Antitumour imidazotetrazines: past, present… and future?

It is 40 years since the publication of the patent that announced the imidazotetrazines temozolomide and mitozolomide to the world and 30 since the discovery that they function as prodrugs of alkyldiazonium reactive intermediates. Temozolomide combined with radiation is established as the first-line treatment for glioma but despite the attentions of the inventors and others, further examples of this intriguing ring system have yet to enter the clinic.