N,N-Bis(2.chlorethyl)-N',N'-di(3-hydroxy-4,4,4-trifluorbut-1-yl)phosphorotriamidat | 57165-86-3

• 英文名称: N,N-Bis(2.chlorethyl)-N',N'-di(3-hydroxy-4,4,4-trifluorbut-1-yl)phosphorotriamidat
• CAS: 57165-86-3
• 化学式: C₁₂H₂₂Cl₂F₆N₃O₃P
• 分子量: 472.195
• InChiKey: LAIXPJCXDRREEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  27.0
• 可旋转键数：
  13.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  84.83
• 氢给体数：
  4.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  双(2-氯乙基)氨基磷酰二氯 、 1-氨基-3-羟基-4,4,4-三氟丁烷 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N,N-Bis(2.chlorethyl)-N',N'-di(3-hydroxy-4,4,4-trifluorbut-1-yl)phosphorotriamidat
  参考文献：
  名称：

  Synthesis and antitumor activity of 6-trifluoromethylcyclophosphamide and related compounds

  摘要：

  In an attempt to increase the combined toxicity of the metabolic end-products [acrolein (4) and phosphoramide mustard (3)] from cyclophosphamide (1), the analog 2-[bis(2-chloroethyl)amino]tetrahydro-6-trifluoromethyl-2H-1,3,2-oxazaphosphorine 2-oxide (2, 6-trifluoromethylcyclophosphamide) was synthesized and its metabolism and antitumor activity studied. Following metabolism of 2 by rat liver microsomes the predicted formation of 4,4,4-trifluorocrotonaldehyde (5) was confirmed by isolation and identification, by mass spectrometry, of its dinitrophenylhydrazone. The therapeutic indices (LD50-/ID90) for 2 against the ADJ/PC6 mouse tumor and the Walker 256 tumor in the rat were 28.6 and 7.7, respectively, and were lower than the corresponding values for 1 (91.8 and 33.2, respectively) although the toxicities toward Walker cells in a bioassay system of 1 and 2 following microsomal metabolism were similar. In order to study the toxicities of 4 and 5 released under drug metabolizing conditions independently of the production of a toxic mustard the analogs 18 [2-(diethylamino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide] and 6 [2-(diethylamino)tetrahydro-6-trifluoromethyl-2H-1,3,2-oxazaphosphorine 2-oxide] were also synthesized. The release of 5 from 6 following metabolism was confirmed and shown by use of the bioassay system to be an event of similar toxicity to release of 4 from 18; in vivo, however, 6 (LD50 330 mg/kg) was more toxic to mice than 18 (LD50 greater than 500 mg/kg).

  DOI：

  10.1021/jm00245a012