N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B

A compound of formula I:

• or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof
• wherein:
• L1 is straight or branched C1-C5 alkylene substituted with OH;
• each R10 and R10′ is independently selected from the group consisting of H;
• C1-C6 alkyl optionally substituted with one or more substituents selected from the group consisting of OH, O—C1-C5 alkyl, OPO3−2M2, OP(O)(OH)2, OC(O) alkyl, and OC(O)O-alkyl where M is a monovalent metal cation;
• and
• cycloalkyl optionally substituted with one or more substituents selected from the group consisting of OH and O—C1-C5 alkyl provided that no more than one oxygen is attached to any carbon;
• or R10 and R10′, together with the nitrogen to which they are attached, may form a heterocycle selected from the group consisting of oxetanyl, azetadinyl, tetrahydrofuranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, and homotropanyl;
• R1 is cycloalkyl, aryl, or heteroaryl, any of which optionally substituted with one or more substituents selected from the group consisting of OH, CN, halogen, —C1-C6alkylaryl, —O—C1-C6alkylaryl, O—R10, OPO3−2M2, OP(O)(OH)2, SH, S—R10, C1-C5 alkyl, branched alkyl, NH2, NHR10, NHS(O)2R10, N(R10)(R10′), and NHCOR10 where M is a monovalent metal cation;
• X is selected from O, S, —S(O)—, and —S(O)2—;
• Y and Y′ are independently H, halogen, or C1-C5 alkyl;
• L2 is a bond, —(CH2)n— or —(CHR11)n—;
• each R11 is independently selected from the group consisting of H, —C1-C5 alkylenyl-, —CO—C1-C5alkylenyl-, and -alkylenyl-CO-alkylenyl-;
• R2 is phenyl, naphthyl, heteroaryl or bicyclic heteroaryl, each of which is optionally substituted with one or more substituents selected from the group consisting of halogen, OH, C1-C6alkyl, OR10, CN, NH2, NHR10, N(R10)(R10′), -nitro, SH, SR10, SOR10, SO2R10, SO2NHR10, SO2N(R10)(R10′), CONH2, CONR10, and CON(R10)(R10′);
• and
• n is 1, 2, or 3;
• wherein cycloalkyl is a monocyclic saturated carbon ring containing 3-18 carbon atoms, and
• wherein heteroaryl is a monocyclic, bicyclic or polycyclic aromatic radical of 5 to 10 ring atoms and containing one or more ring heteroatoms selected from N, O, or S, the remaining ring atoms being C, and when containing two fused rings, the aryl groups may have an unsaturated or partially saturated ring fused with a fully saturated ring.