Dialkylamino alkyl esters of pivagabine as medicaments for the treatment of central nervous system disorders

Abstract

The present embodiments are related to the compound of Formula 1 or Formula 2 below and pharmaceutical formulations thereof as well as treatments for a wide variety of Central Nervous System disorders with the pharmaceutical formulations. Some embodiments include the use of a variety of the instant compounds which surprisingly and advantageously exhibit improved pharmacokinetic and therapeutic profiles in comparison to pivagabine.

1 . A method of treating a symptom of a disease or disorder selected from the group consisting of: premenstrual dysphoric disorder, pre-menstrual syndrome, a psychotic disorder, brief psychotic disorder, schizophrenia, psychotic mood disorder, attention deficit disorder with hyperactivity, attention deficit disorder without hyperactivity, obesity, eating disorders, anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine addiction, alcohol addiction, sexual dysfunction, sexual dysfunction related illnesses, acute pain syndrome, chronic pain syndrome, fibromyalgia, arthritis, chronic low back pain, trigeminal neuralgia visceral pain syndromes, irritable bowel syndrome, noncardiac chest pain, functional dyspepsia, interstitial cystitis, essential vulvodynia, urethral syndrome, orchialgia, temperomandibular disorder, atypical face pain, migraine headache, tension headache, functional somatic disorders, chronic fatigue syndrome, neurologic disorders, seizure disorder, Tourette Syndrome, Parkinson's Disease, Huntington's Chorea, Alzheimer's Disease, subcortical dementia, nonsubcortical dementia, Tardive Dyskinesia, Multiple Sclerosis, Rett Syndrome and amyotrophic lateral sclerosis comprising contacting a patient with an effective amount of a compound with the following structure: 
       
         
           
           
               
               
           
         
         wherein, m is 0, 1, 2, 3 or 4; 
         wherein, n is 1, 2, 3, or 4; 
         wherein A and B are H; 
         and wherein R 1  is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
       
       wherein X is oxygen, and
 an unsymmetrical amine group of the formula 
 
       
         
           
           
               
               
           
         
       
       wherein R 3  and R 4  are independently selected from the group consisting of H, a C 1 -C 8  branched alkyl, and a C 1 -C 8  linear alkyl, or
 a pharmaceutically acceptable salt thereof. 
 
     
     
         2 . The method of  claim 1 , wherein R 1  is 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , wherein n is 1, m is 0 and R 1  is 
       
         
           
           
               
               
           
         
       
     
     
         4 . The Method of  claim 1 , wherein n is 2, m is 0 and R 1  is 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 1 , wherein n is 3, m is 0 and R 1  is 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 1 , wherein n is 2. 
     
     
         7 . The method of  claim 1 , wherein n is 3. 
     
     
         8 . The method of  claim 1 , wherein n is 4. 
     
     
         9 . The method of  claim 1 , wherein R 1  is an unsymmetrical amine group. 
     
     
         10 . The method of  claim 1 , wherein R 1  is 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 1 , wherein n is 1, m is 0 and R 1  is 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 1 , wherein n is 2, m is 0 and R 1  is 
       
         
           
           
               
               
           
         
       
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the disease or disorder is Rett Syndrome or amyotrophic lateral sclerosis. 
     
     
         15 . The method of  claim 1 , wherein the disease or disorder is Multiple Sclerosis. 
     
     
         16 . The method of  claim 1 , wherein the disease or disorder is Tourette Syndrome or Parkinson's Disease. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the disease or disorder is anorexia nervosa or bulimia nervosa. 
     
     
         19 . The method of  claim 1 , wherein the disease or disorder is obsessive compulsive disorder or obesity. 
     
     
         20 . The method of  claim 1 , wherein the disease or disorder is addiction. 
     
     
         21 . The method of  claim 20 , wherein the addiction is alcohol addiction.