Glycyrrhetinic acid derivatives as potent inhibitors of Na+,K+-ATPase. Synthesis and structure-activity relationships

Article abstract of DOI:10.1016/0223-5234(92)90147-S

A series of ring A-modified GA derivatives (26 compounds) has been systematically synthesized and the structure-activity relationship investigated for inhibition of canine kidney Na⁺,K⁺-ATPase in vitro. The most potent inhibitory activity was found with a group of the 3-deoxygenated derivatives including 5, 6, 9, 10 and 11. The high inhibition may be closely related to the hydrophobic character of the A-ring of these compounds. This finding suggests that the ATP-binding site at the active center of the enzyme is located in a hydrophobic environment.