Pharmaceutical compositions for the treatment of chronic...

A - Human Necessities – 61 – K

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A61K 31/519 (2006.01)

Patent

CA 2689438

Disclosed herein is a therapeutic agent for chronic heart failure comprising, as an effective ingredient, 5- [2-propyloxy- 5- (l-methyl-2-pyrrolidinyleneamidosulfonyl) phenyl] - 1 -methyl - propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-one. The compound inhibits phosphodiesterase-5 (PDE-5), which catalyzes the intracellular degradation of cyclic guanosine monophosphatase (cGMP), thereby mitigating several signs of chronic heart failure, that is, thereby preventing left ventricular dilatation, decreasing ventricular wall thinning, lowering elevated cardiac and circulating levels of atrial natriuretic peptide (ANP), and inhibiting ventricular fibrosis. Also, the compound has advantages in that it reaches the maximal plasma level in a short time, has an in vivo half-life longer than conventional PDE-5 inhibitors, allowing decreased administration frequency, and has fewer side effects, thus ensuring safety. Thus, the compound is useful as a therapeutic agent for chronic heart failure.

L'invention concerne un agent thérapeutique pour traiter l'insuffisance cardiaque chronique comprenant comme ingrédient efficace 5- [2-propyloxy- 5- (l-methyl-2-pyrrolidinyleneamidosulfonyl) phenyl] - 1 -methyl - propyl-l,6-dihydro-7H-pyrazolo(4,3-d)pyrimidine-7-one. Ledit composé inhibe la phosphodiestérase-5 (PDE-5), qui catalyse la dégradation intracellulaire de la guanosine monophosphatase cyclique (cGMP), ce qui permet d'atténuer plusieurs signes d'insuffisance cardiaque chronique, c'est-à-dire, d'empêcher la dilatation ventriculaire gauche, de limiter l'amincissement de la paroi ventriculaire, d'abaisser les niveaux cardiaques et de circulation élevés du peptide natriurétique atrial (ANP), et d'inhiber la fibrose ventriculaire. Ledit composé présente également des avantages en ce qu'il atteint un niveau plasmique maximum en peu de temps, en ce qu'il possède une demi-vie in vivo plus longue que les inhibiteurs PDE-5 classiques, en ce qu'il permet une réduction de la fréquence d'administration et en ce qu'il présente peu d'effets secondaires, ce qui le rend sûr. De ce fait, le composé est utilisé comme agent thérapeutique pour traiter l'insuffisance cardiaque chronique.

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