Potential antitumor agents. 20. Structure-activity-site relationships for the...

A series of 87 L1210 active 4'-(9-acridinylamino)alkanesulfonanilides has been screened against L1210 cells (10(5)) implanted at various sites (ip, sc, ic) employing early ip drug administration for a limited time. With each implantation site a different most active congener was selected. For good activity against tumor implanted remotely from the ip drug administration site, an agent should be more lipophilic than that found optimal for ip implanted tumor. An acridine 4-CH3 group appears to assist drug translocation, possibly by sterically hindering binding to nonproductive sites. An unprotected NH2 group on the acridine ring system is incompatible with activity against sc implanted tumor. Agents in which NH2 is shielded by N-acetylation, N-monomethylation, or ortho substitution with a bulky group can inhibit sc implanted tumor.