4'-羟基地西泮 | 17311-35-2

• 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'-羟基地西泮
• 英文名称: 4'-Hydroxy-Diazepam
• 英文别名: p-hydroxydiazepam；7-chloro-5-(4-hydroxy-phenyl)-1-methyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one；7-Chloro-1,3-dihydro-5-(4-hydroxyphenyl)-1-methyl-2H-1,4-benzodiazepin-2-on；4'-Hydroxydiazepam；7-chloro-5-(4-hydroxyphenyl)-1-methyl-3H-1,4-benzodiazepin-2-one
• CAS: 17311-35-2
• 化学式: C₁₆H₁₃ClN₂O₂
• 分子量: 300.744
• InChiKey: IQFWLIWUKIFGKP-UHFFFAOYSA-N

物化性质

• 熔点：
  254-260 °C(Solv: methanol (67-56-1))
• 沸点：
  553.2±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4'-羟基地西泮 、 氢溴酸 生成 5-Chlor-4'-hydroxy-2-methylaminobenzophenon
  参考文献：
  名称：

  EARLEY J. V.; FRYER R. I.; NING R. Y., J. PHARM. SCI., 1979, 68, NO 7, 845-850

  摘要：

  DOI：
• 作为产物：
  描述：

  7-氯-1,3-二氢-5-(4-羟基苯基)-2H-1,4-苯并二氮杂卓-2-酮 、 sodium methylate 、 碘甲烷 以6%的产率得到
  参考文献：
  名称：

  EARLEY J. V.; FRYER R. I.; NING R. Y., J. PHARM. SCI., 1979, 68, NO 7, 845-850

  摘要：

  DOI：

文献信息

• Benzodiazepine radioimmunoassay using I125-label
  申请人：Hoffmann-La Roche, Inc.

  公开号：US04083948A1

  公开（公告）日：1978-04-11

  An improved radioimmunoassay for benzodiazepines such as diazepam, chlordiazepoxide, oxazepam, demoxepam and metabolites thereof is disclosed. Such immunoassay employs novel .sup.125 I-labelled 4'-hydroxy derivatives of these compounds as tracer.

  本发明揭示了一种改进的放射免疫测定法，用于苯二氮平类药物，如地西泮，氯硝西泮，氧西泮，地莫西泮及其代谢物的检测。这种免疫测定法采用新型的 .sup.125 I标记的这些化合物的4'-羟基衍生物作为示踪剂。
• Kinetics of diazepam metabolism in rat hepatic microsomes and hepatocytes and their use in predicting in vivo hepatic clearance
  作者：K. Zomorodi、D. J. Carlile、J. B. Houston

  DOI：10.3109/00498259509046662

  日期：1995.1

  1. The rates of diazepam (DZ) metabolism to the primary metabolites 3-hydroxydiazepam, 4'-hydroxydiazepam and nordiazepam were studied in vitro using rat hepatic microsomes and hepatocytes. 4'-hydroxydiazepam had the largest intrinsic clearance (V-max/K-m ratio, CL(int)) in both microsomes and hepatocytes representing 49 and 70% of total metabolism respectively. Whereas the contribution of 3-hydroxydiazepam was similar in both systems (21-24%), the N-demethylation pathway was greater in microsomes (27%) than hepatocytes (9%).2. The pharmacokinetics of DZ were determined in vivo using the intraportal route to avoid blood flow limitations due to the high clearance of DZ. No dose dependency was observed in either clearance or steady state volume of distribution, which were estimated to be 38 ml/min/SRW (where SRW is a standard rat weight of 250 g) and 1.3 L/SRW respectively. Blood binding of DZ was concentration independent, the unbound fraction being 0.22.3. Scaling factors were used to relate the in vitro CL(int) to the in vivo unbound clearance. Hepatocytes (123 ml/min/SRW) produced a more realistic prediction for the in vivo value (174 ml/min/SRW) than microsomes (41 ml/min/SRW). This situation is believed to arise from the quantitative differences in the three metabolic pathways in the two in vitro systems. It is speculated that end product inhibition is responsible for reduced total metabolism in microsomes whereas hepatocytes operate kinetically in a manner close to in vivo.
• US4083948A
  申请人：——

  公开号：US4083948A

  公开（公告）日：1978-04-11