DEUTERATED ANALOGS OF PRIDOPIDINE USEFUL AS DOPAMINERGIC STABILIZERS
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).