Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR

• Published in: ACS medicinal chemistry letters Vol. 3; no. 12; pp. 965 - 968
• Main Authors: Garelnabi, Elrashied A. E, Pletsas, Dimitrios, Li, Li, Kiakos, Konstantinos, Karodia, Nazira, Hartley, John A, Phillips, Roger M, Wheelhouse, Richard T
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.12.2012; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Letter; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; Imidazotetrazine; aziridinium; cancer; Temozolomide; 13C NMR; DNA; ANTITUMOR DRUG TEMOZOLOMIDE; DECOMPOSITION; C-13 NMR

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 h...