1-(4-chlorophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione | 1572038-77-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-chlorophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
• 英文别名: 3-(4-Chlorophenyl)benzo[f]benzotriazole-4,9-dione
• CAS: 1572038-77-7
• 化学式: C₁₆H₈ClN₃O₂
• 分子量: 309.711
• InChiKey: ROZAKKISAVUZDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-chlorophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione 、 三氟甲烷磺酸甲酯 以 甲苯 为溶剂， 以99%的产率得到1-(4-chlorophenyl)-4,9-dioxo-3-methylnaphtho[2,3-d][1,2,3] triazol-3-ium trifluoromethanesulfonate
  参考文献：
  名称：

  阳离子蒽醌类似物的合成及其抗癌活性关系的研究

  摘要：

  我们合成了一系列新颖的4,9-二氧代-4,9-二氢-1 H-萘[2,3- d ] [1,2,3]三唑-3-鎓盐，可以将其视为类似物阳离子蒽醌。与我们之前报道的类似类似物不同，这些化合物显示出相对较弱的抗菌活性，但发挥了很强的抗癌活性（从低至μM到nM GI 50），尤其是针对黑色素瘤，结肠癌，非小细胞肺癌和中枢神经系统（CNS）癌症的治疗。这些化合物在结构上不同于其前身，因为它们具有直接连接到阳离子蒽醌骨架上的芳基而不是烷基链。对结构-活性关系（SAR）的进一步研究表明，芳环上的给电子取代基在通过共振效应增强抗癌活性方面具有重要作用。这些基团的立体位阻是不利的，但其影响不如共振效应。阳离子蒽醌类似物在N-1位的连接基团的差异是生物活性从抗菌药向抗癌药转换的主要结构因素。

  DOI：

  10.1016/j.ejmech.2014.02.060
• 作为产物：
  描述：

  p-chlorobenzenediazonium tetrafluoroborate 在 sodium azide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 1-(4-chlorophenyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
  参考文献：
  名称：

  Discovery and structure-activity relationship studies of 1-aryl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as potent dual inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and trytophan 2,3-dioxygenase (TDO)

  摘要：

  Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO), which mediate kynurenine pathway of tryptophan degradation, have emerged as potential new targets in immunotherapy for treatment of cancer because of their critical role in immunosuppression in the tumor microenvironment. In this investigation, we report the structural optimization and structure-activity relationship studies of 1-phenyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as a new class of IDO1/TDO dual inhibitors. Among all the obtained dual inhibitors, 1-(3-chloro-4-fluorophenyl)-6-fluoro-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione (38) displayed the most potent IDO1 and TDO inhibitory activities with IC₅₀ (half-maximal inhibitory concentration) values of 5 nM for IDO1 and 4 nM for TDO. It turned out that compound 38 was not a PAINS compound. Compound 38 could efficiently inhibit the biofunction of IDO1 and TDO in intact cells. In LL2 (Lewis lung cancer) and Hepa1-6 (hepatic carcinoma) allograft mouse models, this compound also showed considerable in vivo anti-tumor activity and no obvious toxicity was observed. Therefore, 38 could be a good lead compound for cancer immunotherapy and deserving further investigation.

  DOI：

  10.1016/j.ejmech.2020.112703

文献信息

• A mode of action study of cationic anthraquinone analogs: a new class of highly potent anticancer agents
  作者：Jaya P. Shrestha、Yagya Prasad Subedi、Liaohai Chen、Cheng-Wei Tom Chang

  DOI：10.1039/c5md00314h

  日期：——

  Previously, we reported the synthesis and structure–activity relationship (SAR) study of a series of novel 4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-3-ium salts, which had very potent anti-proliferative activities (low μM to nM GI₅₀) against a broad range of cancer cells.

  之前，我们报告了一系列新型4,9-二氧代-4,9-二氢-1H-萘并[2,3-d][1,2,3]三唑-3-ium盐的合成和结构-活性关系（SAR）研究，这些化合物对广泛范围的癌细胞具有非常强的抗增殖活性（低微摩尔到纳摩尔级的GI50值）。
• DBU catalyzed metal free synthesis of fused 1,2,3-triazoles through [3+2] cycloaddition of aryl azides with activated cyclic C–H acids
  作者：Harjinder Singh、Garima Khanna、Jitender M. Khurana

  DOI：10.1016/j.tetlet.2016.05.082

  日期：2016.7

  DBU catalyzed synthesis of fused 1,2,3-triazoles by [3+2] cycloaddition of aryl azides with activated cyclic C–H acids such as dimedone, cyclohexane-1,3-dione, 5-methylcyclohexane-1,3-dione, and 2-hydroxynaphthalene-1,4-dione in PEG-400 has been reported under heating. The important features of this reaction are high yield products, short reaction times, easy availability of starting materials, and

  DBU通过芳基叠氮化物与活化的环状C–H酸（如二甲酮，环己烷-1,3-二酮，5-甲基环己烷-1,3-二酮）的[3 + 2]环加成反应，催化稠合的1,2,3-三唑的合成据报道，PEG-400中的2-羟基萘-1,4-二酮在加热下。该反应的重要特征是高产率的产物，短的反应时间，容易获得的起始原料以及反应介质和催化剂的可循环性。
• Metal-free cycloaddition to synthesize naphtho[2,3-d][1,2,3]triazole-4,9-diones
  作者：Ping-Fan Chen、Kung-Kai Kuo、Jaya Kishore Vandavasi、Siva Senthil Kumar Boominathan、Chung-Yu Chen、Jeh-Jeng Wang

  DOI：10.1039/c5ob01322d

  日期：——

  A metal-free domino [3 + 2] cycloaddition is reported to construct naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives and provide an alternative approach to the azide–alkyne cycloadditions.

  报道了一种无金属的多米诺[3 + 2]环加成反应，用于构建萘并[2,3-d][1,2,3]三唑-4,9-二酮衍生物，并为叠氮-炔环加成提供了一种替代方法。
• Cerium(III) triflate–catalyzed cycloaddition reaction in aqueous conditions to substituted naphthotriazolediones
  作者：Ya‐Syuan Li、Chien‐Fu Liang

  DOI：10.1002/jccs.202200018

  日期：2022.5

  In this study, the cerium(III) trifluoromethanesulfonate–catalyzed cycloaddition of 1,4-naphthoquinone with functionalized azides in aqueous solutions was used to synthesize naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives. Moreover, our method boasts scalability and completes the synthesis of two key biological compounds. Our method's advantages are environmentally friendly reaction conditions

  本研究采用三氟甲磺酸铈（III）催化的 1,4-萘醌与官能化叠氮化物在水溶液中的环加成反应合成萘并[2,3 - d ][1,2,3]三唑-4,9-二酮衍生物。此外，我们的方法具有可扩展性并完成了两种关键生物化合物的合成。我们的方法的优点是环境友好的反应条件，易于大规模操作，高产率生产的结构多样的产品，以及催化剂的可回收性。
• Tuning the biological activity of cationic anthraquinone analogues specifically toward Staphylococcus aureus
  作者：Yagya Prasad Subedi、Madher N. Alfindee、Jaya P. Shrestha、Cheng-Wei Tom Chang

  DOI：10.1016/j.ejmech.2018.08.018

  日期：2018.9

  Development of new antibacterial agents against drug resistant bacteria is an imminent task, especially against methicillin-resistant Staphylococcus aureus (MRSA). While MRSA can still be treated with broad spectrum antibiotics, the use of which often leads to the disruption of normal microbial flora leading to Clostridium difficile infection (CDI). Herein, a new class of antibacterial agent, cationic anthraquinone analogues specifically against MRSA, has been developed. Through the variation and optimization of substituents, these agents are selective toward MRSA, and not Gram negative bacteria which may avoid the problem of CDI. In addition, newly discovered lead compounds also show significantly reduced cytotoxicity against normal mammalian cells than cancerous cells. This interesting finding can alleviate the toxicity and side effect problems often associate with the use of antibiotics. (C) 2018 Elsevier Masson SAS. All rights reserved.