Mitomycin C analogues with aryl substituents on the 7-amino group.
Mitomycin C analogues with aryl substituents on the 7-amino group.
复制标题
丝裂霉素 C 类似物，7-氨基上带有芳基取代基。
DOI：
10.1021/jm00371a026
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发表时间：
1984
影响因子：
7.3
通讯作者：
Schurig,JE
中科院分区：
文献类型：
--
作者：
Sami,SM;Iyengar,BS;Tarnow,SE;Remers,WA;Bradner,WT;Schurig,JE
A series of 30 different N1-phenyl-substituted mitomycin C analogues, including 25 new compounds, was prepared from mitomycin A. Seven of these compounds were clearly superior to mitomycin C in activity against P-388 murine leukemia. The para-and the meta-substituted derivatives were subjected to Hansch analysis, which revealed that the lipid-water distribution coefficient ir was the only significant factor in determining antitumor potency (MED). The substituent electronegativity factor was statistically insignificant in determining potency, despite the good correlation of with the polarographic quinone-reduction potential. These results suggest that diffusion into the tumor cell or access to the receptor is more important than bioreductive activation in determining antitumor potency for this particular group of mitosanes. Fifteen new mitomycin C analogues with heterocycles on the 7-amino group also were prepared. Twoof them, containing pyrazolyl and aminopyridyl substituents, were more active than mitomycin C against P-388 murine leukemia. No broad correlations could be made amongthe antitumor potencies and physicochemical properties for this type of analogue.A preceding article in this series described mitomycin C analogues with substitutedethylamines at position 7.1 These compounds were chosen in part to permit the study of substituent effects at a site removed from the quinone ring. This study revealed no statistically significant cor-relation between physicochemical properties, such as hy-drophilicity or substituent size, and activity against P-388 leukemia in mice.
