NMDA Receptor Modulators and Uses Thereof

摘要

Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorder such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

主权项

1. A compound represented by Formula I: and pharmaceutically acceptable salts, stereoisomers, and N-oxides thereof; wherein T is, independently for each occurrence, CR4R4′, and n is 0, 1, 2 or 3; A is optionally present and is selected from phenyl or pyridine, wherein A is optionally substituted by one or more substituents selected from Ra; R1 is selected from the group consisting of H, hydroxyl, —S(O)2—C1-C4alkyl; —SO2, C1-C4alkyl, C2-C4alkenyl, phenyl, R7, orwherein C1-C4alkyl, C2-C4alkenyl, or phenyl is optionally substituted by one or more substituents selected from Ra;
X is CH or N; R3 and R3′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C1-C4alkyl, amido, amine, or C2-C4alkenyl, wherein C1-C4alkyl, C2-C4alkenyl and phenyl are optionally substituted by one or more substituents selected from Ra; R4 and R4′ are independently selected from the group consisting of H, halogen, hydroxyl, phenyl, C1-C4alkyl, amido, amine, C1-C4alkoxy or C2-C4alkenyl, wherein C1-C4alkyl, C2-C4alkenyl, C1-C4alkoxy, and phenyl are optionally substituted by one or more substituents selected from Ra; R2 is selected from the group consisting of H, R7, —S(O)2, S(O)2—C1-C4alkyl, C1-C4alkyl, hydroxyl, or phenyl wherein C1-C4alkyl, C2-C4 alkenyl and phenyl are optionally substituted by one or more substituents selected from Ra; R5 and R5′ are each independently selected from group consisting of H, halogen, C1-C4alkyl, C1-C4alkoxy, C2-C4alkenyl, cyano, amino, phenyl, and hydroxyl, wherein C1-C4alkyl, C2-C4alkenyl and phenyl are optionally substituted by one or more substituents selected from Ra; R7 is selected from group consisting of —C(O)—C1-C4alkyl or C(O)—O—C1-C4alkyl, wherein C1-C4 alkyl is optionally substituted by 1, 2 or 3 substituents selected from Rb; R8 is selected from group consisting of H, —C(O)—C1-C4 alkyl or C(O)—O—C1-C4 alkyl, wherein C1-C4alkyl is optionally substituted by 1, 2 or 3 substituents selected from Ra; Ra is selected, independently for each occurrence, from carboxy, hydroxyl, halogen, amino, phenyl, C1-C4 alkyl, and C1-C4 alkoxy; Rb is selected, independently for each occurrence, from the group consisting of carboxy, hydroxyl, halogen, amino, phenyl, C1-C4 alkyl, C1-C4 alkoxy, and —NH—Re; and Rc is selected, independently for each occurrence, —C(O)—O—C1-C4alkyl; and —C(O)—C1-C4alkyl.