CLZox | 173321-32-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: CLZox
• 英文别名: 3-Chloro-6-(4-methylpiperazin-1-ium-1-ylidene)benzo[b][1,4]benzodiazepine
• CAS: 173321-32-9
• 化学式: C₁₈H₁₈ClN₄
• 分子量: 325.821
• InChiKey: SSFSRNHHRNZBOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  31
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  氯氮平 在 甲酸铵 作用下， 以 水 、 乙腈 为溶剂， 生成 CLZox
  参考文献：
  名称：

  探针电喷雾电离质谱与耦合电化学

  摘要：

  提出了使用探针电喷雾电离（PESI）的电化学与质谱（MS）的新耦合方法。由于PESI具有很高的耐盐性，因此首次实现了室温离子液体（RTIL）中电化学反应产物的检测。此外，PESI-MS可以分析不同或多个电极表面上的电化学反应产物。此外，还可以使用PESI-MS直接分析在外部电场存在下通过等电聚焦（IEF）分离的肽和蛋白质，这为IEF技术提供了一种新的快速表征方法。这项研究揭示了EC / PESI-MS的多功能性，这可能会对电化学和生物分析领域产生影响。

  DOI：

  10.1002/cphc.201600033

文献信息

• Covalent Protein Modification by Reactive Drug Metabolites Using Online Electrochemistry/Liquid Chromatography/Mass Spectrometry
  作者：Wiebke Lohmann、Heiko Hayen、Uwe Karst

  DOI：10.1021/ac801699g

  日期：2008.12.15

  We present a rapid and convenient method to perform and evaluate the covalent protein binding of reactive phase I metabolites. The oxidative metabolism of the drugs paracetamol, amodiaquine, and clozapine is simulated in an electrochemical (EC) flow-through cell, which is coupled online to an LC/MS system. Adduct formation of the reactive metabolites with the proteins β-lactoglobulin A and human serum albumin proceeds in a reaction coil between EC cell and injection system of the HPLC system. The formed drug−protein adducts are characterized with online time-of-flight mass spectrometry, and the modification site is localized using FTICR-mass spectrometry. Due to its simple setup, easy handling, and short analysis times, the method provides an interesting tool for the rapid risk assessment of covalent protein binding as well as for the synthesis of covalent drug−protein adducts in high purity and high yield.

  我们提出了一种快速便捷的方法来执行和评估反应性 I 相代谢物的共价蛋白结合。药物扑热息痛、阿莫地喹和氯氮平的氧化代谢在电化学 (EC) 流通池中进行模拟，该池与 LC/MS 系统在线耦合。反应性代谢物与蛋白质β-乳球蛋白A和人血清白蛋白的加合物形成在EC细胞和HPLC系统的注射系统之间的反应线圈中进行。形成的药物-蛋白质加合物通过在线飞行时间质谱进行表征，并使用 FTICR 质谱定位修饰位点。由于其设置简单、操作方便且分析时间短，该方法为共价蛋白结合的快速风险评估以及高纯度和高产率的共价药物-蛋白加合物的合成提供了一种有趣的工具。
• 7-FLUORO-8-CHLORO-5 -DIBENZO[B,E][1,4]DIAZEPINE DERIVATIVES AND USE THEREOF
  申请人：Limited Liability Company "Valentek"

  公开号：EP3192513A1

  公开（公告）日：2017-07-19

  This invention relates to medicine, in particular to pharmacology and psychiatry, and can be used for the manufacture of medications for treatment of treatment-resistant forms of schizophrenia. For this purpose we proposed the use of compounds 11-(piperazine-1-yl)-7-fluoro-8-chloro-5H-dibenzo[b,e][1,4]diazepine, 11-(4-methyl piperazine-1-yl)-7-fluoro-8-chloro-5H-dibenzo[b,e][1,4]diazepine, pharmaceutically acceptable salts, hydrates or solvates thereof. The invention allows developing an effective medication, the use of which in treatment of treatment-resistant forms of schizophrenia allows for eliminating both the positive and negative symptoms of schizophrenia, and cognitive disorders, and the use of which does not cause severe side effects that limit its use, including sedation, tachycardia, orthostatism, agranulocytosis and sialorrhea.

  本发明涉及医学，特别是药理学和精神病学，可用于制造治疗耐药型精神分裂症的药物。为此，我们建议使用化合物 11-(哌嗪-1-基)-7-氟-8-氯-5H-二苯并[b,e][1,4]二氮杂卓、11-(4-甲基哌嗪-1-基)-7-氟-8-氯-5H-二苯并[b,e][1,4]二氮杂卓、其药学上可接受的盐、水合物或溶液。本发明可以开发出一种有效的药物，使用该药物治疗耐药型精神分裂症可以消除精神分裂症的阳性症状和阴性症状以及认知障碍，而且使用该药物不会产生限制其使用的严重副作用，包括镇静、心动过速、正位、粒细胞减少和鼻出血。
• DERIVATIVES OF 7-FLUORO-8-CHLORO-5H-DIBENZO [B,E,] [1,4] DIAZEPINE AND USE THEREOF
  申请人：VALENTEK LLC

  公开号：US20170196883A1

  公开（公告）日：2017-07-13

  This present disclosure generally relates to medicine, and in particular to pharmacology and psychiatry, and discloses active agents and related methods of treatment which can be used for the treatment of treatment-resistant forms of schizophrenia. In some exemplary aspects, such treatments allow for eliminating both the positive and negative symptoms of schizophrenia, and cognitive disorders, without causing severe side effects that limit their use, such as sedation, tachycardia, orthostatism, agranulocytosis and sialorrhea.
• PHARMACEUTICAL COMPOSITION FOR TREATING FUNCTIONAL PSYCHIATRIC DISORDERS
  申请人：OBSCHESTVO S OGRANICHENNOI OTVETSTVENNOSTYU "VALENTIK"

  公开号：US20190275059A1

  公开（公告）日：2019-09-12

  The group of inventions relates to medicine, pharmacology, namely to psychiatry and can be used for effective and safe treatment of mental disorders associated with dysfunction of dopamine and serotonin (5-hydroxytryptamine) neurotransmitter systems. Pharmaceutical compositions containing halogenated clozapine, in an amount effective as selective antagonists of D4 and 5NT2A receptors, and at least one pharmaceutically acceptable carrier, as well as their use and methods of treatment are offered for this purpose. The inventions make it possible to create a new drug with a well-balanced receptor profile, the intake of which will allow to treat mental disorders in an effective way without causing side effects associated with exposure to receptors that are not involved in the pathology of a mental disorder.
• Coupling Electrochemistry with Probe Electrospray Ionization Mass Spectrometry
  作者：Yi Cai、Pengyuan Liu、Michael A. Held、Howard D. Dewald、Hao Chen

  DOI：10.1002/cphc.201600033

  日期：2016.4.18

  A new coupling of electrochemistry with mass spectrometry (MS) using probe electrospray ionization (PESI) is presented. Due to the high salt tolerance of PESI, the detection of electrochemical reaction products in room‐temperature ionic liquids (RTILs) is realized for the first time. Furthermore, PESI‐MS allows the analysis of electrochemical reaction products on different or multiple electrode surfaces

  提出了使用探针电喷雾电离（PESI）的电化学与质谱（MS）的新耦合方法。由于PESI具有很高的耐盐性，因此首次实现了室温离子液体（RTIL）中电化学反应产物的检测。此外，PESI-MS可以分析不同或多个电极表面上的电化学反应产物。此外，还可以使用PESI-MS直接分析在外部电场存在下通过等电聚焦（IEF）分离的肽和蛋白质，这为IEF技术提供了一种新的快速表征方法。这项研究揭示了EC / PESI-MS的多功能性，这可能会对电化学和生物分析领域产生影响。