Antitumour imidazotetrazines. Part 39. Synthesis of bis(imidazotetrazine)swith saturated spacer groups

Bis(imidazotetrazine)s (16), related in structure to the antitumour agents mitozolomide (1a) and temozolomide (1b), but linked through the N(3)-N(3') atoms of the imidazo[5,1-d][1,2,3,5]tetrazine ring-systems, are prepared by interaction of 5-diazoimidazole-4-carboxamide (8) and diisocyanates (15). The presence of the polymethylene linker with/without sulfur and oxygen het eroatoms does not substantially affect the acid stability, base-catalysed d ecomposition, antitumour activity or DNA base alkylation preference charact eristic of the unlinked imidazotetrazines mitozolomide and temozolomide.