Heteroaromatic NMDA receptor modulators and uses thereof

A method for treating a neuropsychiatric disorder selected from schizophrenia, depression, an autism spectrum disorder, and Rett syndrome in a subject comprising administering to said subject a therapeutically effective amount of a compound represented by Formula I

• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
• rings A and B are a fused [5,6] or [6,6] heteroaromatic system;
• Q is N or CR6;
• T is N or CR6;
• and
• y is 0 or 1 wherein
• when y is 1, U1 and U2 are C;
• W and V are each independently selected from CR6;
• one of Y and X is CR3 and one of Y and X is CR6;
• and
• when y is 0:
• X is CR3 or NR33;
• W is selected from the group consisting of CR6, N or S;
• V is selected from the group consisting of N, NR7, CR6, S and O;
• U1 and U2 may each be C or N;
• wherein when one of U1 and U2 is N the other is C;
• and
• when Q is CR6, T is N, W is CR6 and X is CR3;
• V is not S;
• L1 is a bond or C1-4 alkylene optionally interrupted by O, and optionally substituted on a carbon not bound to the ring nitrogen with one, two, or three substituents each independently selected from the group consisting of halogen, OH, cyano and —NRaRb;
• R1 and R2, together with the nitrogen to which they are attached, form a 4-6 membered monocyclic heterocyclic ring optionally substituted on a carbon by one, two or more substituents each selected from the group consisting of halogen, cyano, oxo, hydroxyl and C1-6 alkyl, wherein said C1-6 alkyl is optionally substituted by one, two or three halogens;
• R3 is phenyl, thiophenyl, pyrimidinyl, pyrazinyl or pyridinyl, each optionally substituted by one or two substituents each independently selected from the group consisting of halogen and C1-3alkyl, wherein said C1-3 alkyl is optionally substituted by one, two or three halogens;
• R33 is selected from the group consisting of phenyl, naphthyl, heteroaryl, heterocyclyl and C3-6 cycloalkyl, wherein R33 is optionally substituted with one, two or three substituents each independently selected from the group consisting of C1-4 alkyl, halogen, hydroxyl, C1-4 alkoxy, C2-6alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6alkyl-S(O)2—, C1-6 alkylcarbonyl, RaRbN—SO2—, NRaRb, C(O)OH, C1-4 alkoxycarbonyl, and NRaRbcarbonyl;
• wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6 alkyl-S(O)2— and C1-6 alkylcarbonyl may be optionally substituted by one or more substituents each selected from the group consisting of halogen, hydroxyl, cyano, and NRaRb;
• R6 is independently selected for each occurrence from the group consisting of hydrogen, halogen, cyano, C1-4 alkyl, C(O)OH, C(O)H, —C(═NH)—NRaRc, phenyl, pyridinyl and pyrimidinyl, wherein said C1-4 alkyl for R6 is optionally substituted by one or two substituents each selected from the group consisting of —NRaRb, C1-4alkoxy, halogen, cyano, hydroxyl, C(O)H, and ═NRa, and wherein said phenyl for R6 is optionally substituted by one or two substituents each selected from the group consisting of NRaRb, C1-4 alkoxy, halogen, cyano, hydroxyl, C(O)H, and ═NRa;
• R7 is selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkynyl, C3-6 cycloalkyl, heterocyclyl, heteroaryl, and phenyl;
• wherein C1-6 alkyl, C2-6 alkenyl and C3-6 cycloalkyl may optionally be substituted by one or more substituents each selected from the group consisting of halogen, hydroxyl, C1-4 alkoxy (optionally substituted by halogen or —Si(Rs)0-3 (wherein Rs is H or C1-6alkyl)), cyano, —Si(Rs)0-3 (wherein Rs is H or C1-6 alkyl), —O—Si(Rs)0-3 (wherein Rs is H or C1-6 alkyl), and NRaRb;
• Rc is selected from the group consisting of hydrogen, C1-3alkyl, and hydroxyl;
• and
• Ra and Rb are independently selected, for each occurrence, from the group consisting of hydrogen, C1-4 alkylcarbonyl, —C(O)—O—C1-4alkyl, C3-6 cycloalkyl and C1-3alkyl;
• wherein C1-3alkyl and C3-6 cycloalkyl may optionally be substituted on a carbon not bound to the nitrogen by one or more substituents each selected from the group consisting of fluorine, cyano, oxo and hydroxyl;
• or
• Ra and Rb, 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, or N;
• and wherein the 4-6 membered heterocyclic ring may optionally be substituted on a carbon not bound to the nitrogen by one or more substituents selected from the group consisting of fluorine, methyl, cyano, oxo and hydroxyl.