Denny W A, Atwell G J, Cain B F
J Med Chem. 1977 Oct;20(10):1242-6. doi: 10.1021/jm00220a003.
Tumor inhibition inhibition produced by isomeric, nitro-substituted 4'-(9-acridinylamino)methanesulfonanilide analogues of low base strength (pKa=4.79-5.72) might result from in vivo reduction to the corresponding, higher pKa (7.15-9.80), tumor active amines. The aza analogues,-N=in place of -C(NO2)=, have been prepared as nonclassical bioisosteres and screened in the L1210 system. Significant L1210 inhibition produced by isomeric 3- and 4-azalogues, of similar base strength to the corresponding nitro-substituted derivatives, demonstrates that weakly basic analogues can provide biologic activity when there is no prospect of in vivo reduction to more strongly basic products. Obligatory reduction of nitro function, for biologic activity, need not be postulated in this drug series.
