953772-61-7Relevant 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
, p. 4601 - 4608 (2008)
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.
AMINOOXIME DERIVATIVES OF 2- AND/OR 4-SUBSTITUTED ANDROSTANES AND ANDROSTENES AS MEDICAMENTS FOR CARDIOVASCULAR DISORDERS
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Page/Page column 87-88, (2009/05/30)
New aminooxime derivatives at position 3 of 2-and/or 4-substituted androstanes and androstenes, processes for their preparation, and to pharmaceutical compositions containing them for the treatment of cardiovascular disorders, such as heart failure and hypertension. In particular compounds having the general formula (I) are described,where the radicals have the meanings described in detail in the application.
AMINO DERIVATIVES OF B-HOMOANDROSTANES AND B-HETEROANDROSTANES
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Page/Page column 76, (2008/06/13)
New aminoalkoxyimino derivatives at position 3 of substituted B- homoandrostanes and B-heteroandrostanes, processes for their preparation, and to pharmaceutical compositions containing them for the treatment of cardiovascular disorders, such as heart fail