6-(hydroxyimino)indolo[2,1-b]quinazolin-12(6H)-one | 483349-97-9

• 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: 6-(hydroxyimino)indolo[2,1-b]quinazolin-12(6H)-one
• 英文别名: indolo(2,1-b)quinazoline-6,12-dion-6-oxime；tryptanthrin-6-oxime；6–(hydroxyimino)indolo[2,1-b]quinazolin-12(6H)-one；6-oximotryptanthrin
• CAS: 483349-97-9
• 化学式: C₁₅H₉N₃O₂
• 分子量: 263.255
• InChiKey: PMNWPSRSXHKOQI-UHFFFAOYSA-N

物化性质

• 沸点：
  523.9±33.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.93
• 重原子数：
  20.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.48
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [RuCl2(benzene)]2 、 6-(hydroxyimino)indolo[2,1-b]quinazolin-12(6H)-one 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以88%的产率得到
  参考文献：
  名称：

  芳烃-钌 (II) 与四环肟衍生物的配合物：合成、结构和对人乳腺癌细胞的抗增殖活性

  摘要：

  六种新的芳烃-钌 (II) 配合物，含有两种不同的 η 6 -芳烃配体 - 苯和六甲基苯，以及茚并喹喔啉酮肟类似物 (11 H -茚并[1,2- b ]quinoxalin-11-one oxime, 6 H -indeno[ 1,2- b ]pyrido[3,2- e ]pyrazin-6-one oxime 和 6-(hydroxyimino)indolo[2,1- b ]quinazolin-12(6 H )-one oxime (tryptanthrin-6-oxime )) 作为 N,N'- 螯合配体的报道。通过元素分析、IR、UV-VIS、1 H 和13对配合物进行表征C NMR光谱和单晶X射线结构分析。配合物采用半夹心“钢琴凳”几何形状，肟配体呈阴离子形式，钌 (II) 中心配位一个芳烃、一个 N, N-二齿肟和一个氯化物配体。非共价分子间相互作用的计算分析揭示了肟氧原子与肟

  DOI：

  10.1016/j.ica.2022.120879
• 作为产物：
  描述：

  (1H-indol-1-yl)(2-nitrophenyl)methanone 在 吡啶 、 盐酸 、 盐酸羟胺 、 氧气 、 铁粉 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 11.0h， 生成 6-(hydroxyimino)indolo[2,1-b]quinazolin-12(6H)-one
  参考文献：
  名称：

  可见光诱导的 (2-氨基苯基)(1H-吲哚-1-基) 甲酮的有氧分子内环化：直接获得具有生物活性的色胺酮及其衍生物

  摘要：

  已开发出可见光诱导的温和、过渡金属、碱和无光催化剂的绿色方案，用于色胺酮及其衍生物的合成。本反应与范围广泛的底物相容，产率从好到高。此外，首次通过氰乙酸的脱羧加成实现了色胺酮衍生物的新合成转化。该反应通过可见光诱导的底物和氧气之间的单电子转移进行，然后在不使用外部光催化剂的情况下进行分子内环化。

  DOI：

  10.1002/adsc.202300195

文献信息

• Synthesis, biological evaluation, and molecular modeling of 11H-indeno[1,2-b]quinoxalin-11-one derivatives and tryptanthrin-6-oxime as c-Jun N-terminal kinase inhibitors
  作者：Igor A. Schepetkin、Andrei I. Khlebnikov、Andrei S. Potapov、Anastasia R. Kovrizhina、Vladislava V. Matveevskaya、Maxim L. Belyanin、Dmitriy N. Atochin、Svitlana O. Zanoza、Nadiya M. Gaidarzhy、Sergiy A. Lyakhov、Liliya N. Kirpotina、Mark T. Quinn

  DOI：10.1016/j.ejmech.2018.10.023

  日期：2019.1

  pathologic processes. We synthesized novel 11H-indeno[1,2-b]quinoxalin-11-one oxime analogs and tryptanthrin-6-oxime (indolo[2,1-b]quinazoline-6,12-dion-6-oxime) and evaluated their effects on JNK activity. Several compounds exhibited sub-micromolar JNK binding affinity and were selective for JNK1/JNK3 versus JNK2. The most potent compounds were 10c (11H-indeno[1,2-b]quinoxalin-11-one O-(O-ethylcarboxymethyl)

  c-Jun N末端激酶（JNK）在许多生理和病理过程中起着核心作用。我们合成了新型11H-茚并[1,2-b]喹喔啉-11-一肟类似物和色胺素6-肟（吲哚[2,1-b]喹唑啉-6,12-dion-6-肟），并对其进行了评估。对JNK活性的影响。几种化合物表现出亚微摩尔的JNK结合亲和力，对JNK1 / JNK3和JNK2具有选择性。最有效的化合物是10c（11H-茚并[1,2-b]喹喔啉-11-一个O-（O-乙基羧甲基）肟）和色胺酮-6-肟，它们的JNK1和JNK3的解离常数（Kd）为分别为22和76 nM，以及150和275 nM。分子建模表明在JNK催化位点的结合相互作用的模式，并且所选的肟衍生物是潜在的竞争性JNK抑制剂。化合物的JNK结合活性与其抑制脂多糖（LPS）诱导的人单核THP-1Blue细胞和白介素6（IL-β）中核因子-κB/活化蛋白1（NF-κB/ AP-1）活化的能力有关。
• Novel Tryptanthrin Derivatives with Selectivity as c–Jun N–Terminal Kinase (JNK) 3 Inhibitors
  作者：Igor A. Schepetkin、Oleksander S. Karpenko、Anastasia R. Kovrizhina、Liliya N. Kirpotina、Andrei I. Khlebnikov、Stepan I. Chekal、Alevtyna V. Radudik、Maryna O. Shybinska、Mark T. Quinn

  DOI：10.3390/molecules28124806

  日期：——

  The c-Jun N-terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including cell proliferation and differentiation, cell survival, and inflammation. Because of emerging data suggesting that JNK3 may play an important role in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease, as well as cancer pathogenesis, we sought

  c-Jun N 末端激酶 (JNK) 家族包括三种蛋白 (JNK1-3)，它们调节许多生理过程，包括细胞增殖和分化、细胞存活和炎症。由于新出现的数据表明 JNK3 可能在阿尔茨海默病 (AD) 和帕金森病等神经退行性疾病以及癌症发病机制中发挥重要作用，因此我们试图鉴定对 JNK3 具有更高选择性的 JNK 抑制剂。合成了一组 26 种新型色胺酮-6-肟类似物，并评估了 JNK1-3 结合 (Kd) 和细胞炎症反应的抑制作用。化合物4d（8-甲氧基吲哚并[2,1-b]喹唑啉-6,12-二酮肟）和4e（8-苯基吲哚并[2,1-b]喹唑啉-6，12-二酮肟）对 JNK3 相对于 JNK1 和 JNK2 具有高选择性，并抑制 THP-1Blue 细胞和白细胞介素 6 中脂多糖 (LPS) 诱导的核因子 -κB/激活蛋白 1 (NF-κB/AP-1) 转录活性MonoMac-6 单核细胞在低微摩尔范围内产生
• Tryptanthrin derivatives as Toxoplasma gondii inhibitors—structure–activity-relationship of the 6-position
  作者：Bogdana Krivogorsky、Amber C. Nelson、Kelsi A. Douglas、Peter Grundt

  DOI：10.1016/j.bmcl.2012.12.024

  日期：2013.2

  A panel of derivatives of the natural product tryptanthrin was synthesized and screened for its in vitro activity against the intracellular parasite Toxoplasma gondii. We concentrated on the modification of the 6-keto group of tryptanthrin and prepared a series of oximes, hydrazones and alcohols based on tryptanthrin. We evaluated parasite growth inhibition and host cell cytotoxicity. Our results indicate that in particular alcohol analogs are promising candidates for further investigation. (C) 2012 Elsevier Ltd. All rights reserved.
• Novel indolo[2,1-b]quinazoline analogues as cytostatic agents: synthesis, biological evaluation and structure–activity relationship
  作者：Vedula M. Sharma、P. Prasanna、K.V. Adi Seshu、B. Renuka、C.V. Laxman Rao、G. Sunil Kumar、C.Prasad Narasimhulu、P. Aravind Babu、R.C. Puranik、D. Subramanyam、A. Venkateswarlu、Sriram Rajagopal、K.B.Sunil Kumar、C.Seshagiri Rao、N.V.S.Rao Mamidi、Dhanvanthri S. Deevi、R. Ajaykumar、R. Rajagopalan

  DOI：10.1016/s0960-894x(02)00431-6

  日期：2002.9

  In our endeavor to design and synthesize novel anticancer agents, a new series of indoloquinazoline compounds were prepared and tested initially for anticancer activity in vitro against a panel of human cancer cell lines. Most of these compounds exhibited cytotoxic activity in in vitro screens. Compounds were selected and further evaluated using a modified Hollow Fiber Assay for their preliminary in vivo activity against 12 cell lines implanted in the subcutaneous and intraperitoneal compartments in mice. The results indicate that these compounds may constitute a new class of anticancer agents. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Antimicrobial Activity of Tryptanthrins in <i>Escherichia coli</i>
  作者：Pooja P. Bandekar、Keir Alekseii Roopnarine、Virali J. Parekh、Thomas R. Mitchell、Mark J. Novak、Richard R. Sinden

  DOI：10.1021/jm901847f

  日期：2010.5.13

  Tryptanthrins have potential therapeutic activity against a wide variety of pathogenic organisms, although little is known about their mechanism. Activity against Escherichia colt, however, has not been examined. The effects of tryptanthrin (indolo[2,1-b]quinazolin-6,12-dione) and nine derivatives on growth, survival, and mutagenesis in E. colt were examined. Analogues with a nitrogen atom at the 4-position of tryptanthrin stopped log phase growth of E. coli cultures at concentrations as low as 5 mu M. Tryptanthrins decreased viability during incubation with cells in buffer by factors of 10(-2) to < 10(-6) at 0.2-40 mu M. Derivatives with an oxime group at the 6-position exhibited the greatest bactericidal activity. Most tryptanthrins were not mutagenic in several independent assays, although the 4-aza and 4 aza-8-fluoro derivatives increased frameshift mutations about 22- and 4-fold, respectively. Given the structure of trypanthrins, binding to DNA may occur by intercalation. From analysis using a sensitive linking number assay, several tryptanthrins, especially the 4-aza and 6-oximo derivatives, intercalate into DNA.