Spiro-lactam NMDA receptor modulators and uses thereof

A compound represented by formula II:

• or a pharmaceutically acceptable salt, a stereoisomer, or an N-oxide thereof, wherein
• Rb is selected from the group consisting of H, halogen, hydroxyl, cyano and C1-C6alkyl;
• R is H, C1-C6 alkyl or —C(O)—C1-C6alkyl;
• R1 is H or C1-C6 alkyl;
• R2 is H or C1-C6 alkyl;
• R4 is H or C1-C6 alkyl;
• R5 is H or C1-C6 alkyl;
• X is selected from the group consisting of H, C1-C6 alkyl, —OH, C1-C6 alkoxy, —CO2H, —C(O)NRcRd, and heteroaryl including from 5 to 6 ring atoms wherein 1, 2, or 3 of the ring atoms are independently selected from the group consisting of N, NH, N(C1-C3 alkyl), O, and S, wherein the heteroaryl ring may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6alkoxy, hydroxyl and phenyl;
• and
• Rc and Rd are each independently selected from the group consisting of H, C1-C6 alkyl, and phenyl, or Rc and Rd together with the nitrogen to which they are attached, form heterocyclyl including from 4 to 6 ring atoms;
• wherein the heterocyclyl includes not more than two ring heteroatoms (including the nitrogen atom attached to Rc and Rd), and the second ring heteroatom, when present, is independently selected from the group consisting of N, NH, N(C1-C3 alkyl), O, and S;
• and wherein the heterocyclyl is optionally substituted with from 1-3 substituents independently selected from the group consisting of halogen, cyano, oxo, and C1-C6 alkyl.

A compound represented by formula I:

• and pharmaceutically acceptable salts, stereoisomers, and N-oxides thereof, wherein
• Rb is selected from the group consisting of H, halogen, hydroxyl, cyano and C1-C6alkyl;
• R is H, C1-C6 alkyl or —C(O)—C1-C6alkyl;
• R1 is H or C1-C6 alkyl;
• R2 is H or C1-C6 alkyl;
• R3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, phenyl, or a 4-6 membered heteroaryl with one, two or three heteroatoms each selected from O, S and N, wherein R3 may be optionally substituted with one two or three substituents each selected from the group consisting of amino, halogen, C1-C6 alkyl, C1-C6 alkoxy, hydroxyl, phenyl (optionally substituted by one, two or three substituents each independently selected from Ra) and benzyl (optionally substituted by one two or three substituents each independently selected from Ra);
• Ra is selected from the group consisting of halogen, C1-C6alkyl (optionally substituted by one, two or three halogens), C3-C6 cycloalkyl (optionally substituted by one, two or three halogens), and C1-C6 alkoxy (optionally substituted by one, two or three halogens);
• R4 is H or C1-C6 alkyl;
• R5 is H or C1-C6 alkyl;
• X is selected from the group consisting of H, C1-C6 alkyl, —OH, C1-C6 alkoxy, —CO2H, —C(O)NRcRa, and a 4- to 6-membered heteroaryl ring with one, two or three heteroatoms each selected from O, S and N, wherein the heteroaryl ring may be optionally substituted with one two or three substituents each selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, hydroxyl and phenyl;
• and
• Rc and Rd are each independently selected from the group consisting of H, C1-C6 alkyl, and phenyl, or together with the nitrogen to which they are attached, form a 4-6 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, and N;
• wherein the 4-6 membered heterocyclic ring may optionally be substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, and C1-C6 alkyl.