Use of d-serine derivatives for the treatment of anxiety disorders

Abstract

Compounds of Formula I are useful for the treatment of anxiety disorders such as generalized anxiety disorder (GAD), panic attack, post traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD) and social phobias, wherein: A is chosen from: aryl or heteroaryl, A being optionally substituted with up to 5 independently-selected groups R 8 ; R 1 is chosen from: alkyl or haloalkyl; R 2 is chosen from: H, C(O)R 6 , C(O)OR 6 , SO2R 6 or C(O)NR 6 R 7 ; R 3 , R 4 and R 5 are independently chosen from: H or alkyl; R 6 and R 7 are independently chosen from: H or alkyl; and R 8 is chosen from: OH, CN, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, C(O)R 6 , C(O)OR 6 , SO2R 6 or C(O)NR 6 R 7 .

1 - 20 . (canceled) 
     
     
         21 . A pharmaceutical composition for the treatment of an anxiety disorder, the pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I or a salt, solvate or hydrate thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 A is chosen from: aryl or heteroaryl, A being optionally substituted with up to 5 independently-selected groups R 8 ; 
 R 1  is chosen from: alkyl or haloalkyl; 
 R 2  is chosen from: H, C(O)R 6 , C(O)OR 6 , SO 2 R 6  or C(O)NR 6 R 7 ; 
 R 3 , R 4  and R 5  are independently chosen from: H or alkyl; 
 R 6  and R 7  are independently chosen from: H or alkyl; and 
 R 8  is chosen from: OH, CN, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, C(O)R 6 , C(O)OR 6 , SO 2 R 6  or C(O)NR 6 R 7 . 
 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the compound is an R enantiomer having the following chemical formula: 
       
         
           
           
               
               
           
         
       
       or a salt, solvate or hydrate thereof. 
     
     
         23 . The pharmaceutical composition of  claim 21 , wherein:
 R 2  is chosen from: H, C(O)R 6 , C(O)OR 6 , or SO 2 R 6 ;   R 3 , R 4  and R 5  are each H;   R 6  is alkyl; and   R 8  is chosen from: halo or alkyl.   
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the compound is an R enantiomer having the following chemical formula: 
       
         
           
           
               
               
           
         
       
       or a salt, solvate or hydrate thereof. 
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein:
 R 1  is chosen from: methyl or CHF 2 ; and   R 6  is chosen from: methyl or tert-butyl.   
     
     
         26 . The pharmaceutical composition of  claim 24 , wherein;
 A is aryl, optionally substituted with up to 5 independently-selected groups R 8 ;   R 2  is C(O)R 6 ; and   R 8  is halo.   
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein;
 R 1  is haloalkyl; and   R 6  is methyl.   
     
     
         28 . The pharmaceutical composition of  claim 21 , wherein the compound is 
       
         
           
           
               
               
           
         
       
       or a salt, solvate or hydrate thereof. 
     
     
         29 . The pharmaceutical composition of  claim 21 , wherein the compound is chosen from: 
       
         
           
           
               
               
           
         
       
       or a salt, solvate or hydrate thereof. 
     
     
         30 . The pharmaceutical composition of  claim 21 , wherein the anxiety disorder is chosen from: generalized anxiety disorder (GAD), panic attack, post traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD) or social phobias.