Spiro-lactam nmda modulators and methods of using same

A compound represented by Formula I:

• or a pharmaceutically acceptable salt, a stereoisomer, and/or an N-oxide thereof, wherein:
• m is 0, 1 or 2;
• n is 1 or 2;
• X is O or S;
• R1 is selected from the group consisting of hydrogen, —C1-C6alkyl, —C(O)—C1-C6alkyl, —C(O)—O—C1-C6alkyl, —C1-C6alkylene-C1-C6cycloalkyl, and phenyl;
• R2 is independently selected for each occurrence from the group consisting of hydrogen, cyano, —C1-C6alkyl, and halogen;
• R3 is selected from the group consisting of hydrogen, —C1-C6alkyl, —C(O)—R31, —C(O)—O—R32, and phenyl;
• R31 is selected from the group consisting of hydrogen, —C1-C6alkyl, —C1-C6haloalkyl, —C3-C6cycloalkyl, and phenyl;
• R32 is selected from the group consisting of hydrogen, —C1-C6alkyl, —C1-C6haloalkyl, —C3-C6cycloalkyl, and phenyl;
• wherein any aforementioned C1-C6alkyl, independently for each occurrence, is optionally substituted by one, two or three substituents each independently selected from —C(O)NRaRb, —NRaRb, hydroxyl, —SH, phenyl, —O—CH2-phenyl, and halogen;
• and any aforementioned phenyl, independently for each occurrence, is optionally substituted by one, two or three substituents each independently selected from —C(O)NRaRb, —NRaRb, —C1-C3alkoxy, hydroxyl, and halogen;
• R4 is independently selected for each occurrence from the group consisting of hydrogen, halogen, hydroxyl, cyano, phenyl, —C1-C4alkyl, —C2-4alkenyl, —C1-4alkoxy, —C(O)NRaRb, —NRaRb, —N(Ra)-phenyl, —N(Ra)—C1-C6alkylene-phenyl, —N(Ra)—C(O)—C1-C6alkyl, —N(Ra)—C(O)—C1-C6alkylene-phenyl, —N(Ra)—C(O)—O—C1-C6alkyl, and —N(Ra)—C(O)—O—C1-C6alkylene-phenyl;
• wherein C1-C4alkyl, C1-C6alkylene, C2-C4alkenyl, C1-C4alkoxy, and phenyl are optionally substituted by one or more substituents selected from RP;
• or
• two R4 moieties, when present on adjacent carbons, form a 3-membered carbocyclic ring taken together with the adjacent carbons to which they are attached, optionally substituted by one or two substituents independently selected from the group consisting of halogen, hydroxyl, —C1-C3alkyl, —C1-C3alkoxy, —C(O)NRaRb, and —NRaRb;
• Ra and Rb are each independently for each occurrence selected from the group consisting of hydrogen, —C1-C4alkyl, and —CH2-phenyl;
• or Ra and Rb taken together with the nitrogen to which they are attached form a 4-6 membered heterocyclic ring;
• R5 is independently selected for each occurrence from the group consisting of hydrogen, —C1-C3alkyl, phenyl, and halogen;
• wherein phenyl is optionally substituted by one or more substituents selected from RP;
• or two R5 moieties together with the carbon to which they are attached form a carbonyl or thiocarbonyl moiety;
• R6 is independently selected for each occurrence from the group consisting of hydrogen, —C1-C3alkyl, phenyl and halogen;
• wherein phenyl is optionally substituted by one or more substituents selected from RP;
• or two R6 moieties together with the carbon to which they are attached form a carbonyl or thiocarbonyl moiety;
• and
• RP is independently selected for each occurrence from the group consisting of carboxy, hydroxyl, halogen, —NRaRb, phenyl, —C1-C6alkoxy, and —C1-C6alkyl;
• wherein each phenyl, C1-C6alkoxy and C1-C6alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen and hydroxyl.