氯赛唑仑 | 24166-13-0

• 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: 氯赛唑仑
• 中文别名: 氯噁唑仑
• 英文名称: cloxazolam
• 英文别名: 13-chloro-2-(2-chlorophenyl)-3-oxa-6,9-diazatricyclo[8.4.0.0^2,6]tetradeca-1(10),11,13-trien-8-one；10-chloro-11b-(2-chlorophenyl)-2,3,7,11b-tetrahydrooxazolo[3,2-d][1,4]benzodiazepin-6(5H)-one；akton；10-chloro-11b-(2-chloro-phenyl)-2,3,7,11b-tetrahydro-benzo[f]oxazolo[3,2-d][1,4]diazepin-6-one；10-chloro-11b-(o-chlorophenyl)-2,3,5,11b-tetrahydro-oxazolo[3,2-d][1,4]benzodiazepin-6-(7H)-one；10-chloro-11b-(2-chlorophenyl)-2,3,5,7-tetrahydro-[1,3]oxazolo[3,2-d][1,4]benzodiazepin-6-one
• CAS: 24166-13-0
• 化学式: C₁₇H₁₄Cl₂N₂O₂
• 分子量: 349.216
• InChiKey: ZIXNZOBDFKSQTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

Cloxazolam 由肝脏代谢为活性代谢物 chlordesmethyldiazepam（delorazepam）。

Cloxazolam is metabolised by the liver into the active metabolite chlordesmethyldiazepam (delorazepam). [5]

来源:DrugBank

代谢

克洛沙唑仑通过肝脏代谢为活性代谢物氯去甲基安定（地洛拉唑仑）。[5] 消除途径：肾脏排泄。 半衰期：65小时

Cloxazolam is metabolised by the liver into the active metabolite chlordesmethyldiazepam (delorazepam). [5] Route of Elimination: Renal elimination. Half Life: 65 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

Cloxazolam是一种长效的苯二氮䓬类药物。它作为一种前药，具有药理活性的代谢物，这些代谢物会结合到GABAa受体上，其他苯二氮䓬类药物也是通过与这个受体结合来引发生理反应的。

Cloxazolam is a long acting benzodiazepine. It acts as a prodrug, with pharmacologically active metabolites, which bind to to the GABAa receptor, which other benzodiazepines bind to, to illicit a physiological response.

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

• 症状

嗜睡和共济失调与剂量有关。中枢神经系统毒性可能导致呼吸抑制和意识丧失。因此，预先存在的中枢神经系统抑制和严重肝功能损害是使用该药物的两种特别禁忌症。

Drowsiness and ataxia are dose related. Central nervous system toxicity may result in respiratory depression and loss of consciousness. As such, pre-existing central nervous system depression and severe hepatic impairment are two particular contraindications for use.

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)

吸收、分配和排泄

• 消除途径

肾脏排泄。

Renal elimination.

来源:DrugBank

反应信息

• 作为反应物：
  描述：

  氯赛唑仑 生成 10-chloro-11b-(2-chloro-phenyl)-7-ethyl-2,3,7,11b-tetrahydro-benzo[f]oxazolo[3,2-d][1,4]diazepin-6-one
  参考文献：
  名称：

  抗焦虑镇静剂。1.苯并[6,7] -1,4-二氮杂[5,4-b]恶唑衍生物及其类似物的合成及药理作用。

  摘要：

  DOI：

  10.1021/jm00288a015
• 作为产物：
  描述：

  7-chloro-5-(2-chlorophenyl)-4-(2-hydroxyethyl)-1,3-dihydro-1,4-benzodiazepin-4-ium-2-one 以 乙醇 、 水 为溶剂， 生成 氯赛唑仑
  参考文献：
  名称：

  Kinetics and mechanism of the acid-base equilibrium of mexazolam and comparison with those of other commercial benzodiazepinooxazole drugs.

  摘要：

  研究了美沙班（mexazolam）、氯沙班（cloxazolam）、氟沙班（haloxazolam）和氟噻班（flutazolam）的噻唑啉环开环和闭环反应，采用pH跳跃法，与之前报道的噻唑班（oxazolam）情况类似 [Kurono et al., Chem. Pharm. Bull., 33, 1633 (1985)]。美沙班基本上以单一异构体存在，既可以是顺式，也可以是反式（指的是3-甲基基团和11b-(2'-氯苯基)基团），与噻唑班的情况不同（噻唑班的顺式异构体/反式异构体比例约为1:1）。在pH范围1-13内，pH-速度曲线显示出两步反应。为了对这些曲线进行解释，我们提出了一种反应机制，包括通过动力学方法检测到的中间体，该中间体位于亚胺结构（噻唑啉环开环形式）和闭环形式之间。这些美沙班的动力学特性与其他苯二氮平噻唑类化合物的特性不同，这种差异是由于3-甲基基团的存在，而不是2'-氯原子的存在。根据适当的反应机制，确定了美沙班及其缺乏2'-氯的类似物（3-甲基化合物）、氯沙班、氟沙班和氟噻班的内在速率常数。

  DOI：

  10.1248/cpb.35.3831

文献信息

• [EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2013181135A1

  公开（公告）日：2013-12-05

  The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.

  该披露涉及喹唑啉衍生物、组合物以及相关方法。在某些实施例中，该披露涉及NADPH-氧化酶（Nox酶）和/或髓过氧化物酶的抑制剂。
• 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。
• 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。
• [EN] HETEROCYCLIC COMPOUNDS AND THEIR USE AS RETINOID-RELATED ORPHAN RECEPTOR (ROR) GAMMA-T INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS GAMMA-T DU RÉCEPTEUR ORPHELIN APPARENTÉ AUX RÉCEPTEURS DES RÉTINOÏDES (ROR) )
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2016002968A1

  公开（公告）日：2016-01-07

  Provided are heterocyclic compounds having a RORγt inhibitory action represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  提供的是具有RORγt抑制作用的杂环化合物，其由公式(I)表示：其中每个符号如说明书中定义，或其盐。
• [EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DE RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：ARENA PHARM INC

  公开号：WO2017023679A1

  公开（公告）日：2017-02-09

  Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.

  在某些实施例中提供了一些符合本文所定义的A式化合物，其调节5-HT2C受体的活性。在某些实施例中还提供了一些方法，例如用于体重管理、诱导饱腹感、减少食物摄入，以及预防和治疗肥胖、抗精神病药物引起的体重增加、2型糖尿病、普拉德-威利综合征、烟草/尼古丁依赖、药物成瘾、酒精成瘾、病理性赌博、奖赏缺乏综合征和性成瘾，强迫症谱系障碍和冲动控制障碍（包括咬指甲和咬甲症），睡眠障碍（包括失眠、睡眠结构碎裂和慢波睡眠紊乱），尿失禁，精神障碍（包括精神分裂症、厌食症和暴食症），阿尔茨海默病，性功能障碍，勃起功能障碍，癫痫，运动障碍（包括帕金森病和抗精神病药物引起的运动障碍），高血压，血脂异常，非酒精性脂肪肝病，肥胖相关肾脏疾病和睡眠呼吸暂停症。

表征谱图