Tricyclic [1, 2, 4] triazine 1, 4-dioxides as hypoxia selective cytotoxins

…, K Pchalek, HH Lee, A Blaser, FB Pruijn…

Index: Hay, Michael P.; Hicks, Kevin O.; Pchalek, Karin; Lee, Ho H.; Blaser, Adrian; Pruijn, Frederik B.; Anderson, Robert F.; Shinde, Sujata S.; Wilson, William R.; Denny, William A. Journal of Medicinal Chemistry, 2008 , vol. 51, # 21 p. 6853 - 6865

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Citation Number: 46

Abstract

A series of novel tricyclic triazine-di-N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen-, and nitrogen-containing saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia- selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion ...