Benzothiadiazine compounds

Abstract

The invention relates to compounds of formula (I): wherein: R 1 represents alkyl substituted by one or more halogen atoms, R 2 represents hydrogen, halogen or hydroxy, R 3 represents unsubstituted or substituted aryl, their isomers, and also addition salts thereof. and medicinal products containing the same which are useful in treating or preventing disorders associated with AMPA flux.

1 . A method for treating a living animal body, including a human, afflicted with a condition selected from Alzheimer's disease and disorders of memory and cognition associated with age, such method comprising administering to the living animal body, including a human, a therapeutically effective amount of a compound selected from those of formula (I):  
     
       
         
         
             
             
         
       
       wherein:  
       R 1  represents linear or branched (C 1 -C 6 )alkyl substituted by one or more halogen atoms,  
       R 2  represents hydrogen, halogen or hydroxy,  
       R 3  represents unsubstituted aryl or aryl substituted by one or more identical or different groups selected from: linear or branched (C 1 -C 6 )alkyl; linear or branched (C 1 -C 6 )alkoxy; linear or branched (C 1 -C 6 )polyhaloalkyl; halogens; linear or branched (C 1 -C 6 )alkoxy-carbonyl; linear or branched (C 1 -C 6 )alkylthio; carboxy; linear or branched (C 1 -C 6 )acyl; linear or branched (C 1 -C 6 )polyhaloalkoxy; hydroxy; cyano; nitro amidino, optionally substituted by one or two identical or different groups selected from linear or branched (C 1 -C 6 )alkyl, hydroxy, linear or branched (C 1 -C 6 )alkoxy and  
       
         
           
           
               
               
           
         
       
       amino, optionally substituted by one or two linear or branched (C 1 -C 6 )alkyl; aminocarbonyl, optionally substituted by one or two linear or branched (C 1 -C 6 )alkyl; benzyloxy; (C 1 -C 6 )alkylsulphonylamino, optionally substituted on the nitrogen by linear or branched (C 1 -C 6 )alkyl; trifluoromethylsulphonylamino; a heterocyclic group; and linear or branched (C 1 -C 6 )alkyl substituted by one or more identical or different groups selected from halogen, linear or branched (C 1 -C 6 )alkyl, NR 4 R 5 , S(O) n R 6,  OR 7 , amidino, optionally substituted by one or two identical or different groups selected from linear or branched (C 1 -C 6 )alkyl, hydroxy, linear or branched (C 1 -C 6 )alkoxy and  
       
         
           
           
               
               
           
         
       
       and a heterocyclic group, wherein:  
       R 4  represents hydrogen, linear or branched (C 1 -C 6 )alkyl, S(O) p R 8 , COR 9  or P(O)(OR 10 )(OR 11 ),  
       R 5  represents hydrogen, linear or branched (C 1 -C 6 )alkyl,  
       or R 4  and R 5 , together with the nitrogen atom carrying them, form a heterocyclic group,  
       R 6 , R 8 , R 9 , R 10 , R 11  and R 12 , which may be the same or different, each represent hydrogen or linear or branched (C 1 -C 6 )alkyl optionally substituted by one or more halogen atoms; aryl-(C 1 -C 6 )alkyl wherein the alkyl moiety is linear or branched; or aryl,  
       R 7  represents linear or branched (C 1 -C 6 )alkyl or linear or branched (C 1 -C 6 )acyl,  
       n and p, which may be the same or different, each represent 0, 1 or 2,  
       its enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically-acceptable acid or base.  
     
   
   
       2 . The method of  claim 1 , wherein R 1  represents haloethyl.  
   
   
       3 . The method of  claim 1 , wherein R 2  represents hydrogen.  
   
   
       4 . The method of  claim 1 , wherein R 3  represents unsubstituted phenyl.  
   
   
       5 . The method of  claim 1 , wherein R 3  represents phenyl substituted by amidino, hydroxyamidino, alkoxy, alkylsulphonylamino, optionally substituted on the nitrogen by alkyl, or alkyl substituted by amidino, hydroxyamidino, OR 7 , NH(SO) p R 8  or NHCOR 9 .  
   
   
       6 . The method of  claim 1 , wherein the compound of formula (I) is selected from: 
 N-(4-{[4-(2-fluoroethyl)-1,1-dioxido-3,4-dihydro-2H-1,2,4-benzothiadiazin-7-yl]oxy}benzyl)methanesulphonamide and    N-(4-{[4-(2-chloroethyl)-1,1-dioxido-3,4-dihydro-2H-1,2,4-benzothiadiazin-7-yl]oxy}benzyl)methanesulphonamide, and addition salts thereof with a pharmaceutically-acceptable acid or base.