title: Quantitative structure-inotropy relationship applied to substituted grayanotoxins.
abstract: 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.
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents; D004224:Diterpenes / Q000494:pharmacology*; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D008433:Mathematics; D009200:Myocardial Contraction / Q000187:drug effects; D010126:Ozone; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
chemical_list: D002316:Cardiotonic Agents; D004224:Diterpenes; D010126:Ozone; C020751:grayanotoxin III