Acetylene derivatives

Abstract

The invention provides compounds of formula (I) wherein R 1 represents hydrogen or alkyl; R 2 represents an unsubstituted or substituted heterocycle or R 2 represents an unsubstituted or substituted aryl; R 3 represents alkyl or halogen; X represents a single bond or an alkandiyl-group, optionally interrupted by one or more oxygen atoms or carbonyl groups or carbonyloxy groups in free base or acid addition salt form, processes for their preparation and their use as pharmaceuticals.

1 . A compound of formula (I) 
     
       
         
         
             
             
         
       
       wherein 
       R 1  represents hydrogen or alkyl; 
       R 2  represents an unsubstituted or substituted heterocycle or 
       R 2  represents an unsubstituted or substituted aryl; 
       R 3  represents alkyl or halogen; 
       X represents a single bond or an alkandiyl-group, optionally interrupted by one or more oxygen atoms or carbonyl groups or carbonyloxy groups in free base or acid addition salt form. 
     
   
   
       2 . A compound of formula (I) according to  claim 1  wherein X represent a single bond. 
   
   
       3 . A compound of formula (I) according to  claim 1  wherein R 3  represents chloro. 
   
   
       4 . The trans-Isomer of a compound of formula (I) according  claim 1 . 
   
   
       5 . A process for the preparation of a compound of formula (I) as defined in  claim 1 , or a salt thereof, which comprises the steps of reacting a compound of formula (II) 
     
       
         
         
             
             
         
       
       wherein R 1  and R 3  are as defined in  claim 1 , with a compound of formula (III) 
     
     
       
         
         
             
             
         
       
       wherein X and R 2  are as defined in  claim 1 , and recovering the resulting compound of formula (I) in free base or acid addition salt form. 
     
   
   
       6 . A compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for use as a pharmaceutical. 
   
   
       7 . A compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for use in the prevention, treatment or delay of progression of disorders associated with irregularities of the glutamatergic signal transmission, of the gastro-intestinal and urinary tract and of nervous system disorders mediated full or in part by mGluR5. 
   
   
       8 . 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. 
   
   
       9 . The use of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, in the prevention, treatment or delay of progression of disorders associated with irregularities of the glutamatergic signal transmission, of the gastro-intestinal and urinary tract and of nervous system disorders mediated full or in part by mGluR5. 
   
   
       10 . The use of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form, for the manufacture of a pharmaceutical composition designed for the prevention, treatment or delay of progression of disorders associated with irregularities of the glutamatergic signal transmission, of the gastro-intestinal and urinary tract and of nervous system disorders mediated full or in part by mGluR5. 
   
   
       11 . A method of treating disorders associated with irregularities of the glutamatergic signal transmission, and nervous system disorders mediated full or in part by mGluR5, which method comprises administering to a subject in need of such treatment a therapeutically effective amount of a compound of  claim 1  in free base or pharmaceutically acceptable acid addition salt form. 
   
   
       12 . A compound of formula (I) according to  claim 2  wherein X represent a single bond. 
   
   
       13 . A compound of formula (I) according to  claim 2  wherein R 3  represents chloro. 
   
   
       14 . A compound of formula (I) according to  claim 3  wherein R 3  represents chloro. 
   
   
       15 . A compound of  claim 2  in free base or pharmaceutically acceptable acid addition salt form, for use as a pharmaceutical. 
   
   
       16 . A compound of  claim 3  in free base or pharmaceutically acceptable acid addition salt form, for use as a pharmaceutical.