7-nitropyrido[2,3-b]pyrazine-2,3-diol | 144435-09-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶吡嗪类
• 英文名称: 7-nitropyrido[2,3-b]pyrazine-2,3-diol
• 英文别名: 7-Nitro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione
• CAS: 144435-09-6
• 化学式: C₇H₄N₄O₄
• 分子量: 208.133
• InChiKey: FZAAGBYLDXVMRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  15
• 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：
  117
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-nitropyrido[2,3-b]pyrazine-2,3-diol 在 环丁砜 、 nitronium tetrafluoborate 作用下， 反应 2.0h， 以45%的产率得到6,7-Dinitro-1,4-dihydro-pyrido[2,3-b]pyrazine-2,3-dione
  参考文献：
  名称：

  新型的α-氨基-3-羟基-5-甲基异恶唑-4-丙酸酯受体拮抗剂：6-（1H-咪唑-1-基）-7-硝基-2,3（1H，4H）的合成与构效关系-吡啶并[2,3-b]吡嗪二酮及相关化合物。

  摘要：

  我们已经合成并评估了氮杂喹喔啉酮3a-c在抑制大鼠全脑[3H] AMPA结合中的活性。发现氮杂喹喔啉二酮核在AMPA受体结合中起喹喔啉二酮的生物同工异构体的作用。6-和/或7-取代的2,3（1H，4H）-吡啶并[2,3-b]吡嗪二酮衍生物4、7-1、13、15和16的详细结构-活性关系显示出一些差异与包括6-（1H-咪唑-1-基）-7-硝基-2,3-（1H，4H）-喹喔啉二酮（1）（YM90K）的相应取代喹喔啉二酮的比较。X射线研究表明1.HCl的7-硝基基团与喹喔啉环几乎共面，而6-咪唑-1-基相对于芳环旋转。从NMDA受体结合研究中的甘氨酸位点开始，表明在吡啶并吡嗪二酮上6-取代基的庞大可能是针对甘氨酸位点的选择性的原因。在一系列的氮杂喹喔啉二酮中，6-（1H-咪唑-1-基）-7-硝基-2,3（1H，4H）-吡啶并[2,3-b]吡嗪二酮（8c）表现出最佳亲和力的组合对AMPA受体具有Ki值为0

  DOI：

  10.1021/jm950304+
• 作为产物：
  描述：

  3,5-二硝基-2-氨基吡啶 在 草酸 作用下， 以 甲醇 、 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 为溶剂， 生成 7-nitropyrido[2,3-b]pyrazine-2,3-diol
  参考文献：
  名称：

  8-aza, 6-aza and 6,8-diaza-1,4-dihydroquinoxaline-2,3-diones and the use

  摘要：

  揭示了一种用于治疗或预防与中风、缺血、中枢神经系统创伤或低血糖相关的神经元丧失的方法。该方法包括向动物施用以下化合物的步骤：##STR1## 或其药学上可接受的盐；其中n为零或1；R.sup.4、R.sup.5、R.sup.6分别独立地是氢、硝基、氨基、卤素、卤代烷基、氰基、烷基、环烷基、烯基、炔基、叠氮基、酰胺基、烷基磺酰基、芳基、取代芳基、杂芳基、烷氧基、三烷基硅基取代的烷氧基、芳氧基、取代芳氧基、杂芳氧基、杂环基团、杂环氧基团、芳基烷氧基或卤代烷氧基；且R.sup.c和R.sup.d在规范中有定义。这些化合物具有高结合NMDA受体的甘氨酸位点的能力。

  公开号：

  US05620978A1

文献信息

• NOVEL HETEROCYCLIC DERIVATIVES AND THEIR USES
  申请人：Ho Pil Su

  公开号：US20140315888A1

  公开（公告）日：2014-10-23

  The present invention relates to novel heterocyclic compounds useful in preparing drugs for treatment of diseases associated with various functions of the histamine 4 receptor. Especially, the said drugs are useful for treatment of inflammatory diseases, allergy, pain, nasal polyps, rhinitis, chronic sinusitis, nasal congestion, nasal itch, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis, eczema, pruritus, itchy skin, urticaria, idiopathic chronic urticaria, scleroderma, conjunctivitis, keratoconjunctivitis, ocular inflammation, dry eye, cardiac dysfunction, arrhythmia, atherosclerosis, multiple sclerosis, inflammatory bowel disease (including colitis, Crohn's disease, ulcerative colitis), inflammatory pain, neuropathic pain, osteoarthritic pain, autoimmune thyroid disease, immune-mediated (also known as type I) diabetes, lupus, post-operative adhesions, vestibular disorders and cancer.

  该发明涉及新型杂环化合物，用于制备治疗与组织胺4受体的各种功能相关的疾病的药物。特别是，所述药物适用于治疗炎症性疾病、过敏、疼痛、鼻息肉、鼻炎、慢性鼻窦炎、鼻塞、鼻痒、哮喘、慢性阻塞性肺病、类风湿性关节炎、特应性皮炎、牛皮癣、湿疹、瘙痒、瘙痒皮肤、荨麻疹、特发性慢性荨麻疹、硬皮病、结膜炎、角膜结膜炎、眼部炎症、干眼症、心脏功能障碍、心律失常、动脉粥样硬化、多发性硬化、炎症性肠病（包括结肠炎、克罗恩病、溃疡性结肠炎）、炎症性疼痛、神经痛、骨关节炎疼痛、自身免疫性甲状腺疾病、免疫介导（也称为I型）糖尿病、红斑狼疮、术后粘连、前庭障碍和癌症的药物治疗。
• 5-(<i>N</i>-Oxyaza)-7-substituted-1,4-dihydroquinoxaline-2,3-diones:  Novel, Systemically Active and Broad Spectrum Antagonists for NMDA/glycine, AMPA, and Kainate Receptors
  作者：Sui Xiong Cai、Jin-Cheng Huang、Stephen A. Espitia、Minhtam Tran、Victor I. Ilyin、Jon E. Hawkinson、Richard M. Woodward、Eckard Weber、John F. W. Keana

  DOI：10.1021/jm970396y

  日期：1997.10.1

  A group of 5-aza-7-substituted-1,4-dihydroquinoxaline-2,3-diones (QXs) and the corresponding 5-(N-oxyaza)-7-substituted QXs were prepared and evaluated as antagonists of ionotropic glutamate receptors. The in vitro potency of these QXs was determined by inhibition of [H-3]- 5,7-dichlorokynurenic acid ([H-3]DCKA) binding to N-methyl-D-aspartate (NMDA)/glycine receptors, [H-3]-(S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([H-3]AMPA) binding to AMPA receptors, and [H-3]kainate ([H-3]KA) binding to KA receptors in rat brain membranes. 5-(N-Oxyaza)-QXs 12a-e all have low micromolar or submicromolar potency for NMDA/glycine receptors and low micromolar potencies for AMPA and KA receptors. QXs 12a-e display 2-12-fold selectivity for NMDA/glycine receptors compared to AMPA receptors, and similar to 2-fold difference between AMPA and KA potency. In contrast to other QXs that either show high selectivity for NMDA (such as ACEA 1021) or AMPA (such as NBQX) receptors, these molecules are broad spectrum antagonists of ionotropic glutamate receptors. 7-Nitro-5-(N-oxyaza)-QX (12e) is the most potent inhibitor among 12a-e, having IC50 values of 0.69, 1.3, and 2.4 mu M at NMDA, AMPA, and KA receptors, respectively. In functional assays on glutamate receptors expressed in oocytes by rat cerebral cortex poly(A(+)) RNA, 7-chloro-5-(N-oxyaza)-QX (12a) and 7-nitro-5-(N-oxyaza)-QX (12e) have K-b values of 0.63 and 0.31 mu M for NMDA/glycine receptors, and are 6- and 4-fold selective for NMDA over AMPA receptors, respectively. 5-(N-Oxyaza)-7-substituted-QXs 12a-e all have surprisingly high in vivo potency as anticonvulsants in a mouse maximal electroshock-induced seizure (MES) model. 7-Chloro-5-(N-oxyaza)-QX (12a), 7-bromo-5-(N-oxyaza)-QX (12b), and 7-methyl-5-(N-oxyaza)-QX (12c) have ED50 values of 0.82, 0.87, and 0.97 mg/kg iv, respectively. The high in vivo potency of QXs 12a-e is particularly surprising given their low log P values (similar to-2.7). Separate studies indicate that QXs 12a and 12e are also active in vivo as neuroprotectants and also have antinociceptive activity in animal pain models. In terms of in vivo activity, these 5-(N-oxyaza)-7-substituted-QXs are among the most potent broad spectrum ionotropic glutamate antagonists reported.
• 8-AZA, 6-AZA AND 6,8-DIAZA-1,4-DIHYDROQUINOXALINE-2,3-DIONES AND THE USE THEREOF AS ANTAGONISTS FOR THE GLYCINE/NMDA RECEPTOR
  申请人：ACEA PHARMACEUTICALS, INC.

  公开号：EP0743855A1

  公开（公告）日：1996-11-27
• US5620978A
  申请人：——

  公开号：US5620978A

  公开（公告）日：1997-04-15
• US5863916A
  申请人：——

  公开号：US5863916A

  公开（公告）日：1999-01-26