N¹-(11H-indolo[3,2-c]quinolin-6-yl)propane-1,3-diamine | 1593735-19-3

• 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: N¹-(11H-indolo[3,2-c]quinolin-6-yl)propane-1,3-diamine
• 英文别名: N'-(11H-indolo[3,2-c]quinolin-6-yl)propane-1,3-diamine
• CAS: 1593735-19-3
• 化学式: C₁₈H₁₈N₄
• 分子量: 290.368
• InChiKey: UZSFSIFJNVMYBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  66.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N¹-(11H-indolo[3,2-c]quinolin-6-yl)propane-1,3-diamine 、 苯磺酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以91%的产率得到N-(3-(11H-indolo[3,2-c]quinolin-6-ylamino)propyl)benzenesulfonamide
  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：

  靛红 在 溶剂黄146 、 三氯氧磷 作用下， 反应 12.33h， 生成 N¹-(11H-indolo[3,2-c]quinolin-6-yl)propane-1,3-diamine
  参考文献：
  名称：

  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

  摘要：

  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

  公开号：

  JP2015063476A

文献信息

• Design, Synthesis, and Biological Evaluation of Artemisinin-Indoloquinoline Hybrids as Potent Antiproliferative Agents
  作者：Li Wang、Marta Świtalska、Ning Wang、Zhen-Jun Du、Yuta Fukumoto、Nguyen Diep、Ryo Kiguchi、Junzo Nokami、Joanna Wietrzyk、Tsutomu Inokuchi

  DOI：10.3390/molecules191119021

  日期：——

  A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a–7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested. Nearly all of the tested compounds (7–9, except for compounds 7d and 7e against HCT-116) showed an increased antitumor activity against HCT-116 and A549 cell lines when compared to the dihydroartemisinin control. Especially for the artemisinin-indoloquinoline hybrid 8, with an 11-aminopropylamino-10H-indolo[3,2-b]quinoline substituent, the antiproliferative activity against the A549 cell line had improved more than ten times. The IC50 value of hybrid 8 against A549 cell lines was decreased to 1.328 ± 0.586 μM, while dihydroartemisin showed IC50 value of >20 µM in the same cell line. Thus, these results have proven that the strategy of introducing a planar basic fused aromatic moiety, such as the indoloquinoline skeleton, could improve the antiproliferative activity and selectivity towards cancer cell lines.

  我们设计并合成了一系列青蒿素-吲哚喹啉杂化物，试图开发出强效且具有选择性的抗肿瘤药物。制备并鉴定了化合物 7a-7f、8 和 9。测试了它们在体外对 MV4-11、HCT-116、A549 和 BALB/3T3 细胞系的抗增殖活性。与双氢青蒿素对照组相比，几乎所有受测化合物（7-9，除化合物 7d 和 7e 对 HCT-116 的作用外）对 HCT-116 和 A549 细胞株的抗肿瘤活性都有所提高。特别是青蒿素-吲哚喹啉杂交化合物 8，其 11-氨基丙基氨基-10H-吲哚并[3,2-b]喹啉取代基对 A549 细胞株的抗增殖活性提高了 10 倍以上。杂交 8 对 A549 细胞株的 IC50 值降至 1.328 ± 0.586 μM，而双氢青蒿素对同一细胞株的 IC50 值大于 20 µM。因此，这些结果证明，引入平面碱性融合芳香分子（如吲哚喹啉骨架）的策略可以提高抗癌细胞株的抗增殖活性和选择性。
• Synthesis and evaluation of artesunate–indoloquinoline hybrids as antimalarial drug candidates
  作者：Ning Wang、Kathryn J. Wicht、Elkhabiry Shaban、Tran Anh Ngoc、Ming-Qi Wang、Ikuya Hayashi、Md. Imran Hossain、Yoshihiko Takemasa、Marcel Kaiser、Ibrahim El Tantawy El Sayed、Timothy J. Egan、Tsutomu Inokuchi

  DOI：10.1039/c4md00091a

  日期：——

  individual, non-hybridized compounds. Furthermore, these hybrids were stronger β-haematin inhibitors than the corresponding molecules from which they were derived. The most effective antimalarial hybrid showed an IC50 value of 0.45 nM against the CQS strain. At the same time this hybrid also showed effective activity against the CQR strain, with an IC50 value of 0.42 nM and an RI value of 0.93. With the

  合成了青蒿琥酯-吲哚[2,3- b ]喹啉，–indolo [3,2- c ]喹啉和–indolo [3,2- b ]喹啉的杂种，并筛选了它们对两种不同疟疾菌株的抗疟原虫活性（ CQS和CQR）及其对正常细胞的细胞毒活性进行了评估。相对于单独的非杂交化合物，所有合成的杂种均显示出降低的细胞毒性和增强的抗疟活性。此外，这些杂种比它们衍生自的相应分子是更强的β-血红素抑制剂。最有效的抗疟杂种表现出IC 50CQS菌株的0.45 nM值。同时，该杂种还显示出对CQR菌株的有效活性，IC 50值为0.42 nM，RI值为0.93。将青蒿琥酯-吲哚并[2,3- b ]喹啉的剂量设定为连续10天每天连续10天，剂量为10 mg kg -1时，第4天的寄生虫血症显着降低，抗寄生虫活性为89.6％，平均小鼠存活时间为7.7天。
• 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.
• 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.
• 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