氯普唑仑 | 61197-73-7

• 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: 氯普唑仑
• 中文别名: 劳哌唑仑
• 英文名称: loprazolam
• 英文别名: 6-o-chlorophenyl-2,4-dihydro-2-(4-methyl-1-piperazinyl)methylene-8-nitro-1H-imidazo<1,2-a><1,4>benzodiazepin-1-one；6-(2-chloro-phenyl)-2-(4-methyl-piperazin-1-ylmethylene)-8-nitro-2,4-dihydro-benzo[6,7]imidazo[1,2-a][1,4]diazepin-1-one；(2Z)-6-(2-chlorophenyl)-2-[(4-methylpiperazin-1-yl)methylidene]-8-nitro-4H-imidazo[1,2-a][1,4]benzodiazepin-1-one
• CAS: 61197-73-7
• 化学式: C₂₃H₂₁ClN₆O₃
• 分子量: 464.911
• InChiKey: UTEFBSAVJNEPTR-RGEXLXHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  97.3
• 氢给体数：
  0
• 氢受体数：
  7

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，介导睡眠，以及与BNZ2结合，影响肌肉放松、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）受体相连，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，防止细胞进一步兴奋。

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，同时静脉输液，并保持气道通畅。低血压可以通过使用去甲肾上腺素或美拉明来对抗。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方法。尽管苯二氮卓可以通过活性炭吸收，但在纯苯二氮卓过量时，使用活性炭进行胃部净化并不有益，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。只有在苯二氮卓与其他可能从净化中受益的药物联合使用时，才建议使用。胃灌洗（胃抽吸）或全肠灌洗也不推荐。

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)

安全信息

• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 3249

反应信息

• 作为反应物：
  描述：

  氯普唑仑 在 palladium on activated charcoal 环己烯 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以80%的产率得到8-amino-6-o-chlorophenyl-2,4-dihydro-2-(4-methyl-1-piperazinyl)methylene-1H-imidazo<1,2-a><1,4>benzodiazepin-1-one
  参考文献：
  名称：

  Danswan; Kennewell; Tully, European Journal of Medicinal Chemistry, 1985, vol. 20, # 6, p. 541 - 546

  摘要：

  DOI：
• 作为产物：
  描述：

  8-nitro-1,2-dihydro-6-o-chlorophenyl-1H,4H-imidazo-[1,2-a][1,4]-benzodiazepin-1-one 、 1-(二甲氧基甲基)-4-甲基哌嗪 生成 氯普唑仑
  参考文献：
  名称：

  PROST-MARECHAL, J.

  摘要：

  DOI：

文献信息

• [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）。
• D-AMINO ACID OXIDASE INHIBITORS AND THERAPEUTIC USES THEREOF
  申请人：Tsai Guochuan Emil

  公开号：US20190112289A1

  公开（公告）日：2019-04-18

  The present invention relates to compounds of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: each of A, B, C, D, and E, independently, is C, N, N—H, O, S, or absent is a single bond or a double bond; each of X, Y, and Z, independently, is aryl, heteroaryl, aralkyl, H, or absent; each of L 1 and L 2 , independently, is a moiety selected from O, CH 2 , C═O, C 2-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, —((CH 2 ) n —W)—, wherein n=0, 1, 2, 3, 4, or 5, and W is O or S, or absent; and when L 2 is absent, Z is aryl or heteroaryl fused with B C. Also provided in the present invention is a method for inhibiting, treating and/or reducing the risk of a neuropsychiatric disorder, comprising administering a subject in need a composition comprising a compound of Formula (I).

  本发明涉及以下式（I）的化合物： 或其药学上可接受的盐，其中：A、B、C、D 和 E 中的每一个独立地是 C、N、N—H、O、S 或不存在 是单键或双键；X、Y 和 Z 中的每一个独立地是芳基、杂环芳基、芳基烷基、H 或不存在；L 1 和 L 2 中的每一个独立地是从 O、CH 2 、C═O、C 2-10 烷基、C 2-10 烯基、C 2-10 炔基、—((CH 2 ) n —W)— 中选择的基团，其中 n=0、1、2、3、4 或 5，W 是 O 或 S，或不存在；当 L 2 不存在时，Z 是与 B 相融合的芳基或杂环芳基。本发明还提供了一种用于抑制、治疗和/或减少神经精神障碍风险的方法，包括向需要的受试者施用包含式（I）化合物的组合物。
• SOLUBLE GUANYLATE CYCLASE STIMULATORS
  申请人：Berger Raphaelle

  公开号：US20170174693A1

  公开（公告）日：2017-06-22

  The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R 1 , R 2 , R 4 , R a , and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

  该发明提供了Formula (I)的化合物或其药用盐，其中X、Y、Z、R1、R2、R4、Ra以及下标m、p和q如本文所述。这些化合物或其药用盐可以调节人体对环鸟苷酸单磷酸（“cGMP”）的产生，并通常适用于治疗和预防与扰乱的cGMP平衡相关的疾病。该发明还提供了包含Formula (I)的化合物或其药用盐的药物组合物。该发明还涉及使用这些化合物或其药用盐在治疗和预防上述疾病以及为此目的制备药物的方法。
• [EN] ANGIOTENSIN II RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS DE L'ANGIOTENSINE II
  申请人：NICOX SA

  公开号：WO2010015447A1

  公开（公告）日：2010-02-11

  A compound having the structure (formula 1) wherein R is a "sartan family" moiety Z is a nitroxy carrying moiety, or a pharmaceutically acceptable salt thereof. The compounds are active against hypertension.

  一种具有结构（式1）的化合物，其中R是“沙坦家族”基团，Z是携带亚硝基的基团，或其药用盐。这些化合物对高血压具有活性。