Isoquinolin-1 (2h) -one derivatives as parp-1 inhibitors

Details Isoquinolin-1 (2h) -one derivatives as parp-1 inhibitors Isoquinolin-1 (2h) -one derivatives as parp-1 inhibitors

C - Chemistry, Metallurgy

07

D

C07D 217/24 (2006.01) A61K 31/472 (2006.01) A61K 31/4725 (2006.01) A61P 9/00 (2006.01) A61P 25/00 (2006.01) A61P 29/00 (2006.01) A61P 35/00 (2006.01) C07D 401/04 (2006.01)

Patent

CA 2762226

There are provided substituted isoquinolin-1(2H)-one derivatives which selectively inhibit the activity of poly (ADP- ribose) polymerase PARP-1 with respect to poly (ADP-ribose) polymerase PARP-2. The compounds of the present invention are therefore useful in treating diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds. A screening method for the identification of compounds capable of binding several PARP proteins, as well the probes used in such method, are further objects of the invention.

L'invention concerne des dérivés isoquinoléin-1(2H)-one substitués inhibant sélectivement l'activité de la poly(ADP-ribose)polymérase PARP-1 par rapport à la poly(ADP-ribose)polymérase PARP-2. Les composés de l'invention sont donc utiles dans le traitement de maladies telles que le cancer, les maladies cardio-vasculaires, la lésion du système nerveux et différentes formes d'inflammation. L'invention porte également sur des méthodes de préparation de ces composés, sur des compositions pharmaceutiques comprenant lesdits composés, sur des méthodes de traitement de maladies au moyen de compositions pharmaceutiques comprenant lesdits composés. Une méthode de criblage pour l'identification de composés capables de fixer plusieurs protéines PARP ainsi que les sondes utilisées dans ladite méthode, sont également décrites.

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