N-(2-chloroethyl)-N'-(aziridinyl) ifosfamide mustard

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: N-(2-chloroethyl)-N'-(aziridinyl) ifosfamide mustard
• 英文别名: N-(2-chloroethyl)-N'-ethanophosphoric acid diamide；aziridin-1-yl-N-(2-chloroethyl)phosphonamidic acid
• 化学式: C₄H₁₀ClN₂O₂P
• 分子量: 184.562
• InChiKey: NAFVGKNCETZZFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  葡磷酰胺 在 cacodylate buffer 作用下， 生成 帕利伐米 、 N-(2-chloroethyl)-N'-(aziridinyl) ifosfamide mustard 、 N-(2-Chloroethyl)-Na(2)-(2-hydroxyethyl)phosphorodiamidic acid 、 dihydroxyIPM
  参考文献：
  名称：

  Hydrolytic Pathway of Glufosfamide, a New Phosphorylated Anticancer Agent

  摘要：

  P-31 NMR was used to demonstrate that glufosfamide is hydrolyzed into isophosphoramide mustard (IPM) with a half-life of about 25 h at 37degreesC and pH 7.4 in buffer as well as in human plasma. Through a cascade of reactions, IPM gives rise to three final products, dihydroxyIPM, phosphate ion, and phosphorylethanolamine, which is by far the major compound.

  DOI：

  10.1080/10426500212229

文献信息

• Glutathione Conjugation of the Cytostatic Drug Ifosfamide and the Role of Human Glutathione S-Transferases
  作者：Hubert A. A. M. Dirven、Luc Megens、Martin J. Oudshoorn、Maria A. Dingemanse、Ben van Ommen、Peter J. van Bladeren

  DOI：10.1021/tx00049a012

  日期：1995.10

  Development of drug resistance against alkylating cytostatic drugs has been associated with higher intracellular concentrations of glutathione (GSH) and increased expression of glutathione S-transferase (GST) enzymes. Therefore, enhanced detoxification by the glutathione/glutathione S-transferase pathway has been proposed as a major factor in the development of drug resistance toward alkylating agents. In

  对烷基化细胞生长抑制药物的耐药性的发展与细胞内谷胱甘肽（GSH）浓度升高和谷胱甘肽S-转移酶（GST）酶表达增加有关。因此，已经提出通过谷胱甘肽/谷胱甘肽S-转移酶途径增强的解毒作用是发展对烷基化剂的耐药性的主要因素。在本文中，我们描述了31P NMR和HPLC研究自发和谷胱甘肽S-转移酶催化异环磷酰胺的两种代谢物即4-羟基异环磷酰胺和异环磷酰胺芥子的谷胱甘肽共轭物形成的过程。与没有GSH的孵育（t1 / 2 = 266分钟）相比，在25摄氏度时，存在10倍过量的GSH（t1 / 2 = 107分钟）时，活化的异环磷酰胺（= 4-羟基异环磷酰胺+醛固磷酰胺）消失得更快。没有发现形成4-谷胱甘肽异环磷酰胺的证据。异环磷酰胺的最终烷基化物质是异环磷酰胺芥末（IM）。在不存在谷胱甘肽的情况下，在25摄氏度（pH 7）下异环磷酰胺芥末信号消失的速率常数为1.98 x 10（-3）min-1（t1 /
• Hydrolytic Pathway of Glufosfamide, a New Phosphorylated Anticancer Agent
  作者：Marie-Caroline Aoust de Rouvèze、Veronique Gilard、Robert Martino、Myriam Malet-Martino、Ulf Niemeyer

  DOI：10.1080/10426500212229

  日期：2002.6.1

  P-31 NMR was used to demonstrate that glufosfamide is hydrolyzed into isophosphoramide mustard (IPM) with a half-life of about 25 h at 37degreesC and pH 7.4 in buffer as well as in human plasma. Through a cascade of reactions, IPM gives rise to three final products, dihydroxyIPM, phosphate ion, and phosphorylethanolamine, which is by far the major compound.