Details

Autor(en) / Beteiligte

• Cerri, Alberto
• Serra, Fulvio
• Ferrari, Patrizia
• Folpini, Elena
• Padoani, Gloria
• Melloni, Piero

Titel

Synthesis, Cardiotonic Activity, and Structure−Activity Relationships of 17β-Guanylhydrazone Derivatives of 5β-Androstane-3β,14β-diol Acting on the Na+,K+-ATPase Receptor

Ist Teil von

• Journal of medicinal chemistry, 1997-10, Vol.40 (21), p.3484-3488

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

1997

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• A series of digitalis-like compounds, with the lactone ring shifted from the original position through a spacer or replaced by a series of guanylhydrazone substituent-bearing chains, was synthesized and evaluated for inhibition of Na+,K+-ATPase and for inotropic activity. The highest Na+,K+-ATPase inhibition (IC50) and inotropic activity (EC50) were reached with the vinylogous guanylhydrazone 5 where a cardenolide-like polarized α,β-unsaturated system and a basic guanidino group were both present at the 17β-position; for this compound IC50 and EC50 values were comparable to or higher than those of Thomas' parent guanylhydrazone 1, digitoxigenin, and digoxin. A substantial improvement of the desired positive inotropic activity versus the toxic arrhythmogenic concentration was not reached within this series; only a slightly better therapeutic index can be envisaged for compounds 5 and 4, even though, for the latter, to the detriment of potency, presumably because of a weaker interaction with the receptor, due to the lack of a cardenolide-like polarized system.