Indoline derivatives useful as 5-HT-2C receptor antagonists

Abstract

The invention relates to heterocyclic compounds of formula (I) or a salt thereof wherein R 1 is hydrogen or C 1-6 alkyl; R 2 , R 3 and R 4 groups are independently hydrogen, halogen or C 1-6 alkyl optionally substituted by one or more fluorine atoms, having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS disorders such as anxiety.

1 . A compound of formula (I) or a salt thereof:  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 1  is hydrogen or C 1-6  alkyl;  
 R 2 , R 3  and R 4  groups arc independently hydrogen, halogen or C 1-6  alkyl optionally substituted by one or more fluorine atoms.  
 
     
     
         2 . A compound according to  claim 1  in which R 1  is hydrogen.  
     
     
         3 . A compound according to  claim 1  or  2  in which R 2  is hydrogen or CF 3 .  
     
     
         4 . A compound according to any one of  claims 1  to  3  in which R 3  is hydrogen, bromine, CF 3  or methyl.  
     
     
         5 . A compound according to any one of  claims 1  to  4  in which R 4  is hydrogen or C 1-6  alkyl.  
     
     
         6 . A compound according to  claim 1  which is: 
 5-Methyl-1-[2-(pyridin-2-ylmethyloxy)pyridin-5-ylcarbamoyl]-6-trifluoromethylindoline, 1-[2-(Pyridin-2-ylmethyloxy)pyridin-5-ylcarbamoyl]-5-trifluoromethylindoline, 5-Methyl-1-[2-(pyridin-2-yimethyloxy)-3-methylpyridin-5-ylcarbamoyl]-6-trifluoromethylindoline, 5-Bromo-1-[2-(pyridin-2-ylmethyloxy)pyridin-5-ylcarbamoyl]-indoline, 1-[2-(Pyridin-2-ylmethyloxy)pyridin-5-ylcarbamoyl]-6-trifluoromethyl-indoline, and pharmaceutically acceptable salts thereof.  
 
     
     
         7 . A process for the preparation of a compound of formula (I) which comprises the reaction of a compound of formnula (II)  
       
         
           
           
               
               
           
         
       
       with a compound of formula (III);  
       
         
           
           
               
               
           
         
       
       in which R 1 , R 2 , R 3  and R 4  are as defined in formula (I) and A and B contain the appropriate finctional group(s) necessary to form the moiety —NHCO— when coupled and thereafter optionally forming a pharmaceutically acceptable salt thereof Suitable examples of groups A and B include: 
 (i) A is —N═C═O and B is hydrogen,  
 (ii) A is —NHCOL and B is hydrogen,  
 (iii) A is —NH 2  and B is COL, or  
 (iv) A is halogen and B is —CONH 2    
 wherein L is a leaving group. Examples of suitable leaving groups L include halogen such as chloro, bromo, imidazole, phenoxy or phenylthio optionally substituted, for example, with halogen.  
 
     
     
         8 . A compound according to any one of  claims 1  to  6  for use in therapy.  
     
     
         9 . A pharmaceutical composition which comprises a compound according to any one of  claims 1  to  6  and a pharmaceutically acceptable carrier or excipient.  
     
     
         10 . Use of a compound according to any one of  claims 1  to  6  for the manufacture of a medicament for the treatnent of anxiety and/or depression.