A new class of nitrosoureas. I. Synthesis and antitumor activity of 1-(2-chloroethyl)-3,3-disubstituted-1-nitrosoureas having a hydroxyl group at the .BETA.-position of the substituents.

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Abstract
1-(2-Chloroethyl)-3,3-disubstituted-1-nitrosoureas, a new class of nitrosoureas, were synthesized and tested for antitumor activities against [mouse] leukemia L1210 cells and [mouse] Ehrlich ascites carcinoma cells. The nitrosoureas having a hydroxyl group at the .beta.-position of the substituents showed remarkable antitumor activities. In particular, 1-(2-chloroethyl)-3,3-bis(2-hydroxyethyl)-1-nitrosourea had excellent activities and showed 5 and 16 times greater therapeutic ratios than 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea against leukemia L1210 and Ehrlich ascites carcinoma, respectively. These nitrosoureas appear to be activated nonenzymatically by attack of the hydroxyl group on the carbonyl group to give the oxazolidinones and chloroethyl diazohydroxide without generation of the isocyanates.