11H-indeno[1,2-b]quinoxalin-11-one oxime | 23146-22-7

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: 11H-indeno[1,2-b]quinoxalin-11-one oxime
• 英文别名: N-indeno[1,2-b]quinoxalin-11-ylidenehydroxylamine
• CAS: 23146-22-7
• 化学式: C₁₅H₉N₃O
• 分子量: 247.256
• InChiKey: SZHHSFHOIDCNLD-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO：可溶，2mg/mL，澄清（加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.84
• 重原子数：
  19.0
• 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：
  58.37
• 氢给体数：
  1.0
• 氢受体数：
  4.0

安全信息

• 危险类别：
  4.1
• 危险性防范说明：
  P240,P210,P241,P264,P280,P302+P352,P370+P378,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险品运输编号：
  1325
• 危险性描述：
  H315,H319,H228
• 包装等级：
  II
• 储存条件：
  2-8℃

制备方法与用途

生物活性

IQ-1S 是一种 JNK3 抑制剂，对 JNK3、JNK2 和 JNK1 的 Kd 值分别为 87 nM、360 nM 和 390 nM。

Target	Value
JNK3 (细胞外测定)	87 nM
JNK2 (细胞外测定)	360 nM
JNK1 (细胞外测定)	390 nM

体外研究

化合物 IQ-1S 是一种强效且非细胞毒性的抗炎因子（包括人和小鼠单核/巨噬细胞中的 IL-1α、IL-1β、IL-6、IL-10、TNF-α、干扰素-γ 和粒细胞-巨噬细胞集落刺激因子）以及一氧化氮的抑制剂。其效果评估了 LPS 引起的人 PBMCs 细胞因子产生情况。在分析的 12 种细胞因子中，LPS（200 ng/mL）一致诱导五个（IL-1α、IL-1β、IL-6、IL-10 和 TNF-α）。所有这些细胞因子的生产量均被 20 μM IQ-1S 显著抑制。其中，TNF-α 的产生完全被 IQ-1S 抑制（＞99%），IL-1α、IL-1β 和 IL-10 的水平分别下降了 85%，而 IL-6 的生产量则减少了 33%。

体内研究

当小鼠以 12.5 mg/kg 和 30 mg/kg（碘化钠盐）腹腔注射 IQ-1S 时，化合物的血清暴露良好，AUC_0-12h 值分别为 2.9 μM/h 和 7.4 μM/h。

反应信息

• 作为反应物：
  描述：

  氯乙酸 、 11H-indeno[1,2-b]quinoxalin-11-one oxime 在 potassium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 以52%的产率得到11H-indeno[1,2-b]quinoxalin-11-one O-carboxymethyl oxime
  参考文献：
  名称：

  合成，生物学评估和分子模拟的11 H-茚并[1,2-b]喹喔啉-11-1衍生物和类胰蛋白酶-6-肟作为c-Jun N端激酶抑制剂。

  摘要：

  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。

  DOI：

  10.1016/j.ejmech.2018.10.023
• 作为产物：
  描述：

  11H-茚并[1,2-b]喹喔啉-11-酮 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以94%的产率得到11H-indeno[1,2-b]quinoxalin-11-one oxime
  参考文献：
  名称：

  Discovery of indeno[1,2- b ]quinoxaline derivatives as potential anticancer agents

  摘要：

  We have synthesized certain indeno[1,2-b]quinoxaline derivatives for antiproliferative evaluation. Among them, 11-{[3-(dimethylamino)propoxy]imino}-N-[3-(dimethylamino) propyl]-11H-indeno(1,2-b] quinoxaline-6-carboxamide (10a) was active against the growth of MDA-MB231, PC-3, and Huh-7 with IC50 values of 0.87 (selectivity index, SI = 36.22), 0.82 (SI = 38.43), and 0.64 mu M (SI = 49.23) respectively. Compound 10a was inactive against the growth of normal human fetal lung fibroblast cell line (MRC-5) with an IC50 value of 31.51 mu M. Its analogs, 10b and 10c, were also active against the growth of MB231, PC-3, and Huh-7 with IC50 values of <1.0.mu M in each case. Our results have also indicated compounds 10a-10c exhibited comparable inhibitory activities against topo I and topo II with the positive compound 2 at a concentration of 10 mu M. Mechanism studies indicated that compound 10a induced cell cycle arrest at S phase via activation of caspase-3, -7 and an increase in the protein expression of Bad and Bax but a decrease in expression of Bcl-2 and PARP, which consequently cause cell death. In addition, compound 10a attenuated the levels of phosphorylated Src, Akt-1, and Akt-2 protein levels but did not affect the total protein expression of Akt. We have also implanted human hepatocellular carcinoma cells into the yolk sac of zebrafish larvae and incubated larvae with various concentrations of 10a. Our results of the zebrafish xenograft assay confirmed the anti-tumor effect of 10a in vivo. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.031

文献信息

• An indeno-quinoxaline based oxime ligand for the synthesis of polynuclear Ni(ii) clusters
  作者：Angelos B. Canaj、Lydia E. Nodaraki、Aggelos Philippidis、Demetrios I. Tzimopoulos、Eirini Fotopoulou、Milosz Siczek、Tadeusz Lis、Constantinos J. Milios

  DOI：10.1039/c3ra41455h

  日期：——

  The reaction of Ni(OAc)2·4H2O with LH (LH = 11H-indeno[1,2-b]quinoxalin-11-one oxime) in a mixture of solvents comprising MeCN/MeOH (1 : 1) under solvothermal conditions in the presence of NEt3 forms the complex [Ni3(L)5(OAc)(MeOH)]·2.6MeCN·0.7MeOH·0.2H2O (1·2.6MeCN·0.7MeOH·0.2H2O) in moderate yield. Repeating the reaction in MeOH produces the complex [Ni6(L)6(OAc)4(OMe)2]·1.5MeOH·1.3H2O (2·1.5MeOH·1.3H2O) in good yield, while the reaction between Ni(ClO4)2·6H2O and LH in the presence of NEt3 in MeOH under solvothermal conditions yields complex [Ni5(L)6(OMe)2(OH)(H2O)2(MeOH)2](ClO4)·8.8MeOH·1.4H2O (3·8.8MeOH·1.4H2O). Furthermore, the reaction between Ni(ClO4)2·6H2O, LH and 2-amino-isobutyric acid, aibH, in MeCN in the presence of NEt3 forms complex [Ni7(L)7(aib)4(OH)(MeCN)0.5(H2O)0.5](ClO4)2·4MeCN·0.25H2O (4·4MeCN·0.25H2O) under high temperature/pressure, while the same reaction in MeOH yields complex [Ni8(L)8(aib)3(OMe)3](ClO4)2·0.75MeOH·4.2H2O (5·0.75MeOH·4.2H2O). Variable temperature dc magnetic susceptibility studies show that all 1–5 clusters display a small or a diamagnetic ground-state, S.

  在 NEt3 存在下，Ni(OAc)2-4H2O 与 LH（LH = 11H-茚并[1,2-b]喹喔啉-11-酮肟）在 MeCN/MeOH (1 : 1) 混合溶剂中发生溶热反应，生成复合物 [Ni3(L)5(OAc)(MeOH)]-2。6MeCN-0.7MeOH-0.2H2O（1-2.6MeCN-0.7MeOH-0.2H2O），产率中等。在 MeOH 中重复该反应可生成复合物 [Ni6(L)6(OAc)4(OMe)2]-1.5MeOH-1.3H2O （2-1.5MeOH-1.3H2O），收率良好；而在溶热条件下，Ni(ClO4)2-6H2O 和 LH 在 NEt3 存在下于 MeOH 中发生反应，得到复合物 [Ni5(L)6(OMe)2(OH)(H2O)2(MeOH)2](ClO4)-8.8MeOH-1.4H2O（3-8.8MeOH-1.4H2O）。此外，在 NEt3 的存在下，Ni(ClO4)2-6H2O、LH 和 2-氨基异丁酸 aibH 在 MeCN 中反应形成复合物 [Ni7(L)7(aib)4(OH)(MeCN)0.5(H2O)0.5](ClO4)2-4MeCN-0.25H2O (4-4MeCN-0.25H2O)，而在 MeOH 中进行相同的反应则可得到复合物 [Ni8(L)8(aib)3(OMe)3](ClO4)2-0.75MeOH-4.2H2O(5-0.75MeOH-4.2H2O)。变温直流磁感应强度研究表明，所有 1-5 个团簇都显示出较小或二磁性的基态 S。
• Arene-ruthenium(II) complexes with tetracyclic oxime derivatives: synthesis, structure and antiproliferative activity against human breast cancer cells
  作者：Vladislava V. Matveevskaya、Dmitry I. Pavlov、Denis G. Samsonenko、Laura Bonfili、Massimiliano Cuccioloni、Enrico Benassi、Riccardo Pettinari、Andrei S. Potapov

  DOI：10.1016/j.ica.2022.120879

  日期：2022.5

  cytotoxic activity of the complexes was evaluated against human breast cancer cell line MCF-7 and cisplatin-resistant human breast cancer cell line MCF-7CR as well as non-cancerous human breast epithelial cell line MCF10A. The cytotoxicity tests show micromolar IC50 values and tryptanthrin-6-oxime hexamethylbenzene-ruthenium(II) complex was found to exhibit the best antiproliferative activity among the

  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
• A family of polynuclear cobalt complexes upon employment of an indeno-quinoxaline based oxime ligand
  作者：Angelos B. Canaj、Lydia E. Nodaraki、Katarzyna Ślepokura、Milosz Siczek、Demetrios I. Tzimopoulos、Tadeusz Lis、Constantinos J. Milios

  DOI：10.1039/c4ra01914h

  日期：——

  The employment of an indeno-quinoxaline based oxime ligand in cobalt chemistry afforded a new family of polynuclear cobalt clusters.

  在钴化学中使用一种基于茚并喹啉的羟肟配体，得到了一类新的多核钴簇。
• Discovery of indeno[1,2- b ]quinoxaline derivatives as potential anticancer agents
  作者：Chih-Hua Tseng、You-Ren Chen、Cherng-Chyi Tzeng、Wangta Liu、Chon-Kit Chou、Chien-Chih Chiu、Yeh-Long Chen

  DOI：10.1016/j.ejmech.2015.11.031

  日期：2016.1

  We have synthesized certain indeno[1,2-b]quinoxaline derivatives for antiproliferative evaluation. Among them, 11-[3-(dimethylamino)propoxy]imino}-N-[3-(dimethylamino) propyl]-11H-indeno(1,2-b] quinoxaline-6-carboxamide (10a) was active against the growth of MDA-MB231, PC-3, and Huh-7 with IC50 values of 0.87 (selectivity index, SI = 36.22), 0.82 (SI = 38.43), and 0.64 mu M (SI = 49.23) respectively. Compound 10a was inactive against the growth of normal human fetal lung fibroblast cell line (MRC-5) with an IC50 value of 31.51 mu M. Its analogs, 10b and 10c, were also active against the growth of MB231, PC-3, and Huh-7 with IC50 values of <1.0.mu M in each case. Our results have also indicated compounds 10a-10c exhibited comparable inhibitory activities against topo I and topo II with the positive compound 2 at a concentration of 10 mu M. Mechanism studies indicated that compound 10a induced cell cycle arrest at S phase via activation of caspase-3, -7 and an increase in the protein expression of Bad and Bax but a decrease in expression of Bcl-2 and PARP, which consequently cause cell death. In addition, compound 10a attenuated the levels of phosphorylated Src, Akt-1, and Akt-2 protein levels but did not affect the total protein expression of Akt. We have also implanted human hepatocellular carcinoma cells into the yolk sac of zebrafish larvae and incubated larvae with various concentrations of 10a. Our results of the zebrafish xenograft assay confirmed the anti-tumor effect of 10a in vivo. (C) 2015 Elsevier Masson SAS. All rights reserved.
• 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。