Potential antitumor agents. 22. Latentiated congeners of the 4'-(9-acridinylamino)methanesulfonanilides.
N1-Acyl derivatives of the tumor inhibitory 4'-(9-acridinylamino)methanesulfonanilide agents act as prodrugs undergoing deacylation to liberate the core agents on incubation with pH 7.5 buffer or mouse blood. Against L1210 tumor implanted remotely from the drug administration site, lower acyl derivatives often provide enhanced effects over that obtained with nonacylated precursor alone. In certain homologous series of acyl derivatives, toxicity first increased with increasing lipophilic character, until greater than that of the core agent alone, and then at higher lipophilic levels decreased. Tumor inhibitory properties of the acyl derivatives in such series appeared inversely related to their toxicity. Several 3-(3,3-dialkyl-1-triazeno)acridine-substituted congeners provided excellent L1210 activity. Contrasting with most other tumor-active triazenes, one alkyl group need not be a methyl group of antileukemic activity to be observed. 3-Methyl-3-propyl-1-triazene and 3,3-diethyl-1-trazene analogues had comparable lipophilic-hydrophilic balance, toxicity, and antileukemic effectiveness; usual metabolic activation of the triazene N-methyl group may make little contribution to antitumor properties in the examples presented. Prepared as a nonalkylated triazene analogue, a 3-azidoacridine congener had high L1210 activity.
D000813:Anilides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D007939:Leukemia L1210 / Q000188:drug therapy; D008055:Lipids; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D012995:Solubility; D013329:Structure-Activity Relationship
D000813:Anilides; D000970:Antineoplastic Agents; D008055:Lipids