N-[bis(2-chloroethyl)amino-[(5-nitrothiophen-2-yl)methoxy]phosphoryl]-2-chloro-N-(2-chloroethyl)ethanamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: N-[bis(2-chloroethyl)amino-[(5-nitrothiophen-2-yl)methoxy]phosphoryl]-2-chloro-N-(2-chloroethyl)ethanamine
• 化学式: C₁₃H₂₀Cl₄N₃O₄PS
• 分子量: 487.171
• InChiKey: SOAKTIROLUOYTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-硝基噻吩-2-甲醛 在 sodium tetrahydroborate 、 三乙胺 、 三氯化磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 1.17h， 生成 N-[bis(2-chloroethyl)amino-[(5-nitrothiophen-2-yl)methoxy]phosphoryl]-2-chloro-N-(2-chloroethyl)ethanamine
  参考文献：
  名称：

  Synthesis and Evaluation of Nitroheterocyclic Phosphoramidates as Hypoxia-Selective Alkylating Agents

  摘要：

  A series of novel nitroheterocyclic phosphoramidates has been prepared, and the cytotoxicity of these compounds has been evaluated in clonogenic assays against B16, wild-type and cyclophosphamide-resistant MCF-7, and HT-29 cells under aerobic conditions and HT-29 cells under hypoxic conditions. All compounds were comparable in toxicity to wild-type and resistant MCF-7 cells and were also selectively toxic to HT-29 cells under hypoxic conditions (selectivity ratios 1.7 to >20). Analogues lacking the nitro group were not cytotoxic. Electron-withdrawing substituents increased cytotoxicity under aerobic conditions and thereby decreased hypoxic selectivity. In contrast, an electron-donating substituent markedly decreased both aerobic and hypoxic cytotoxicity but enhanced hypoxic selectivity. Chemical reduction of the nitro group resulted in rapid expulsion of the cytotoxic phosphoramide mustard. The most potent of these compounds show significant cytotoxicity under both aerobic and hypoxic conditions.

  DOI：

  10.1021/jm0001020

文献信息

• Phosphoramidate alkylator prodrugs
  申请人：Threshold Pharmaceuticals, Inc.

  公开号：EP2336141A2

  公开（公告）日：2011-06-22

  Phosphoramidate alkylator prodrugs can be used to treat cancer when administered alone or in combination with one or more other anti-neoplastic agents.

  磷酰胺烷化剂原药可单独或与一种或多种其他抗肿瘤药物联合用于治疗癌症。
• [EN] PHOSPHORAMIDATE ALKYLATOR PRODRUGS<br/>[FR] PRODROGUES D'ALKYLATEUR DE PHOSPHORAMIDATE
  申请人：THRESHOLD PHARMACEUTICALS INC

  公开号：WO2007002931A2

  公开（公告）日：2007-01-04

  [EN] Phosphoramidate alkylator prodrugs can be used to treat cancer when administered alone or in combination with one or more anti-neoplastic agents.
  [FR] La présente invention a trait à des prodrogues d'alkylateur de phosphoramidate apte à être utilisés pour le traitement du cancer lorsqu'ils sont administrés seuls ou en combinaison avec un ou des agents anti-néoplasiques.