Nitrogen analogues of 1,4-benzoquinones. Activities against the ascitic sarcoma 180 of mice.

Compounds having the basic structure N-(R)-substituted ring-substituted 4-iminocyclohexadienone have been synthesized and tested as antitumor agents against the ascitic sarcoma 180 tumor in Swiss mice. Among these compounds, the dimethylindoanilines [R = 4-(CH3)2NC6H4] are most stable in water at pH 7.0 and at 25 degrees C, the oximes (R = oh) are less stable, and the N-halo compounds (R = Br and Cl) are least stable. The N-halo derivatives have the highest redox potentials under the conditions used, the greatest effect against ascitic sarcoma 180 in Swiss mice, and the greatest acute toxicity when injected ip in the Swiss mice. Discriminant analysis of the results indicates that substituents with positive values of F and negative values of pi increase the antitumor activities, whereas those with positive values of sigma and R should lower the toxicity. The redox potential, a molecular parameter, is the best single variable for discriminating between the groups based on antitumor activities.