The structure-antitumor activity relationship of 1-(2-chloroethyl)-3-(4-substituted-2, 3-dioxo-1-piperazinylalkyl)-1-nitrosoureas I was investigated. The cytotoxocity against HeLa cells was most efective when the distribution coefficient of I in CHCl3-H2O (pH 7) was about 20. The antitumor activity against L1210 leukemia by intraperitoneal injection was related to the 4-substitutent R of the 2, 3-dioxopiperazine ring and the carbon number n between the nitrosourea moiety and the 2, 3-dioxopiperazine ring. Therefore, the more effective substituent R was H, Me, Et and the favorable carbon number n was 2-4. The acute toxicity in mice by intravenous injection was decreased along with an increase of the lipophilicity of I. Among the compounds of this series, 3, 5 and 11 were found to have a higher therapeutic ratio (LD50/ED60).
