Substituted 4-azaindoles and their use as GluN2B receptor modulators

A method of treating a subject suffering from or diagnosed with a disease, disorder, or medical condition mediated by NR2B receptor activity, comprising administering to a subject in need of such treatment an effective amount of at least one compound selected from compounds of Formula (I):

• and pharmaceutically acceptable salts, solvates, and N-oxides of compounds of Formula (I),
• wherein:
• R1 is selected from the group consisting of:
• H, 3H, halo, C1-3alkyl, and C1-3haloalkyl;
• R2 is selected from the group consisting of:
• phenyl optionally substituted with one, two, or three members independently selected from:
• halo, C1-5alkyl, and C1-5haloalkyl;
• pyridinyl optionally substituted with halo, C1-5alkyl, C1-5haloalkyl, and —CN;
• thiazolyl optionally substituted with C1-5alkyl;
• benzothiophenyl;
• and thienyl optionally substituted with one, two or three members independently selected from:
• halo, C1-5alkyl, and C1-5haloalkyl;
• R3 is
• wherein ring A is a 4-7 membered heterocycloalkyl optionally containing an additional oxygen heteroatom selected from the group consisting of:
• azetidinyl optionally substituted with one or two members independently selected from the group consisting of:
• halo, C1-5alkyl, C1-5haloalkyl, CH2OH, C1-5alkoxy, OH, and CN;
• pyrrolidinyl optionally substituted with one or two members independently selected from the group consisting of:
• halo, C1-5alkyl, C1-5alkoxy, and OH;
• morpholino optionally substituted with one or two C1-5alkyl members;
• piperidinyl optionally substituted with one or two members independently selected from the group consisting of:
• halo, C1-5alkyl, C1-5haloalkyl, C1-5alkoxy, and OH;
• 3-azabicyclo[3.1.0]hexan-3-yl;
• 5-azaspiro[2.3]hexan-5-yl;
• and pyrrolidin-3-one;
• or
• wherein R3a is H, or C1-5alkyl;
• and R3b is selected from the group consisting of:
• C1-5alkyl optionally substituted with OH, halo, or OCH3;
• C1-5haloalkyl;
• benzyl;
• CH2cyclopropyl;
• cyclopropyl optionally substituted with C1-5alkyl;
• and cyclobutyl;
• or
• wherein R3c is selected from the group consisting of:
• cyclopropyl;
• cyclobutyl;
• pyrimidinyl optionally substituted with halo;
• pyridinyl;
• pyridazinyl;
• furanyl optionally substituted with C1-5haloalkyl;
• oxazolyl;
• isoxazolyl optionally substituted with C1-5alkyl;
• oxadiazolyl optionally substituted with C1-5alkyl;
• pyrazolyl optionally substituted with C1-5alkyl;
• triazolyl optionally substituted with C1-5alkyl;
• tetrahydrofuranyl;
• tetrahydropyranyl;
• oxetanyl;
• and oxiranyl;
• or
• wherein R3d is CH2-cyclopropyl or cyclobutyl;
• or
• wherein R3e is selected from the group consisting of:
• OH, C1-5alkyl, cyclopropyl, cyclobutyl, and phenyl optionally substituted with one halo substituent;
• or
• (f) C1-5alkyl optionally substituted with OH or C1-5alkoxy;
• CH2S(CH3);
• CH2(S═O)CH3;
• CH2(SO2)CH3;
• or CH2CH2(C═O)CH3;
• or
• and
• R4 is H, 2H or C1-3alkyl.