Sosnovsky G, Paul B D
J Med Chem. 1984 Jun;27(6):782-8. doi: 10.1021/jm00372a014.
A number of N,N:N',N':N",N"-tri-1,2- ethanediylphosphoric triamide (TEPA) and N,N:N',N':N",N"-tri-1,2- ethanediylphosphorothioic triamide (thio-TEPA) derivatives containing either two aziridine moieties (1a) or two (2-chloroethyl)amino functions (1b) and either a 2,2,6,6-tetramethylpiperidine, 1-oxy-2,2,6,6-tetramethylpiperidine or 1-hydroxy-2,2,6,6-tetramethylpiperidine component were synthesized and tested against lymphocytic leukemia P388 in mice. In a structure-activity comparison it was found that at optimum dose all compounds containing the nitroxyl radical were more active than the corresponding hydroxylamine derivatives. The open-chain compounds (1b) were less active than the corresponding aziridine ring compounds (1a). The replacement of the X = bridge in 1a with the X = N(CH3) group resulted in lowering of the anticancer activity.
合成了许多含有两个氮丙啶部分（1a）或两个（2-氯乙基）氨基官能团（1b）以及2,2,6,6-四甲基哌啶、1-氧代-2,2,6,6-四甲基哌啶或1-羟基-2,2,6,6-四甲基哌啶成分的N,N:N',N':N",N"-三-1,2-乙二基磷三酰胺（TEPA）和N,N:N',N':N",N"-三-1,2-乙二基硫代磷三酰胺（硫代-TEPA）衍生物，并在小鼠中针对淋巴细胞白血病P388进行了测试。在结构-活性比较中发现，在最佳剂量下，所有含硝酰自由基的化合物比相应的羟胺衍生物更具活性。开链化合物（1b）比相应的氮丙啶环化合物（1a）活性低。在1a中用X = N(CH3)基团取代X =桥导致抗癌活性降低。
