4-carboxamido-isoindolinone derivatives as selective PARP-1 inhibitors

Abstract

There are provided substituted 4-carboxamido-isoindolinone 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 this 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.

The invention claimed is: 
     
       1. A compound selected from the group consisting of:
 2-(1-cyclohexyl-piperidin-4-yl)-3-oxo-2,3-dihydro-1H-isoindole-4-carboxylic acid amide; and 
 2-(1-cyclohexyl-piperidin-4-yl)-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxylic acid amide; 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
       2. An in vitro method for selectively inhibiting PARP-1 protein activity, which comprises contacting the said protein with an effective amount of a compound of  claim 1 . 
     
     
       3. A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient, carrier or diluent. 
     
     
       4. A product comprising a compound of  claim 1  or a pharmaceutically acceptable salt thereof and one or more chemotherapeutic agents, as a combined preparation.