N‐nitrosonorlevofloxacin | 1152314-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N‐nitrosonorlevofloxacin
• 英文别名: (3S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-nitroso-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic Acid；(2S)-7-fluoro-2-methyl-6-(4-nitrosopiperazin-1-yl)-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid
• CAS: 1152314-62-9
• 化学式: C₁₇H₁₇FN₄O₅
• 分子量: 376.344
• InChiKey: GNTZPZBXVIOIQQ-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N‐nitrosonorlevofloxacin 在 溶剂黄146 、 锌 作用下， 以 水 为溶剂， 反应 0.75h， 生成 (S)-(-)-9-(4-aminopiperazin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid trifluoroacetate
  参考文献：
  名称：

  [EN] KYNURENINE-AMINOTRANSFERASE INHIBITORS
  [FR] INHIBITEURS DE LA KYNURÉNINE-AMINOTRANSFÉRASE

  摘要：

  公开号：

  WO2009064836A3
• 作为产物：
  描述：

  9-氟-3-甲基-7-氧代-10-(1-哌嗪基)-2,3-二氢-7H-[1,4]恶嗪并[2,3,4-Ij]喹啉-6-羧酸 在 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 4.5h， 生成 N‐nitrosonorlevofloxacin
  参考文献：
  名称：

  [EN] KYNURENINE-AMINOTRANSFERASE INHIBITORS
  [FR] INHIBITEURS DE LA KYNURÉNINE-AMINOTRANSFÉRASE

  摘要：

  公开号：

  WO2009064836A3

文献信息

• Risk assessment for nitrosated pharmaceuticals: A future perspective in drug development
  作者：Sebastian Schmidtsdorff、Jonas Neumann、Alexander H. Schmidt、Maria K. Parr

  DOI：10.1002/ardp.202100435

  日期：2022.4

  drugs, antihistamines, and antibiotics also became the subject of investigation. The occurrence of NAs has shown that pharmaceutical companies and regulatory agencies did not focus on these substances in the past during drug development. In this study, we incorporated a nitrosation assay procedure into high-resolution supercritical fluid chromatography (SFC)–mass spectrometry screening to test the potential

  自 2018 年 6 月以来，由于意外存在亚硝胺 (NA)，不得不召回来自世界各地的数千种药品。从沙坦类药物组开始，降糖药、抗组胺药和抗生素也成为研究对象。NAs的出现表明，过去制药公司和监管机构在药物开发过程中并没有关注这些物质。在这项研究中，我们将亚硝化测定程序纳入高分辨率超临界流体色谱 (SFC)-质谱筛选中，以测试活性药物成分 (API) 直接亚硝化的潜力。强制降解研究使用相对于药物物质摩尔过量四倍的亚硝酸钠，在 pH 3-4 下，在 37°C 下持续 4 小时。通过 SFC 在多孔石墨碳柱上进行色谱分离。然后质量分析集中在直接 N-亚硝化或脱烷基化后形成N-亚硝基化合物 (NOC)。评估了来自不同药物类别的物质 ( n  = 67)，其中 49.3% 形成了 NOC，其中 21.2% 尚未在文献中报道。此外，对于已知形成一个未识别的 NOC 的两个 API，可以识别其结构。少数物质还显示出多种
• Crystal Structure-Based Selective Targeting of the Pyridoxal 5′-Phosphate Dependent Enzyme Kynurenine Aminotransferase II for Cognitive Enhancement
  作者：Franca Rossi、Casazza Valentina、Silvia Garavaglia、Korrapati V. Sathyasaikumar、Robert Schwarcz、Shin-ichi Kojima、Keisuke Okuwaki、Shin-ichiro Ono、Yasushi Kajii、Menico Rizzi

  DOI：10.1021/jm100464k

  日期：2010.8.12

  Fluctuations in the brain levels of the neuromodulator kynurenic acid may control cognitive processes and play a causative role in several catastrophic brain diseases. Elimination of the pyridoxal 5'-phosphate dependent enzyme kynurenine aminotransferase II reduces cerebral kynurenic acid synthesis and has procognitive effects. The present description of the crystal structure of human kynurenine aminotransferase II in complex with its potent and specific primary amine-bearing fluoroquinolone inhibitor (S)-(-)-9-(4-aminopiperazin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-azaphenalene-5-carboxylic acid (BFF-122) should facilitate the structure-based development of cognition-enhancing drugs. From a medicinal chemistry perspective our results demonstrate that the issue of inhibitor specificity for highly conserved PLP-dependent enzymes could be successfully addressed.
• KYNURENINE-AMINOTRANSFERASE INHIBITORS
  申请人：Schwarcz Robert

  公开号：US20100273787A1

  公开（公告）日：2010-10-28

  Compounds of formula (I): prodrug derivatives and/or pharmaceutically acceptable salt thereof, selectively inhibit the enzyme kynurenine aminotransferase, thereby reducing the synthesis of kynurenic acid. The compounds are used for the treatment of psychiatric and neurological diseases which benefit from an increase in glutamatergic and/or cholinergic neurotransmission, such as schizophrenia, depression, bipolar illness, anxiety and Alzheimer's disease. Furthermore, the compounds of the invention are useful for stimulating attention, memory and other cognitive processes in normal individuals of any age, including children, adolescents and the elderly. Additionally, the compounds of the invention are also useful for treatment of patients suffering from malaria by preventing parasite gametogenesis and fertility based on reduction of xanthurenic acid formation from its bioprecursor 3-hydroxy kynurenine.