Deuterated analogs of pridopidine useful as dopaminergic stabilizers

Abstract

In other aspects the invention relates to pharmaceutical compositions comprising a deuterated analog of Pridopidine of the invention, and to therapeutic applications of these analogs.

1 - 11 . (canceled) 
     
     
         12 . A pharmaceutical composition comprising a compound represented by Formula 1 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 at least one of R 1 -R 23  represents deuterium (D); and 
 the remaining of R 1 -R 23  represent hydrogen (H); 
 
       wherein the abundance of molecules of the compound having deuterium at a position designated by the at least one of R 1 -R 23  is substantially greater than the natural abundance of deuterium at that position. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein
 R 1 -R 2  represent deuterium (D); and   all of R 3 -R 23  represent hydrogen (H).   
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein at least one of R 1 -R 7  represents deuterium (D); and
 the remaining of R 1 -R 23  represent hydrogen (H).   
     
     
         15 . The pharmaceutical composition of  claim 12 , wherein
 all of R 1 -R 7  represent deuterium (D); and   all of R 8 -R 23  represent hydrogen (H).   
     
     
         16 . The pharmaceutical composition of  claim 12 , wherein
 R 8 , R 9 , R 10  and R 11  represent deuterium (D); and   all of R 1 -R 7  and R 12 -R 23  represent hydrogen (H).   
     
     
         17 . The pharmaceutical composition of  claim 12 , wherein
 R 12  represents deuterium (D); and   all of R 1 -R 11  and R 13 -R 23  represent hydrogen (H).   
     
     
         18 . The pharmaceutical composition of  claim 12 , wherein
 R 17 -R 20  represent deuterium (D); and   all of R 1 -R 16  and R 21 -R 23  represent hydrogen (H).   
     
     
         19 . The pharmaceutical composition of  claim 12 , wherein the compound or the pharmaceutically acceptable salt thereof is 4-(3-Methanesulfonyl-phenyl)-1-propyl-d7-piperidine hydrochloride. 
     
     
         20 . The pharmaceutical composition of  claim 12 , wherein the abundance of molecules of the compound having deuterium at a position designated by the at least one of R 1 -R 23  is at least 3,340 times greater than the natural abundance of deuterium at that position, at least 3,500 times greater than the natural abundance of deuterium at that position, at least 4,000 times greater than the natural abundance of deuterium at that position, at least 5,000 times greater than the natural abundance of deuterium at that position, at least 6,000 times greater than the natural abundance of deuterium at that position, at least 6,466.7 times greater than the natural abundance of deuterium at that position, or at least 6,633.3 times greater than the natural abundance of deuterium at that position. 
     
     
         21 . The pharmaceutical composition of  claim 12 , comprising the pharmaceutically acceptable salt of the compound. 
     
     
         22 . A therapeutically effective amount of the pharmaceutical composition of  claim 12  together with at least one pharmaceutically acceptable carrier, excipient or diluent. 
     
     
         23 . The pharmaceutical composition according to claim wherein
 R 1 -R 2  represent deuterium (D); and   all of R 3 -R 23  represent hydrogen (H).   
     
     
         24 . The pharmaceutical composition according to  claim 22 , wherein
 at least one of R 1 -R 7  represents deuterium (D); and   the remaining of R 1 -R 23  represent hydrogen (H).   
     
     
         25 . The pharmaceutical composition according to  claim 22 , wherein
 all of R 1 -R 7  represent deuterium (D); and   all of R 8 - R 23  represent hydrogen (H).   
     
     
         26 . The pharmaceutical composition according to  claim 22 , wherein
 R 8 , R 9 , R 10  and R 11  represent deuterium (D); and   all of R 1 -R 7  and R 12 -R 23  represent hydrogen (H).   
     
     
         27 . The pharmaceutical composition according to  claim 22 , wherein
 R 12  represents deuterium (D); and   all of R 1 -R 11  and R 13 -R 23  represent hydrogen (H).   
     
     
         28 . The pharmaceutical composition according to  claim 22 , wherein
 R 17 - R 20  represent deuterium (D); and   all of R 1 -R 16  and R 21 -R 23  represent hydrogen (H).   
     
     
         29 . The pharmaceutical composition of  claim 22  comprising the pharmaceutically acceptable salt of the compound. 
     
     
         30 . A method of treating, preventing, or alleviating a symptom of, a dopamine mediated disorder in a living animal which comprises administering to the living animal a therapeutically effective amount of the pharmaceutical composition of  claim 12 . 
     
     
         31 . A method of treating, or alleviating a symptom of, Huntington's Disease in a living animal which comprises administering to the living animal a therapeutically effective amount of the pharmaceutical composition of  claim 12 .