DISUBSTITUTED OCTAHYDROPYRROLO[3,4-c]PYRROLES AS OREXIN RECEPTOR MODULATORS

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

• wherein:
• R1 is a member selected from the group consisting of:
• A) phenyl substituted or unsubstituted with one or two Ra members and substituted in the ortho position with Rb;
• Ra is independently selected from the group consisting of:
• —H, halo, —C1-4alkyl, —C1-4alkoxy, and —NO2, wherein two adjacent Ra members may come together to form a six membered aromatic ring;
• Rb is a member selected from the group consisting of:
• a) halo, —C1-4alkoxy, —C1-4alkyl, —CF3, —OCF3, or —CN;
• b) 5-membered heteroaryl ring containing one oxygen or one sulfur members;
• c) 5-6 membered heteroaryl ring containing one, two or three nitrogen members, optionally containing one oxygen member, substituted or unsubstituted with halo or —C1-4alkyl;
• and
• d) phenyl substituted or unsubstituted with halo, —CH3, or —CF3;
• B) pyridine substituted or unsubstituted with one or two Rc members and substituted with Rd, wherein Rd is positioned adjacent to the point of attachment by R1;
• Rc is C1-4alkyl;
• Rd is a member selected from the group consisting of:
• a) 5-6 membered heteroaryl ring selected from the group consisting of:
• 1H-1,2,3-triazol-1-yl, 2H-1,2,3-triazol-2-yl, 1H-pyrazol-5-yl, 3-methyl-1,2,4-oxadiazol-5-yl, pyridinyl, 3-methyl-pyridin-2-yl;
• 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl), phenyl, and pyrimidin-2-yl;
• and
• b) —CF3, —Br, and —C1-4alkoxy;
• C) 5-membered heteroaryl ring selected from the group consisting of:
• 2-methyl-1,3-thiazol-yl, 1H-pyrazol-5-yl, oxazole, isoxazolyl, thiophen-2-yl, and furan-2-yl, each substituted with phenyl substituted or unsubstituted with —F;
• and
• D) 5-13 membered aryl or heteroaryl ring selected from the group consisting of:
• 3-methylfuran-2-yl, 9H-fluorene, quinoline, cinnoline;
• 3-(1H-pyrrol-1-yl)thiophen-2-yl, 8-[1,2,3]-triazol-2-yl-naphthalen-1-yl, 2,3-dihydro-1,4-benzodioxin-5-yl, 1H-indol-7-yl, 4-fluoronaphthalen-1-yl, and naphthalen-1-yl;
• R2 is a member selected from the group consisting of:
• A) 6-membered heteroaryl ring containing two nitrogen members substituted with one or more members independently selected from the group consisting of:
• halo, —C1-4alkyl, —CD3, -D, —C1-4alkoxy, cyclopropyl, morpholin-2-yl, —CO2C1-4alkyl, —CO2H, —CH2OH, —C(O)N(C1-4alkyl)2, —CF3, —CN, —OH, —NO2, —N(C1-4alkyl)2, phenyl, furan-2-yl, thiophen-2-yl, 1H-pyrazol-4-yl, and pyrrolidin-1-yl;
• B) pyridine substituted with one or two members independently selected from the group consisting of:
• halo, —C1-4alkyl, —C1-4alkoxy, and —CF3;
• C) 9-membered heteroaryl ring selected from the group consisting of benzooxazol-2-yl, 6-fluoro-1,3-benzothiazole, 1,3-benzothiazole, 6-methoxy-1,3-benzothiazole, 6-methyl-1,3-benzothiazole, 6-chloro-benzothiazol-2-yl, and 4-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine;
• D) 10-membered heteroaryl ring selected from the group consisting of quinoxalin-2-yl, 3-methylquinoxalin-2-yl, 6,7-difluoroquinoxalin-2-yl, 3-(trifluoromethyl)quinoxaline, quinoline, 4-methylquinoline, and 6-fluoroquinazolin-2-yl;
• and
• E) 4-methyl-1,3,5-triazin-2-yl or 2-methylpyrimidin-4(3H)-one;
• and pharmaceutically acceptable salts of compounds of Formula (I).