Potential antitumor agents. 42. Structure-activity relationships for acridine-substituted dimethyl phosphoramidate derivatives of 9-anilinoacridine.

Replacement of the 1'-methanesulfonamide group of the 9-anilinoacridine class of antitumor agents with the 1'-(dimethyl phosphoramidate) group provides compounds that are generally more lipophilic and bind more tightly to DNA. On the average, the dimethyl phosphoramidates are twice as dose potent as the corresponding methanesulfonamide (AMSA) compounds against P388 leukemia in vivo, but also show about twice the acute toxicity and no resultant improvement in tumor cell selectivity (ILSmax values) is seen. A pairwise comparison of a range of acridine-substituted compounds shows that structure-activity relationships within each series are similar and dominated by the acridine substitution pattern.