Anderson W K, Milowsky A S
Department of Medicinal Chemistry, School of Pharmacy, State University of New York at Buffalo 14260.
J Med Chem. 1987 Nov;30(11):2144-7. doi: 10.1021/jm00394a036.
The 2,3-bis[[(N-methylcarbamoyl)oxy]methyl]-3-pyrroline 1-oxide 5 was synthesized and tested in the murine P388 lymphocytic leukemia model. The compound showed significant reproducible activity and was more potent than indicine N-oxide. 1-Methyl-2-phenyl-3,4-bis[[(N-2- propylcarbamoyl)oxy]methyl]-3-pyrroline N-oxide (6) was less active than 5, and the 5,5-dimethyl analogue of 6, the pyrroline N-oxide 7, was inactive. The N-oxide 7 cannot be converted to a pyrrole in vivo because of the gem-dimethyl substitution at C-5.
合成了2,3-双[[(N-甲基氨基甲酰基)氧基]甲基]-3-吡咯啉1-氧化物5，并在小鼠P388淋巴细胞白血病模型中进行了测试。该化合物显示出显著的可重复活性，且比印度防己碱N-氧化物更有效。1-甲基-2-苯基-3,4-双[[(N-2-丙基氨基甲酰基)氧基]甲基]-3-吡咯啉N-氧化物(6)的活性低于5，而6的5,5-二甲基类似物吡咯啉N-氧化物7无活性。由于C-5位的偕二甲基取代，N-氧化物7在体内不能转化为吡咯。
