Carbamate compounds for use in preventing or treating anxiety disorders

Abstract

This invention is directed to a method for preventing or treating anxiety disorders comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of Formula (I) and Formula (II): wherein phenyl is substituted at X with one to five halogen atoms selected from the group consisting of fluorine, chlorine, bromine and iodine; and, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently selected from the group consisting of hydrogen and C 1 -C 4 alkyl; wherein C 1 -C 4 alkyl is optionally substituted with phenyl (wherein phenyl is optionally substituted with substituents independently selected from the group consisting of halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, amino, nitro and cyano).

1 . A method for preventing or treating anxiety disorders comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of Formula (I) and Formula (II):  
     
       
         
         
             
             
         
       
     
     wherein 
 phenyl is substituted at X with one to five halogen atoms selected from the group consisting of fluorine, chlorine, bromine and iodine; and,  
 R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are independently selected from the group consisting of hydrogen and C 1 -C 4  alkyl; wherein C 1 -C 4  alkyl is optionally substituted with phenyl (wherein phenyl is optionally substituted with substituents independently selected from the group consisting of halogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, amino, nitro and cyano).  
 
   
   
       2 . The method of  claim 1  wherein X is chlorine.  
   
   
       3 . The method of  claim 1  wherein X is substituted at the ortho position of the phenyl ring.  
   
   
       4 . The method of  claim 1  wherein R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are selected from hydrogen.  
   
   
       5 . A method for preventing or treating anxiety disorders comprising administering to a subject in need thereof a therapeutically effective amount of an enantiomer selected from the group consisting of Formula (I) and Formula (II) or enantiomeric mixture wherein one enantiomer selected from the group consisting of Formula (I) and Formula (II) predominates:  
     
       
         
         
             
             
         
       
     
     wherein 
 phenyl is substituted at X with one to five halogen atoms selected from the group consisting of fluorine, chlorine, bromine and iodine; and,  
 R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are independently selected from the group consisting of hydrogen and C 1 -C 4  alkyl; wherein C 1 -C 4  alkyl is optionally substituted with phenyl (wherein phenyl is optionally substituted with substituents independently selected from the group consisting of halogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, amino, nitro and cyano).  
 
   
   
       6 . The method of  claim 5  wherein X is chlorine.  
   
   
       7 . The method of  claim 5  wherein X is substituted at the ortho position of the phenyl ring.  
   
   
       8 . The method of  claim 5  wherein R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are selected from hydrogen.  
   
   
       9 . The method of  claim 5  wherein one enantiomer selected from the group consisting of Formula (I) and Formula (II) predominates to the extent of about 90% or greater.  
   
   
       10 . The method of  claim 5  wherein one enantiomer selected from the group consisting of Formula (I) and Formula (II) predominates to the extent of about 98% or greater.  
   
   
       11 . The method of  claim 5  wherein the enantiomer selected from the group consisting of Formula (I) and Formula (II) is an enantiomer selected from the group consisting of Formula (Ia) and Formula (IIa):  
     
       
         
         
             
             
         
       
     
     wherein 
 phenyl is substituted at X with one to five halogen atoms selected from the group consisting of fluorine, chlorine, bromine and iodine; and,  
 R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are independently selected from the group consisting of hydrogen and C 1 -C 4  alkyl; wherein C 1 -C 4  alkyl is optionally substituted with phenyl (wherein phenyl is optionally substituted with substituents independently selected from the group consisting of halogen, C 1 -C 4  alkyl, C 1 -C 4  alkoxy, amino, nitro and cyano).  
 
   
   
       12 . The method of  claim 11  wherein X is chlorine.  
   
   
       13 . The method of  claim 11  wherein X is substituted at the ortho position of the phenyl ring.  
   
   
       14 . The method of  claim 11  wherein R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are selected from hydrogen.  
   
   
       15 . The method of  claim 11  wherein one enantiomer selected from the group consisting of Formula (Ia) and Formula (IIa) predominates to the extent of about 90% or greater.  
   
   
       16 . The method of  claim 11  wherein one enantiomer selected from the group consisting of Formula (Ia) and Formula (IIa) predominates to the extent of about 98% or greater.  
   
   
       17 . The method of  claim 5  wherein the enantiomer selected from the group consisting of Formula (I) and Formula (II) is an enantiomer selected from the group consisting of Formula (Ib) and Formula (IIb):  
     
       
         
         
             
             
         
       
     
   
   
       18 . The method of  claim 17  wherein one enantiomer selected from the group consisting of Formula (Ib) and Formula (IIb) predominates to the extent of about 90% or greater.  
   
   
       19 . The method of  claim 17  wherein one enantiomer selected from the group consisting of Formula (Ib) and Formula (IIb) predominates to the extent of about 98% or greater.  
   
   
       20 . The method as in claims  1  or  5  wherein anxiety disorders are selected from generalized anxiety disorder, panic disorders, impulse control disorders, phobic disorders, posttraumatic stress disorder, dissociative states (selected from amnesia, somnambulism, dissociative identity disorder or depersonalization), presurgical anxiety states, postsurgical anxiety states or other medical or psychiatric induced anxiety conditions (selected from anxiety resulting from traumatic brain injury, chronic pain disorders or other chronic disease conditions).  
   
   
       21 . The method of  claim 20  wherein anxiety disorders are selected from generalized anxiety disorder, panic disorders, impulse control disorders, phobic disorders or posttraumatic stress disorder.  
   
   
       22 . The method of  claim 21  wherein the anxiety disorder is posttraumatic stress disorder.  
   
   
       23 . The method of  claim 21  wherein panic disorders are selected from panic disorders with agoraphobia, panic disorders without agoraphobia, anticipatory anxiety, recurrent sleep panic attacks, distressing symptoms (selected from dyspnea, tachycardia, palpitations, headaches, dizziness, paresthesias, choking, smothering feeling, nausea or bloating) or feelings of impending doom; wherein phobic disorders are selected from social phobia, global social phobia, specific social phobia, simple phobia, agoraphobia, apiphobia, tropophobia, astrapophobia, triskaidekaphobia, blennophobia, thalassophobia, claustrophobia, spheksophobia, cynophobia, sciophobia, decidophobia, eletrophobia, scholionophobia, eremophobia, pyrophobia, gamophobia, pnigerophobia, ophidiophobia, odynophobia, nyctophobia, ochlophobia, musophobia, keraunophobia, katagelophobia, kakorraphiophobia, hydrophobia, gynophobia, gatophobia, gephyrophobia, acrophobia or amathophobia.  
   
   
       24 . (canceled)  
   
   
       25 . The method as in claims  1  or  5  wherein the therapeutically effective amount is from about 0.01 mg/Kg/dose to about 100 mg/Kg/dose.