Spiro-lactam nmda receptor modulators and uses thereof

Abstract

Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

1 . A compound represented by: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt and/or stereoisomer thereof, wherein:
 X is NR 2 ; 
 R 1  is C 1 -C 6 alkyl; 
 R 2  is C(O)—C 1 -C 6 alkyl; 
 p is 2; 
 R 5  is for each occurrence H; 
 R 3  is H; and 
 R 7  is for each occurrence H
 wherein any aforementioned C 1 -C 6  alkyl, independently for each occurrence, is optionally substituted by one, two or three substituents each independently selected from phenyl and halogen, and any aforementioned phenyl, independently for each occurrence, is optionally substituted by one, two or three substituents each independently selected from hydroxyl, halogen, methyl, and CF 3 . 
 
 
     
     
         2 .- 3 . (canceled) 
     
     
         4 . The compound of  claim 1 , wherein R 1  is C 1 -C 6 alkyl, optionally substituted by phenyl. 
     
     
         5 .- 7 . (canceled) 
     
     
         8 . The compound of  claim 4 , wherein R 1  is benzyl. 
     
     
         9 .- 14 . (canceled) 
     
     
         15 . The compound of  claim 1 , wherein R 2  is —C(O)—C 1 -C 6 alkyl. 
     
     
         16 .- 27 . (canceled) 
     
     
         28 . A pharmaceutical composition comprising a compound of  claim 1 , and a pharmaceutically acceptable excipient. 
     
     
         29 .- 34 . (canceled) 
     
     
         35 . The compound of  claim 4 , wherein R 1  is benzyl, and the phenyl is optionally substituted by one, two or three substituents each independently selected from halogen, methyl, and CF 3 . 
     
     
         36 . The compound of  claim 4 , wherein R 1  is benzyl, and the phenyl is substituted by one, two or three substituents each independently selected from halogen, methyl, and CF 3 . 
     
     
         37 . The compound of  claim 1 , wherein R 2  is —C(O)—C 1 -C 6 alkyl and C 1 -C 6  alkyl is substituted by one substituent selected from halogen. 
     
     
         38 . The compound of  claim 37 , wherein the halogen is fluoro. 
     
     
         39 . The compound of  claim 37 , wherein the halogen is chloro. 
     
     
         40 . The compound of  claim 37 , wherein the halogen is bromo. 
     
     
         41 . The compound of  claim 37 , wherein the halogen is iodo. 
     
     
         42 . The compound of  claim 35 , wherein R 2  is —C(O)—C 1 -C 6 alkyl and C 1 -C 6  alkyl is methylene substituted by one substituent selected from halogen. 
     
     
         43 . The compound of  claim 42 , wherein the halogen is fluoro. 
     
     
         44 . The compound of  claim 42 , wherein the halogen is chloro. 
     
     
         45 . The compound of  claim 36 , wherein R 2  is —C(O)—C 1 -C 6 alkyl and C 1 -C 6  alkyl is substituted by one substituent selected from halogen. 
     
     
         46 . The compound of  claim 45 , wherein the halogen is fluoro. 
     
     
         47 . The compound of  claim 45 , wherein the halogen is chloro. 
     
     
         48 . The compound of  claim 45 , wherein the halogen is bromo. 
     
     
         49 . The compound of  claim 45 , wherein the halogen is iodo.