Potential antitumor agents. 20. Structure-activity-site relations for the 4'-(9-acridinylamino)alkanesulfonanilides

Abstract

A series of 87 L1210 active 4''-(9-acridinylamino)alkanesulfonanilides was screened against L1210 mouse leukemia cells (105) implanted at various sites (i.p., s.c., ic [intracerebrally]) employing early i.p. 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 i.p. drug administration site, an agent should be more lipophilic than that found optimal for i.p. 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 s.c. implanted tumor. Agents in which NH2 is shielded by N-acetylation, N-monomethylation or ortho substitution with a bulky group can inhibit s.c. implanted tumor.