Ion channel modulating compounds and uses thereof

Abstract

Ion channel modulating compounds are disclosed. The compounds of the present invention may be incorporated in compositions and kits. The present invention also discloses a variety of in vitro and in vivo uses for the compounds and compositions, including the treatment of arrhythmia and the production of analgesia and local anesthesia.

1 . Ion channel modulating compounds that block cardiac early repolarising currents and cardiac sodium currents. 
     
     
         2 . Ion channel modulating compounds according to  claim 1  that block the cardiac ion channels responsible for early repolarising currents and sodium currents. 
     
     
         3 . Ion channel modulating compounds according to  claim 1  that block cardiac early repolarising currents and cardiac sodium currents under conditions where an arrhythmogenic substrate is present in the heart. 
     
     
         4 . Ion channel modulating compounds according to  claim 1  that block the cardiac ion channels responsible for early repolarising currents and sodium currents under conditions where an arrhythmogenic substrate is present in the heart. 
     
     
         5 . Ion channel modulating compounds according to  claim 1  that block cardiac early repolarising currents and cardiac sodium currents from extracellular loci in cardiac cells. 
     
     
         6 . Ion channel modulating compounds according to  claim 1  wherein the ion channel modulating compounds have pKa values of between 4-9. 
     
     
         7 . Ion channel modulating compounds according to  claim 1  wherein the ion channel modulating compounds have pKa values of between 5-7.5. 
     
     
         8 . Ion channel modulating compounds according to  claim 1  wherein the cardiac early repolarising currents comprise ionic currents which activate rapidly after depolarisation of membrane voltage and which effect repolarisation of the cell. 
     
     
         9 . Ion channel modulating compounds according to  claim 1  wherein the early repolarising currents comprise the cardiac transient outward potassium current (I to ) and/or the ultrarapid delay rectifier current (I Kur ). 
     
     
         10 . Ion channel modulating compounds according to  claim 9  wherein the cardiac transient outward potassium current (I to ) and/or the ultrarapid delay rectifier current (I Kur ) comprise at least one of the Kv4.2, Kv4.3, Kv2.1, Kv1.4 and Kv1.5 currents. 
     
     
         11 . A composition comprising one or more ion channel modulating compounds according to  claim 1  in combination with a pharmaceutically acceptable carrier, excipient or diluent. 
     
     
         12 . A compound or composition according to any one of  claim 1  or  11  for use in a method for treating or preventing arrhythmia in a warm-blooded animal. 
     
     
         13 . A compound or composition according to any one of  claim 1  or  11  for use in a method for modulating ion channel activity in a warm-blooded animal. 
     
     
         14 . A compound or composition according to any one of  claim 1  or  11  for use in a method for modulating ion channel activity in vitro. 
     
     
         15 . Use of a compound according to  claim 1  in a manufacture of a medicament. 
     
     
         16 . A pharmaceutical composition comprising an amount of a compound according to  claim 1  effective to treat or prevent atrial arrhythmia in a warm-blooded animal in need of the treatment or prevention, and a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
         17 . A method for treating or preventing atrial arrhythmia in a warm-blooded animal comprising administering to a warm-blooded animal in need thereof a therapeutically effective amount of a compound according to  claim 1  or a composition according to  claim 16 . 
     
     
         18 - 159 . (canceled)