Modulators of dopamine neurotransmission
View Patent ↗New 3-substituted 4-(phenyl-N-alkyl)-piperazine and 4-(phenyl-N-alkyl)-piperidine compounds of Formula (1), wherein X N, CH, or C, however X may only be C when the compound comprises a double bond at the dotted line; R 1 is OSO 2 CF 3 , OSO 2 CH 3 , SOR 3 , SO 2 R 3 , COR 3 , NO 2 , or CONHR 3 and when X is CH or C R 1 may also be CF 3 , CN, F, Cl, Br, or I; R 2 is a C 1 -C 4 alkyl, an allyl, CH 2 SCH 3 , CH 2 CH 2 OCH 3 , CH 2 CH 2 CH 2 F, CH 2 CF 3 , 3,3,3-trifluoropropyl, 4,4,4,-trifluorobutyl, or —(CH 2 )—R 4 ; R 3 is a C 1 -C 3 alkyl CF 3 , or N(R 2 ) 2 ; R 4 is a C 3 -C 6 cycloalkyl, 2-tetrahydrofurane or 3-tetra-hydrofurane, as well as pharmaceutically acceptable salts thereof are disclosed. Also pharmaceutical compositions comprising the above compounds and methods wherein the above compounds are used for treatment of disorders in the central nervous system are disclosed
1. A 4-(phenyl-N-alkyl)-piperidine compound of Formula 1:
wherein:
R 1 is selected from the group consisting of OSO 2 CF 3 , OSO 2 CH 3 , SOR 3 , SO 2 R 3 , COCH 3 , and COCH 2 CH 3 , wherein R 3 is as defined below;
R 2 is selected from the group consisting of C 2 -C 4 branched or unbranched alkyls, terminal allyl, CH 2 CH 2 OCH 3 , CH 2 CH 2 CH 2 F, CH 2 CF 3 , 3,3,3-trifluoropropyl, and 4,4,4-trifluorobutyl,
R 3 is selected from the group consisting of C 1 -C 3 alkyls, CF 3 , and N(CH 3 ) 2 ;
or a pharmaceutically acceptable salt thereof, wherein the compound does not have a high binding affinity to sigma receptors.
2. A compound according to claim 1 , wherein R 1 is selected from the group consisting of OSO 2 CF 3 , OSO 2 CH 3 , SO 2 CH 3 , SO 2 CF 3 , COCH 3 , and SO 2 N(CH 3 ) 2 .
3. A compound according to claim 2 , wherein R 1 is selected from the group consisting of SO 2 CF 3 , SO 2 CH 3 , and COCH 3 .
4. A compound according to claim 1 , wherein R 2 is selected from the group consisting of n-propyl and ethyl.
5. A compound according to claim 1 , wherein said compound is 4-(3-methanesulfonylphenyl)-1-propyl-piperidine.
6. A pharmaceutical composition comprising a compound according to claim 1 and one or more pharmaceutically acceptable carriers or diluants.
7. The pharmaceutical composition according to claim 6 , wherein the pharmaceutical composition is formulated for oral administration.
8. The pharmaceutical composition according to claim 7 , wherein said pharmaceutical composition is formulated as a tablet.
9. The pharmaceutical composition according to claim 7 , wherein said pharmaceutical composition is formulated as a capsule.
10. The pharmaceutical composition according to claim 6 , formulated for intravenous (i.v.) administration.
11. A method for treatment of a patient suffering from a condition selected from the group consisting of iatrogenic and non-iatrogenic Parkinsonism, dyskinesias, dystonias, and Tourette's disease, comprising administering a therapeutically active amount of a compound according to claim 1 to said patient.
12. A method for treatment of a patient suffering from a condition selected from the group consisting of iatrogenic and non-iatrogenic psychoses and hallucinoses, comprising administering a therapeutically active amount of a compound according to claim 1 to said patient.
13. A method for treatment of a patient suffering from a condition selected from the group consisting of mood and anxiety disorders, comprising administering a therapeutically active amount of a compound according to claim 1 to said patient.
14. A method for treatment of a patient suffering from a sleep disorder, comprising administering a therapeutically active amount of a compound according to claim 1 to said patient.
15. A method for treatment of a patient suffering from a condition selected from the group consisting of autism spectrum disorder, ADHD, Huntington's disease and age-related cognitive impairment, comprising administering a therapeutically active amount of a compound according to claim 1 to said patient.
16. A method for treatment of a patient suffering from a disorder related to abuse of alcohol and substances used as narcotics, comprising administering a therapeutically active amount of a compound according to claim 1 to said patient.
17. The method according to claim 12 , wherein the non-iatrogenic psychoses and hallucinoses are schizophrenia or schizophreniform disorders.
18. The method according to claim 13 , wherein the mood and anxiety disorder is manodepressive illness, depression or obsessive-compulsive disease.
19. A method for treatment of a patient suffering from Parkinson's disease, comprising administering a therapeutically active amount of a compound according to claim 1 to said patient.
20. A method for treatment of a patient suffering from a condition selected from the group consisting of iatrogenic and non-iatrogenic Parkinsonism, dyskinesias, dystonias, and Tourette's disease comprising administering a therapeutically active amount of a compound according to claim 5 to said patient.
21. A method for treatment of a patient suffering from a condition selected from the group consisting of iatrogenic and non-iatrogenic psychoses and hallucinoses, comprising administering a therapeutically active amount of a compound according to claim 5 to said patient.
22. A method for treatment of a patient suffering from a condition selected from the group consisting of mood and anxiety disorders, comprising administering a therapeutically active amount of a compound according to claim 5 to said patient.
23. A method for treatment of a patient suffering from a sleep disorder, comprising administering a therapeutically active amount of a compound according to claim 5 to said patient.
24. A method for treatment of a patient suffering from a condition selected from the group consisting of autism spectrum disorders, ADHD, Huntington's disease and age-related cognitive impairment, comprising administering a therapeutically active amount of a compound according to claim 5 to said patient.
25. A method for treatment of a patient suffering from a disorder related to abuse of alcohol and substances used as narcotics, comprising administering a therapeutically active amount of a compound according to claim 5 to said patient.
26. The method according to claim 21 , wherein the non-iatrogenic psychoses and hallucinoses are schizophenia or schizophreniform disorders.
27. The method according to claim 22 , wherein the mood and anxiety disorder is manodepressive illness, depression or obsessive-compulsive disease.
28. A method for treatment of a patient suffering from Parkinson's disease, comprising administering a therapeutically active amount of a compound according to claim 5 to said patient.
29. A method for treatment of a patient suffering from a condition selected from the group consisting of iatrogenic and non-iatrogenic Parkinsonism, dyskinesias, dystonias, and Tourette's disease, comprising administering a therapeutically active amount of a pharmaceutical composition according to claim 6 to said patient.
30. A method for treatment of a patient suffering from a condition selected from the group consisting of iatrogenic and non-iatrogenic psychoses and hallucinoses, comprising administering a therapeutically active amount of a pharmaceutical composition according to claim 6 to said patient.
31. A method for treatment of a patient suffering from a condition selected from the group consisting of mood and anxiety disorders, comprising administering a therapeutically active amount of a pharmaceutical composition according to claim 6 to said patient.
32. A method for treatment of a patient suffering from a sleep disorder, comprising administering a therapeutically active amount of a pharmaceutical composition according to claim 6 to said patient.
33. A method for treatment of a patient suffering from a condition selected from the group consisting of autism spectrum disorder, ADHD, Huntington's disease and age-related cognitive impairment, comprising administering a therapeutically active amount of a pharmaceutical composition according to claim 6 to said patient.
34. A method for treatment of a patient suffering from a disorder related to abuse of alcohol and substances used as narcotics, comprising administering a therapeutically active amount of a pharmaceutical composition according to claim 6 to said patient.
35. The method according to claim 30 , wherein the non-iatrogenic psychoses and hallucinoses are schizophrenia or schizophreniform disorders.
36. The method according to claim 31 , wherein the mood and anxiety disorder is manodepressive illness, depression or obsessive-compulsive disease.
37. A method for treatment of a patient suffering from Parkinson's disease, comprising administering a therapeutically active amount of a pharmaceutical composition according to claim 6 to said patient.