Quantitative structure-inotropy relationship applied to substituted grayanotoxins.

Nine 14 beta-O-acylated grayanotoxins were synthesized by ozonolysis of 14,16-alkylidenegrayanotoxin III. The correlation between positive inotropic potency (PIE) in guinea pigs and physicochemical parameters (Vw, Mw, and Rm50) in 14 14-substituted grayanotoxins were quantitatively analyzed. It became clear that a parabolic relation existed between the bulkiness of the 14-substituents and PIE and that some electronic factor and the hydrophilic-hydrophobic balance would be related to the development of PIE.