3-羟基氟硝西泮 | 67739-71-3

• 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: 3-羟基氟硝西泮
• 英文名称: 3-Hydroxyflunitrazepam
• 英文别名: flunitrazepam；5-(2-fluoro-phenyl)-3-hydroxy-1-methyl-7-nitro-1,3-dihydro-benzo[e][1,4]diazepin-2-one；7-Nitro-5-(2-fluorphenyl)-1,3-dihydro-3-hydroxy-1-methyl-2H-1,4-benzodiazepin-2-on；5-(2-fluorophenyl)-3-hydroxy-1-methyl-7-nitro-3H-1,4-benzodiazepin-2-one
• CAS: 67739-71-3
• 化学式: C₁₆H₁₂FN₃O₄
• 分子量: 329.287
• InChiKey: KJTUBZKMFRILQD-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：30mg/mL； DMF:PBS(pH 7.2)(1:1)：0.5 mg/ml； DMSO：25mg/mL；乙醇：1mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 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：
  98.7
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

3-羟基氟硝西泮是氟硝西泮的人类已知代谢物。

3-hydroxyflunitrazepam is a known human metabolite of flunitrazepam.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  氟硝西泮 在 human hepatocytes 、 Williams' Medium E cell culture medium 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 3-羟基氟硝西泮
  参考文献：
  名称：

  Prediction of metabolic clearance using fresh human hepatocytes: Comparison with cryopreserved hepatocytes and hepatic microsomes for five benzodiazepines

  摘要：

  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.

  DOI：

  10.1080/00498250701834665

文献信息

• Arzneimittel, enthaltend 5-(2-Fluorphenyl)-1,3-dihydro-3-hydroxy-7-nitro- oder 5-(2-Fluorphenyl)-1,3-dihydro-3-hydroxy-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-on und Verfahren zur deren Herstellung
  申请人：Dolorgiet Beteiligungs-GmbH

  公开号：EP0158267A2

  公开（公告）日：1985-10-16

  5-(2-Fluorphenyl)-1,3-dihydro-3-hydroxy-1-methyl-7-nitro- und 5-(2-Fluorphenyl)-1,3-dihydro-3-hydroxy-7-nitro-2H-1,4-benzodiazepin-2-on sind unbedeutende Metabolite des Flunitrazepams, die selbst ausgezeichnete pharmakologische Wirksamkeit aufweisen. Außer der Verwendung zur Herstellung von Arzneimitteln wird die Herstellung dieser Substanzen beschrieben.

  5-(2-氟苯基)-1,3-二氢-3-羟基-1-甲基-7-硝基-和 5-(2-氟苯基)-1,3-二氢-3-羟基-7-硝基-2H-1,4-苯并二氮杂卓-2-酮是氟硝西泮的微量代谢物，它们本身具有出色的药理活性。除了用于制药外，还介绍了这些物质的制造方法。
• POSSELT, K.;WAGENER, H. H.;GRUBER, K.
  作者：POSSELT, K.、WAGENER, H. H.、GRUBER, K.

  DOI：——

  日期：——
• 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.