溴西泮 | 1812-30-2

• 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: 溴西泮
• 中文别名: 7-溴-5-(2-吡啶基)-3H-1,4-苯并二氮杂卓-2(1H)-酮；滇西泮
• 英文名称: bromazepam
• 英文别名: 7-bromo-5-(pyridin-2-yl)-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one；7-bromo-5-pyridin-2-yl-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 1812-30-2
• 化学式: C₁₄H₁₀BrN₃O
• 分子量: 316.157
• InChiKey: VMIYHDSEFNYJSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

肝脏通过氧化途径（通过细胞色素P450酶家族的一种酶）进行代谢。主要的代谢物之一是3-羟基溴安定。它具有药理活性，半衰期与母体化合物相似。

Hepatically, via oxidative pathways (via an enzyme belonging to the Cytochrome P450 family of enzymes). One of the main metabolites is 3-hydroxybromazepam. It is pharmacologically active and the half life is similar to that of the parent compound.

来源:DrugBank

代谢

溴马扎苯已知的人类代谢物包括3-羟基溴马扎苯。

Bromazepam has known human metabolites that include 3-Hydroxybromazepam.

来源:NORMAN Suspect List Exchange

代谢

肝脏通过氧化途径（通过细胞色素P450酶家族的一种酶）代谢。主要代谢物之一是3-羟基溴安定。它具有药理活性，半衰期与母体化合物相似。 消除途径：尿液（69%），以代谢物形式排出。 半衰期：10-20小时

Hepatically, via oxidative pathways (via an enzyme belonging to the Cytochrome P450 family of enzymes). One of the main metabolites is 3-hydroxybromazepam. It is pharmacologically active and the half life is similar to that of the parent compound. Route of Elimination: Urine (69%), as metabolites Half Life: 10-20 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

Bromazepam 结合到 GABA 受体 GABA_A 上，引起构象改变并增加 GABA 的抑制效果。其他神经递质不受影响。

Bromazepam binds to the GABA receptor GABA_A, causing a conformational change and increasing inhibitory effects of GABA. Other neurotransmitters are not influenced.

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名录）。

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

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

它们会导致说话含糊不清、迷失方向和“醉酒”行为。它们在身体和心理上都具有成瘾性。

They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

生物利用度为84%。达到最高血浆浓度的时间为1-4小时。溴酸唑仑在口服给药后通常能很好地吸收。

Bioavailability is 84% following oral administration. The time to peak plasma level is 1 - 4 hours. Bromazepam is generally well absorbed after oral administration.

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，同时配合静脉输液，并保持呼吸道通畅。低血压可以通过使用norepinephrine（去甲肾上腺素）或metaraminol（美拉明）来对抗。透析的价值有限。Flumazenil（安易醒）是一种竞争性的苯二氮卓受体拮抗剂，可以用作苯二氮卓类药物过量的解毒剂。特别是，flumazenil非常有效地逆转与苯二氮卓类药物相关的中枢神经系统抑制作用，但对逆转呼吸抑制的效果较差。然而，其使用存在争议，因为它有许多禁忌症。长期使用苯二氮卓类药物的患者、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。一般来说，医疗观察和支持性护理是治疗苯二氮卓类药物过量的主要方法。尽管苯二氮卓类药物可以被活性炭吸收，但在纯苯二氮卓类药物过量的情况下，使用活性炭进行胃部净化并无益处，因为不良反应的风险通常超过了该程序可能带来的任何潜在益处。只有在苯二氮卓类药物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)

吸收、分配和排泄

• 吸收

生物利用度为84%。达到最高血浆浓度的时间为1-4小时。溴氮平在口服给药后通常能很好地吸收。

Bioavailability is 84% following oral administration. The time to peak plasma level is 1 - 4 hours. Bromazepam is generally well absorbed after oral administration.

来源:DrugBank

吸收、分配和排泄

• 消除途径

尿液（69%），作为代谢物

Urine (69%), as metabolites

来源:DrugBank

吸收、分配和排泄

• 分布容积

1.56 升/千克

1.56 L/kg

来源:DrugBank

吸收、分配和排泄

• 清除

0.82毫升/分钟/千克。

0.82 mL/min/kg.

来源:DrugBank

反应信息

• 作为反应物：
  描述：

  溴西泮 在 tetraphosphorus decasulfide 作用下， 以 吡啶 为溶剂， 反应 1.0h， 以0.559 g的产率得到7-brom-1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepin-2-thion
  参考文献：
  名称：

  1-（氨基烷基）-6-芳基-4-Hs-三唑并[4,3-a] [1,4]苯并二氮杂卓具有抗焦虑和抗抑郁活性。

  摘要：

  已经制备了一系列的1-（氨基烷基）-6-芳基-4H-s-三唑并[4，3-a] [1，4]苯并二氮杂并评估中枢神经系统活性。我们发现该系列的成员在旨在检测抗焦虑和抗抑郁活性的药理学测试系统中具有活性。每种类型的活性可以通过适当的取代基选择独立地变化。

  DOI：

  10.1021/jm00178a009
• 作为产物：
  描述：

  di(4-oxo-3-(4-bromo-2-(2-pyridylcarbonyl)phenyl)imidazolidin-1-yl)methane 在 ammonium chloride 作用下， 以 乙醇 为溶剂， 以95%的产率得到溴西泮
  参考文献：
  名称：

  咪唑啉丁-4-酮的合成及其转化为1,4-苯并二氮杂-2-酮

  摘要：

  α-卤代乙酰苯胺Ia-e与乙醇中的六胺反应，生成双咪唑啉丁-4-酮衍生物IIa-e，该衍生物在酸性介质中水解成相应的单咪唑啉丁-4-酮Ⅲa-e。在不同条件下，在多种试剂的存在下，化合物IIa-d被转化为1,4-苯并二氮杂-2-酮。产率在50％至100％之间。

  DOI：

  10.1002/jhet.5570180523

文献信息

• [EN] COMPOUNDS AND THEIR USE AS BACE INHIBITORS<br/>[FR] COMPOSÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BACE
  申请人：ASTRAZENECA AB

  公开号：WO2016055858A1

  公开（公告）日：2016-04-14

  The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.

  本申请涉及式(I)、(Ia)或(Ib)的化合物及其药物组合物/制剂。本申请进一步涉及治疗或预防与Αβ相关的病理学，如唐氏综合症，β-淀粉样蛋白血管病，如但不限于脑淀粉样蛋白血管病或遗传性脑出血，与认知损害相关的疾病，如但不限于MCI（“轻度认知损害”），阿尔茨海默病，记忆丧失，与阿尔茨海默病相关的注意力缺陷症状，与疾病如阿尔茨海默病或痴呆症相关的神经退行性疾病，包括混合性血管性和退行性起源的痴呆，早老性痴呆，老年性痴呆和与帕金森病相关的痴呆的方法。
• 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] IMIDAZOPYRIDINE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS IMIDAZOPYRIDINE ET LEURS UTILISATIONS
  申请人：NEOMED INST

  公开号：WO2014117274A1

  公开（公告）日：2014-08-07

  This invention generally relates to substituted imidazopyridine compounds, particularly substituted 4-(imidazo[1,2-a]pyridin-2-yl)benzamide compounds and salts thereof. This invention also relates to pharmaceutical compositions and kits comprising such a compound, uses of such a compound (including, for example, treatment methods and medicament preparations), processes for making such a compound, and intermediates used in such processes.

  这项发明通常涉及取代咪唑吡啶化合物，特别是取代的4-(咪唑[1,2-a]吡啶-2-基)苯甲酰胺化合物及其盐。这项发明还涉及包含这种化合物的药物组合物和试剂盒，以及这种化合物的用途（包括治疗方法和药物制剂等），制备这种化合物的方法，以及用于这些方法的中间体。
• [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）。

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