dihydro-6H-indolo[3,2-c]quinolin-6-one
  参考文献：
  名称：

  Synthesis and cytotoxic activity evaluation of indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones and 6-anilinoindoloquinoline derivatives

  摘要：

  Certain indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones 4a,b, 6, 8, 16a-c and 6-anilinoindoloquinoline derivatives 10a,b, 11a,b, 12a,b have been synthesized and evaluated in vitro against a 3-cell lines panel consisting of MCF7 (Breast), NCI-H460 (Lung), and SF-268 (CNS). Those active compounds 4a,b, 6, 8, 10a,b, 11a,b, 12a,b were then evaluated in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results have shown that cytotoxicity decreases in the order of 6-anilinoindoloquinolines>indoloquinolin-2(1H)-ones>pyrroloquinolin-2(1H)-ones>benzofuroquinolin-2(1H)-ones. Among them, 1-[3-(11H-indolo[3,2-c]quinolin-6ylamino)phenyl]ethanone oxime hydrochloride (14a) and its 2-chloro derivative (11b) were most active, with mean GI(50) values of 1.70 and 1.35 muM, respectively. Both compounds 11a,b were also found to inhibit the growth of SNB-75 (CNS cancer cell) with a GI(50) value of less than 0.01 muM, and, therefore, were selected for further evaluation for in vivo antitumor activity. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(02)00111-6

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
• Studies of the reactions between indole-2,3-diones (isatins) and 2-aminobenzylamine
  作者：Jan Bergman、Robert Engqvist、Claes Stålhandske、Hans Wallberg

  DOI：10.1016/s0040-4020(02)01647-2

  日期：2003.2

  yields. A proposed mechanism involving initial formation of a spiro compound is given. This isolable intermediate subsequently rearranges via a sequential isocyanate ring opening and a cyclisation process to a urea derivative which finally cyclized to the indolo[3,2-c]quinolin-6-ones. The urea derivative could be prepared separately and cyclized selectively to indolo[3,2-c]quinolin-6-one. Reaction of N-acetylisatin

  等摩尔量的2-氨基苄胺和靛红在乙酸中的回流以良好的产率产生了吲哚[3，2 - c ]喹啉-6-酮。提出了一种涉及螺环化合物初始形成的机制。该可分离的中间体随后通过顺序的异氰酸酯开环和环化过程重排为脲衍生物，该脲衍生物最终环化为吲哚[3，2 - c ]喹啉-6-酮。尿素衍生物可单独制备并选择性环化为吲哚[3,2- c]喹啉-6一。N-乙酰基Isatin与2-氨基苄基胺在室温下反应生成1,4-苯并二氮杂酮3-（2-乙酰氨基苯基）-1,5-二氢-1,4-苯并二氮杂-2-酮，而其异构体2（2-乙酰氨基苯并室温下由2-（2-乙酰氨基苯基）-N-（2-氨基苄基）-2-氧乙酰胺在乙酸中获得）-4，5-二氢-1，4-苯并二氮杂-3-酮。
• CuI-catalyzed photochemical or thermal reactions of 3-(2-azidobenzylidene)lactams. Application to the synthesis of fused indoles
  作者：Zongjun Shi、Yuwei Ren、Bing Li、Shenci Lu、Wei Zhang

  DOI：10.1039/c001715a

  日期：——

  afforded fused indoles such as indolo[3,2-c]quinolin-6-ones, pyrido[4,3-b]indol-1-ones and other similar compounds in moderate to high yields via cyclization-ring expansion reactions. The photolytic process was much more facile than the thermal process and could be further improved by addition of CuI.

  3-（2-叠氮基亚苄基）-内酰胺的光化学或热反应提供了稠合的吲哚，例如吲哚[3,2-c]喹啉-6-酮，吡啶并[4,3-b]吲哚-1-酮和其他类似化合物通过环化环扩环反应以中等到高收率。光解过程比热过程容易得多，可以通过添加CuI进一步改善。
• Synthesis and in vitro cytotoxic effect of 6-amino-substituted 11H- and 11Me-indolo[3,2-c]quinolines
  作者：Ning Wang、Marta Świtalska、Ming-Yu Wu、Kento Imai、Tran Anh Ngoc、Cui-Qing Pang、Li Wang、Joanna Wietrzyk、Tsutomu Inokuchi

  DOI：10.1016/j.ejmech.2014.03.038

  日期：2014.5

  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.
• Ruthenium− and Osmium−Arene Complexes of 2-Substituted Indolo[3,2-<i>c</i>]quinolines: Synthesis, Structure, Spectroscopic Properties, and Antiproliferative Activity
  作者：Lukas K. Filak、Gerhard Mühlgassner、Felix Bacher、Alexander Roller、Mathea Sophia Galanski、Michael A. Jakupec、Bernhard K. Keppler、Vladimir B. Arion

  DOI：10.1021/om101004z

  日期：2011.1.24

  The synthesis of new modified indolo[3,2-c]quinoline ligands L-1-L-8 with metal-binding sites is reported. By coordination to ruthenium- and osmium-arene moieties 16 complexes of the type [(eta(6)-p-cymene)M(L)Cl]Cl (1a,b-8a,b), where M is Ru-II or Os-II and L is L-1-L-8, have been prepared. All compounds were comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, IR, UV-vis, and NMR spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction (2a, 4a, 4b, 5a, 7a, and 7b). The complexes were tested for antiproliferative activity in vitro in three human cancer cell lines, namely, CH1 (ovarian carcinoma), SW480 (colon adenocarcinoma), and A549 (non-small-cell lung cancer), yielding IC50 values in the submicromolar or low micromolar range.