1046809-08-8Relevant academic research and scientific papers
Novel synthesis method of Istaroxime
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, (2016/10/10)
The invention belongs to the field of pharmaceutical chemistry, and discloses a novel synthesis method of Istaroxime. The method comprises the following steps: by using dehydrogenated epiandrosterone as an initial raw material, carrying out epoxidation, ring opening, reduction, oxidation and other reactions to prepare an intermediate M-06; by using ethyl benzoate as an initial raw material, reacting the ethyl benzoate with hydroxylamine hydrochloride to obtain phenyl hydroximic acid, carrying out hydrochlorination and chlorination by using ethanolamine as a raw material to obtain dichloroacetate, and carrying out substitution, hydrolysis and other reactions on the dichloroacetate and the phenyl hydroximic acid to obtain an intermediate M-11; and finally, reacting the M-06 with the M-11 to obtain the end product Istaroxime. According to the method, in the intermediate M-06 synthesis process, the polarity of all the intermediates has great differences from that of the impurities and reaction reagents; and in the intermediate 11 synthesis process, the active spots capable of participating in the chemical reaction in the reaction substrate are simple. Therefore, the method can achieve the requirements without carrying out column chromatography purification, thereby simplifying the synthesis after-treatment process.
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
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.
6-Hydroxy and 6-oxo-androstane derivatives active on the cardiovascular system and pharmaceutical compositions containing same
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, (2008/06/13)
6-hydroxy and 6-oxo-androstane derivatives of formula (I), active on the cardiovascular system. STR1 wherein: the symbol A represents CH--OR, C=N--OR, CH--CH=N--OR and C=CH--N--OR; and R1, R2 and R3 are as defined herein.
