7-(4-methylpiperazin-1-yl)indolo[2,1-b]quinazoline-6,12-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7-(4-methylpiperazin-1-yl)indolo[2,1-b]quinazoline-6,12-dione
• 化学式: C₂₀H₁₈N₄O₂
• 分子量: 346.389
• InChiKey: QKOWLCOXQALKFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  56.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯靛红 在 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 甲苯 为溶剂， 反应 6.0h， 生成 7-(4-methylpiperazin-1-yl)indolo[2,1-b]quinazoline-6,12-dione
  参考文献：
  名称：

  Discovery of Tryptanthrins as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents

  摘要：

  Plant diseases seriously affect the yield and quality of crops and are difficult to control. Tryptanthrin and its derivatives (tryptanthrins) were synthesized and evaluated for their antiviral activities and fungicidal activities. We found that tryptanthrins have good antiviral activities against tobacco mosaic virus (TMV) for the first time. Most of the tryptanthrins showed higher anti-TMV activities than that of ribavirin (inhibitory rates of 40, 37, and 38% at 500 mu g/mL for inactivation, curative, and protection activities in vivo, respectively). Compound 3n (inhibitory rates of 52, 49, and 54% at 500 mu g/mL for inactivation, curative, and protection activities in vivo, respectively) and compound 14 (inhibitory rates of 51, 48, and 53% at 500 mu g/mL for inactivation, curative, and protection activities in vivo, respectively) emerged as new antiviral lead compounds with excellent antiviral activities. Compound 16 was selected for further antiviral mechanism research, which revealed that compound 16 could inhibit virus assembly by decomposing 20S coat protein (CP) disk. Molecular docking results showed that compounds 3n and 14, which have higher antiviral activities in vivo than that of compound 16, do show stronger interaction with TMV CP. Further fungicidal activity tests showed that tryptanthrins displayed broad-spectrum fungicidal activities, especially for compound 16. These compounds showed good selectivity to Physalospora piricola. In the current study, a small molecular library of tryptanthrin was constructed and the bioactivity spectrum of these compounds was broadened, which lays a foundation for their application in plant protection.

  DOI：

  10.1021/acs.jafc.0c02101

文献信息

• Indolo[2,1-biquinazoline-6,12-dione antibacterial compounds and methods
  申请人：PathoGenesis Corporation

  公开号：US05441955A1

  公开（公告）日：1995-08-15

  Methods, compounds and compositions are provided form inhibiting the growth of pathogenic mycobacteria in vitro and of treatment of pathogenic mycobacterial infections in vivo using indolo[2,1-b]quinazoline-6,12-dione compounds of the formula (I): ##STR1## wherein A, B, C, D, E, F, G and H are independently selected from carbon and nitrogen, or A and B or C and D can be taken together to be nitrogen or sulfur, and the pharmaceutically acceptable salts thereof. The methods, compounds and compositons are particularly useful for inhibiting the growth of Mycobacterium tuberculosis, and may be used alone, or in combination with other anti-Mycobacterium tuberculosis agents, such as isoniazid, rifampin, pyrazinamide, rifabutin, streptomycin and ciprofloxacin, to provide new agents for the treatment of tuberculosis, including multidrug-resistant tuberculosis (MDRTB).

  提供了一种用于体外抑制病原性分枝杆菌生长和用于体内治疗病原性分枝杆菌感染的方法、化合物和组合物，使用式(I)的吲哚并[2,1-b]喹唑啉-6,12-二酮化合物：##STR1## 其中A、B、C、D、E、F、G和H独立地选自碳和氮，或A和B或C和D可以结合在一起成为氮或硫，并且其药学上可接受的盐。这些方法、化合物和组合物特别适用于抑制结核分枝杆菌的生长，并可单独使用，或与其他抗结核分枝杆菌药物（如异烟肼、利福平、吡嗪酰胺、利福布汀、链霉素和环丙沙星）结合使用，以提供用于治疗结核病的新药物，包括多药耐药结核病（MDRTB）。
• Synthesis of substituted tryptanthrin via aryl halides and amines as antitumor and anti-MRSA agents
  作者：Xudong Zheng、Baolong Hou、Rui Wang、Yinyin Wang、Cuiling Wang、Huan Chen、Li Liu、Jilin Wang、Xiumei Ma、Jianli Liu

  DOI：10.1016/j.tet.2019.05.030

  日期：2019.11

  tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione), and its analogues are found to exhibit potent antitumor and anti-MRSA activities. An efficient and convenient method has been developed for the synthesis of tryptanthrin D-ring derivatives through the reaction of substituted tryptanthrins and secondary amines in moderate to good yields. Some of the new compounds exhibited antitumor activities against the human

  发现天然生物碱类胰蛋白酶（吲哚[2,1-b]喹唑啉-6,12-二酮）及其类似物表现出有效的抗肿瘤和抗-MRSA活性。已经开发了一种有效且方便的方法，该方法通过使取代的色胺酮与仲胺反应以中等至良好的产率合成色胺酮D-环衍生物。一些新化合物对人肿瘤细胞系A549，HCT116和MDA-MB-231表现出抗肿瘤活性，低微摩尔水平的平均IC 50值。此外，某些化合物显示出优异的抗MRSA活性，并且比万古霉素更有效，Mu50，RN4220和Newman菌株的MIC值为0.31–1.25μg/ mL。
• Targeting topoisomerase II with trypthantrin derivatives: Discovery of 7-((2-(dimethylamino)ethyl)amino)indolo[2,1-b]quinazoline-6,12-dione as an antiproliferative agent and to treat cancer
  作者：Elena Catanzaro、Nibal Betari、Jose M. Arencibia、Serena Montanari、Claudia Sissi、Angela De Simone、Ivano Vassura、Alan Santini、Vincenza Andrisano、Vincenzo Tumiatti、Marco De Vivo、Dmitri V. Krysko、Marco B.L. Rocchi、Carmela Fimognari、Andrea Milelli

  DOI：10.1016/j.ejmech.2020.112504

  日期：2020.9

  appearance of resistance mechanisms upon treatment with topoII-targeted anticancer drugs. In the present investigation, we report the discovery of a new topoII inhibitor, whose design was based on the structure of the natural product trypthantrin, a natural alkaloidal compound containing a basic indoloquinazoline moiety. This new topoII inhibitor, here numbered compound 5, is found to inhibit topoII with

  几十年来，针对人类拓扑异构酶II（topoII）的药物一直在临床实践中使用。然而，由于继发性恶性肿瘤的出现以及以靶向topoII的抗癌药物治疗后出现的耐药机制，迫切需要新的和更安全的topoII抑制剂。在本研究中，我们报告了一种新的topoII抑制剂的发现，该抑制剂的设计基于天然产物胰蛋白p聚糖的结构，胰蛋白ant呤是一种含有碱性吲哚并喹唑啉部分的天然生物碱化合物。发现这种新的topoII抑制剂（此处编号为化合物5）以26.6± 4.7μM的IC 50抑制topoII 。值得注意的是，化合物5它比模板化合物胰蛋白聚糖更有效，甚至比广泛使用的靶向topoII的临床药物依托泊苷更有效。另外，化合物5还显示出高水溶性，对不同的肿瘤细胞系例如急性白血病，结肠癌和乳腺癌有希望的抗增殖活性。根据这些结果，化合物5代表了开发新的topoII抑制剂作为抗癌治疗剂的有希望的先导。
• USE OF TRYPTANTHRIN COMPOUNDS FOR IMMUNE POTENTIATION
  申请人：VALIANTE Nicholas M.

  公开号：US20120244182A1

  公开（公告）日：2012-09-27

  The invention provides immunostimulatory compositions and methods of administration thereof. Also provided are methods of administering a tryptanthrin compound in an effective amount to enhance the immune response of a subject to an antigen. Also provided are methods of administering an effective amount of a tryptanthrin to stimulate the immune response in a subject for the treatment of cancer. Further provided are methods of administering a tryptanthrin compounds as an immunotherapeutic in the treatment of infectious diseases.

  本发明提供了免疫刺激组合物及其给药方法。还提供了一种给予吲哚丹宁化合物有效量的方法，以增强受体对抗原的免疫反应。还提供了一种给予有效量的吲哚丹宁化合物的方法，以刺激受体对癌症的免疫反应。此外，还提供了将吲哚丹宁化合物作为免疫治疗剂治疗传染病的方法。
• Discovery and Mechanism of Novel 7-Aliphatic Amine Tryptanthrin Derivatives against Phytopathogenic Bacteria
  作者：Xuesha Long、Guanglong Zhang、Haitao Long、Qin Wang、Congyu Wang、Mei Zhu、Wenhang Wang、Chengpeng Li、Zhenchao Wang、Guiping Ouyang

  DOI：10.3390/ijms241310900

  日期：——

  Rice bacterial leaf blight is a destructive bacterial disease caused by Xanthomonas oryzae pv. oryzae (Xoo) that seriously threatens crop yields and their associated economic benefits. In this study, a series of improved dissolubility 7-aliphatic amine tryptanthrin derivatives was designed and synthesized, and their potency in antibacterial applications was investigated. Notably, compound 6e exhibited

  水稻细菌性叶枯病是由米黄单胞菌引起的一种破坏性细菌病害。米曲霉 (Xoo) 严重威胁作物产量及其相关经济效益。在本研究中，设计并合成了一系列溶解度提高的7-脂肪胺色胺酮衍生物，并研究了它们在抗菌应用中的效力。值得注意的是，与阳性对照双甲噻唑 (EC50 = 35.0 μg/mL) 和噻二唑铜 (EC50 = 79.4 μg/mL) 相比，化合物 6e 对 Xoo 表现出优异的活性，EC50 值为 2.55 μg/mL。体内实验表明6e对水稻叶片具有显着的保护作用。暴露后，扫描电镜观察发现细菌形态部分萎缩。此外，6e 增加了细胞内活性氧的积累，引起细胞凋亡和细菌生物膜的形成。所有结果表明6e可能是一种潜在的控制植物病原菌的农用化学杀菌剂。