4"-amino-substituted second-generation compounds

On the basis of both structural correlation between benzotriazine and Qx nucleus and mode of action reported for QDO, Monge et al. described at a first time 3-amino-2-cyano-substituted QDO as selective hypoxic cy-totoxins, bioreductive compounds, i.e., compounds 38-41 (Table 6) [27]. In this first approach, the best compounds were the 7-electron-withdrawing substituted derivatives. Electrochemical properties, assessed via voltammet-ric studies, showed that as the electron-withdrawing nature of the 6-(7)-substituent increases, the reduction potential becomes more positive. Compounds with reduction potential more positive are more hypoxia-cytotoxic. However, due to the poor solubility in water of these derivatives, a new generation of compounds was designed and synthesized, i.e., compounds 42-45 (Table 6) [28]. In this second generation of compounds it is possible to highlight derivatives 42 and 45 (Table 6) with excellent hypoxic potency... 

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