A Strategy for Imidazotetrazine Prodrugs with Anti-cancer Activity Independent of MGMT and MMR

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Garelnabi, EAE ; Pletsas, D ; Li, L ; Kiakos, K ; Karodia, N ; Hartley, JA ; Phillips, Roger ; Wheelhouse, RT (2012)
  • Publisher: ACS Publications
  • Subject: RM

The imidazotetrazine ring is an acid-stable precursor and prodrug of highly-reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of temozolomide.
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