Studies on Antitumor-active 2, 3-Dioxopiperazine Derivatives. II. Synthesis and Structure-Antitumor Activity Relationship of 1-Benzyl-2, 3-dioxopiperazine Derivatives

2, 3-Dioxopiperazine derivatives, which are antitumor agents of a new type, were synthesized and the structure-activity relationship was investigated from the viewpoint of lipophilic-hydrophilic balance. It was found that 1-(4-diethylaminobenzyl)-4-n-hexyl-2, 3-dioxopiperazine (12n) possessed significant in vitro cytotoxicity and in vivo antitumor activity against transplanted tumor, but this in vivo antitumor activity did not reflect the in vitro cytotoxicity. The metabolism of 12n in rats and mice was then studied. It was found that the Et2N-group of 12n was easily metabolized to an AcNH-group in vivo.