Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR.
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ABSTRACT:
SUBMITTER: Garelnabi EA
PROVIDER: S-EPMC4025673 | biostudies-literature | 2012 Dec
REPOSITORIES: biostudies-literature
Publications
Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR.
Garelnabi Elrashied A E EA Pletsas Dimitrios D Li Li L Kiakos Konstantinos K Karodia Nazira N Hartley John A JA Phillips Roger M RM Wheelhouse Richard T RT
ACS medicinal chemistry letters 20120918 12
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. ...[more]
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