Document Report Card

ID: ALA1122747

Journal: J Med Chem

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

Authors: Rewcastle GW, Atwell GJ, Baguley BC, Denny WA.

Abstract: 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.

CiteXplore: 6747989

DOI: 10.1021/jm00374a020