Derivatives of 3-digitoxigenone amidinohydrazone: synthesis and effect on the digitalis receptor of several species. Part 7: Compounds with positive inotropic activity.
2-Digitoxigenone amidinohydrazone (1), a compound with known digitalis-like activity, and Schiff bases 2-11 of 3-digitoxigenone were synthesized and tested pharmacologically in order to further determine possible structural requirements at the 3-position of digitalis compounds. The inotropic activity was screened using guinea-pig atria, and the interaction with the digitalis receptor was further examined using [3H]ouabain binding to cardiac membranes from guinea pig, rat, pit and man. All compounds revealed activities intermediate between 3-digitoxigenone and ouabain, and the potency of the derivatives covered approximately one order of magnitude. The absolute potency varied among species, but the rank order of potency was rather similar, yielding good correlations between species. This indicates no pronounced preference of these compounds for a particular (Na+/K+)-ATPase isoform of any of the species studied.
Heber
D
D
Department of Pharmaceutical Chemistry, University of Kiel.
Herzig
S
S
Moosig
F
F
Neujahr
H
H
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004071:Digitalis Glycosides / Q000378:metabolism*; D004073:Digitoxigenin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine
D002316:Cardiotonic Agents; D004071:Digitalis Glycosides; D006835:Hydrazones; C027082:digitalis receptor; D004073:Digitoxigenin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase