Methods for using amino acids with affinity for the alpha2delta-protein

Abstract

This invention relates to certain β-amino acids that bind to the alpha-2-delta (α2δ) subunit of a calcium channel. These compounds and their pharmaceutically acceptable salts are useful in the treatment of a variety of psychiatric, pain and other disorders.

1 - 5 . (canceled)  
   
   
       6 . A method of treating a disorder or condition in a mammal, including a human, the disorder or condition selected from epilepsy, abstinence from addictive substances and dependencies, smoking cessation, post herpetic neuralgia, chronic headache, lower back pain, and surgical pain, the method comprising administering to the mammal in need of such treatment a therapeutically effective amount of a compound represented by having the formula IA  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
 R 1  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;  
 R 2  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms; and  
 R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, or (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms  
 with the proviso that when R 1  is hydrogen, R 2  is not hydrogen.  
 
   
   
       7 . (canceled)  
   
   
       8 . A method according to  claim 6 , the compound represented by formula IA-1 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
 R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, or (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms.  
 
   
   
       9 . (canceled)  
   
   
       10 . A method according to  claim 6 , the compound represented by formula IA-2 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
 R 1  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms;  
 R 2  is hydrogen or (C 1 -C 3 )alkyl optionally substituted with from one to five fluorine atoms; and  
 R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, or (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms  
 with the proviso that when R 1  is hydrogen, R 2  is not hydrogen.  
 
   
   
       11 - 12 . (canceled)  
   
   
       13 . A method according to  claim 6 , wherein the compound is selected from: 
 3-Amino-5,8-dimethyl-nonanoic acid;    3-Amino-5,5,7-trimethyl-octanoic acid;    3-Amino-5,5,8-trimethyl-nonanoic acid;    3-Amino-5,5,6-trimethyl-heptanoic acid;    (3S,5 S)-3-Amino-5,8-dimethyl-nonanoic acid;    (3S,5R)-3-Amino-5,8-dimethyl-nonanoic acid;    (3S)-3-Amino-5,5,6-trimethyl-heptanoic acid;    (3S)-3-Amino-5,5,7-trimethyl-octanoic acid;    (3S)-3-Amino-5,5,8-trimethyl-nonanoic acid;    (3S)-3-Amino-5,5,9-trimethyl-decanoic acid;    3-Amino-6-cyclobutyl-5-methyl-hexanoic acid;    3-Amino-7-cyclopropyl-5-methyl-heptanoic acid;    3-Amino-7-cyclobutyl-5-methyl-heptanoic acid;    3-Amino-7-cyclopentyl-5-methyl-heptanoic acid;    3-Amino-7-cyclohexyl-5-methyl-heptanoic acid;    3-Amino-8-cyclopropyl-5-methyl-octanoic acid;    3-Amino-8-cyclobutyl-5-methyl-octanoic acid;    3-Amino-8-cyclopentyl-5-methyl-octanoic acid;    3-Amino-8-cyclohexyl-5-methyl-octanoic acid;    3-Amino-6-cyclopropyl-5,5-dimethyl-hexanoic acid;    3-Amino-6-cyclobutyl-5,5-dimethyl-hexanoic acid;    3-Amino-6-cyclopentyl-5,5-dimethyl-hexanoic acid;    3-Amino-6-cyclohexyl-5,5-dimethyl-hexanoic acid;    3-Amino-7-cyclopropyl-5,5-dimethyl-heptanoic acid;    3-Amino-7-cyclobutyl-5,5-dimethyl-heptanoic acid;    3-Amino-7-cyclopentyl-5,5-dimethyl-heptanoic acid;    3-Amino-7-cyclohexyl-5,5-dimethyl-heptanoic acid;    (3S,5R)-3-Amino-6-cyclobutyl-5-methyl-hexanoic acid;    (3S,5R)-3-Amino-7-cyclopropyl-5-methyl-heptanoic acid;    (3S,5R)-3-Amino-7-cyclobutyl-5-methyl-heptanoic acid;    (3S,5R)-3-Amino-7-cyclopentyl-5-methyl-heptanoic acid;    (3S,5R)-3-Amino-7-cyclohexyl-5-methyl-heptanoic acid;    (3S,5R)-3-Amino-8-cyclopropyl-5-methyl-octanoic acid;    (3S,5R)-3-Amino-8-cyclobutyl-5-methyl-octanoic acid;    (3S,5R)-3-Amino-8-cyclopentyl-5-methyl-octanoic acid;    (3S,5R)-3-Amino-8-cyclohexyl-5-methyl-octanoic acid;    (3S,5S)-3-Amino-6-cyclobutyl-5-methyl-hexanoic acid;    (3S,5S)-3-Amino-7-cyclopropyl-5-methyl-heptanoic acid;    (3S,5S)-3-Amino-7-cyclobutyl-5-methyl-heptanoic acid;    (3S,5S)-3-Amino-7-cyclopentyl-5-methyl-heptanoic acid;    (3S,5S)-3-Amino-7-cyclohexyl-5-methyl-heptanoic acid;    (3S,5S)-3-Amino-8-cyclopropyl-5-methyl-octanoic acid;    (3S,5S)-3-Amino-8-cyclobutyl-5-methyl-octanoic acid;    (3S,5S)-3-Amino-8-cyclopentyl-5-methyl-octanoic acid;    (3S,5S)-3-Amino-8-cyclohexyl-5-methyl-octanoic acid;    (3S)-3-Amino-6-cyclopropyl-5,5-dimethyl-hexanoic acid;    (3S)-3-Amino-6-cyclobutyl-5,5-dimethyl-hexanoic acid;    (3S)-3-Amino-6-cyclopentyl-5,5-dimethyl-hexanoic acid;    (3S)-3-Amino-6-cyclohexyl-5,5-dimethyl-hexanoic acid;    (3S)-3-Amino-7-cyclopropyl-5,5-dimethyl-heptanoic acid;    (3S)-3-Amino-7-cyclobutyl-5,5-dimethyl-heptanoic acid;    (3S)-3-Amino-7-cyclopentyl-5,5-dimethyl-heptanoic acid;    (3S)-3-Amino-7-cyclohexyl-5,5-dimethyl-heptanoic acid;    3-Amino-5-methyl-heptanoic acid;    3-Amino-5-methyl-octanoic acid;    3-Amino-5-methyl-nonanoic acid;    3-Amino-5,5-dimethyl-nonanoic acid;    3-Amino-5,5-dimethyl-decanoic acid;    (3S)-3-Amino-5,5-dimethyl-nonanoic acid;    (3S)-3-Amino-5,5-dimethyl-decanoic acid; and    their pharmaceutically acceptable salts.    
   
   
       14 . A method according to  claim 6 , wherein the compound is selected from: 
 3-Amino-5-methyl-heptanoic acid;    3-Amino-5-methyl-octanoic acid;    3-Amino-5-methyl-nonanoic acid;    (3S,5R)-3-Amino-5-methyl-heptanoic acid;    (3S,5R)-3-Amino-5-methyl-octanoic acid;    (3S,5R)-3-Amino-5-methyl-nonanoic acid; and    their pharmaceutically acceptable salts.