Optical isomers of an iloperidone metabolite

Abstract

The invention provides compounds of formulae (I) and (II), their preparation and their use as pharmaceuticals.

1 . (R)-1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl}-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanol of formula I  
       
         
           
           
               
               
           
         
       
       in free base or acid addition salt form.  
     
     
         2 . (S)-1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanol of formula II  
       
         
           
           
               
               
           
         
       
       in free base or acid addition salt form.  
     
     
         3 . A process for the production of the compound of formula I according to  claim 1 , and its salts, comprising the reduction of Iloperidone of formula III  
       
         
           
           
               
               
           
         
       
       with an optically active boran complex of formula IV  
       
         
           
           
               
               
           
         
       
       and recovering the resulting compound in free base or acid addition salt form.  
     
     
         4 . A compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for use as a pharmaceutical.  
     
     
         5 . A compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for use in the treatment of psychotic disorders.  
     
     
         6 . A pharmaceutical composition comprising a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent.  
     
     
         7 . The use of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, as a pharmaceutical for the treatment of psychotic disorders.  
     
     
         8 . The use of a compound of  claim 1  free base or pharmaceutically acceptable acid addition salt form, for the manufacture of a medicament for the treatment of psychotic disorders.  
     
     
         9 . A method for the treatment of psychotic disorders in a subject in need of such treatment, which comprises administering to such subject a therapeutically effective amount of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form.  
     
     
         10 . A combination comprising a therapeutically effective amount of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, and a second drug substance, for simultaneous or sequential administration.  
     
     
         11 . A process for the production of the compound of formula II according to  claim 2 , and its salts, comprising the reduction of Iloperidone of formula III  
       
         
           
           
               
               
           
         
       
       with an optically active boran complex of formula IV  
       
         
           
           
               
               
           
         
       
       and recovering the resulting compound in free base or acid addition salt form.  
     
     
         12 . A compound of  claim 2  in free base or pharmaceutically acceptable acid addition salt form, for use as a pharmaceutical.  
     
     
         13 . A compound of  claim 2  in free base or pharmaceutically acceptable acid addition salt form, for use in the treatment of psychotic disorders.  
     
     
         14 . A pharmaceutical composition comprising a compound of  claim 2  in free base or pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent.  
     
     
         15 . The use of a compound of  claim 2  in free base or pharmaceutically acceptable acid addition salt form, as a pharmaceutical for the treatment of psychotic disorders.  
     
     
         16 . The use of a compound of  claim 2  in free base or pharmaceutically acceptable acid addition salt form, for the manufacture of a medicament for the treatment of psychotic disorders.  
     
     
         17 . A method for the treatment of psychotic disorders in a subject in need of such treatment, which comprises administering to such subject a therapeutically effective amount of a compound of  claim 2  in free base or pharmaceutically acceptable acid addition salt form.  
     
     
         18 . A combination comprising a therapeutically effective amount of a compound of  claim 2  in free base or pharmaceutically acceptable acid addition salt form, and a second drug substance, for simultaneous or sequential administration.