7-氯-1,3-二氢-5-(4-羟基苯基)-2H-1,4-苯并二氮杂卓-2-酮 | 17270-12-1

• 物质功能分类: 医药中间体
• 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: 7-氯-1,3-二氢-5-(4-羟基苯基)-2H-1,4-苯并二氮杂卓-2-酮
• 英文名称: 4'-hydroxy-N-desmethyldiazepam
• 英文别名: 7-chloro-5-(4-hydroxy-phenyl)-1,3-dihydro-benzo[e][1,4]diazepin-2-one；7-chloro-1,3-dihydro-5-(4-hydroxyphenyl)-2H-1,4-benzodiazepin-2-one；2H-1,4-Benzodiazepin-2-one, 7-chloro-1,3-dihydro-5-(4-hydroxyphenyl)-；7-chloro-5-(4-hydroxyphenyl)-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 17270-12-1
• 化学式: C₁₅H₁₁ClN₂O₂
• 分子量: 286.718
• InChiKey: WVHIBVZUJQMFON-UHFFFAOYSA-N

物化性质

• 熔点：
  271-272 °C
• 沸点：
  509.9±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 储存条件：
  |-20°C|

反应信息

• 作为反应物：
  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 生成 7-氯-5-(4-甲氧基苯基)-1-甲基-3H-1,4-苯并二氮杂-2-酮
  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：

  去甲西泮 在 mouse liver microsomes 、 还原型辅酶II(NADPH)四钠盐 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 0.07h， 生成 7-氯-1,3-二氢-5-(4-羟基苯基)-2H-1,4-苯并二氮杂卓-2-酮
  参考文献：
  名称：

  Concentration-dependent metabolism of diazepam in mouse liver

  摘要：

  Previous mouse liver studies with diazepam (DZ), N-desmethyldiazepam (NZ), and temazepam (TZ) confirmed that under first-order conditions, DZ formed NZ and TZ in parallel. Oxazepam (OZ) was generated via NZ and not TZ despite that performed NZ and TZ were both capable of forming OZ. In the present studies, the concentration-dependent sequential metabolism of DZ was studied in perfused mouse livers and microsomes, with the aim of distinguishing the relative importance of NZ and TZ as precursors of OZ. In microsomal studies, the K(m)s and V(max)s, corrected for binding to microsomal proteins, were 34 mu M and 3.6 nmole/min per mg and 239 mu M and 18 nmole/min per mg, respectively, for N-demethylation and C-3-hydroxylation of DZ. The K(m)s and V(max)s for N-demethylation and C-3-hydroxylation of TZ and NZ, respectively, to form OZ, were 58 mu M and 2.5 nmole/min per mg and 311 mu M and 2 nmole/min per mg, respectively. The constants suggest that at low DZ concentrations, NZ formation predominates and is a major source of OZ, whereas at higher, DZ concentrations, TZ is the important source of OZ. In livers perfused will DZ at input concentrations of 13 to 35 mu M, the extraction ratio of DZ (E{DZ}) decreased from 0.83 to 0.60. NZ was the major metabolite formed although its appearance was less than proportionate with increasing DZ input concentration. By contrast, the formation of TZ increased disproportionately with increasing DZ concentration, whereas that for OZ decreased and paralleled the behavior of NZ. Computer simulations based on a tubular flow model and the in vitro enzymatic parameters provided a poor in vitro-organ correlation. The E{DZ}, appearance rates of the metabolites, and tire extraction ratio of formed NZ (E{NZ, DZ}) were poorly predicted; TZ was incorrectly identified as the major precursor of OZ. Simulations with optimized parameters improved the correlations and identified NZ as the major contributor of OZ. Saturation of DZ N-demethylation at higher DZ concentrations increased the role of TZ in the formation of OZ. The poor aqueous solubility (limiting the concentration range of substrates used in vitro), avid tissue binding mid the coupling of enzymatic reactions in liver favoring sequential metabolism, are possible explanations for the poor in vitro-organ correlation. This work emphasizes tire complexity of tire hepatic intracellular milieu for drug metabolism and the need for additional modeling efforts to adequately describe metabolite kinetics.

  DOI：

  10.1007/bf02354284

文献信息

• Immunoassay for N-desmethyldiazepam
  申请人：Hoffmann-La Roche Inc.

  公开号：US04191738A1

  公开（公告）日：1980-03-04

  Highly specific antibodies to N-desmethyldiazepam are obtained by using as an immunogen 4'-hydrazinocarbonylmethoxy-N-desmethyldiazepam coupled to an immunogenic carrier material such as bovine serum albumin. These antibodies can be employed in immunoassays for N-desmethyldiazepam which is a major metabolite of three important psychoactive drugs diazepam, chlordiazepoxide and clorazepate.

  通过使用4'-hydrazinocarbonylmethoxy-N-desmethyldiazepam作为免疫原，与免疫原载体材料（如牛血清白蛋白）偶联，可以获得高度特异性的N-去甲基地西泮抗体。这些抗体可以用于N-去甲基地西泮的免疫分析，N-去甲基地西泮是地西泮、氯硝西泮和克洛硝泮三种重要精神活性药物的主要代谢物。
• 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。
• Methods and compositions for treating diseases and conditions associated with mitochondrial function
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：EP2216073A1

  公开（公告）日：2010-08-11

  The present invention relates to chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, mitochondrial F1F0 ATP hydrolase associated disorders, and the like.

  本发明涉及化合物、发现化合物的方法及其治疗用途。特别是，本发明提供了作为治疗剂的化合物，用于治疗与程序性细胞死亡、自身免疫、炎症、过度增殖、线粒体 F1F0 ATP水解酶相关紊乱等过程的调节失误有关的多种疾病。
• Benzodiazepines and compositions and uses thereof
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：EP2422788A2

  公开（公告）日：2012-02-29

  The present invention relates to a compound represented by: or a pharmaceutically acceptable salt thereof; wherein R2 is selected from the group consisting of Hydrogen, alkyl, and substituted alkyl; R3 is selected from the group consisting of hydrogen, halogen, alkyl, substituted alkyl, carboxylic acid, amide SO2NH2, NHSO2alkyl, and NO2; X is selected from the group consisting of alkyl, substituted alkyl, sulfolamide, SO2alkyl, NHSO2, CH2, CH2CH2, SO2, CH2SO2, SO2CH2, OCH2CH2O, SO, CH2CH2SO, SOCH2CH2; and L, M and N are present or absent, and are selected from the group consisting of alkyl, NO2, halogen, OH, O-Alkyl, methyl ester, propyl ester, ethyl ester, CO2H, CF3, aniline, nitro, heterocycle, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl, hydrogen, SO2NH2, SO2NH-alkyl, SOalkyl, and NHSO2alkyl; Y is selected from the group consisting of hydrogen, alkyl, substituted alkyl, halogen, OH, O-Alkyl, methyl ester, propyl ester, ethyl ester, CO2H, nitro, heterocycle, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl, SOalkyl, SO2NH2, SO2NH-alkyl, NHSO2alkyl, and WW, XX, YY and ZZ are present or absent, and are selected from the group consisting of alkyl, halogen, OH, O-Alkyl, methyl ester, propyl ester, ethyl ester, CO2H, aniline, nitro, heterocycle, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl, hydrogen, SO2NH2, SO2NH-alkyl, and NHSO2alkyl; and Z is selected from the group consisting of wherein R5 is selected from the group consisting of alkyl, mono-substituted alkyl, di-substituted alkyl, and tri-substituted alkyl.

  本发明涉及一种由以下物质代表的化合物： 或其药学上可接受的盐； 其中 R2 选自由氢、烷基和取代烷基组成的组； R3选自由氢、卤素、烷基、取代烷基、羧酸、酰胺SO2NH2、NHSO2烷基和NO2组成的组； X 选自以下组成的组 烷基、取代 X选自由烷基、取代烷基、磺酰胺、SO2烷基、NHSO2、CH2、 、SO2、 SO2、SO2 、O O、SO、 SO、SO 组成的组；以及 L、M 和 N 存在或不存在，且选自由烷基、 、卤素、OH、O-烷基、甲酯、丙酯、乙酯、CO2H、CF3、苯胺、硝基、杂环、单取代烷基、二取代烷基、三取代烷基、氢、SO2NH2、SO2NH-烷基、SO 烷基和 NHSO2 烷基组成的组； Y 选自由氢、烷基、取代烷基、卤素、OH、O-烷基、甲酯、丙酯、乙酯、CO2H、硝基、杂环、单取代烷基、二取代烷基、三取代烷基、SO 烷基、SO2NH2、SO2NH-烷基、NHSO2 烷基组成的组、 和 WW、XX、YY 和 ZZ 存在或不存在，且选自由烷基、卤素、OH、O-烷基、甲酯、丙酯、乙酯、CO2H、苯胺、硝基、杂环、单取代烷基、二取代烷基、三取代烷基、氢、SO2NH2、SO2NH-烷基和 NHSO2 烷基组成的组；以及 Z 选自以下组成的组 其中 R5 选自由烷基、单取代烷基、二取代烷基和三取代烷基组成的组。
• Unsolvated benzodiazepine compositions and methods
  申请人：Glick D. Gary

  公开号：US20070043033A1

  公开（公告）日：2007-02-22

  The present invention relates to systems and methods for generating new forms of benzodiazepine and benzodiazepine related compounds as well as new compounds and formulations generated by such methods. In particular, the present invention provides high throughput systems and methods for generating and identifying new crystalline benzodiazepine and benzodiazepine related polymorphs and new unsolvated, solvated, and other forms of the compounds that find use as improved drugs and drug formations.