Partial synthetic derivatization of canrenone and characterization of its impact on the inhibitory effect on Na+/K+-ATPase activity in human heart muscle

Abstract To improve the weak inhibitory effect of 3-oxo-17α-pregna-4,6-diene-21,17-carbolactone (canrenone, II) on Na + /K + -ATPase activity in human heart muscle, we have investigated the impact of hydrogenation, reduction, glycosidation, and the introduction of a 3-sulfonamido residue on the inhibitory potency of canrenone. The greatest increase in potency (>20 times) was found for 3β-(α- l -rhamnopyranosyloxy)-5β,17α-pregnane-21,17-carbolactone (IX). The 3-O-glycosides IX–XI are the first representatives of C/D-trans steroids with effector-receptor complex decay half-times longer than those of therapeutically used cardenolides.