Mitomycin C analogs with secondary amines at position 7

• Published in: Journal of medicinal chemistry Vol. 26; no. 10; pp. 1453 - 1457
• Main Authors: Iyengar, Bhashyam S, Sami, Salah M, Tarnow, Shirley E, Remers, William A, Bradner, William T, Schurig, John E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.10.1983
• Subjects: Animals; Antibiotics, Antineoplastic - chemical synthesis; Chemistry; Drug Evaluation, Preclinical; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Indicators and Reagents; Leukemia P388 - drug therapy; Leukemia, Experimental - drug therapy; Methods; Mice; Mitomycins - chemical synthesis; Mitomycins - therapeutic use; Organic chemistry; Preparations and properties; Structure-Activity Relationship; Antineoplastic agent; Substituent effect; Structure activity relation; Angular nitrogen heterocycle; Quinone; Tertiary amine; Urethane; Tetracyclic compound; Biological activity
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00364a018

A series of mitomycin C analogues with secondary amines at position 7 was prepared from mitomycin A. Eleven of the 20 new compounds in this series were more active than mitomycin C against P-388 murine leukemia, and 2 of these 11 were significantly less leukopenic. The two substituents conferring these superior properties were 4-formylpiperazine and 2-cyanoaziridine. No quantitative correlations could be made among antitumor activities and physicochemical properties of the analogues, although the relative ease of quinone reduction might be related to the good potencies (minimum effective doses) of many of them.