1046809-27-1Relevant articles and documents
Novel analogues of istaroxime, a potent inhibitor of Na+,K +-ATPase: Synthesis and structure-activity relationship
Gobbini, Mauro,Armaroli, Silvia,Banfi, Leonardo,Benicchio, Alessandra,Carzana, Giulio,Fedrizzi, Giorgio,Ferrari, Patrizia,Giacalone, Giuseppe,Giubileo, Michele,Marazzi, Giuseppe,Micheletti, Rosella,Moro, Barbara,Pozzi, Marco,Scotti, Piero Enrico,Torri, Marco,Cerri, Alberto
supporting information; experimental part, p. 4601 - 4608 (2009/06/06)
We report the synthesis and biological properties of novel inhibitors of the Na+,K+-ATPase as positive inotropic compounds. Following our previously described model from which Istaroxime was generated, the 5α,14α-androstane skeleton was used as a scaffold to study the space around the basic chain of our lead compound. Some compounds demonstrated higher potencies than Istaroxime on the receptor and the (E)-3-[(R)-3- pyrrolidinyl]oxime derivative, 15, was the most potent; as further confirmation of our model, the E isomers of the oxime are more potent than the Z form. The compounds tested in the guinea pig model induced positive inotropic effects, which are correlated to the in vitro inhibitory potency on the Na +,K+-ATPase. The finding that all tested compounds resulted less proarrhythmogenic than digoxin, a currently clinically used positive inotropic agent, suggests that this could be a feature of the 3-aminoalkyloxime derivative class of 5α,14α-androstane.
