Xy. Bu et al., Synthesis and cytotoxic activity of 7-Oxo-7H-dibenz[f,ij]isoquinoline and 7-oxo-7H-benzo[e]perimidine derivatives, J MED CHEM, 44(12), 2001, pp. 2004-2014
A series of 7-oxo-7H-dibenz [f,ij]isoquinoline and 7-oxo-7H-benzo[e] perimi
dines bearing cationic side chains were prepared from aminoanthraquinones.
The perimidines were prepared from 1-aminoanthraquinone by initial condensa
tion with urea or dimethylacetamide. A series of 2-, 4-, 8-, and 11-carboxy
derivatives of the dibenzisoquinolines were prepared from aminoan-thraquin
onecarboxylic acids. The cationic derivatives were prepared from these via
amide, amine, or methylene linkers to study the effects of side chain posit
ioning on biological activity. Within the series of carboxamide-linked comp
ounds, the order of increasing cytotoxicity was 8- < 4- < 2- < 11-. The 2-
and 4-carboxamides showed substantial growth delays against in vivo subcuta
neous colon 38 tumors in mice, but the 11-carboxamide had curative activity
in this refractory model and is being investigated further.