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 - 2 . (canceled)  
     
     
         3 . A compound of formula II,  
       
         
           
           
               
               
           
         
       
       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;  
 R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -c 3 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, pyridyl-(C 1 -C 3 )alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties is optionally substituted with from one to five fluorine atoms, and wherein each of the foregoing phenyl and pyridyl moieties is optionally substituted with from one to three substituents independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 ) alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms, and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms;  
 with the proviso that when R 1  is hydrogen, R 2  is not hydrogen.  
 
     
     
         4 . (canceled)  
     
     
         5 . A compound according to  claim 3 , or a pharmaceutically acceptable salt thereof, the compound represented by formula IIA,  
       
         
           
           
               
               
           
         
         wherein R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, pyridyl-(C 1 -C 3 )alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be is optionally substituted with from one to five fluorine atoms, and wherein each of the foregoing phenyl and pyridyl moieties is optionally substituted with from one to three substituents independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms, and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms.  
       
     
     
         6 . (canceled)  
     
     
         7 . A compound of formula III,  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof; 
 wherein R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, pyridyl-(C 1 -C 3 )alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties is optionally substituted with from one to five fluorine atoms, and wherein each of the foregoing phenyl and pyridyl moieties is optionally substituted with from one to three substituents-, independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms, and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms.  
 
     
     
         8 . A compound of formula IV,  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof; 
 wherein R 1  is hydrogen or (C 1 -C 6 )alkyl optionally substituted with from one to five fluorine atoms; and  
 R 3  is wherein R 3  is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 3 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, pyridyl-(C 1 -C 3 )alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties is optionally substituted with from one to five fluorine atoms, and wherein each of the foregoing phenyl and pyridyl and the moieties is optionally substituted with from one to three substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms, and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms.  
 
     
     
         9 - 14 . (canceled)  
     
     
         15 . A compound according to  claim 3 , or a pharmaceutically acceptable salt thereof, the compound selected from: 
 2-aminomethyl-4-methyl-7-phenyl-heptanoic acid;    2-aminomethyl-4-methyl-6-phenyl-hexanoic acid;    2-aminomethyl-7-(4-fluoro-phenyl)-4-methyl-heptanoic acid;    2-aminomethyl-7-(3-fluoro-phenyl)-4-methyl-heptanoic acid;    2-aminomethyl-7-(2-fluoro-phenyl)-4-methyl-heptanoic acid;    2-aminomethyl-7-(2,4-difluoro-phenyl)-4-methyl-heptanoic acid;    2-aminomethyl-7-(3,4-difluoro-phenyl)-4-methyl-heptanoic acid;    2-aminomethyl-4-methyl-7-(2-trifluoromethyl-phenyl)-heptanoic acid;    2-aminomethyl-4-methyl-7-(3-trifluoromethyl-phenyl)-heptanoic acid;    2-aminomethyl-4-methyl-7-(4-trifluoromethyl-phenyl)-heptanoic acid;    2-aminomethyl-4-methyl-6-phenylamino-hexanoic acid;    2-aminomethyl-4-methyl-7-phenylamino-heptanoic acid;    2-aminomethyl-4-methyl-8-phenylamino-octanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-7-phenyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-6-phenyl-hexanoic acid;    (2R, 4R)-2-aminomethyl-7-(4-fluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-7-(3-fluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-7-(2-fluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-7-(2,4-difluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-7-(3,4-difluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-7-(2-trifluoromethyl-phenyl)-heptanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-7-(3-trifluoromethyl-phenyl)-heptanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-7-(4-trifluoromethyl-phenyl)-heptanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-6-phenylamino-hexanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-7-phenylamino-heptanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-8-phenylamino-octanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-7-phenyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-6-phenyl-hexanoic acid;    (2R, 4S)-2-aminomethyl-7-(4-fluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-7-(3-fluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-7-(2-fluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-7-(2,4-difluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-7-(3,4-difluoro-phenyl)-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-7-(2-trifluoromethyl-phenyl)-heptanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-7-(3-trifluoromethyl-phenyl)-heptanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-7-(4-trifluoromethyl-phenyl)-heptanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-6-phenylamino-hexanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-7-phenylamino-heptanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-8-phenylamino-octanoic acid;    (2R, 4S)-2-aminomethyl-6-cyclohexyl-4-ethyl-hexanoic acid;    2-aminomethyl-4-ethyl-hexanoic acid;    2-aminomethyl-4-ethyl-5-methyl-hexanoic acid;    2-aminomethyl-4-ethyl-heptanoic acid;    2-aminomethyl-4-ethyl-6-methyl-heptanoic acid;    2-aminomethyl-4-ethyl-octanoic acid;    2-aminomethyl-4-ethyl-7-methyl-octanoic acid;    2-aminomethyl-4-ethyl-nonanoic acid;    2-aminomethyl-4-ethyl-8-methyl-nonanoic acid;    2-aminomethyl-4,4-dimethyl-heptanoic acid;    2-aminomethyl-4,6-dimethyl-heptanoic acid;    2-aminomethyl-4,4,8-trimethyl-nonanoic acid    (2R, 4S)-2-aminomethyl-6-cyclopentyl-4-ethyl-hexanoic acid;    (2R, 4S)-2-aminomethyl-6-cyclobutyl-4-ethyl-hexanoic acid;    (2R, 4S)-2-aminomethyl-6-cyclopropyl-4-ethyl-hexanoic acid;    2-aminomethyl-4-methyl-hexanoic acid;    2-aminomethyl-4-methyl-heptanoic acid;    2-aminomethyl-4-methyl-octanoic acid;    2-aminomethyl-4-methyl-nonanoic acid;    2-aminomethyl-4-methyl-decanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-hexanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-octanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-nonanoic acid;    (2R, 4R)-2-aminomethyl-4-methyl-decanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-hexanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-octanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-nonanoic acid;    (2R, 4S)-2-aminomethyl-4-methyl-decanoic acid;    2-aminomethyl-5-cyclopropyl-4-methyl-pentanoic acid;    2-aminomethyl-5-cyclobutyl-4-methyl-pentanoic acid;    2-aminomethyl-5-cyclopentyl-4-methyl-pentanoic acid;    2-aminomethyl-5-cyclohexyl-4-methyl-pentanoic acid;    2-aminomethyl-6-cyclopropyl-4-methyl-hexanoic acid;    2-aminomethyl-6-cyclobutyl-4-methyl-hexanoic acid;    2-aminomethyl-6-cyclopentyl-4-methyl-hexanoic acid;    2-aminomethyl-6-cyclohexyl-4-methyl-hexanoic acid;    2-aminomethyl-7-cyclopropyl-4-methyl-heptanoic acid;    2-aminomethyl-7-cyclobutyl-4-methyl-heptanoic acid;    2-aminomethyl-7-cyclopentyl-4-methyl-heptanoic acid;    2-aminomethyl-7-cyclohexyl-4-methyl-heptanoic acid;    2-aminomethyl-8-cyclopropyl-4-methyl-octanoic acid;    2-aminomethyl-8-cyclobutyl-4-methyl-octanoic acid;    2-aminomethyl-8-cyclopentyl-4-methyl-octanoic acid;    2-aminomethyl-8-cyclohexyl-4-methyl-octanoic acid;    (2R, 4S)-2-aminomethyl-5-cyclopropyl-4-methyl-pentanoic acid;    (2R, 4S)-2-aminomethyl-5-cyclobutyl-4-methyl-pentanoic acid;    (2R, 4S)-2-aminomethyl-5-cyclopentyl-4-methyl-pentanoic acid;    (2R, 4S)-2-aminomethyl-5-cyclohexyl-4-methyl-pentanoic acid;    (2R, 4S)-2-aminomethyl-6-cyclopropyl-4-methyl-hexanoic acid;    (2R, 4S)-2-aminomethyl-6-cyclobutyl-4-methyl-hexanoic acid;    (2R, 4S)-2-aminomethyl-6-cyclopentyl-4-methyl-hexanoic acid;    (2R, 4S)-2-aminomethyl-6-cyclohexyl-4-methyl-hexanoic acid;    (2R, 4S)-2-aminomethyl-7-cyclopropyl-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-7-cyclobutyl-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-7-cyclopentyl-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-7-cyclohexyl-4-methyl-heptanoic acid;    (2R, 4S)-2-aminomethyl-8-cyclopropyl-4-methyl-octanoic acid;    (2R, 4S)-2-aminomethyl-8-cyclobutyl-4-methyl-octanoic acid;    (2R, 4S)-2-aminomethyl-8-cyclopentyl-4-methyl-octanoic acid;    (2R, 4S)-2-aminomethyl-8-cyclohexyl-4-methyl-octanoic acid;    (2R, 4R)-2-aminomethyl-5-cyclopropyl-4-methyl-pentanoic acid;    (2R, 4R)-2-aminomethyl-5-cyclobutyl-4-methyl-pentanoic acid;    (2R, 4R)-2-aminomethyl-5-cyclopentyl-4-methyl-pentanoic acid;    (2R, 4R)-2-aminomethyl-5-cyclohexyl-4-methyl-pentanoic acid;    (2R, 4R)-2-aminomethyl-6-cyclopropyl-4-methyl-hexanoic acid;    (2R, 4R)-2-aminomethyl-6-cyclobutyl-4-methyl-hexanoic acid;    (2R, 4R)-2-aminomethyl-6-cyclopentyl-4-methyl-hexanoic acid;    (2R, 4R)-2-aminomethyl-6-cyclohexyl-4-methyl-hexanoic acid;    (2R, 4R)-2-aminomethyl-7-cyclopropyl-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-7-cyclobutyl-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-7-cyclopentyl-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-7-cyclohexyl-4-methyl-heptanoic acid;    (2R, 4R)-2-aminomethyl-8-cyclopropyl-4-methyl-octanoic acid;    (2R, 4R)-2-aminomethyl-8-cyclobutyl-4-methyl-octanoic acid;    (2R, 4R)-2-aminomethyl-8-cyclopentyl-4-methyl-octanoic acid; and    (2R, 4R)-2-aminomethyl-8-cyclohexyl-4-methyl-octanoic acid.    
     
     
         16 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 3 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
     
     
         17 . A method of treating a disorder or condition in a mammal, including a human, the method comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound according to  claim 3 , or a pharmaceutically acceptable salt thereof, wherein the disorder or condition is selected from inflammatory pain, chronic pain, acute pain, neuropathic pain, sleep disorders, hot flashes, fibromyalgia, or anxiety.  
     
     
         18 . A method according to  claim 17 , wherein the disorder or condition is neuropathic pain.  
     
     
         19 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
     
     
         20 . A method of treating a disorder or condition in a mammal, including a human, the method comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound according to  claim 7 , or a pharmaceutically acceptable salt thereof, wherein the disorder or condition is selected from inflammatory pain, chronic pain, acute pain, neuropathic pain, sleep disorders, hot flashes, fibromyalgia, or anxiety.  
     
     
         21 . A method according to  claim 20 , wherein the disorder or condition is neuropathic pain.  
     
     
         22 . A compound according to  claim 8 , or a pharmaceutically acceptable salt thereof, the compound selected from: 
 2-aminomethyl-5-ethyl-heptanoic acid;    2-aminomethyl-5-ethyl-6-methyl-heptanoic acid;    2-aminomethyl-7-cyclopropyl-5-ethyl-heptanoic acid;    2-aminomethyl-7-cyclobutyl-5-ethyl-heptanoic acid;    2-aminomethyl-7-cyclopentyl-5-ethyl-heptanoic acid;    2-aminomethyl-7-cyclohexyl-5-ethyl-heptanoic acid;    2-aminomethyl-5-ethyl-octanoic acid;    2-aminomethyl-5-ethyl-7-methyl-octanoic acid;    2-aminomethyl-5-ethyl-nonanoic acid;    2-aminomethyl-5-ethyl-8-methyl-nonanoic acid;    2-aminomethyl-6-cyclopropyl-5-methyl-hexanoic acid;    2-aminomethyl-6-cyclobutyl-5-methyl-hexanoic acid;    2-aminomethyl-6-cyclopentyl-5-methyl-hexanoic acid;    2-aminomethyl-6-cyclohexyl-5-methyl-hexanoic acid;    2-aminomethyl-7-cyclopropyl-5-methyl-heptanoic acid;    2-aminomethyl-7-cyclobutyl-5-methyl-heptanoic acid;    2-aminomethyl-7-cyclopentyl-5-methyl-heptanoic acid;    2-aminomethyl-7-cyclohexyl-5-methyl-heptanoic acid;    2-aminomethyl-8-cyclopropyl-5-methyl-octanoic acid;    2-aminomethyl-8-cyclobutyl-5-methyl-octanoic acid;    2-aminomethyl-8-cyclopentyl-5-methyl-octanoic acid;    2-aminomethyl-8-cyclohexyl-5-methyl-octanoic acid;    2-aminomethyl-5-methyl-heptanoic acid;    2-aminomethyl-5-methyl-octanoic acid;    2-aminomethyl-5-methyl-nonanoic acid;    2-aminomethyl-8-methyl-nonanoic acid;    (2R, 6S)-2-aminomethyl-6-cyclopropyl-5-methyl-hexanoic acid;    (2R, 6S)-2-aminomethyl-6-cyclobutyl-5-methyl-hexanoic acid;    (2R, 6S)-2-aminomethyl-6-cyclopentyl-5-methyl-hexanoic acid;    (2R, 6S)-2-aminomethyl-6-cyclohexyl-5-methyl-hexanoic acid;    (2R, 6S)-2-aminomethyl-7-cyclopropyl-5-methyl-heptanoic acid;    (2R, 6S)-2-aminomethyl-7-cyclobutyl-5-methyl-heptanoic acid;    (2R, 6S)-2-aminomethyl-7-cyclopentyl-5-methyl-heptanoic acid;    (2R, 6S)-2-aminomethyl-7-cyclohexyl-5-methyl-heptanoic acid;    (2R, 6S)-2-aminomethyl-8-cyclopropyl-5-methyl-octanoic acid;    (2R, 6S)-2-aminomethyl-8-cyclobutyl-5-methyl-octanoic acid;    (2R, 6S)-2-aminomethyl-8-cyclopentyl-5-methyl-octanoic acid;    (2R, 6S)-2-aminomethyl-8-cyclohexyl-5-methyl-octanoic acid;    (2R, 6S)-2-aminomethyl-5-methyl-heptanoic acid;    (2R, 6S)-2-aminomethyl-5-methyl-octanoic acid;    (2R, 6S)-2-aminomethyl-5-methyl-nonanoic acid;    (2R, 6R)-2-aminomethyl-6-cyclopropyl-5-methyl-hexanoic acid;    (2R, 6R)-2-aminomethyl-6-cyclobutyl-5-methyl-hexanoic acid;    (2R, 6R)-2-aminomethyl-6-cyclopentyl-5-methyl-hexanoic acid;    (2R, 6R)-2-aminomethyl-6-cyclohexyl-5-methyl-hexanoic acid;    (2R, 6R)-2-aminomethyl-7-cyclopropyl-5-methyl-heptanoic acid;    (2R, 6R)-2-aminomethyl-7-cyclobutyl-5-methyl-heptanoic acid;    (2R, 6R)-2-aminomethyl-7-cyclopentyl-5-methyl-heptanoic acid;    (2R, 6R)-2-aminomethyl-7-cyclohexyl-5-methyl-heptanoic acid;    (2R, 6R)-2-aminomethyl-8-cyclopropyl-5-methyl-octanoic acid;    (2R, 6R)-2-aminomethyl-8-cyclobutyl-5-methyl-octanoic acid;    (2R, 6R)-2-aminomethyl-8-cyclopentyl-5-methyl-octanoic acid;    (2R, 6R)-2-aminomethyl-8-cyclohexyl-5-methyl-octanoic acid;    (2R, 6R)-2-aminomethyl-5-methyl-heptanoic acid;    (2R, 6R)-2-aminomethyl-5-methyl-octanoic acid; and    (2R, 6R)-2-aminomethyl-5-methyl-nonanoic acid.    
     
     
         23 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
     
     
         24 . A method of treating a disorder or condition in a mammal, including a human, the method comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound according to  claim 8 , or a pharmaceutically acceptable salt thereof, wherein the disorder or condition is selected from inflammatory pain, chronic pain, acute pain, neuropathic pain, sleep disorders, hot flashes, fibromyalgia, or anxiety.  
     
     
         25 . A method according to  claim 24 , wherein the disorder or condition is neuropathic pain.  
     
     
         26 . A compound selected from the following and their pharmaceutically acceptable salts: 
 2-aminomethyl-3-(1-methyl-cyclopropyl)-propionic acid;    2-aminomethyl-3-(1-ethyl-cyclopropyl)-propionic acid;    2-aminomethyl-3-(1-propyl-cyclopropyl)-propionic acid;    2-aminomethyl-3-(1-isopropyl-cyclopropyl)-propionic acid;    2-aminomethyl-3-(1-butyl-cyclopropyl)-propionic acid;    2-aminomethyl-3-(1-isobutyl-cyclopropyl)-propionic acid;    2-aminomethyl-3-[1-(4-methyl-pentyl)-cyclopropyl]-propionic acid;    2-aminomethyl-3-(1-methyl-cyclobutyl)-propionic acid;    2-aminomethyl-3-(1-ethyl-cyclobutyl)-propionic acid;    2-aminomethyl-3-(1-propyl-cyclobutyl)-propionic acid;    2-aminomethyl-3-(1-methyl-cyclopentyl)-propionic acid;    2-aminomethyl-3-(1-ethyl-cyclopentyl)-propionic acid;    2-aminomethyl-3-(1-propyl-cyclopentyl)-propionic acid;    2-aminomethyl-3-(1-methyl-cyclohexyl)-propionic acid;    2-aminomethyl-3-(1-ethyl-cyclohexyl)-propionic acid;    2-aminomethyl-3-(1-propyl-cyclohexyl)-propionic acid;    2-aminomethyl-4-cyclopropyl-butyric acid;    2-aminomethyl-4-(1-methyl-cyclopropyl)-butyric acid;    2-aminomethyl-4-(1-ethyl-cyclopropyl)-butyric acid;    2-aminomethyl-4-cyclobutyl-butyric acid;    2-aminomethyl-4-(1-methyl-cyclobutyl)-butyric acid;    2-aminomethyl-4-(1-ethyl-cyclobutyl)-butyric acid;    2-aminomethyl-4-cyclopentyl-butyric acid;    2-aminomethyl-4-(1-methyl-cyclopentyl)-butyric acid;    2-aminomethyl-4-(1-ethyl-cyclopentyl)-butyric acid;    2-aminomethyl-4-cyclohexyl-butyric acid;    2-aminomethyl-4-(1-methyl-cyclohexyl)-butyric acid; and    2-aminomethyl-4-(1-ethyl-cyclohexyl)-butyric acid.    
     
     
         27 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 26 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
     
     
         28 . A method of treating a disorder or condition in a mammal, including a human, the method comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound according to  claim 26 , or a pharmaceutically acceptable salt thereof, wherein the disorder or condition is selected from inflammatory pain, chronic pain, acute pain, neuropathic pain, sleep disorders, hot flashes, fibromyalgia, or anxiety.  
     
     
         29 . A method according to  claim 28 , wherein the disorder or condition is neuropathic pain.