2-(p-tolylthio)ethyl N,N'-bis(2-chloroethyl)phosphorodiamidate | 735327-46-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(p-tolylthio)ethyl N,N'-bis(2-chloroethyl)phosphorodiamidate
• 英文别名: 2-chloro-N-[(2-chloroethylamino)-[2-(4-methylphenyl)sulfanylethoxy]phosphoryl]ethanamine
• CAS: 735327-46-5
• 化学式: C₁₃H₂₁Cl₂N₂O₂PS
• 分子量: 371.268
• InChiKey: WLWRALNCAAVKLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  75.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(p-tolylthio)ethyl N,N'-bis(2-chloroethyl)phosphorodiamidate 在 ammonium molybdate 、 双氧水 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以99%的产率得到2-chloro-N-[(2-chloroethylamino)-[2-(4-methylphenyl)sulfonylethoxy]phosphoryl]ethanamine
  参考文献：
  名称：

  Sulfonyl-Containing Aldophosphamide Analogues as Novel Anticancer Prodrugs Targeted against Cyclophosphamide-Resistant Tumor Cell Lines

  摘要：

  A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were synthesized as potential anticancer prodrugs that liberate the cytotoxic phosphoramide mustards (PM, IPM, and tetrakis-PM) via beta-elimination, a nonenzymatic activation mechanism. Kinetic studies demonstrated that all these compounds spontaneously liberate phosphoramide mustards with half-lives in the range of 0.08-15.2 h under model physiological conditions in 0.08 M phosphate buffer at pH 7.4 and 37 degreesC. Analogous to Aldo, the rates of beta-elimination in all compounds was enhanced in reconstituted human plasma under same conditions. The compounds were more potent than the corresponding phosphoramide mustards against V-79 Chinese hamster lung fibroblasts in vitro (IC50 = 1.8-69.1 muM). Several compounds showed excellent in vivo antitumor activity in CD2F1 mice against both P388/0 (Wild) and P388/CPA (CP-resistant) tumor cell lines.

  DOI：

  10.1021/jm0304764
• 作为产物：
  描述：

  2-(对甲苯硫代)-乙醇 在 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 生成 2-(p-tolylthio)ethyl N,N'-bis(2-chloroethyl)phosphorodiamidate
  参考文献：
  名称：

  Sulfonyl-Containing Aldophosphamide Analogues as Novel Anticancer Prodrugs Targeted against Cyclophosphamide-Resistant Tumor Cell Lines

  摘要：

  A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were synthesized as potential anticancer prodrugs that liberate the cytotoxic phosphoramide mustards (PM, IPM, and tetrakis-PM) via beta-elimination, a nonenzymatic activation mechanism. Kinetic studies demonstrated that all these compounds spontaneously liberate phosphoramide mustards with half-lives in the range of 0.08-15.2 h under model physiological conditions in 0.08 M phosphate buffer at pH 7.4 and 37 degreesC. Analogous to Aldo, the rates of beta-elimination in all compounds was enhanced in reconstituted human plasma under same conditions. The compounds were more potent than the corresponding phosphoramide mustards against V-79 Chinese hamster lung fibroblasts in vitro (IC50 = 1.8-69.1 muM). Several compounds showed excellent in vivo antitumor activity in CD2F1 mice against both P388/0 (Wild) and P388/CPA (CP-resistant) tumor cell lines.

  DOI：

  10.1021/jm0304764

文献信息

• Sulfonyl-Containing Aldophosphamide Analogues as Novel Anticancer Prodrugs Targeted against Cyclophosphamide-Resistant Tumor Cell Lines
  作者：Monish Jain、Junying Fan、Nesrine Z. Baturay、Chul-Hoon Kwon

  DOI：10.1021/jm0304764

  日期：2004.7.1

  A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were synthesized as potential anticancer prodrugs that liberate the cytotoxic phosphoramide mustards (PM, IPM, and tetrakis-PM) via beta-elimination, a nonenzymatic activation mechanism. Kinetic studies demonstrated that all these compounds spontaneously liberate phosphoramide mustards with half-lives in the range of 0.08-15.2 h under model physiological conditions in 0.08 M phosphate buffer at pH 7.4 and 37 degreesC. Analogous to Aldo, the rates of beta-elimination in all compounds was enhanced in reconstituted human plasma under same conditions. The compounds were more potent than the corresponding phosphoramide mustards against V-79 Chinese hamster lung fibroblasts in vitro (IC50 = 1.8-69.1 muM). Several compounds showed excellent in vivo antitumor activity in CD2F1 mice against both P388/0 (Wild) and P388/CPA (CP-resistant) tumor cell lines.