7-fluoro-3-phenylquinoxaline-2-carbonitrile 1,4-dioxide | 1079038-80-4

• 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-fluoro-3-phenylquinoxaline-2-carbonitrile 1,4-dioxide
• 英文别名: 7-Fluoro-1,4-dioxido-3-phenyl-quinoxaline-1,4-diium-2-carbonitrile；7-fluoro-1-oxido-4-oxo-3-phenylquinoxalin-4-ium-2-carbonitrile
• CAS: 1079038-80-4
• 化学式: C₁₅H₈FN₃O₂
• 分子量: 281.246
• InChiKey: RKISERQJTKMQIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-fluoro-3-phenylquinoxaline-2-carbonitrile 1,4-dioxide 在 盐酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 7-(3-(S)-aminopyrrolidine-1-yl)-3-phenylquinoxaline-2-carbonitrile 1,4-dioxide hydrochloride
  参考文献：
  名称：

  发现6（7）-氨基-3-苯基喹喔啉-2-甲腈1,4-二氧化物的衍生物：新型，缺氧选择性HIF-1α抑制剂，具有强大的抗雌激素能力

  摘要：

  在本文中，我们描述了在位置6或7带有环状二胺残基的3-苯基喹喔啉-2-腈1,4-二氧化物的合成。合成是基于卤素的亲核取代。与参考药物替拉帕明对乳腺腺癌细胞系（MCF7，MDA-MB-231）相比，所有合成的6（7）-氨基喹喔啉-2-甲腈1,4-二氧化物3-6表现出更高的细胞毒性和低氧选择性。二胺残基的结构和位置显着影响喹喔啉-2-腈1,4-二氧化物的抗增殖性能。在4a的喹喔啉环的7位引入卤素原子会大大增加化合物5a和6a的细胞毒性在常氧和低氧条件下。然而，最缺氧的选择性衍生物是未卤代的7-氨基取代的3-苯基喹喔啉-2-腈1,4-二氧化物3a–j。在这32种新的合成衍生物中，约20种6（7）-氨基-3-苯基喹喔啉-2-甲腈1,4-二氧化物显示出对野生型白血病细胞K562和耐药亚株K562 / 4的高抗增殖潜能。 p-糖蛋白（p-gp）的表达与参考药物阿霉素相比，后者对K562 / 4细胞的活

  DOI：

  10.1016/j.bioorg.2020.104324
• 作为产物：
  描述：

  苯甲酰乙腈 、 6-fluorobenzofuroxan 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 7-fluoro-3-phenylquinoxaline-2-carbonitrile 1,4-dioxide
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 3-phenylquinoxaline 1,4-di-N-oxide derivatives as antimalarial agents

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2007.11.024

文献信息

• 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.
• 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.
• Discovery of derivatives of 6(7)-amino-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: novel, hypoxia-selective HIF-1α inhibitors with strong antiestrogenic potency
  作者：Galina I. Buravchenko、Alexander M. Scherbakov、Lyubov G. Dezhenkova、Evgeny E. Bykov、Svetlana E. Solovieva、Alexander A. Korlukov、Danila V. Sorokin、Lianet Monzote Fidalgo、Andrey E. Shchekotikhin

  DOI：10.1016/j.bioorg.2020.104324

  日期：2020.11

  increases the cytotoxicity of compounds 5a and 6a under both normoxic and hypoxic conditions. However, the most hypoxia-selective derivatives were non-halogenated 7-aminosubstituted 3-phenylquinoxaline-2-carbonitrile 1,4-dioxides 3a–j. Of the 32 novel synthesized derivatives, approximately 20 of the 6(7)-amino-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides demonstrated high antiproliferative potency

  在本文中，我们描述了在位置6或7带有环状二胺残基的3-苯基喹喔啉-2-腈1,4-二氧化物的合成。合成是基于卤素的亲核取代。与参考药物替拉帕明对乳腺腺癌细胞系（MCF7，MDA-MB-231）相比，所有合成的6（7）-氨基喹喔啉-2-甲腈1,4-二氧化物3-6表现出更高的细胞毒性和低氧选择性。二胺残基的结构和位置显着影响喹喔啉-2-腈1,4-二氧化物的抗增殖性能。在4a的喹喔啉环的7位引入卤素原子会大大增加化合物5a和6a的细胞毒性在常氧和低氧条件下。然而，最缺氧的选择性衍生物是未卤代的7-氨基取代的3-苯基喹喔啉-2-腈1,4-二氧化物3a–j。在这32种新的合成衍生物中，约20种6（7）-氨基-3-苯基喹喔啉-2-甲腈1,4-二氧化物显示出对野生型白血病细胞K562和耐药亚株K562 / 4的高抗增殖潜能。 p-糖蛋白（p-gp）的表达与参考药物阿霉素相比，后者对K562 / 4细胞的活
• Anti-T. cruzi activities and QSAR studies of 3-arylquinoxaline-2-carbonitrile di-N-oxides
  作者：Esther Vicente、Pablo R. Duchowicz、Diego Benítez、Eduardo A. Castro、Hugo Cerecetto、Mercedes González、Antonio Monge

  DOI：10.1016/j.bmcl.2010.06.101

  日期：2010.8

  In a continuing effort to identify new active compounds for combating Chagas disease and other neglected diseases, our research group synthesized and evaluated 23 3-arylquinoxaline-2-carbonitrile di-N-oxides against Trypanosoma cruzi. Five of them presented IC50 values of the same magnitude as the standard drug Nifurtimox, making them valid as new lead compounds. The optimized molecular structures of 23 derivatives represented by 1497 types of DRAGON descriptors were subjected to linear regression analysis, and the derived QSAR was shown to be predictive. In this way, we achieved a rational guide for the proposal of new candidate structures whose activities still remain unknown. (C) 2010 Elsevier Ltd. All rights reserved.