1-phenyl-3-butenyl N,N-bis(2-chloroethyl)phosphorodiamidate | 129253-37-8

• 英文名称: 1-phenyl-3-butenyl N,N-bis(2-chloroethyl)phosphorodiamidate
• 英文别名: N-[amino(1-phenylbut-3-enoxy)phosphoryl]-2-chloro-N-(2-chloroethyl)ethanamine
• CAS: 129253-37-8
• 化学式: C₁₄H₂₁Cl₂N₂O₂P
• 分子量: 351.213
• InChiKey: BCRZCLWCMUKTQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-phenyl-3-butenyl N,N-bis(2-chloroethyl)phosphorodiamidate 在 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 水 、 丙酮 、 叔丁醇 为溶剂， 反应 2.0h， 以67%的产率得到4-[amino-[bis(2-chloroethyl)amino]phosphoryl]oxy-4-phenylbutane-1,2-diol
  参考文献：
  名称：

  Synthesis and antitumor properties of activated cyclophosphamide analogs

  摘要：

  A series of 5- and 6-substituted cyclophosphamide analogues has been prepared, and their P-31 NMR kinetics of phosphoramide mustard (PDA) release and in vitro and in vivo cytotoxicity have been evaluated. cis-4-Hydroxy-5-methoxycyclophosphamide equilibrated very slowly and to a minor extent with the ring-opened aldophosphamide analogues in aqueous buffer; release of PDA was observed to a minor extent and only at high (1 M) buffer concentrations. This analogue was essentially inactive in vitro against L1210 and P388 leukemia cells. 6-Phenylcyclophosphamide and its 4-hydroperoxy derivative were potent inhibitors of blood acetylcholinesterase and were lethal at therapeutic doses in mice. In contrast, 4-hydroperoxy-6-(4-pyridyl)cyclophosphamide did not inhibit acetylcholinesterase and showed significant antitumor activity in vitro and in vivo against both wild-type and cyclophosphamide-resistant L1210 leukemia. The 4-hydroperoxy-6-arylcyclophosphamides were generally active in vitro against both wild-type and cyclophosphamide-resistant L1210 and P388 cells, and several analogues showed significant activity in vivo. Surprisingly, there was no correlation between antitumor activity in vitro and the rate of PDA release in aqueous buffer. Several compounds that showed essentially no release of PDA in aqueous buffer over several hours were highly cytotoxic to leukemia cells following a 1-h exposure in vitro. These results show that activated cyclophosphamide analogues substituted at the 6-position are not cross-resistant in these leukemia cell lines, and that a specific intracellular activation mechanism may be catalyzing PDA release in these analogues.

  DOI：

  10.1021/jm00114a013
• 作为产物：
  描述：

  在 氨 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 生成 1-phenyl-3-butenyl N,N-bis(2-chloroethyl)phosphorodiamidate
  参考文献：
  名称：

  Synthesis and antitumor properties of activated cyclophosphamide analogs

  摘要：

  A series of 5- and 6-substituted cyclophosphamide analogues has been prepared, and their P-31 NMR kinetics of phosphoramide mustard (PDA) release and in vitro and in vivo cytotoxicity have been evaluated. cis-4-Hydroxy-5-methoxycyclophosphamide equilibrated very slowly and to a minor extent with the ring-opened aldophosphamide analogues in aqueous buffer; release of PDA was observed to a minor extent and only at high (1 M) buffer concentrations. This analogue was essentially inactive in vitro against L1210 and P388 leukemia cells. 6-Phenylcyclophosphamide and its 4-hydroperoxy derivative were potent inhibitors of blood acetylcholinesterase and were lethal at therapeutic doses in mice. In contrast, 4-hydroperoxy-6-(4-pyridyl)cyclophosphamide did not inhibit acetylcholinesterase and showed significant antitumor activity in vitro and in vivo against both wild-type and cyclophosphamide-resistant L1210 leukemia. The 4-hydroperoxy-6-arylcyclophosphamides were generally active in vitro against both wild-type and cyclophosphamide-resistant L1210 and P388 cells, and several analogues showed significant activity in vivo. Surprisingly, there was no correlation between antitumor activity in vitro and the rate of PDA release in aqueous buffer. Several compounds that showed essentially no release of PDA in aqueous buffer over several hours were highly cytotoxic to leukemia cells following a 1-h exposure in vitro. These results show that activated cyclophosphamide analogues substituted at the 6-position are not cross-resistant in these leukemia cell lines, and that a specific intracellular activation mechanism may be catalyzing PDA release in these analogues.

  DOI：

  10.1021/jm00114a013

文献信息

• BORCH, RICHARD F.;VALENTE, RONALD R.
  作者：BORCH, RICHARD F.、VALENTE, RONALD R.

  DOI：——

  日期：——
• US5190929A
  申请人：——

  公开号：US5190929A

  公开（公告）日：1993-03-02