Synthesis, Structure Analysis, and Antitumor Evaluation of 3,6‐Dimethyl‐1,2,4,5‐tetrazine‐1,4‐dicarboxamide Derivatives

Abstract 3,6‐Dimethyl‐1,2,4,5‐tetrazine‐1,4‐dicarboxamide derivatives were synthesized, and their structures were confirmed by single‐crystal X‐ray diffraction. This reaction yields the 1,4‐dicarboxamide derivatives rather than the 1,2‐dicarboxamide derivatives. Their in vitro antitumor activities were evaluated against SGC‐7901, HO‐8910, MCF‐7, and A‐549 cells. The results showed several compounds to be endowed with cytotoxicity in the low micromolar range. One compound (IC 50 =0.57 μ M ) was further evaluated in vivo against an A‐549 xenograft in BALB/cA nude mice; it effected 76.4 % inhibition of tumor weight through intraperitoneal (i.p.) administration of 40 mg kg −1 body weight. Moreover, its acute toxicity was evaluated, and the i.p. LD 50 value was 325 mg kg −1 in mice.