3-Pyrroline N-Oxide Bis(carbamate) Tumor Inhibitors as Analogues of Indicine N-Oxide

The 2,3-bis[[(Nniethylcarbamoyl)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 [[(iV-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.