Antitumor Imidazotetrazines. 32.1 Synthesis of Novel Imidazotetrazinones and Related Bicyclic Heterocycles To Probe the Mode of Action of the Antitumor Drug …

…, MJ Tisdale, RT Wheelhouse, BJ Denny…

Index: Clark; Deans; Stevens; Tisdale; Wheelhouse; Denny; Hartley Journal of Medicinal Chemistry, 1995 , vol. 38, # 9 p. 1493 - 1504

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Citation Number: 105

Abstract

The chemical mechanism underlying the antitumor properties of temozolomide (1) and mitozolomide (2)(Figure 1) is reasonably clear. Temozolomide is a prodrug which undergoes base-catalyzed hydrolytic ring opening followed by loss of a molecule of carbon dioxide to generate 5-(3-methyltriazen-l-yl) imidazole-4-carbox-amide (MTIC, 4); 2 this further fragments to the methyldiazonium species 6 as the proximal DNA-methylating ...