Compounds and their use as ikach blockers

Abstract

The invention relates to compounds according to Formula I: or a pharmaceutically acceptable salt thereof, wherein m, n, R 1 , R 2 , R 3 , R 4 , R 5 , x and y are as defined herein. Compounds according to Formula I are pharmacologically effective as potassium channel inhibitors, in particular inhibitors of the acetylcholine operated inward rectifying potassium channel current (i.e. IKACh blockers), and are believed to be useful in the treatment of cardiac arrhythmias, in particular supraventricular tacharrhythmias, such as atrial fibrillation and atrial flutter.

1 - 11 . (canceled) 
     
     
         12 . A method of treating a disease, disorder and/or condition which is affected and/or mediated by IKACh and where treatment by IKACh blockade is beneficial to a patient in need of such treatment, wherein:
 the method comprises administering a therapeutically effective amount of a compound or pharmaceutically acceptable salt to the patient; and   the compound corresponds in structure to Formula I:   
       
         
           
           
               
               
           
         
       
       wherein:
 each R 5  is independently selected from fluoro, nitrile, hydroxy, oxo, C 1-5  alkyl, C 3-5  cycloalkyl, C 1-5  alkoxy or C 1-5  alkoxyalkyl, wherein:
 any alkyl, cycloalkyl or alkoxy group is substituted by 0, 1 or 2 substituents independently selected from fluoro, nitrile or hydroxy, 
 
 R 1  is selected from C 1-6  alkyl, C 3-6  cycloalkyl or C 1-6  alkoxyalkyl, wherein:
 any alkyl, cycloalkyl or alkoxy group is substituted by 0, 1 or 2 substituents independently selected from fluoro or nitrile, 
 
 R 2  is selected from hydrogen or C 1-3  alkyl; 
 R 3  is selected from C 1-6  alkyl, C 3-6  cycloalkyl or C 1-6  alkoxyalkyl, wherein:
 any alkyl or cycloalkyl group is substituted by 0, 1 or 2 substituents independently selected from fluoro, nitrile or hydroxy; 
 
 each R 4  is independently selected from halo, nitrile, hydroxy, C 1-3  alkyl, C 1-3  alkoxy, C 1-3  alkoxyalkyl or C 1-3  alkylsulfide, wherein:
 any alkyl or alkoxy group is substituted by 0, 1, 2 or 3 substituents independently selected from halo, nitrile or hydroxy; 
 
 m is selected from 1, 2 or 3; 
 n is selected from 1 or 2; 
 x is selected from 0, 1, 2, or 3; and 
 y is selected from 0, 1, 2 or 3. 
 
     
     
         13 . A method of treating cardiac arrhythmias or a complication associated with cardiac arrhythmias in a patient in need of such treatment, wherein:
 the method comprises administering a therapeutically effective amount of a compound or pharmaceutically acceptable salt to the patient; and   the compound corresponds in structure to Formula I:   
       
         
           
           
               
               
           
         
       
       wherein:
 each R 5  is independently selected from fluoro, nitrile, hydroxy, oxo, C 1-5  alkyl, C 3-5  cycloalkyl, C 1-5  alkoxy or C 1-5  alkoxyalkyl, wherein:
 any alkyl, cycloalkyl or alkoxy group is substituted by 0, 1 or 2 substituents independently selected from fluoro, nitrile or hydroxy, 
 
 R 1  is selected from C 1-6  alkyl, C 3-6  cycloalkyl or C 1-6  alkoxyalkyl, wherein:
 any alkyl, cycloalkyl or alkoxy group is substituted by 0, 1 or 2 substituents independently selected from fluoro or nitrile, 
 
 R 2  is selected from hydrogen or C 1-3  alkyl; 
 R 3  is selected from C 1-6  alkyl, C 3-6  cycloalkyl or C 1-6  alkoxyalkyl, wherein:
 any alkyl or cycloalkyl group is substituted by 0, 1 or 2 substituents independently selected from fluoro, nitrile or hydroxy; 
 
 each R 4  is independently selected from halo, nitrile, hydroxy, C 1-3  alkyl, C 1-3  alkoxy, C 1-3  alkoxyalkyl or C 1-3  alkylsulfide, wherein:
 any alkyl or alkoxy group is substituted by 0, 1, 2 or 3 substituents independently selected from halo, nitrile or hydroxy; 
 
 m is selected from 1, 2 or 3; 
 n is selected from 1 or 2; 
 x is selected from 0, 1, 2, or 3; and 
 y is selected from 0, 1, 2 or 3. 
 
     
     
         14 . A method of restoring and/or maintaining sinus rhythm in a patient in need of such treatment, wherein:
 the method comprises administering a therapeutically effective amount of a compound or pharmaceutically acceptable salt to the patient; and   the compound corresponds in structure to Formula I:   
       
         
           
           
               
               
           
         
       
       wherein:
 each R 5  is independently selected from fluoro, nitrile, hydroxy, oxo, C 1-5  alkyl, C 3-5  cycloalkyl, C 1-5  alkoxy or C 1-5  alkoxyalkyl, wherein:
 any alkyl, cycloalkyl or alkoxy group is substituted by 0, 1 or 2 substituents independently selected from fluoro, nitrile or hydroxy, 
 
 R 1  is selected from C 1-6  alkyl, C 3-6  cycloalkyl or C 1-6  alkoxyalkyl, wherein:
 any alkyl, cycloalkyl or alkoxy group is substituted by 0, 1 or 2 substituents independently selected from fluoro or nitrile, 
 
 R 2  is selected from hydrogen or C 1-3  alkyl; 
 R 3  is selected from C 1-6  alkyl, C 3-6  cycloalkyl or C 1-6  alkoxyalkyl, wherein:
 any alkyl or cycloalkyl group is substituted by 0, 1 or 2 substituents independently selected from fluoro, nitrile or hydroxy; 
 
 each R 4  is independently selected from halo, nitrile, hydroxy, C 1-3  alkyl, C 1-3  alkoxy, C 1-3  alkoxyalkyl or C 1-3  alkylsulfide, wherein:
 any alkyl or alkoxy group is substituted by 0, 1, 2 or 3 substituents independently selected from halo, nitrile or hydroxy; 
 
 m is selected from 1, 2 or 3; 
 n is selected from 1 or 2; 
 x is selected from 0, 1, 2, or 3; and 
 y is selected from 0, 1, 2 or 3. 
 
     
     
         15 - 16 . (canceled)