Oxazepam hemisuccinate | 4700-56-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: Oxazepam hemisuccinate
• 英文别名: (±)-oxazepam hemisuccinate；Oxazepam succinate；succinic acid mono-(7-chloro-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl) ester；(7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-benzo-1,4-diazepin-3-yl) hydrogen succinate；7-Chlor-1,4-dihydro-3-hemisuccinyl-oxy-5-phenyl-2H-1,4-benzodiazepin-2-on, Oxazepam-hemi-succ.；4-[(7-chloro-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl)oxy]-4-oxobutanoic acid
• CAS: 4700-56-5
• 化学式: C₁₉H₁₅ClN₂O₅
• 分子量: 386.791
• InChiKey: UCUOKZUJHTYPJT-UHFFFAOYSA-N

物化性质

• 熔点：
  173-174 °C
• 沸点：
  625.6±55.0 °C(Predicted)
• 密度：
  1.3207 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 储存条件：
  库房应保持低温、通风和干燥的环境。

制备方法与用途

类别：有毒物质

毒性分级：中毒

急性毒性：

• 口服（小鼠）LD50：1148毫克/公斤
• 腹腔注射（小鼠）LD50：375毫克/公斤

可燃性危险特性：可燃；火场分解产生有毒的氯化氢和氮氧化物气体

储运特性：库房应低温、通风且干燥

灭火剂：水、二氧化碳、泡沫或沙土

反应信息

• 作为反应物：
  描述：

  Oxazepam hemisuccinate 反应 0.25h， 以38.6%的产率得到舒宁
  参考文献：
  名称：

  Maksay; Kardos; Simonyi, Arzneimittel-Forschung/Drug Research, 1981, vol. 31, # 6, p. 979 - 981

  摘要：

  DOI：
• 作为产物：
  描述：

  在 fetal bovine serum 作用下， 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 生成 舒宁 、 Oxazepam hemisuccinate
  参考文献：
  名称：

  Oxazepam–Dopamine Conjugates Increase Dopamine Delivery into Striatum of Intact Rats

  摘要：

  The neurotransmitter dopamine (DA) was covalently linked to oxazepam (OXA), a well-known positive allosteric modulator of gamma-aminobutyric acid type-A (GABA(A)) receptor, through a carbamate linkage (4) or a succinic spacer (6). These conjugates were synthesized with the aim of improving the delivery of DA into the brain and enhancing GABAergic transmission, which may be useful for the long-term treatment of Parkinson disease (PD). Structure-based permeability properties, in vitro stability, and blood brain barrier (BBB) permeability studies led to identify the OXA-DA carbamate conjugate 4a as the compound better combining sufficient stability and ability to cross BBB. Finally, in vivo microdialysis experiments in freely moving rats demonstrated that 4a (20 mg/kg, i.p.) significantly increases extracellular DA levels into striatum, with a peak (more than 15-fold increase over the baseline) at about 80 min after a single administration. The stability and delivery data proved that 4a may be a promising candidate for further pharmacological studies in animal models of PD.

  DOI：

  10.1021/acs.molpharmaceut.7b00405

文献信息

• Janssen; Hulst; Kellogg, Pharmazie, 2000, vol. 55, # 1, p. 42 - 48
  作者：Janssen、Hulst、Kellogg、Hendriks、Ensing、De Zeeuw

  DOI：——

  日期：——
• Oxazepam–Dopamine Conjugates Increase Dopamine Delivery into Striatum of Intact Rats
  作者：Tommaso Cassano、Antonio Lopalco、Modesto de Candia、Valentino Laquintana、Angela Lopedota、Annalisa Cutrignelli、Mara Perrone、Rosa M. Iacobazzi、Gaurav Bedse、Massimo Franco、Nunzio Denora、Cosimo D. Altomare

  DOI：10.1021/acs.molpharmaceut.7b00405

  日期：2017.9.5

  The neurotransmitter dopamine (DA) was covalently linked to oxazepam (OXA), a well-known positive allosteric modulator of gamma-aminobutyric acid type-A (GABA(A)) receptor, through a carbamate linkage (4) or a succinic spacer (6). These conjugates were synthesized with the aim of improving the delivery of DA into the brain and enhancing GABAergic transmission, which may be useful for the long-term treatment of Parkinson disease (PD). Structure-based permeability properties, in vitro stability, and blood brain barrier (BBB) permeability studies led to identify the OXA-DA carbamate conjugate 4a as the compound better combining sufficient stability and ability to cross BBB. Finally, in vivo microdialysis experiments in freely moving rats demonstrated that 4a (20 mg/kg, i.p.) significantly increases extracellular DA levels into striatum, with a peak (more than 15-fold increase over the baseline) at about 80 min after a single administration. The stability and delivery data proved that 4a may be a promising candidate for further pharmacological studies in animal models of PD.
• Maksay; Kardos; Simonyi, Arzneimittel-Forschung/Drug Research, 1981, vol. 31, # 6, p. 979 - 981
  作者：Maksay、Kardos、Simonyi、Tegyey、Otvoes

  DOI：——

  日期：——