Compounds for the treatment of seizures and other central nervous system disorders and conditions

Abstract

The present application relates to novel compounds comprising a moiety that leads to the metabolic production of ketones bonded to a ketone-potentiated anti-epileptic drug, compositions comprising these compounds, and their use, for example for the treatment of epilepsy, and other CNS diseases, disorders or conditions. In particular, the present application includes compounds of Formula I, and compositions and uses thereof:

1 . A compound of Formula I(b): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is C 4-15 -n-alkyl, C 8-15 -branched-alkyl, C 4-15 alkenyl, C 3-10 cycloalkyleneC 1-10  alkyl, C 5-10 cycloalkenyleneC 1-10 alkyl, C 3-10 cycloalkyleneC 2-10 alkenyl or C 5-10 cycloalkenyleneC 2-10 alkenyl; 
 n and m are each independently 0, 1, 2 or 3; and 
 R 4  and R 5  are each independently selected from H, C 1-8 alkyl and C 2-8 alkenyl, provided that at least one of R 4  and R 5  is selected from C 1-8 alkyl and C 2-8 alkenyl; or 
 R 4  and R 5  together with the carbon atom to which they are bonded form a C 3-10 cycloalkane or a C 5-10 cycloalkene, 
 or a pharmaceutically acceptable salt, solvate and/or prodrug thereof. 
 
     
     
         2 . The compound of  claim 1 , wherein both n and m are 1. 
     
     
         3 . The compound of  claim 1 , wherein n is 2 and m is 0. 
     
     
         4 . The compound of  claim 1 , wherein n is 0 and m is 2. 
     
     
         5 . The compound of  claim 1 , wherein at least one of R 4  and R 5  is C 1-8 alkyl or C 2-8 alkenyl. 
     
     
         6 . The compound of  claim 1 , wherein at least one of R 4  and R 5  is C 1-6 alkyl or C 2-8 alkenyl. 
     
     
         7 . The compound of  claim 1 , wherein at least one of R 4  and R 5  is C 1-6 alkyl. 
     
     
         8 . The compound of  claim 1 , wherein at least one of R 4  and R 5  is 2-methylpropyl. 
     
     
         9 . The compound of  claim 1 , wherein at least one of R 4  and R 5  is C 2-6 alkenyl. 
     
     
         10 . The compound of  claim 1 , wherein at least one of R 4  and R 5  is vinyl. 
     
     
         11 . The compound of  claim 1 , having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound of  claim 1 , wherein R 4  and R 5  together with the carbon atom to which they are bonded form a C 3-10 cycloalkane or a C 5-10 cycloalkene. 
     
     
         13 . The compound of  claim 1 , wherein R 4  and R 5  together with the carbon atom to which they are bonded form a C 3-10 cycloalkane. 
     
     
         14 . The compound of  claim 1 , wherein R 4  and R 5  together with the carbon atom to which they are bonded form a C 5-8 cycloalkane 
     
     
         15 . The compound of  claim 1 , having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 1 , wherein R 1  is selected from n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, 3-methylheptyl, 1-propylbutyl, 3-ethylheptyl and 4-butylcyclohexyl. 
     
     
         17 . The compound of  claim 1 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate and/or prodrug thereof. 
     
     
         18 . A pharmaceutical composition comprising the compound of  claim 1  or a pharmaceutically acceptable salt, solvate and/or prodrug thereof, and a pharmaceutically acceptable carrier. 
     
     
         19 . A method of treating a CNS disease, disorder or condition selected from epilepsy, non-epileptic seizures, cognitive dysfunction, cognitive performance, anxiety and chronic pain comprising administering a compound of  claim 1  or a pharmaceutically acceptable salt, solvate and/or prodrug thereof to a subject in need thereof. 
     
     
         20 . The method of  claim 19 , wherein the CNS disease, disorder or condition is epilepsy.