(2-chloroethyl)-[3-(2-chloroethyl)-2-oxo-4-pentyloxy-2λ⁵-[1,3,2]oxazaphosphinan-2-yl]amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧氮杂膦
• 英文名称: (2-chloroethyl)-[3-(2-chloroethyl)-2-oxo-4-pentyloxy-2λ⁵-[1,3,2]oxazaphosphinan-2-yl]amine
• 英文别名: N,3-bis(2-chloroethyl)-2-oxo-4-pentoxy-1,3,2lambda5-oxazaphosphinan-2-amine；N,3-bis(2-chloroethyl)-2-oxo-4-pentoxy-1,3,2λ5-oxazaphosphinan-2-amine
• 化学式: C₁₂H₂₅Cl₂N₂O₃P
• 分子量: 347.222
• InChiKey: GJWYIBCUPMZGSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  20.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  50.8
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  4-methoxy-ifosfamide 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 1.75h， 生成 (2-chloroethyl)-[3-(2-chloroethyl)-2-oxo-4-pentyloxy-2λ⁵-[1,3,2]oxazaphosphinan-2-yl]amine
  参考文献：
  名称：

  Preactivated Oxazaphosphorines Designed for Isophosphoramide Mustard Delivery as Bulk Form or Nanoassemblies: Synthesis and Proof of Concept

  摘要：

  Oxazaphosphorines are alkylating agents used in routine clinical practices for treatment of cancer for many years. They are antitumor prodrugs that require cytochrome P450 bioactivation leading to 4-hydroxy derivatives. In the case of ifosfamide (IFO), the bioactivation produces two toxic metabolites: acrolein, a urotoxic compound, concomitantly generated with the isophosphoramide mustard; and chloroacetaldehyde, a neurotoxic and nephrotoxic compound, arising from the oxidation of the side chains. To improve the therapeutic index of IFO, we have designed preactivated IFO derivatives with the covalent binding of several O- and S-alkyl moieties including polyisoprenoid groups at the C-4 position of the oxazaphosphorine ring to avoid cytochrome bioactivation favoring the release of the active entity and limiting the chloroacetaldehyde release. Thanks to the grafted terpene moieties, some of these new conjugates demonstrated spontaneous self-assembling properties into nanoassemblies when dispersed in water. The cytotoxic activities on a panel of human tumor cell lines of these novel oxazaphosphorines, in bulk form or as nanoassemblies, and the release of 4-hydroxy-IFO from these preactivated IFO analogues in plasma are reported.

  DOI：

  10.1021/jm501224x

文献信息

• NOVEL DERIVATIVES OF OXAZAPHOSPHORINES THAT ARE PRE-ACTIVATED, USE AND METHOD OF PREPARATION
  申请人：Paci Angelo

  公开号：US20130261088A1

  公开（公告）日：2013-10-03

  The present invention relates to novel derivatives of oxazaphosphorines that are pre-activated, to the methods for preparing same, to the pharmaceutical compositions containing same and to the therapeutic use thereof, in particular for treating cancer.

  本发明涉及新型的预激活的氧杂磷酰胺衍生物，其制备方法，含有它们的制药组合物以及它们在治疗癌症方面的治疗用途。
• Derivatives of oxazaphosphorines that are pre-activated, use and method of preparation
  申请人：INSTITUT GUSTAVE ROUSSY

  公开号：US10125157B2

  公开（公告）日：2018-11-13

  The present invention relates to novel derivatives of oxazaphosphorines that are pre-activated, to the methods for preparing same, to the pharmaceutical compositions containing same and to the therapeutic use thereof, in particular for treating cancer.

  本发明涉及预活化的噁唑膦的新型衍生物、制备方法、含有这些衍生物的药物组合物及其治疗用途，特别是用于治疗癌症。
• NOUVEAUX DERIVES D'OXAZAPHOSPHORINES PRE-ACTIVEES, UTILISATION ET METHODE DE PREPARATION
  申请人：Institut Gustave Roussy

  公开号：EP2649084B1

  公开（公告）日：2017-02-22
• NOVEL DERIVATIVES OF OXAZAPHOSPHORINES AND THERAPEUTIC USES THEREOF
  申请人：INSTITUT GUSTAVE ROUSSY

  公开号：US20170071959A1

  公开（公告）日：2017-03-16

  The present invention relates to novel derivatives of oxazaphosphorines, pharmaceutical compositions and therapeutic use thereof, in particular for treating or preventing cancer.
• US9073957B2
  申请人：——

  公开号：US9073957B2

  公开（公告）日：2015-07-07