6-chloro-7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-carbonitrile | 170098-80-3

• 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-chloro-7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-carbonitrile
• 英文别名: 6-Chloro-5-cyano-7-nitro-1,4-dihydroquinoxaline-2,3-dione；6-chloro-5-cyano-7-nitroquinoxaline-2(1H),3(4H)-dione；6-chloro-7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-5-carbonitrile
• CAS: 170098-80-3
• 化学式: C₉H₃ClN₄O₄
• 分子量: 266.6
• InChiKey: FGKQPVBBUINHMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-chloro-7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-carbonitrile 在 盐酸 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 30.0h， 生成 6,7-dichloro-5-cyano-1,4-dihydroquinoxaline-2,3-dione
  参考文献：
  名称：

  Synthesis and SAR of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones related to licostinel (Acea 1021) as NMDA/glycine site antagonists

  摘要：

  A series of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones (QXs) related to licostinel (Acea 1021) was synthesized and evaluated as antagonists for the glycine site of the N-methyl-D-asparate (NMDA) receptor. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [H-3]-5,7-dichlorokynurenic acid ([H-3]DCKA) in rat brain cortical membranes. Structure-activity relationship studies indicate that a cyano group is a good replacement for the nitro group in the 5-position of licostinel while 5-carboxy, 5-ester, 5-ketone and 5-amide derivatives showed reduced potency. 5,6-Cyclized analogues of licostinel also showed significantly reduced potency. Among the trisubstituted QXs investigated, 5-cyano-6,7-dichloro QX and 5-cyano-7-chloro-6-methyl QX are the most potent with IC50 values of 32 nM and 26 nM, respectively. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00059-2
• 作为产物：
  描述：

  2,6-二氯-3-硝基苯肼 在 硝酸 、 三氟乙酸 、 tin(ll) chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.5h， 生成 6-chloro-7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-carbonitrile
  参考文献：
  名称：

  Synthesis and SAR of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones related to licostinel (Acea 1021) as NMDA/glycine site antagonists

  摘要：

  A series of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones (QXs) related to licostinel (Acea 1021) was synthesized and evaluated as antagonists for the glycine site of the N-methyl-D-asparate (NMDA) receptor. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [H-3]-5,7-dichlorokynurenic acid ([H-3]DCKA) in rat brain cortical membranes. Structure-activity relationship studies indicate that a cyano group is a good replacement for the nitro group in the 5-position of licostinel while 5-carboxy, 5-ester, 5-ketone and 5-amide derivatives showed reduced potency. 5,6-Cyclized analogues of licostinel also showed significantly reduced potency. Among the trisubstituted QXs investigated, 5-cyano-6,7-dichloro QX and 5-cyano-7-chloro-6-methyl QX are the most potent with IC50 values of 32 nM and 26 nM, respectively. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00059-2

文献信息

• Alkyl, azido, alkoxy, and fluoro-substituted and fused quinoxalinediones
  申请人：State of Oregon, acting by and through the Oregon State Board of Higher

  公开号：US05631373A1

  公开（公告）日：1997-05-20

  Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, and inducing anesthesia are disclosed by administering to an animal in need of such treatment an alkyl or azido-substituted 1,4-dihydroquinoxaline-2,3-dione or pharmaceutically acceptable salts thereof, which have high binding to the glycine receptor.

  治疗或预防与中风、缺血、中枢神经系统创伤、低血糖和手术有关的神经元丧失的方法，以及治疗包括阿尔茨海默病、肌萎缩侧索硬化、亨廷顿病和唐氏综合征在内的神经退行性疾病，治疗或预防兴奋性氨基酸过度活跃的不良后果，以及治疗焦虑、慢性疼痛、抽搐和诱导麻醉的方法是通过给需要这种治疗的动物投予烷基或偶氮取代的1,4-二氢喹喔啉-2,3-二酮或其药学上可接受的盐来实现，这些物质对甘氨酸受体具有高结合能力。
• [EN] ALKYL, AZIDO, ALKOXY, AND FLUORO-SUBSTITUTED AND FUSED QUINOXALINEDIONES AND THE USE THEREOF AS GLYCINE RECEPTOR ANTAGONISTS<br/>[FR] QUINOXALINEDIONES CONDENSEES ET SUBSTITUEES PAR ALKYLE, AZIDO, ALCOXY ET FLUORO ET LEUR UTILISATION COMME ANTAGONISTES DU RECEPTEUR DE LA GLYCINE
  申请人：ACEA PHARMACEUTICALS, INC.

  公开号：WO1995012417A1

  公开（公告）日：1995-05-11

  (EN) Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, and inducing anesthesia are disclosed by administering to an animal in need of such treatment an alkyl or azido-substituted 1,4-dihydroquinoxaline-2,3-dione or pharmaceutically acceptable salts thereof, which have high binding to the glycine receptor.(FR) L'invention concerne des procédés de traitement ou de prévention de baisses de l'activité neuronale associées aux ictus, à l'ischémie, aux traumatismes du système nerveux central, à l'hypoglycémie et aux opérations chirurgicales, ainsi que de traitement de maladies dégénératives du système nerveux, notamment la maladie d'Alzheimer, la sclérose latérale amyotrophique, la chorée de Huntington, et le mongolisme. L'invention concerne également le traitement ou la prévention des conséquences négatives de l'hyperactivité des acides aminés excitateurs, de même que le traitement de l'anxiété, des douleurs chroniques, des convulsions, et la manière d'induire l'anesthésie, par administration à un animal requérant ce type de traitement, d'une 1,4-dihydroquinoxaline-2,3-dione substituée par alkyle ou par azido ou de ses sels pharmaceutiquement acceptables, qui ont un pouvoir de fixation élevé sur le récepteur de la glycine.

  (中) 本发明涉及一种治疗或预防与中风、缺血、中枢神经系统创伤、低血糖和手术相关的神经元丧失，以及治疗包括阿尔茨海默病、肌萎缩性侧索硬化症、亨廷顿病和唐氏综合症等神经退行性疾病，治疗或预防兴奋性氨基酸过度活跃的不良后果，以及治疗焦虑、慢性疼痛、惊厥和诱导麻醉的方法，通过向需要此类治疗的动物注射具有高度结合甘氨酸受体的烷基或偶氮基取代的1,4-二氢喹噁啉-2,3-二酮或其药学上可接受的盐。
• Alkyl, azido, alkoxy and fluoro-substituted and fused quinoxalinediones
  申请人：CoCensys, Inc.

  公开号：US06147075A1

  公开（公告）日：2000-11-14

  Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, and inducing anesthesia are disclosed by administering to an animal in need of such treatment an alkyl or azido-substituted 1,4-dihydroquinoxaline-2,3-dione or pharmaceutically acceptable salts thereof, which have high binding to the glycine receptor.

  本发明揭示了通过向需要此类治疗的动物投与具有高结合甘氨酸受体的烷基或偶氮基取代的1,4-二氢喹啉-2,3-二酮或其药学上可接受的盐，来治疗或预防与中风、缺血、中枢神经系统创伤、低血糖和手术相关的神经元丢失，以及治疗包括阿尔茨海默病、肌萎缩性侧索硬化症、亨廷顿病和唐氏综合征在内的神经退行性疾病，治疗兴奋性氨基酸过度活跃的不良后果，以及治疗焦虑、慢性疼痛、惊厥和诱导麻醉的方法。
• EP0732942A4
  申请人：——

  公开号：EP0732942A4

  公开（公告）日：2000-03-22
• ALKYL, AZIDO, ALKOXY, AND FLUORO-SUBSTITUTED AND FUSED QUINOXALINEDIONES AND THE USE THEREOF AS GLYCINE RECEPTOR ANTAGONISTS
  申请人：ACEA PHARMACEUTICALS, INC.

  公开号：EP0732942A1

  公开（公告）日：1996-09-25