Anderson W K, Milowsky A S
J Med Chem. 1986 Nov;29(11):2241-9. doi: 10.1021/jm00161a019.
A series of bis[(carbamoyloxy)methyl]pyrrolines 2-4 were synthesized from either the appropriate alpha-silylated iminium salt, or an aziridine, or a 2H-azirine in a sequence involving 1,3-dipolar cycloaddition reactions. The antineoplastic activities of the pyrrolines were compared to the corresponding pyrroles. The C-2 gem-dimethyl-substituted pyrroline, 4, which cannot be converted to the pyrrole in vivo, was inactive. The activity of the 2-phenyl-substituted pyrrolines 3 was markedly dependent on the nature of the phenyl substituent, although the corresponding phenylpyrroles all showed comparable activity. The differences in the activities of the pyrrolines 3 may be due to the rate of metabolic conversion of the pyrroline to the pyrrole. Electron-withdrawing substituents on the phenyl ring appear to retard this process.
通过一系列涉及1,3 - 偶极环加成反应的步骤，由合适的α-硅烷基化亚胺盐、氮丙啶或2H - 氮杂环丙烯合成了一系列双[(氨基甲酰氧基)甲基]吡咯啉2 - 4。将吡咯啉的抗肿瘤活性与相应的吡咯进行了比较。C - 2偕二甲基取代的吡咯啉4在体内不能转化为吡咯，无活性。2 - 苯基取代的吡咯啉3的活性明显取决于苯基取代基的性质，尽管相应的苯基吡咯都表现出相当的活性。吡咯啉3活性的差异可能归因于吡咯啉向吡咯代谢转化的速率。苯环上的吸电子取代基似乎会阻碍这一过程。
