1-(3'-carboxylpropyl)-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one | 64581-01-7

• 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: 1-(3'-carboxylpropyl)-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one
• 英文别名: 4-(7-chloro-2-oxo-5-phenyl-3H-1,4-benzodiazepin-1-yl)butanoic acid
• CAS: 64581-01-7
• 化学式: C₁₉H₁₇ClN₂O₃
• 分子量: 356.809
• InChiKey: FQFVWTHMUIUKPD-UHFFFAOYSA-N

物化性质

• 沸点：
  632.4±55.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3'-carboxylpropyl)-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 、 4-(bis(2-chloroethyl)amino)-L-phenylalanine ethyl ester trifluoroacetate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 生成 1-[4-butanoyl-(p-bis(2-chloroethyl)amino)-L-phenylalanine ethyl ester]-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  Modulation of Melphalan Resistance in Glioma Cells with a Peripheral Benzodiazepine Receptor Ligand−Melphalan Conjugate

  摘要：

  Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of mitochondria, and their density is increased in brain tumors. Thus, they may serve as a unique intracellular and selective target for antineoplastic agents. A PBR ligand-melphalan conjugate (PBR-MEL) was synthesized and evaluated for cytotoxicity and affinity for PBRs. PBR-MEL (9) (i.e., 670 amu) was synthesized by coupling of two key intermediates: 4-[bis(2-chloroethyl)amino]-L-phenylalanine ethyl ester trifluoroacetate (6) and 1-(3'-carboxylpropyl)-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (8). On the basis of receptor-binding displacement assays in rat brain and glioma cells, 9 had appreciable binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50 values between 289 and 390 nM. 9 displayed differential cytotoxicity to a variety of rat and human brain tumor cell lines. In some of the cell lines tested including rat and human melphalan-resistant cell lines, 9 demonstrated appreciable cytotoxicity with IC50 values in the micromolar range, lower than that of melphalan alone. The enhanced activity of 9 may reflect increased membrane permeability, increased intracellular retention, or modulation of melphalan's mechanisms of resistance. The combined data support additional studies to determine how 9 may modulate melphalan resistance, its mechanisms of action, and if target selectivity can be achieved in in vivo glioma models.

  DOI：

  10.1021/jm960592p
• 作为产物：
  描述：

  去甲西泮 在 氢氧化钾 、 sodium hydride 作用下， 以 甲醇 为溶剂， 反应 2.5h， 生成 1-(3'-carboxylpropyl)-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  Modulation of Melphalan Resistance in Glioma Cells with a Peripheral Benzodiazepine Receptor Ligand−Melphalan Conjugate

  摘要：

  Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of mitochondria, and their density is increased in brain tumors. Thus, they may serve as a unique intracellular and selective target for antineoplastic agents. A PBR ligand-melphalan conjugate (PBR-MEL) was synthesized and evaluated for cytotoxicity and affinity for PBRs. PBR-MEL (9) (i.e., 670 amu) was synthesized by coupling of two key intermediates: 4-[bis(2-chloroethyl)amino]-L-phenylalanine ethyl ester trifluoroacetate (6) and 1-(3'-carboxylpropyl)-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (8). On the basis of receptor-binding displacement assays in rat brain and glioma cells, 9 had appreciable binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50 values between 289 and 390 nM. 9 displayed differential cytotoxicity to a variety of rat and human brain tumor cell lines. In some of the cell lines tested including rat and human melphalan-resistant cell lines, 9 demonstrated appreciable cytotoxicity with IC50 values in the micromolar range, lower than that of melphalan alone. The enhanced activity of 9 may reflect increased membrane permeability, increased intracellular retention, or modulation of melphalan's mechanisms of resistance. The combined data support additional studies to determine how 9 may modulate melphalan resistance, its mechanisms of action, and if target selectivity can be achieved in in vivo glioma models.

  DOI：

  10.1021/jm960592p

文献信息

• 一种地西泮半抗原、人工抗原及其制备方法与应用
  申请人：北京维德维康生物技术有限公司

  公开号：CN111533705A

  公开（公告）日：2020-08-14

  本发明公开了一种地西泮半抗原、人工抗原及其制备方法与应用。本发明所提供的地西泮人工抗原为将式I所示的地西泮半抗原与载体蛋白偶联所得的抗原。本发明所提供地西泮人工抗原合成方法简单，纯度高和产率高，对于地西泮抗体的制备，以及地西泮药物残留检测具有重大价值。
• Modulation of Melphalan Resistance in Glioma Cells with a Peripheral Benzodiazepine Receptor Ligand−Melphalan Conjugate
  作者：Lidia Kupczyk-Subotkowska、Teruna J. Siahaan、Anthony S. Basile、Henry S. Friedman、Patricia E. Higgins、Di Song、James M. Gallo

  DOI：10.1021/jm960592p

  日期：1997.5.1

  Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of mitochondria, and their density is increased in brain tumors. Thus, they may serve as a unique intracellular and selective target for antineoplastic agents. A PBR ligand-melphalan conjugate (PBR-MEL) was synthesized and evaluated for cytotoxicity and affinity for PBRs. PBR-MEL (9) (i.e., 670 amu) was synthesized by coupling of two key intermediates: 4-[bis(2-chloroethyl)amino]-L-phenylalanine ethyl ester trifluoroacetate (6) and 1-(3'-carboxylpropyl)-7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (8). On the basis of receptor-binding displacement assays in rat brain and glioma cells, 9 had appreciable binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50 values between 289 and 390 nM. 9 displayed differential cytotoxicity to a variety of rat and human brain tumor cell lines. In some of the cell lines tested including rat and human melphalan-resistant cell lines, 9 demonstrated appreciable cytotoxicity with IC50 values in the micromolar range, lower than that of melphalan alone. The enhanced activity of 9 may reflect increased membrane permeability, increased intracellular retention, or modulation of melphalan's mechanisms of resistance. The combined data support additional studies to determine how 9 may modulate melphalan resistance, its mechanisms of action, and if target selectivity can be achieved in in vivo glioma models.