Cardenolide analogues. 7. Synthesis and biological activity of some new steroidal guanylhydrazones.
The synthesis, proof of structure, and biological activity of some new steroidal 17beta-formyl guanylhydrazones are described. The guanylhydrazones of nondigitalis-like steroids inhibited myocardial Na+,K+-ATPase but had only a depressant effect on myocardial contractility. By comparison, the corresponding guanylhydrazone of a digitalis-like steroid gave a positive inotropic effect in concentrations that also inhibited Na+,K+-ATPase. The nondigitalis-like guanylhydrazones also inhibited membrane Mg2+-ATPase and this may infer that the compounds act nonspecifically by membrane stabilization rather than by interaction with stereoselective receptors. Biological activity was determined in the guinea pig.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011278:Pregnanes / Q000138:chemical synthesis / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical
D006146:Guanidines; D006835:Hydrazones; D011278:Pregnanes; D012964:Sodium; D000251:Adenosine Triphosphatases; D008274:Magnesium; D011188:Potassium