P,P-bis(2,2-dimethyl-1-aziridinyl)-N-(3-methoxy-1-propyl)phosphinic amide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: P,P-bis(2,2-dimethyl-1-aziridinyl)-N-(3-methoxy-1-propyl)phosphinic amide
• 英文别名: N-bis(2,2-dimethylaziridin-1-yl)phosphoryl-3-methoxypropan-1-amine
• 化学式: C₁₂H₂₆N₃O₂P
• 分子量: 275.331
• InChiKey: BKVQHYDYWZJAHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  44.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  P,P-bis(2,2-dimethyl-1-aziridinyl)-N-(3-methoxy-1-propyl)phosphinic amide 、 水 生成 2,2-二甲基氮丙啶
  参考文献：
  名称：

  MACDIARMID, J. E.;ROSE, W. C.;BIDDLE, W. C.;PERLMAN, M. E.;BREINER, R. G.+, J. MED. CHEM., 1985, 28, N 11, 1685-1691

  摘要：

  DOI：
• 作为产物：
  描述：

  bis(2,2-dimethyl-1-aziridinyl)phosphinic chloride 、 3-甲氧基丙胺 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以58.5%的产率得到P,P-bis(2,2-dimethyl-1-aziridinyl)-N-(3-methoxy-1-propyl)phosphinic amide
  参考文献：
  名称：

  Synthesis and properties of bis(2,2-dimethylaziridinyl)phosphinic amides: a series of new antineoplastic agents

  摘要：

  In continuation of efforts to improve the antitumor selectivity of the 2,2-dimethylaziridine class of alkylating agents, a series of N-substituted bis(2,2-dimethyl-1-aziridinyl)phosphinic amides has been synthesized and evaluated. All of these compounds (3-15) were tested in vivo against leukemia P-388 in mice, where most of them caused significant increase of survival time at nontoxic dose levels. Some of the most active compounds were also tested against leukemia L1210, B16 melanoma, and colon 26 carcinoma; in the latter tests, the parent unsubstituted amide 3 appeared to show the highest antitumor activity. Since the dose-limiting toxicity of the clinically tested prototypes of this class of anticancer agents AB-132 (1) and AB-163 (2) had been found to be CNS toxicity attributable mainly to the inhibition of cholinesterase, the compounds were tested in vitro against the cholinesterases from horse serum, electric eel, and bovine erythrocytes, as well as in vivo for the inhibition of the cholinesterase present in the whole blood of mice. In all of these assays, the various members of the present series showed a wide range of anticholinesterase activities, ranging from almost zero (for 3) to even higher potency than that of the prototype 2. A similarly wide range of stability was observed toward hydrolytic ring opening of the 2,2-dimethylaziridine moieties. Several of the compounds, particularly 3, deserve further study.

  DOI：

  10.1021/jm00149a025

文献信息

• Bis(2,2-dimethyl-1-aziridinyl)phosphinic amides for use in the treatment
  申请人：The Research Foundation of State University of New York

  公开号：US04544501A1

  公开（公告）日：1985-10-01

  Novel bis(2,2-dimethyl-1-aziridinyl)phosphinic amide antineoplastic agents are disclosed of the formula: ##STR1## wherein R and R' are each, independently, hydrogen, alkyl, substituted alkyl, phenyl and substituted phenyl and, Z is oxygen or sulfur.

  揭示了一种新型的双(2,2-二甲基-1-氮杂环丙基)膦酰胺抗肿瘤剂，其化学结构式为: ##STR1## 其中R和R'分别独立地为氢、烷基、取代烷基、苯基和取代苯基，Z为氧或硫。
• US4544501A
  申请人：——

  公开号：US4544501A

  公开（公告）日：1985-10-01
• US4886790A
  申请人：——

  公开号：US4886790A

  公开（公告）日：1989-12-12