Cm. Ahn et al., SYNTHESIS OF 6-AZIRIDINYLBENZIMIDAZOLE DERIVATIVES AND THEIR IN-VITROANTITUMOR ACTIVITIES, Archives of pharmacal research, 21(5), 1998, pp. 599-609
In search for new antitumor agents, twelve 6-aziridinylbenzimidazole d
erivatives were synthesized and their cytotoxicities were tested again
st three cancer cell lines (mouse lymphocytic leukemia P388 and B16, a
nd human gastric carcinoma SNU-16). From 4-amino-3-nitrotoluene as the
starting material, 2-(acetoxymethyl)benzimidazoles (5a-d) were obtain
ed by Phillips reaction. These benzimidazoles were then reacted with F
remyls salt to give a mixture of three 2-(acetoxymethyl) (8a-c) and fo
ur 2-(hydroxymethyl)benzimidazole-4,7-diones (9a-d). Addition of these
quinones with aziridine afforded 6-aziridinyl-2-(acetoxymethyl) (10a-
c) and 6-aziridinyl-2-(hydroxymethyl)benzimidazole-4, 7-diones (11a-d)
. Utilizing 2-(hydroxymethyl)benzimidazole-4,7-diones (9b,d), esters 1
0d and 13e-h were prepared by the sequential reactions of esterificati
on and addition. The synthesized compounds show potent cytotoxicity ag
ainst all of three cell lines tested. The cytotoxicities of 10a-d or 1
1a-d against SNU-16 were superior to those of 13e-h, and were equal to
or slightly higher than that of mitomycin C. Compounds 11a-d were sli
ghtly more cytotoxic than 10a-d in all cell lines tested.