Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR
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- 作者：Elrashied A. E. Garelnabi ; Dimitrios Pletsas ; Li Li ; Konstantinos Kiakos ; Nazira Karodia ; John A. Hartley ; Roger M. Phillips ; Richard T. Wheelhouse
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：December 13, 2012
- 年：2012
- 卷：3
- 期：12
- 页码：965-968
- 全文大小：273K
- 年卷期：v.3,no.12(December 13, 2012)
- ISSN：1948-5875
文摘
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.