Abstract
A series of six 3-substituted 1-(2-chloroethyl)-3-(trans-2-hydroxycyclohexyl)-1-nitrosoureas (IVa-f) was prepared and tested for antitumor activities. Heating of cyclohexene oxide with various alkylamines followed by reaction with 2-chloroethyl isocyanate gave the corresponding ureas (IIIa-f), which were nitrosated with dinitrogen tetroxide to give the nitrosoureas (IVa-f). Decomposition of IVa and IV (IVd) d with aqueous sodium bicarbonate gave VIIa and VIIId, respectively, suggesting different modes activation. All the compounds obtained were remarkably active against leukemia L1210 and showed greater therapeutic ratios than the positive control : 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Against Ehrlich ascites tumor, the nitrosoureas (IVa-c) having one β-hydroxyl group on a cyclohexyl moiety exhibited rather weak activities, but the compounds (IVd-f) having two kinds of β-hydroxyl groups showed strong activities and large therapeutic ratios. This seems to be due to the difference in activation mode between these types of nitrosoureas.
