Deuterated 2-amino-3-hydroxypropanoic acid derivatives

Abstract

This invention relates to novel 2-amino-3-hydroxypropanoic acid derivatives and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering an NMDA glycine-site antagonist.

1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 Y 1  is selected from CH 3 , CH 2 D, CHD 2  or CD 3 ; 
 each Z variable is independently selected from hydrogen or deuterium; and 
 each R variable is independently selected from hydrogen or deuterium; 
 wherein any atom not designated as deuterium is present at its natural isotopic abundance; and wherein for each site designated as deuterium, deuterium incorporation is at least 90%. 
 
     
     
         2 . The compound of  claim 1  wherein Y 1  is CH 3  or CD 3 . 
     
     
         3 . The compound of  claim 1  wherein Y 1  is CH 3 . 
     
     
         4 . The compound of  claim 1  wherein each R variable is hydrogen. 
     
     
         5 . The compound of  claim 1  wherein each Z variable is hydrogen. 
     
     
         6 . The compound of  claim 1  wherein each R variable is hydrogen and each Z variable is hydrogen. 
     
     
         7 . The compound of  claim 1  wherein each R variable is hydrogen and each Z variable is deuterium. 
     
     
         8 . The compound of  claim 1  wherein each R 1  variable is deuterium, each R 2  and R 3  variable is hydrogen, and each Z variable is hydrogen. 
     
     
         9 . The compound of  claim 1  wherein each R 1  and R 2  variable is deuterium, each R 3  variable is hydrogen, and each Z variable is hydrogen. 
     
     
         10 . The compound of  claim 1  wherein each R variable is deuterium and each Z variable is hydrogen. 
     
     
         11 . The compound of  claim 1  wherein each R 1  variable is deuterium, each R 2  and R 3  variable is hydrogen, and each Z variable is deuterium. 
     
     
         12 . The compound of  claim 1  wherein each R 1  and R 2  variable is deuterium, each R 3  variable is hydrogen, and each Z variable is deuterium. 
     
     
         13 . The compound of  claim 1  wherein each R variable is deuterium and each Z variable is deuterium. 
     
     
         14 . (canceled) 
     
     
         15 . The compound of  claim 1  wherein each R 1  is deuterium. 
     
     
         16 - 19 . (canceled) 
     
     
         20 . The compound of  claim 1  which is selected from the group consisting of the following: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt of any of the foregoing. 
     
     
         21 . The compound of  claim 20 , wherein the compound is an (R) enantiomer, or a pharmaceutically acceptable salt thereof, which is substantially free of the corresponding (S) enantiomer. 
     
     
         22 - 24 . (canceled) 
     
     
         25 . A composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         26 . The composition of  claim 25  for use in treating a disease or disorder associated with aberrant NMDA receptor function. 
     
     
         27 . The composition of  claim 25  for use in treating epilepsy, diabetic neuropathic pain, fibromyalgia, osteoarthritis, or migraine. 
     
     
         28 . The compound of  claim 1 , wherein the compound has the formula: 
       
         
           
           
               
               
           
         
       
       127, or a pharmaceutically acceptable salt thereof.