Pirazino(AZA) indole derivatives

Abstract

Chemical compounds of formula (I): and pharmaceutically acceptable salts and addition compounds and prodrugs thereof are useful in therapy, particularly for the treatment of disorders of the central nervous system; damage to the central nervous system; cardiovascular disorders; gastrointestinal disorders; diabetes inspidus, and sleep apnea.

1 - 34 . (canceled)  
   
   
       35 . A chemical compound of formula (I):  
     
       
         
         
             
             
         
       
       wherein:  
       R 1  to R 3  are independently selected from hydrogen and lower alkyl;  
       X 1  is selected from N and C—R 4 ;  
       X 2  is selected from N and C—R 5 ;  
       X 3  is selected from N and C—R 6 ;  
       X 4  is selected from N and C—R 7 ;  
       wherein only one of X 1  to X 4  is N;  
       R 4 , R 5  and R 7  are independently selected from hydrogen, halogen, hydroxy, alkyl, aryl, alkoxy, aryloxy, alkoyl, aryloyl, haloalkyl, alkylthio, arylthio, alkylsulfoxyl, arylsulfoxyl, alkylsulfonyl, arylsulfonyl, amino, alkylamino, dialkylamino, nitro, cyano, carboalkoxy, carboaryloxy and carboxy; and  
       R 6  is selected from hydrogen, halogen, alkyl, aryl, aryloxy, haloalkyl, alkylthio, arylthio, alkylsulfoxyl, arylsulfoxyl, alkylsulfonyl, arylsulfonyl, amino, alkylamino, dialkylamino and cyano;  
       with the proviso that R 4  to R 7  are not all selected as hydrogen,  
       or a pharmaceutically acceptable salt thereof.  
     
   
   
       36 . A compound according to  claim 35 , wherein R 1  is selected from hydrogen and methyl.  
   
   
       37 . A compound according to  claim 35 , wherein R 2  is hydrogen.  
   
   
       38 . A compound according to  claim 35 , wherein R 3  is selected from hydrogen and methyl.  
   
   
       39 . A compound according to  claim 35 , wherein X 2  is C—R 5 .  
   
   
       40 . A compound according to  claim 35 , wherein X 3  is C—R 6 .  
   
   
       41 . A compound according to  claim 35 , wherein X 4 is C—R 7 .  
   
   
       42 . A compound according to  claim 35 , wherein X 1  is C—R 4 .  
   
   
       43 . A compound according to  claim 35 , wherein two of R 4 , R 5 , R 6  and R 7  are hydrogen.  
   
   
       44 . A compound according to  claim 43 , wherein R 4  and R 6  are hydrogen.  
   
   
       45 . A compound according to  claim 35 , wherein two of R 4 , R 5 , R 6  and R 7  are independently selected from hydrogen, chlorine, fluorine, trifluoromethyl and bromine.  
   
   
       46 . A compound according to  claim 35 , wherein three of R 4 , R 5 , R 6  and R 7  are hydrogen.  
   
   
       47 . A compound according to  claim 46 , wherein R 4 , R 6  and R 7  are hydrogen.  
   
   
       48 . A compound according to  claim 35 , wherein R 4  is hydrogen.  
   
   
       49 . A compound according to  claim 35 , wherein R 5  is halogen.  
   
   
       50 . A compound according to  claim 35 , wherein R 6  is hydrogen.  
   
   
       51 . A compound according to  claim 35 , wherein R 7  is halogen.  
   
   
       52 . A compound according to  claim 35 , wherein the compound is: 
 (RS) 7-Chloro-1,2,3,4,10,10a-hexahydro-6-aza-pyrazino[1,2-a]indole furmarate.    
   
   
       53 . A method of treatment of disorders of obesity in a patient in need thereof comprising administering to the patient an effective dose of a compound of formula (I) as set out in  claim 35 .  
   
   
       54 . A pharmaceutical composition comprising a compound of formula (I) as set out in  claim 35  in combination with a pharmaceutically acceptable carrier or excipient.  
   
   
       55 . A method of making a pharmaceutical composition comprising combining a compound of formula (I) as set out in  claim 35  with a pharmaceutically acceptable carrier or excipient.  
   
   
       56 . A process for the preparation of a compound of formula (I) according to  claim 35 , said process comprising the steps of: 
 (i) treating a compound of formula (IX) with an aldehyde of formula RCHO and then exposing the compound to acid to obtain a compound of formula (X), wherein X 1 , X 2 , X 3 , X 4 , R 2  and R 3  are as described in  claim 35 , and                          (ii) reduction of a compound of formula (X).