Spiro-lactam and bis-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 - 52 . (canceled) 
     
     
         53 . A compound represented by Formula V: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt and/or a stereoisomer thereof, wherein:
 R 3  is selected from the group consisting of hydrogen, —C 1 -C 6 alkyl, —C(O)—R 31 , and —C(O)—O—R 32 ; 
 R 31  is selected from the group consisting of hydrogen, —C 1 -C 6 alkyl, and phenyl; 
 R 32  is selected from the group consisting of hydrogen, —C 1 -C 6 alkyl, and phenyl; 
 wherein any aforementioned C 1 -C 6 alkyl is optionally substituted by one, two or three substituents each independently selected from hydroxyl, phenyl, and halogen; and any aforementioned phenyl is optionally substituted by one, two or three substituents each independently selected from —C 1 -C 3 alkoxy, hydroxyl, and halogen. 
 
     
     
         54 . The compound of  claim 53 , wherein R 3  is —C 1 -C 6 alkyl. 
     
     
         55 . The compound of  claim 53 , wherein R 3  is methyl, isobutyl, or —CH 2 -phenyl. 
     
     
         56 . The compound of  claim 53 , wherein the compound is represented by: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt and/or a stereoisomer thereof. 
     
     
         57 . The compound of  claim 53 , wherein the compound is represented by: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         58 . The compound of  claim 53 , wherein the compound is represented by: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         59 . A compound represented by: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt and/or a stereoisomer thereof. 
     
     
         60 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         61 . A pharmaceutical composition comprising the compound of  claim 53 , and a pharmaceutically acceptable excipient. 
     
     
         62 . A pharmaceutical composition comprising the compound of  claim 59 , and a pharmaceutically acceptable excipient. 
     
     
         63 . A pharmaceutical composition comprising the compound of  claim 60 , and a pharmaceutically acceptable excipient. 
     
     
         64 . A method of lessening or reducing one or more symptoms of depression, Alzheimer's disease, attention deficit disorder, schizophrenia, or anxiety, in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of  claim 53 . 
     
     
         65 . A method of lessening or reducing one or more symptoms of a migraine, neuropathic pain, or traumatic brain injury in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of  claim 53 . 
     
     
         66 . A method of lessening or reducing one or more symptoms of depression, Alzheimer's disease, attention deficit disorder, schizophrenia, or anxiety, in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of  claim 59 . 
     
     
         67 . A method of lessening or reducing one or more symptoms of a migraine, neuropathic pain, or traumatic brain injury in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of  claim 59 . 
     
     
         68 . A method of lessening or reducing one or more symptoms of depression, Alzheimer's disease, attention deficit disorder, schizophrenia, or anxiety, in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of  claim 60 . 
     
     
         69 . A method of lessening or reducing one or more symptoms of a migraine, neuropathic pain, or traumatic brain injury in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of  claim 60 .