Botryllazine B analogues of diverse substitution patterns have been prepared, and their in vitro inhibitory activities against recombinant human aldose reductase (h-ALR2) evaluated. Among the 15 compounds tested, 6-(4-aminophenyl)-2-(4-hydroxyphenyl) carbonylpyrazine (7b) proved to be the most potent inhibitor, with IC50= 0.91 μM. Kinetic analyses of 7b and botryllazine B (1) revealed that these inhibitors exhibit an unprecedented mixed-type ...