Prodrugs of gaba analogs, compositions and uses thereof

Abstract

The present invention provides prodrugs of GABA analogs, pharmaceutical compositions of prodrugs of GABA analogs and methods for making prodrugs of GABA analogs. The present invention also provides methods for using prodrugs of GABA analogs and methods for using pharmaceutical compositions of prodrugs of GABA analogs for treating or preventing common diseases and/or disorders.

1 - 41 . (canceled) 
     
     
         42 . A compound of formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or hydrate thereof, wherein:
 n is 0; 
 Y is oxygen; 
 R 3 , R 6 , and R 7  are each hydrogen; 
 R 13  and R 14  are each independently selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenethyl, and 3-pyridyl; and 
 R 25  is selected from: 
 methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, 1-(1,3-dioxolan-2-yl)-ethyl, 1-(1,3-dioxan-2-yl)-ethyl, 1,1-dimethoxypropyl, 1,1-diethoxypropyl, 1-(1,3-dioxolan-2-yl)-propyl, 1-(1,3-dioxan-2-yl)-propyl, 1,1-dimethoxybutyl, 1,1-diethoxybutyl, 1-(1,3-dioxolan-2-yl)-butyl, 1-(1,3-dioxan-2-yl)-butyl, 1,1-dimethoxybenzyl, 1,1-diethoxybenzyl, 1-(1,3-dioxolan-2-yl)-benzyl, 1-(1,3-dioxan-2-yl)-benzyl, 1,1-dimethoxy-2-phenethyl, 1,1-diethoxy-2-phenethyl, 1-(1,3-dioxolan-2-yl)-2-phenethyl, 1-(1,3-dioxan-2-yl)-2-phenethyl, acetyl, propionyl, butyryl, benzoyl, phenacetyl, phenyl, 4-methoxyphenyl, benzyl, phenethyl, styryl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and 3-pyridyl. 
 
     
     
         43 . The compound or a pharmaceutically acceptable salt or hydrate thereof according to  claim 42  having the Formula: 
       
         
           
           
               
               
           
         
       
     
     
         44 . The compound or a pharmaceutically acceptable salt or hydrate thereof according to  claim 42  having the Formula: 
       
         
           
           
               
               
           
         
       
     
     
         45 . The compound or a pharmaceutically acceptable salt or hydrate thereof according to  claim 42  having the Formula: 
       
         
           
           
               
               
           
         
       
     
     
         46 . The compound or a pharmaceutically acceptable salt or hydrate thereof according to  claim 42 , wherein:
 R 13  is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; and   R 14  is hydrogen.   
     
     
         47 . The compound or a pharmaceutically acceptable salt or hydrate thereof according to  claim 46 , wherein R 13  is methyl. 
     
     
         48 . The compound or a pharmaceutically acceptable salt or hydrate thereof according to  claim 46 , wherein R 13  is isopropyl. 
     
     
         49 . compound or a pharmaceutically acceptable salt or hydrate thereof according to  claim 42 , wherein R 25  is methyl, ethyl, propyl, isopropyl, butyl, 1,1-dimethoxyethyl or 1,1-diethoxyethyl. 
     
     
         50 . A pharmaceutical composition comprising a compound of  claim 42 , or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable vehicle. 
     
     
         51 . The pharmaceutical composition of  claim 50 , which is an oral sustained release dosage form. 
     
     
         52 . A method of treating preventing epilepsy, depression, anxiety, psychosis, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, panic, pain, inflammatory disease, insomnia, gastrointestinal disorders or ethanol withdrawal syndrome comprising administering a compound of  claim 42  to a patient, wherein the compound treats or prevents epilepsy, depression, anxiety, psychosis, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, panic, pain, inflammatory disease, insomnia, gastrointestinal disorders or ethanol withdrawal syndrome. 
     
     
         53 . The method of  claim 52 , wherein the pain is selected from neuropathic pain, muscular pain and skeletal pain. 
     
     
         54 . The method of  claim 52 , wherein the inflammatory disease is arthritis.