N-[amino-[(5-nitro-2-furyl)methoxy]phosphoryl]-2-bromo-N-(2-bromoethyl)ethanamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: N-[amino-[(5-nitro-2-furyl)methoxy]phosphoryl]-2-bromo-N-(2-bromoethyl)ethanamine
• 英文别名: N-[amino-[(5-nitrofuran-2-yl)methoxy]phosphoryl]-2-bromo-N-(2-bromoethyl)ethanamine
• 化学式: C₉H₁₄Br₂N₃O₅P
• 分子量: 435.009
• InChiKey: VUBQJZIZBRBAGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  双(2-溴乙基)胺氢溴酸盐 在 氨 、 三乙胺 、 lithium hexamethyldisilazane 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.05h， 生成 N-[amino-[(5-nitro-2-furyl)methoxy]phosphoryl]-2-bromo-N-(2-bromoethyl)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：US20140170240A1

  公开（公告）日：2014-06-19

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

  磷酰胺酸烷基化剂前药可单独或与一个或多个抗肿瘤药物联合使用治疗癌症。
• PHOSPHORAMIDATE ALKYLATOR PRODRUGS
  申请人：Threshold Pharmaceuticals, Inc.

  公开号：US20130303778A1

  公开（公告）日：2013-11-14

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

  磷酰胺烷基化剂前药可单独或与一个或多个抗肿瘤药物联合使用以治疗癌症。
• 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。
• Potent and Highly Selective Hypoxia-Activated Achiral Phosphoramidate Mustards as Anticancer Drugs
  作者：Jian-Xin Duan、Hailong Jiao、Jacob Kaizerman、Timothy Stanton、James W. Evans、Leslie Lan、Gustavo Lorente、Monica Banica、Don Jung、Jinwei Wang、Huaiyu Ma、Xiaoming Li、Zhijian Yang、Robert M. Hoffman、W. Steve Ammons、Charles P. Hart、Mark Matteucci

  DOI：10.1021/jm701028q

  日期：2008.4.1

  A series of achiral hypoxia-activated prodrugs were synthesized on the basis of the DNA cross-linking toxin of the prodrug, ifosfamide. The hypoxia-selective cytotoxicity of several of the compounds was improved over previously reported racemic mixtures of chiral bioreductive phosphorami date prodrugs. Prodrugs activated by 2-nitroimidazole reduction demonstrated up to 400-fold enhanced cytotoxicity toward H460 cells in culture under hypoxia versus their potency under aerobic conditions. Compounds were further assessed for their stability to cytochrome P450 metabolism using a liver microsome assay. The 2-nitroimidazole containing lead compound 3b (TH-302) was selectively potent under hypoxia and stable to liver microsomes. It was active in an in vivo MIA PaCa-2 pancreatic cancer orthotopic xenograft model as a monotherapy and demonstrated dramatic efficacy when used in combination with gemcitabine, extending survival with one of eight animals tumor free at day-44. Compound 3b has emerged as a promising antitumor agent that shows excellent in vivo efficacy and is currently being evaluated in the clinic.
• US8507464B2
  申请人：——

  公开号：US8507464B2

  公开（公告）日：2013-08-13