1-Aza-Bicyclo3.3.1Nonanes

Abstract

The present invention relates to 1-aza-bicycloalkyl derivatives of Formula (I); wherein the substituents are as defined in the specification, to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them. Formula (I), wherein A represents O or N(R 1 ); Y represents a group of formula, or wherein the left bond is attached to the A group and the right bond is attached to the R group; R represents a substituted or unsubstituted C 5 -C 10aryl , substituted or unsubstituted hetero-C 5 -C 10 aryl, a group N(R 1 )(R 4 ), or a group N(R 2 )(CHP 3 R 4 ); R represent a hydrogen, C 1 -C 4 alkyl, or CF 3 ; R 2 represents hydrogen, C 1 -C 4 alkyl, or CF 3 ; R 3 represents hydrogen, C 1 -C 4 alkyl, or CF 3 ; R 4 represents a substituted or unsubstituted C 5 -C 10 aryl or a substituted or unsubstituted C 5 -C 10 heteroaryl; in free base or acid addition salt form.

1 . A compound of formula I  
     
       
         
         
             
             
         
       
     
     wherein 
 A represents O or N(R 1 );  
 Y represents a group of formula  
                     wherein the left bond is attached to the A group and the right bond is attached to the R group;    
 R represents a substituted or unsubstituted C 5 -C 10 aryl, substituted or unsubstituted hetero-C 5 -C 10 aryl, a group N(R 1 )(R 4 ), or a group N(R 2 )(CHR 3 R 4 );  
 R 1  representa hydrogen, C 1 -C 4 alkyl, or CF 3 ;  
 R 2  represents hydrogen, C 1 -C 4 alkyl, or CF 3 ;  
 R 3  represents hydrogen, C 1 -C 4 alkyl, or CF 3 ;  
 R 4  represents a substituted or unsubstituted C 5 -C 10 aryl or a substituted or unsubstituted C 5 -C 10 heteroaryl;  
 in free base or acid addition salt form.  
 
   
   
       2 . A compound of formula I according to  claim 1  wherein A represents oxygen  
   
   
       3 . A compound of formula I according to  claim 1  wherein Y represents one of the following groups  
     
       
         
         
             
             
         
       
     
   
   
       4 . A process for the preparation of a compound of formula I as defined in  claim 1 , or a salt thereof, which comprises the step of reacting a compound of formula II 
       Z—Y—R  (II) 
     wherein Y and R are as defined in  claim 1  and Z is a leaving group with a compound of formula III  
     
       
         
         
             
             
         
       
     
     and recovering the so obtained compound of formula I in free base or acid addition salt form.  
   
   
       5 . A compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for use as a pharmaceutical.  
   
   
       6 . A compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for use in the prevention and treatment of psychotic and neurodegenerative disorders.  
   
   
       7 . 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.  
   
   
       8 . The use of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, as a pharmaceutical for the prevention and the treatment of psychotic and neurodegenerative disorders.  
   
   
       9 . The use of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for the manufacture of a medicament for the prevention and treatment of psychotic and neurodegenerative disorders.  
   
   
       10 . A method for the prevention and treatment of psychotic and neurodegenerative 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.  
   
   
       11 . A compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for use in the treatment or prevention of a disease or condition in which α7 nAChR activation plays a role or is implicated.  
   
   
       12 . The use of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, as a pharmaceutical for the treatment or prevention of a disease or condition in which α7 nAChR activation plays a role or is implicated.  
   
   
       13 . A method for treating or preventing a disease or condition in which α7 nAChR activation plays a role or is implicated, 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.  
   
   
       14 . A product obtained according to the process of  claim 2  characterized in that (−)-1-Aza-bicyclo[3.3.1]nonan-4-ol is used as starting material.