2,6-dichloro-11H-indolo[3,2-c]quinoline | 483995-53-5

• 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: 2,6-dichloro-11H-indolo[3,2-c]quinoline
• CAS: 483995-53-5
• 化学式: C₁₅H₈Cl₂N₂
• 分子量: 287.148
• InChiKey: FEOWFGSSKVNJLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 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：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2,6-dichloro-11H-indolo[3,2-c]quinoline 以 四氢呋喃 为溶剂， 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：

  2-chloro-5,11-dihydro-6H-indolo[3,2-c]quinolin-6-one 在 三氯氧磷 作用下， 生成 2,6-dichloro-11H-indolo[3,2-c]quinoline
  参考文献：
  名称：

  Ruthenium− and Osmium−Arene Complexes of 2-Substituted Indolo[3,2-c]quinolines: Synthesis, Structure, Spectroscopic Properties, and Antiproliferative Activity

  摘要：

  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.

  DOI：

  10.1021/om101004z

文献信息

• 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.
• Synthesis and cytotoxic activity evaluation of indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones and 6-anilinoindoloquinoline derivatives
  作者：Yeh-Long Chen、Chao-Ho Chung、I.-Li Chen、Po-Hsu Chen、Haw-Yaun Jeng

  DOI：10.1016/s0968-0896(02)00111-6

  日期：2002.8

  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.
• Ruthenium- and osmium-arene complexes of 8-substituted indolo[3,2-c]quinolines: Synthesis, X-ray diffraction structures, spectroscopic properties, and antiproliferative activity
  作者：Lukas K. Filak、Simone Göschl、Stefanie Hackl、Michael A. Jakupec、Vladimir B. Arion

  DOI：10.1016/j.ica.2012.06.004

  日期：2012.12

  Six novel ruthenium(II)- and osmium(II)-arene complexes with indoloquinoline modified ligands containing methyl and halo substituents in position 8 of the molecule backbone have been synthesised and comprehensively characterised by spectroscopic methods (H-1, C-13 NMR, UV-Vis), ESI mass spectrometry and X-ray crystallography. Binding of indoloquinolines to a metal-arene scaffold makes the products soluble enough in biological media to allow for assaying their antiproliferative activity. The complexes were tested in three human cancer cell lines, namely A549 (non-small cell lung cancer), SW480 (colon carcinoma) and CH1 (ovarian carcinoma), yielding IC50 values in the 10(-6)-10(-7) M concentration range after continuous exposure for 96 h. Compounds with halo substituents in position 8 are more effective cytotoxic agents in vitro than the previously reported species halogenated in position 2 of the indoloquinoline backbone. High antiproliferative activity of both series of substances may be due at least in part to their potential to act as DNA intercalators. (C) 2012 Elsevier B.V. All rights reserved.
• 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.
• 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.