N-boc-L-3-(4-bis(hydroxyethyl)aminophenyl)alanine ethyl ester | 189744-27-2

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丙氨酸类衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-boc-L-3-(4-bis(hydroxyethyl)aminophenyl)alanine ethyl ester
• 英文别名: Ethyl (S)-3-(4-(bis(2-hydroxyethyl)amino)phenyl)-2-((tert-butoxycarbonyl)amino)propanoate；ethyl (2S)-3-[4-[bis(2-hydroxyethyl)amino]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 189744-27-2
• 化学式: C₂₀H₃₂N₂O₆
• 分子量: 396.484
• InChiKey: UWMMWVOVONQYKP-KRWDZBQOSA-N

物化性质

• 沸点：
  575.4±50.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-boc-L-3-(4-bis(hydroxyethyl)aminophenyl)alanine ethyl ester 在 盐酸 、 水 、 三氯氧磷 作用下， 以 醋酸异丙酯 为溶剂， 反应 14.5h， 生成 美法仑
  参考文献：
  名称：

  [EN] PROCESS FOR THE PURIFICATION OF MELPHALAN
  [FR] PROCÉDÉ DE PURIFICATION DE MELPHALANE

  摘要：

  描述了一种用于纯化和制备甲氨蝶呤的方法，可以获得纯度高于99.5%的甲氨蝶呤。

  公开号：

  WO2014191426A1
• 作为产物：
  描述：

  BOC-4-硝基-苯丙氨酸乙酯 在 palladium on activated charcoal 氢气 、 ammonium formate 作用下， 以 甲醇 、 水 、 溶剂黄146 为溶剂， 反应 25.0h， 生成 N-boc-L-3-(4-bis(hydroxyethyl)aminophenyl)alanine ethyl ester
  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

• [EN] PROCESS FOR THE PURIFICATION OF MELPHALAN<br/>[FR] PROCÉDÉ DE PURIFICATION DE MELPHALANE
  申请人：FARMABIOS SPA

  公开号：WO2014191426A1

  公开（公告）日：2014-12-04

  A method for the purification and preparation of melphalan that allows to obtain melphalan with purity higher than 99.5% is described.

  描述了一种用于纯化和制备甲氨蝶呤的方法，可以获得纯度高于99.5%的甲氨蝶呤。
• 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.