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 23  represents deuterium (D); and 
         the remaining of R 1 -R 23  represent hydrogen (H). 
       
     
     
         2 . The deuterated analog according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 R 1 -R 2  represent deuterium (D); and   all of R 3 -R 23  represent hydrogen (H).   
     
     
         3 . The deuterated analog according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 at least one of R 1 -R 7  represents deuterium (D); and   the remaining of R 1 -R 23  represent hydrogen (H).   
     
     
         4 . The deuterated analog according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 all of R 1 -R 7  represent deuterium (D); and   all of R 8 -R 23  represent hydrogen (H).   
     
     
         5 . The deuterated analog according to  claim 1 , or a pharmaceutically acceptable salt thereof, 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).   
     
     
         6 . The deuterated analog according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 R 12  represents deuterium (D); and   all of R 1 -R 11  and R 13 -R 23  represent hydrogen (H).   
     
     
         7 . The deuterated analog according to  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 R 17 -R 20  represent deuterium (D); and   all of R 1 -R 16  and R 21 -R 23  represent hydrogen (H).   
     
     
         8 . A pharmaceutical composition, comprising a therapeutically effective amount of a deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine according to any one of  claims 1 - 7 , or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, excipient or diluent. 
     
     
         9 . The deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine according to any one of  claims 1 - 7 , or a pharmaceutically acceptable salt thereof, for use as a medicament. 
     
     
         10 . Use of the deuterated analog according to any one of  claims 1 - 7 , or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament. 
     
     
         11 . A method for treatment, prevention or alleviation of a dopamine mediated disorder of a living animal body, including a human, which method comprises the step of administering to such a living animal body in need thereof a therapeutically effective amount of a deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine according to any one of the  claims 1 - 7 , or a pharmaceutically acceptable salt thereof.