6-methyl-3-phenylquinoxaline-2-carbonitrile 1,4-dioxide

• 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-methyl-3-phenylquinoxaline-2-carbonitrile 1,4-dioxide
• 英文别名: 7-methyl-3-phenylquinoxaline-2-carbonitrile-1,4-dioxide；3-cyano-6-methyl-2-phenylquinoxaline 1,4-di-N-oxide；2-Quinoxalinecarbonitrile, 7-methyl-3-phenyl-, 1,4-dioxide；7-methyl-1-oxido-4-oxo-3-phenylquinoxalin-4-ium-2-carbonitrile
• 化学式: C₁₆H₁₁N₃O₂
• 分子量: 277.282
• InChiKey: IMAYRYRXLABKQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苯甲酸乙酯 在 sodium methylate 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 6-methyl-3-phenylquinoxaline-2-carbonitrile 1,4-dioxide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 3-Aryl-quinoxaline-2-carbonitrile 1,4-Di-N-oxide Derivatives as Hypoxic Selective Anti-tumor Agents

  摘要：

  一系列3-芳基-2-喹喔啉-氰化物1,4-二-N-氧化物衍生物被设计、合成并评估了其在缺氧和正常氧环境下对人类SMMC-7721、K562、KB、A549和PC-3细胞系的细胞毒性活性。与TX-402和TPZ相比，这些新化合物中许多在肿瘤细胞的评估中显示出了更强的缺氧细胞毒性，这证实了我们的假设，即用取代芳环替代3-氨基可增加缺氧抗肿瘤活性。初步的结构活性关系（SAR）显示，3-氯是苯环中有利的取代基，能够增强缺氧细胞毒性，而7-甲基或7-甲氧基取代的衍生物则对大多数测试的细胞系表现出更好的缺氧选择性。最具活性化合物7-甲基-3-(3-氯苯基)-喹喔啉-2-氰化物1,4-二氧化物（9h）被选定进行进一步抗肿瘤评估和机制研究。它在缺氧环境下对BEL-7402、HepG2、HL-60、NCI-H460、HCT-116和CHP126细胞系表现出显著的细胞毒性活性，IC50值范围为0.31至3.16 μM，初步机制研究表明，9h通过依赖caspase的途径诱导细胞凋亡。

  DOI：

  10.3390/molecules17089683

文献信息

• A Comparative Study of Conventional and Microwave-Assisted Synthesis of Quinoxaline 1,4-di-<i>N</i>-oxide<i>N</i>-acylhydrazones Derivatives Designed as Antitubercular Drug Candidates
  作者：Guilherme Felipe dos Santos Fernandes、Elsa Moreno-Viguri、Mery Santivañez-Veliz、Rocio Paucar、Chung Man Chin、Silvia Pérez-Silanes、Jean Leandro dos Santos

  DOI：10.1002/jhet.2830

  日期：2017.7

  N‐acylhydrazone subunit. Four different synthetic routes were evaluated by using different benzofuroxan derivatives in the Beirut's reaction. The synthetic route D, which employed a dioxolan‐benzofuroxan derivative, has shown to be the best condition to obtain the desired hybrid quinoxaline. MW drastically reduces the reaction time to obtain all compounds compared to conventional heating. For compound 13, for

  喹喔啉1,4-二-N-氧化物（QdNO）和N酰基hydr亚基由于其广泛的生物活性，例如抗菌，抗结核，抗病毒，抗癌和抗真菌，被认为是药物化学中的特权支架。贝鲁特反应是获得QdNO最常用的合成方法。然而，延长的时间，低的收率和副产物的形成是在合成过程中观察到的共同特征。微波辅助有机合成（MW）作为加速化学反应，提高产率和多种反应选择性的有效方法而受到欢迎。因此，为了合成具有结核病治疗潜力的化合物，我们在这里报道了使用MW作为获得含有N的新QdNO衍生物的工具的用途。酰基hydr亚基。在贝鲁特反应中使用不同的苯并呋喃类衍生物评估了四种不同的合成路线。使用二氧戊环-苯并呋喃衍生物的合成路线D已证明是获得所需杂合喹喔啉的最佳条件。与常规加热相比，MW大大减少了获得所有化合物的反应时间。例如，对于化合物13，使用MW代替常规加热能够将反应时间减少192倍。总之，使用苯氧呋喃衍生物而不需要除N-氧化氮以
• Selective activity against Mycobacterium tuberculosis of new quinoxaline 1,4-di-N-oxides
  作者：Esther Vicente、Silvia Pérez-Silanes、Lidia M. Lima、Saioa Ancizu、Asunción Burguete、Beatriz Solano、Raquel Villar、Ignacio Aldana、Antonio Monge

  DOI：10.1016/j.bmc.2008.10.086

  日期：2009.1

  New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 mu g/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly compound 7-methyl-3-(4'-fluoro) phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide (MIC <0.2 mu g/mL and SI > 500). (C) 2008 Elsevier Ltd. All rights reserved.
• Zarranz, Belen; Jaso, Andres; Aldana, Ignacio, Arzneimittel-Forschung/Drug Research, 2005, vol. 55, # 12, p. 754 - 761
  作者：Zarranz, Belen、Jaso, Andres、Aldana, Ignacio、Monge, Antonio、Maurel, Severine、Deharo, Eric、Jullian, Valerie、Sauvain, Michel

  DOI：——

  日期：——
• Synthesis and structure–activity relationship of 3-phenylquinoxaline 1,4-di-N-oxide derivatives as antimalarial agents
  作者：Esther Vicente、Lidia M. Lima、Emily Bongard、Sarah Charnaud、Raquel Villar、Beatriz Solano、Asunción Burguete、Silvia Perez-Silanes、Ignacio Aldana、Livia Vivas

  DOI：10.1016/j.ejmech.2007.11.024

  日期：2008.9

  As a continuation of our research and with the aim of obtaining new antimalarial agents, new series of 3-phenylquinoxaline 1,4-di-N-oxide derivatives have been synthesized following the classical Beirut reaction. Antiplasmodial activity was evaluated in vitro against Plasmodium falciparum by the incorporation of [H-3]-hypoxanthine. Cytotoxicity was tested in KB cells by AlamarBlue assay. Twenty-one of the 60 compounds that were assayed against 3D7 (CQ-sensitive) showed enough activity to be also evaluated against K1 (CQ-resistant) strain. Ten of them were shown to be more active than chloroquine in the resistant strain. The most interesting compounds are 7-(methyl or methoxy)-3-(4'-fluoro or chloro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxides because of their low IC50 and their high SI shown for the K1 strain, making them valid new leads. (C) 2007 Elsevier Masson SAS. All rights reserved.