Deuterated analogs of pridopidine useful as dopaminergic stabilizers

Abstract

The present invention provides novel deuterated analogs of Pridopidine, i.e. 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine. Pridopidine is a drug substance currently in clinical development for the treatment of Huntington's disease. 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 . A fully or partially deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine represented by Formula 1 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein at least one of R 1 -R 21  represents deuterium (D); and the remaining of R 1 -R 23  represent hydrogen (H). 
     
     
         2 . The deuterated analog or pharmaceutically acceptable salt thereof according to  claim 1 , wherein
 R 1 -R 2  represent deuterium (D); and   all of R 1 -R 23  represent hydrogen (H); or   at least one of R 1 -R 7  represents deuterium (D); and   the remaining of R 1 -R 23  represent hydrogen (H); or   all of R 1 -R 7  represent deuterium (D); and   all of R 8 -R 2  represent hydrogen (H); or   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); or   R 12  represents deuterium (D); and   all of R 1 -R 11  and R 13 -R 23  represent hydrogen (H); or   R 17 -R 20  represent deuterium (D); and   all of R 1 -R 16  and R 21 -R 23  represent hydrogen (H).   
     
     
         3 - 7 . (canceled) 
     
     
         8 . A pharmaceutical composition which comprises a therapeutically effective amount of a deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof according to  claim 1 , together with at least one pharmaceutically acceptable carrier, excipient or diluent. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . A method for treatment, prevention or alleviation of a dopamine mediated disorder of a living animal which comprises administering to such a living animal body a therapeutically effective amount of a deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof according to  claim 1 . 
     
     
         12 . A pharmaceutical composition which comprises a therapeutically effective amount of a deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof according to  claim 2  together with at least one pharmaceutically acceptable carrier, excipient or diluent. 
     
     
         13 . A method for treatment, prevention or alleviation of a dopamine mediated disorder of a living animal which comprises administering to such a living animal body a therapeutically effective amount of a deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof according to  claim 2 . 
     
     
         14 . The deuterated analog or pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 R 1 -R 2  represent deuterium (D); and   all of R 3 -R 23  represent hydrogen (H).   
     
     
         15 . The deuterated analog or pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 at least one of R 1 -R 7  represents deuterium (D); and   the remaining of R 1 -R 23  represent hydrogen (H).   
     
     
         16 . The deuterated analog or pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 all of R 1 -R 7  represent deuterium (D); and   all of R 8 -R 23  represent hydrogen (H).   
     
     
         17 . The deuterated analog or pharmaceutically acceptable salt thereof according to  claim 2 , 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).   
     
     
         18 . The deuterated analog or pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 R 12  represents deuterium (D); and   all of R 1 -R 11  and R 13 -R 23  represent hydrogen (H).   
     
     
         19 . The deuterated analog or pharmaceutically acceptable salt thereof according to  claim 2 , wherein
 R 17 -R 20  represent deuterium (D); and   all of R 1 -R 16  and R 21 -R 23  represent hydrogen (H).   
     
     
         20 . A pharmaceutical composition according to  claim 12 , wherein in the deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof,
 R 1 -R 2  represent deuterium (D); and   all of R 3 -R 23  represent hydrogen (H).   
     
     
         21 . A pharmaceutical composition according to  claim 12 , wherein in the deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof,
 at least one of R 1 -R 7  represents deuterium (D); and   the remaining of R 1 -R 23  represent hydrogen (H).   
     
     
         22 . A pharmaceutical composition according to  claim 12 , wherein in the deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof,
 all of R 1 -R 7  represent deuterium (D); and   all of R 8 -R 23  represent hydrogen (H).   
     
     
         23 . A pharmaceutical composition according to  claim 12 , wherein in the deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof,
 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).   
     
     
         24 . A pharmaceutical composition according to  claim 12 , wherein in the deuterated analog of 4-(3-methanesulfonyl-phenyl)-1 -propyl-piperidine or a pharmaceutically acceptable salt thereof,
 R 12  represents deuterium (D); and   all of R 1 -R 11  and R 13 -R 23  represent hydrogen (H).   
     
     
         25 . A pharmaceutical composition according to  claim 12 , wherein in the deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof,
 R 17 -R 20  represent deuterium (D); and   all of R 1 -R 16  and R 21 -R 23  represent hydrogen (H).   
     
     
         26 . A method according to  claim 13 , wherein in the deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof,
 R 1 -R 2  represent deuterium (D); and   all of R 3 -R 23  represent hydrogen (H).   
     
     
         27 . A method according to  claim 13 , wherein in the deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine or a pharmaceutically acceptable salt thereof,
 at least one of R 1 -R 7  represents deuterium (D); and   the remaining of R 1 -R 23  represent hydrogen (H).