New quinoxalinecarbonitrile 1,4-di-N-oxide derivatives as hypoxic-cytotoxic agents

We report the synthesis and biological in vitro activities of 16 new 2-quin oxalinecarbonitrile 1,4-di-N-oxides. These compounds present new basic late ral chains (piperazines and anilines) in the 3 position as well as differen t substituents in the 6 and/or 7 positions of the quinoxaline ring. Among p iperazine derivatives, 4b (a 7-chloro-3-(4-methylpiperaiin-1-yl) derivative ) was the most potent (P = 0.5 x 10(-6) M). In general, aniline derivatives were more potent and selective than the former, compound 12b (with a 4-(me thylphenyl)amino moiety in the 3 position and a chlorine atom in the 7 posi tion) being the best one (P = 3 x 10-6 M and HCR > 16). (C) 2000 Editions s cientifiques et medicales Elsevier SAS.