4-羟基阿普唑仑 | 30896-57-2

• 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: 4-羟基阿普唑仑
• 英文名称: 4-Hydroxyalprazolam
• 英文别名: 8-chloro-1-methyl-6-phenyl-4H-s-triazolo<4,3-a><1,4>benzodiazepin-4-ol；(8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazol[4,3-a][1,4]benzodiazepin-4-ol)；α-hydroxyalprazolam；8-chloro-1-methyl-6-phenyl-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-4-ol；1-methyl-4-hydroxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine；8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-ol
• CAS: 30896-57-2
• 化学式: C₁₇H₁₃ClN₄O
• 分子量: 324.769
• InChiKey: CEYGCFLPQFNPST-UHFFFAOYSA-N

物化性质

• 熔点：
  160-1620C
• 沸点：
  559.2±60.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：8mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

4-羟基安普那唑仑是人代谢安普那唑仑的已知产物。

4-Hydroxyalprazolam is a known human metabolite of alprazolam.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-羟基阿普唑仑 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以64.5%的产率得到8-chloro-5,6-dihydro-1-methyl-6-phenyl-4H-s-triazolo<4,3-a><1,4>benzodiazepin-4-one
  参考文献：
  名称：

  8-Chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4

  摘要：

  A series of 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4 was prepared and evaluated for antianxiety potential. It was found that substitution at this position generally decreased the activity in this series.

  DOI：

  10.1021/jm00180a012
• 作为产物：
  描述：

  阿普唑仑 在 sodium hydroxide 、 溶剂黄146 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 均三甲苯 为溶剂， 反应 19.75h， 生成 4-羟基阿普唑仑
  参考文献：
  名称：

  8-Chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4

  摘要：

  A series of 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4 was prepared and evaluated for antianxiety potential. It was found that substitution at this position generally decreased the activity in this series.

  DOI：

  10.1021/jm00180a012

文献信息

• Preparation of triazolo benzodiazepines and novel compounds
  申请人：Hoffman-La Roche Inc.

  公开号：US03954728A1

  公开（公告）日：1976-05-04

  Novel preparations of triazolobenzodiazepines are disclosed. Novel 6-pyridyl-4H-triazolo[4,3-a]-1,4-benzodiazepines and novel intermediates are also disclosed which are useful as anti-convulsants, muscle relaxants and sedative agents.

  揭示了三唑苯二氮䓬类化合物的新制备方法。还揭示了新的6-吡啶基-4H-三唑并[4,3-a]-1,4-苯二氮䓬类化合物和新的中间体，可用作抗抽搐药、肌肉松弛剂和镇静剂。
• One drop chemical derivatization - DESI-MS analysis for metabolite structure identification
  作者：Arnaud Lubin、Deirdre Cabooter、Patrick Augustijns、Filip Cuyckens

  DOI：10.1002/jms.3604

  日期：2015.7

  development process of new pharmaceutical drugs. Liquid Chromatography (LC) in combination with Mass Spectrometry (MS) is usually the technique of choice for structural identification but cannot always provide precise structural identification of the studied metabolite (e.g. site of hydroxylation and site of glucuronidation). In order to identify those metabolites, different approaches are used combined

  代谢物的结构阐明是新药物开发和发现过程中的重要组成部分。液相色谱（LC）结合质谱（MS）通常是结构鉴定的首选技术，但不能始终提供所研究代谢物的精确结构鉴定（例如，羟基化位点和葡萄糖醛酸化位点）。为了鉴定这些代谢物，将不同的方法与MS数据结合使用，包括核磁共振，氢/氘交换和化学衍生化，然后进行LC-MS。这些技术通常很耗时，并且/或者需要额外的样品预处理。
• Benzodiazepines and their therapeutic use
  申请人：THE UPJOHN COMPANY

  公开号：EP0139460A2

  公开（公告）日：1985-05-02

  For treating the negative symptoms of schizophrenia in humans, a benzodiazepine of the formula wherein X is H, CH3, CH2OH, alkoxymethyl, alkanoyloxymethyl or carboxyalkanoyloxymethyl, Y is H or OH and Z is H or Cl, is used.

  为治疗人类精神分裂症的阴性症状，可使用一种苯二氮卓类药物，其式中 X 为 H、CH3、CH2OH、烷氧基甲基、烷酰氧基甲基或羧基烷酰氧基甲基，Y 为 H 或 OH，Z 为 H 或 Cl。
• Prediction of metabolic clearance using fresh human hepatocytes: Comparison with cryopreserved hepatocytes and hepatic microsomes for five benzodiazepines
  作者：D. Hallifax、A. Galetin、J. B. Houston

  DOI：10.1080/00498250701834665

  日期：2008.4

  1. Predictions of in vivo intrinsic clearance from cryopreserved human hepatocytes may be systematically low. In the current study, the metabolite kinetics of a series of CYP3A4 substrates (benzodiazepines) in fresh human hepatocytes from five donors, via a major UK supplier, were investigated and compared with those previously reported (by the authors' laboratory) for cryopreserved human hepatocytes and hepatic microsomes.2. A high incidence of autoactivation (up to tenfold) and heteroactivation (by testosterone, up to 14-fold) among the major pathways was observed. CYP capacity (V-max) was marginally lower and 'affinity' constants (K-M, S-50) were marginally greater compared with cryopreserved hepatocytes.3. Average intrinsic clearance (based on maximal clearance, CLmax) was sevenfold lower than in cryopreserved hepatocytes (reflecting sensitivity of intrinsic clearance estimation in vitro to mechanistic parameter values, particularly those involving atypical kinetics), but scaled intrinsic clearances for fresh (and cryopreserved) hepatocytes were within the range previously determined in hepatic microsomes.4. There was no evidence from this series of studies that fresh hepatocytes provide quantitatively improved estimates of intrinsic clearance over cryopreserved hepatocytes.
• 3-Fluorobenzodiazepines
  作者：W.J. Middleton、E.M. Bingham、D.H. Smith

  DOI：10.1016/s0022-1139(00)85140-4

  日期：1983.12