1-(2-Chloroethyl)-3-(4-subustituted-2,3-dioxo-1-piperazinylalkyl)-1-nitrosoureaの構造-抗腫瘍活性相関

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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 CHCl_3-H_2O (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 (LD_<50>/ED_<60>).
社団法人日本薬学会の論文
1979-07-25