Antitumor Imidazotetrazines. 1. Synthesis and Chemistry of 8-Carbamoyl-3-(2-chloroethyl)imidazo-1,2,3,5-tetrazin-4(3H)-one, a Novel Broad-Spectrum Antitumor Agent

Article abstract of DOI:10.1021/jm00368a016

Interaction of 5-diazoimidazole-4-carboxamide and alkyl and aryl isocyanates in the dark affords 8-carbamoyl-3-substituted-imidazo<5,1-d>-1,2,3,5-tetrazin-4(3H)-ones.In cold methanol or ethanol, the 3-(2-chloroethyl) derivative 7a decomposes to afford 2-azahypoxanthine (14) and methyl and ethyl N-(2-chloroethyl)carbamates, respectively.Compound 7a has curative activity against L-1210 and P388 leukemia and may act as a prodrug modification of the acyclic triazene 5-<3-(2-chloroethyl)triazen-1-yl>imidazole-4-carboxamide (MCTIC), since it ring opens to form the triazene in aqueous sodium carbonate.