麦达西泮 | 2898-12-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 麦达西泮
• 中文别名: 美达西泮
• 英文名称: medazepam
• 英文别名: 7-chloro-5-phenyl-1-methyl-2,3-dihydro-1H-1,4-benzodiazepine；7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine；7-chloro-2,3-dihydro-1-methyl-5-phenyl-1,4-benzodiazepine；7-chloro-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin；7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepine；7-chloro-1-methyl-5-phenyl-2,3-dihydro-1,4-benzodiazepine
• CAS: 2898-12-6
• 化学式: C₁₆H₁₅ClN₂
• 分子量: 270.762
• InChiKey: YLCXGBZIZBEVPZ-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：
  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  15.6
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

毒理性

• 毒性总结

苯二氮卓类药物非特异性地与苯二氮卓受体BNZ1结合，后者介导睡眠，以及与BNZ2结合，影响肌肉松弛、抗惊厥活性、运动协调和记忆。由于认为苯二氮卓受体与γ-氨基丁酸-A (GABAA) 受体相耦合，这通过增加GABA对GABA受体的亲和力来增强GABA的效果。抑制性神经递质GABA结合到该位点时，会打开氯离子通道，导致细胞膜超极化，阻止细胞进一步兴奋。

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露处理

一般支持性措施应予以实施，包括静脉输液，并保持气道通畅。低血压可以通过使用去甲肾上腺素或美芬丁胺来对抗。透析的价值有限。氟马西尼（安易醒）是一种竞争性的苯二氮卓受体拮抗剂，可以用作苯二氮卓过量的解毒剂。特别是，氟马西尼在逆转与苯二氮卓相关的中枢神经系统抑制方面非常有效，但在逆转呼吸抑制方面效果较差。然而，其使用存在争议，因为它有许多禁忌症。长期使用苯二氮卓的患者、摄入降低癫痫发作阈值的物质的患者，或有心动过速或癫痫病史的患者禁忌使用。通常情况下，医疗观察和支持性护理是治疗苯二氮卓过量的主要手段。尽管苯二氮卓可以被活性炭吸收，但在纯苯二氮卓过量中，使用活性炭进行胃部净化并不有益，因为不良反应的风险往往超过了该程序可能带来的任何潜在好处。只有在苯二氮卓与其他可能从净化中受益的药物一起服用时，才建议使用。胃灌洗（胃抽吸）或全肠道灌洗也不建议使用。

General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. Flumazenil (Anexate) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. In particular, flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. Its use, however, is controversial as it has numerous contraindications. It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia or a history of seizures. As a general rule, medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects often outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended.

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  麦达西泮 在 水 、 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 9-chloro-4,5,6,10b-tetrahydro-1-amino-6-methyl-10b-phenylazetidino<1,2-d><1,4>benzodiazepine-2-one tosylate
  参考文献：
  名称：

  Gunda, Tamas E.; Enebaeck, Carl, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1983, vol. 37, # 1, p. 75 - 76

  摘要：

  DOI：
• 作为产物：
  描述：

  地西泮 在 盐酸 、 二硼烷(4) 作用下， 以 四氢呋喃 、 ice-water 为溶剂， 生成 麦达西泮
  参考文献：
  名称：

  Process for preparing 1,4-benzodiazepines

  摘要：

  1,4-苯二氮䓬啉衍生物的化学式为，其中R₁为氢、较低的烷基、卤代烷基、环烷基烷基、烷氧基烷基、酰氧基烷基、烷硫基烷基、烷基氨基烷基、二烷基氨基烷基、羟基烷基、氨基甲酰基或N-烷基甲酰基；R₂为氢或较低的烷基；X为氢、卤素、硝基或三氟甲基；A为化学式的基团，其中Y和Z分别表示氢、卤素、较低的烷基或硝基，并且其盐，通过将化学式的1,4-苯二氮䓬啉-2-酮化合物与二硼烷在惰性溶剂中反应制备。

  公开号：

  US04044003A1

文献信息

• Substituted 1,3-thiazole compounds, their production and use
  申请人：——

  公开号：US20040053973A1

  公开（公告）日：2004-03-18

  (1) A 1,3-thiazole compound of which the 5-position is substituted with a 4-pyridyl group having a substituent including no aromatic group or (2) a 1,3-thiazole compound of which the 5-position is substituted with a pyridyl group having at the position adjacent to a nitrogen atom of the pyridyl group a substituent including no aromatic group has an excellent p38 MAP kinase inhibitory activity.

  (1) 一种1,3-噻唑化合物，其5位被取代为含有一个取代基的4-吡啶基团，该取代基不包括芳香基，或者(2) 一种1,3-噻唑化合物，其5位被取代为一个吡啶基团，该吡啶基团的氮原子邻近位置有一个取代基，该取代基不包括芳香基，具有出色的p38 MAP激酶抑制活性。
• [EN] TREATMENT OF AUTISM SPECTRUM DISORDERS, OBSESSIVE-COMPULSIVE DISORDER AND ANXIETY DISORDERS<br/>[FR] TRAITEMENT DE TROUBLES DU SPECTRE AUTISTIQUE, DE TROUBLES OBSESSIVO-COMPULSIFS ET DE TROUBLES DE L'ANXIÉTÉ
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2018098128A1

  公开（公告）日：2018-05-31

  Disclosed are methods for treating NMDA receptor-mediated disorders by administering certain NR2B subunit-selective NMDA (N methyl-D aspartate) antagonists. NMDA receptor-mediated disorders include autism spectrum disorders, obsessive-compulsive disorder and anxiety disorders.

  揭示了通过给予特定NR2B亚单位选择性NMDA（N-甲基-D-天冬氨酸）拮抗剂来治疗NMDA受体介导的疾病的方法。NMDA受体介导的疾病包括自闭症谱系障碍、强迫症和焦虑症。
• [EN] TREATMENT OF ANXIETY DISORDERS AND AUTISM SPECTRUM DISORDERS<br/>[FR] TRAITEMENT DES TROUBLES DE L'ANXIÉTÉ ET DES TROUBLES DU SPECTRE AUTISTIQUE
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2016049048A1

  公开（公告）日：2016-03-31

  Disclosed are methods for treating autism spectrum disorders and/or anxiety disorders by administering certain NR2B subunit-selective NMDA (N methyl-D aspartate) antagonists. Anxiety disorders include agoraphobia (with or without panic disorder), generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder (PD), post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD).

  本文披露了通过给予特定NR2B亚单位选择性NMDA（N-甲基-D-天冬氨酸）拮抗剂来治疗自闭症谱系障碍和/或焦虑障碍的方法。焦虑障碍包括广场恐惧症（伴有或不伴有惊恐障碍）、广泛性焦虑障碍（GAD）、社交焦虑障碍（SAD）、惊恐障碍（PD）、创伤后应激障碍（PTSD）和强迫症（OCD）。
• A direct preparation of 1,4-benzodiazepines. The synthesis of medazepam and related compounds via a common intermediate
  作者：George A. Kraus、Hiroshi Maeda

  DOI：10.1016/0040-4039(94)88461-7

  日期：1994.12

  The benzodiazepine skeleton was prepared from benzoquinone in three steps. Medazepam was prepared from 9.

  苯二氮卓骨架是由苯醌分三步制备的。美沙西m是从9准备的。
• BENZAZEPINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1422228A1

  公开（公告）日：2004-05-26

  The present invention provides a novel benzazepine derivative represented by formula : wherein, R1 is a 5- or 6-membered aromatic ring, R2 is lower alkyl group, etc., Y is an optionally substituted imino group, ring A and ring B are independently an optionally substituted aromatic ring, W is formula -W1-X2-W2- (W1 and W2 are independently S(O)m1 (m1 is 0, 1 or 2), etc., and X2 is an optionally substituted alkylene groupetc. ), a preparation method and use thereof.

  本发明提供了一种新型的苯并氮杂环衍生物，其由以下公式表示： 其中，R1是一个5-或6-成员的芳香环，R2是低级烷基团等，Y是可选地取代的亚氨基，环A和环B是独立地选自一个可选地取代的芳香环，W是公式-W1-X2-W2-（W1和W2是独立地为S(O)m1（m1是0、1或2）等，X2是一个可选地取代的亚烷基团等），其制备方法及其用途。

表征谱图