Modulators of dopamine neurotransmission

Abstract

New 3-substituted 4-(phenyl-N-alkyl)-piperazine and 4-(phenyl-N-alkyl)-piperidine compounds of Formula (1) wherein X is N, CH, or C, however X may only be C when the compound comprises a double bind at the dotted line; R 1 is CF 3 , OSO 2 CF 3 , OSO 2 CH 3 , SOR 7 , SO 2 R 7 , COR 7 , CN, OR 3 , NO 2 , CONHR 3 , 3-thiophene, 2-thiophene, 3-furane, 2-furane, F, Cl, Br, or I; R 2 is F, Cl, Br, I, CN, CF 3 , CH 3 , OCH 3 , OH, and NH 2 ; R 3 and R 4 are independently H or a C 1 -C 4 alkyl; R 5 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 6 ; R 6 is a C 3 -C 6 cycloalkyl, 2-tetrahydrofurane, or 3-tetra-hydrofurane; R 7 is a C 1 -C 3 alkyl, CF 3 , or N(R 4 ) 2 , and 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 substituted 4-(phenyl-N-alkyl)-piperidine compound of Formula 1: 
                 
 
       wherein:
 R 1  is selected from the group consisting of CF 3 , OSO 2 CF 3 , OSO 2 CH 3 , SOR 7 , SO 2 R 7 , COR 7 ,  CN, OR 3 , NO 2 , CONHR 3 , F, Cl, Br, and I, wherein R 7  is as defined below  and SO 2   CH   3 ;  
 R 2  is selected from the group consisting of F,  and Cl, Br, I, CN, CF 3 , CH 3 , OCH 3 , OH, and NH 2  ;  
 R 3  is H;  
 R 4  is H; and  
 R 5  is selected from the group consisting of  C 1 -C 4  alkyl, 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, and 4,4,4-trifluorobutyl;  
 R 7  is selected from the group consisting of C 1 -C 3  alkyls, CF 3 , NH 2  and N(C1-C4 alkyl)2, ;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
       2. A compound or pharmaceutically acceptable salt according to claims  1 , wherein R 2  is CH 3 , F or Cl. 
     
     
       3. A compound according to  claim 1 , wherein R 1  is CF 3 , R 2  is Cl, R 3  is H, R 4  is H, and R 5  is n-propyl. 
     
     
       4. A compound according to  claim 1 , wherein said compound is 4-(4-chloro-3-trifluoromethyl-phenyl)-1-propyl-piperidine. 
     
     
       5. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt according to  thereof of  claim 1  and one or more pharmaceutically acceptable carriers, or  diluents, or combinations thereof. 
     
     
       6. A compound according to  claim 1 , wherein R 5  is selected from the group consisting of n-propyl and ethyl. 
     
     
       7. A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 1  is SO 2 CH 3 , SO 2 CF 3 , COCH 3 , CN or CF 3 . 
     
     
       8. The compound or pharmaceutically acceptable salt of  claim 1 , wherein R 1    is CF   3 . 
     
     
       9. The compound or pharmaceutically acceptable salt of  claim 1 , wherein R 1    is CN.   
     
     
       10. The compound or pharmaceutically acceptable salt of  claim 1 , wherein R 1    is SO   2   CH   3 . 
     
     
       11. The compound or pharmaceutically acceptable salt of  claim 1 , wherein R 2    is F.   
     
     
       12. The compound or pharmaceutically acceptable salt of  claim 1 , wherein R 2    is Cl.   
     
     
       13. The compound or pharmaceutically acceptable salt thereof of  claim 1 , wherein R 5    is selected from the group consisting of butyl, n - propyl and ethyl.   
     
     
       14. The compound or pharmaceutically acceptable salt thereof of  claim 1 , wherein R 5    is selected from the group consisting of n - propyl and ethyl.   
     
     
       15. The compound or pharmaceutically acceptable salt thereof of  claim 1 , wherein R 5    is butyl.   
     
     
       16. The compound or pharmaceutically acceptable salt thereof of  claim 1 , wherein R 5    is n - propyl.   
     
     
       17. The compound or pharmaceutically acceptable salt thereof of  claim 1 , wherein R 5    is ethyl.