Heteroaromatic Compounds and their Use as Dopamine D1 Ligands

Abstract

The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds and the uses of such compounds for the treatment of D1-mediated (or D1-associated) disorders including cognitive and motivational impairments and negative symptoms associated with illnesses such as schizophrenia, depression, bipolar disorder, Parkinson's disease, Mild cognitive impairment (MCI), Alzheimer's disease, lupus, Huntington's disease, Parkinson's, dyskinesia, ADHD, post-traumatic stress disorder, autism spectrum disorder, treatment-resistant depression, major depressive disorder (MDD), drug dependence, Tourette's syndrome, tardive dyskinesias as well as impairments associated with age, chronic stress, sleep deprivation, combat, chronic fatigue; endocrine or metabolic diseases such as hyperglycemia, dislipidemia, diabetes, obesity, and sepsis; and cardiovascular disorder such as hypertension.

What is claimed is: 
     
         1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         or an N-oxide thereof, or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein: 
         X 1  is O or S; 
         Y 1  is O, S, or NR N ; 
         Q 1  is an N-containing 5- to 10-membered heterocycloalkyl, an N-containing 5- to 10-membered heteroaryl, or phenyl, wherein the heterocycloalkyl or heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 independently selected R 7 ; and the phenyl is optionally substituted with 1, 2, 3, 4, or 5 independently selected R 7a ; 
         R T1  and R T2  are each independently selected from the group consisting of H, C 1-3  alkyl, C 1-3  fluoroalkyl, cyclopropyl, fluorocyclopropyl, C 1-3  alkoxy, C 1-3  haloalkoxy, —C(═O)—O—(C 1-3  alkyl), and —C(═O)OH; 
         R 1  is selected from the group consisting of H, F, —C(═O)OH, —C(═O)—O—(C 1-3  alkyl), C 1-3  alkyl, C 1-3  fluoroalkyl, C 3-6  cycloalkyl, and C 3-6  fluorocycloalkyl, wherein said C 3-6  cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, and C 1-4  haloalkoxy; 
         R 2  is selected from the group consisting of H, halogen, —CN, —OH, C(═O)OH, C(═O)—O—(C 1-3  alkyl), C 1-3  alkoxy, C 1-3  haloalkoxy, —N(R 8 )(R 9 ), C 1-3  alkyl, C 1-3  fluoroalkyl, C 3-6  cycloalkyl, C 3-6  fluorocycloalkyl, C 2-6  alkenyl, and C 2-6  alkynyl, wherein said C 3-6  cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, and C 1-4  haloalkoxy; 
         R 3  and R 4  are each independently selected from the group consisting of H, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  alkoxy, C 1-6  haloalkoxy, —CN, C 3-6  cycloalkyl, —C(═O)OH, C(═O)—O—(C 1-4  alkyl), and halogen, wherein each of said C 1-6  alkyl and C 3-6  cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, —OH, —CN, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, and C 1-4  haloalkoxy; 
         R 5  and R 6  are each independently selected from the group consisting of H, halogen, —OH, —NO 2 , —CN, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  haloalkoxy, C 2-6  alkenyl, C 2-6  alkynyl, C 3-7  cycloalkyl, a 4- to 10-membered heterocycloalkyl, —N(R 8 )(R 9 ), —N(R 10 )(C(═O)R 11 ), —C(═O)—N(R 8 )(R 9 ), —C(═O)—R 12 , —C(═O)—OR 12 , and —OR 13 , wherein each of said C 1-6  alkyl, C 3-7  cycloalkyl, and heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —OH, C 1-3  alkyl, C 1-3  alkoxy, C 1-3  haloalkyl, C 1-3  haloalkoxy, C 3-6  cycloalkyl, —N(R 14 )(R 15 ), —N(R 16 )(C(═O)R 17 ), —C(═O)—OR 18 , —C(═O)H, —C(═O)R 18 , —C(═O)N(R 14 )(R 15 ), and —OR 19 ; 
         or R 5  and R 3  together with the two carbon atoms to which they are attached form a fused N-containing 5- or 6-membered heteroaryl, a fused N-containing 5- or 6-membered heterocycloalkyl, a fused 5- or 6-membered cycloalkyl, or a fused benzene ring, each optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, —CN, —OH, C 1-3  alkyl, C 1-3  alkoxy, C 1-3  haloalkyl, and C 1-3  haloalkoxy; 
         R 7  and R 7a  are each independently selected from the group consisting of halogen, —OH, —CN, —NO 2 , oxo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  hydroxylalkyl, C 1-6  alkoxy, C 1-6  haloalkoxy, C 3-7  cycloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 6-10  aryl, a 4- to 10-membered heterocycloalkyl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, —CH═N—O—(C 1-3  alkyl), —N(R 14 )(R 15 ), —N(R 16 )(C(═O)R 17 ), —S(═O) 2 N(R 14 )(R 15 ), —C(═O)N(R 14 )(R 15 ), —C(═O)—R 12 , —C(═O)—OR 18 , and —OR 19 , wherein each of said C 1-6  alkyl, C 3-7  cycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, heteroarylalkenyl, C 6- aryl, heterocycloalkyl and heteroaryl is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, OH, —CN, —NO 2 , C 1-4  alkyl, C 1-4  hydroxylalkyl, C 1-4  alkoxy, —N(R 14 )(R 15 ), —S—(C 1-3  alkyl), —S(═O) 2 —(C 1-4  alkyl), aryloxy, arylalkyloxy optionally substituted with 1 or 2 C 1-4  alkyl, oxo, —C(═O)H, —C(═O)—C 1-4  alkyl, —C(═O)O—C 1-4  alkyl, —C(═O)NH 2 , —NHC(═O)H, —NHC(═O)—(C 1-4  alkyl), C 3-7  cycloalkyl, a 5- or 6-membered heteroaryl, C 1-4  haloalkyl, and C 1-4  haloalkoxy; 
         or two adjacent R 7a  together with the two carbon atoms to which they are attached form a fused 5- or 6-membered cycloalkyl, a fused 5- or 6-membered heterocycloalkyl, or a fused benzene ring, each optionally substituted with 1, 2, 3, or 4 R 7b , wherein each R 7b  is independently selected from the group consisting of halo, —CN, —NO 2 , —NH 2 , —NH(C 1-4  alkyl), —N(C 1-4  alkyl) 2 , azetidin-1-yl, pyrrolidin-1-yl, pyridin-1-yl, OH, oxo, C 1-4  alkyl, C 1-4  alkoxy, C 1-4  hydroxylalkyl, C 1-4  haloalkyl, and C 1-4  haloalkoxy; 
         R 8  and R 9  are each independently selected from the group consisting of H, C 1-6  alkyl, C 1-6  haloalkyl, C 3-10  cycloalkyl, a 4- to 10-membered heterocycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said C 1-6  alkyl, C 3-10  cycloalkyl, 4- to 10-membered heterocycloalkyl, cycloalkylalkyl, arylalkyl, and heteroarylalkyl is optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of —OH, —CN, C 1-3  alkyl, C 3-7  cycloalkyl, C 1-3  hydroxylalkyl, —S—C 1-3  alkyl, —C(═O)H, —C(═O)—C 1-3  alkyl, —C(═O)—O—C 1-3  alkyl, —C(═O)—NH 2 , —C(═O)—N(C 1-3  alkyl) 2 , C 1-3  haloalkyl, C 1-3  alkoxy, and C 1-3  haloalkoxy; 
         or R 8  and R 9  together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or heteroaryl optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —OH, oxo, —C(═O)H, —C(═O)OH, —C(═O)—C 1-3  alkyl, —C(═O)—NH 2 , —C(═O)—N(C 1-3  alkyl) 2 , —CN, C 1-3  alkyl, C 1-3  alkoxy, C 1-3  hydroxylalkyl, C 1-3  haloalkyl, and C 1-3  haloalkoxy; 
         R 10  is selected from the group consisting of H, C 1-3  alkyl, and C 3-7  cycloalkyl; 
         R 11  is selected from the group consisting of C 1-6  alkyl, C 3-7  cycloalkyl, a 4- to 14-membered heterocycloalkyl, C 6-10  aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF 3 , —CN, —OH, oxo, —S—C 1-3  alkyl, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-7  cycloalkyl, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
         R 12  is H or is selected from the group consisting of C 1-10  alkyl, C 3-7  cycloalkyl, a 4- to 14-membered heterocycloalkyl, C 6-10  aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF 3 , —CN, —OH, —C(═O)OH, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-7  cycloalkyl, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
         R 13  is selected from the group consisting of C 1-10  alkyl, C 1-6  haloalkyl, C 3-7  cycloalkyl, a 4- to 14-membered heterocycloalkyl, C 6-10  aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally substituted with 1, 2, 3, or 4 substituents each independently selected from the group consisting of halogen, —N(R 14 )(R 15 ), —C(═O)N(R 14 )(R 15 ), —N(R 16 )(C(═O)R 17 ), —C(═O)H, —C(═O)N(R 16 )(OR 18 ), —C(═O)—R 18 , —C(═O)—OR 18 , —O—C(═O)R 18 , —CF 3 , —CN, —OH, —O—(C 1-6  hydroxylalkyl), C 1-6  alkyl, oxo, C 1-6  hydroxylalkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-7  cycloalkyl, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
         R 14  and R 15  are each independently selected from the group consisting of H, C 1-6  alkyl, C 2-6  alkenyl, C 3-10  cycloalkyl, a 4- to 14-membered heterocycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, wherein each of said C 1-6  alkyl, C 3-7  cycloalkyl, cycloalkylalkyl, arylalkyl, and heteroarylalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of —OH, —CN, oxo, —NHC(═O)—(C 1-3  alkyl), —C(═O)N(C 1-3  alkyl) 2 , —O—(C 1-6  hydroxylalkyl), —S(═O) 2 —C 1-3  alkyl, —S—C 1-3  alkyl, C 1-3  alkyl, C 3-7  cycloalkyl, C 1-3  hydroxylalkyl, a 5- to 10-membered heteroaryl, C 1-3  alkoxy, C 1-3  haloalkyl, and C 1-3  haloalkoxy; 
         or R 14  and R 15  together with the N atom to which they are attached form a 4- to 10-membered heterocycloalkyl or 5- to 10-membered heteroaryl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, oxo, —OH, C 1-3  alkyl, C 1-3  alkoxy, C 1-3  haloalkyl, C 1-3  haloalkoxy, C 1-3  hydroxylalkyl, C 2-4  alkoxyalkyl, oxo, a 5- to 6-membered heteroaryl, —NH 2 , —N(C 1-3  alkyl) 2 , —S(═O) 2 —C 1-3  alkyl, —S—C 1-3  alkyl, —C(═O)H, —C(═O)OH, —C(═O)NH 2 , and —C(═O)—C 1-3  alkyl; 
         R 16  is selected from the group consisting of H, C 1-3  alkyl, and C 3-7  cycloalkyl; 
         R 17  is selected from the group consisting of C 1-6  alkyl, C 3-7  cycloalkyl, a 4- to 14-membered heterocycloalkyl, C 6-10  aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF 3 , —CN, —OH, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-7  cycloalkyl, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
         R 18  is H or is selected from the group consisting of C 1-6  alkyl, C 3-7  cycloalkyl, a 4- to 14-membered heterocycloalkyl, C 6-10  aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CF 3 , —CN, —OH, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-7  cycloalkyl, C 1-6  alkoxy, and C 1-6  haloalkoxy; 
         R 19  is selected from the group consisting of C 1-6  alkyl, C 1-6  haloalkyl, C 3-7  cycloalkyl, a 4- to 14-membered heterocycloalkyl, C 6-10  aryl, a 5- to 10-membered heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —N(R 14 )(R 15 ), —C(═O)N(R 14 )(R 15 ), —N(R 16 )(C(═O)R 17 ), —C(═O)—R 18 , —C(═O)—OR 18 , —CF 3 , —CN, —OH, C 1-6  alkyl, C 1-6  haloalkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-7  cycloalkyl, C 1-6  alkoxy, and C 1-6  haloalkoxy; and 
         R N  is selected from the group consisting of H, C 1-6  alkyl, C 3-6  cycloalkyl, C 3-6  fluorocycloalkyl, heteroarylalkyl, and arylalkyl, wherein each of said C 3-6  cycloalkyl, heteroarylalkyl, and arylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halo, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, and C 1-4  haloalkoxy. 
       
     
     
         2 . The compound of  claim 1 , or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein Y 1  is O. 
     
     
         3 . The compound of  claim 1 , or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein X 1  is O. 
     
     
         4 . The compound of  claim 1 , or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein Q 1  is selected from quinolinyl, isoquinolinyl, 1H-imidazo[4,5-c]pyridinyl, imidazo[1,2-a]pyridinyl, 1H-pyrrolo[3,2-c]pyridinyl, imidazo[1,2-a]pyrazinyl, imidazo[2,1-c][1,2,4]triazinyl, imidazo[1,5-a]pyrazinyl, imidazo[1,2-a]pyrimidinyl, 1H-indazolyl, 9H-purinyl, pyrimidinyl, pyrazinyl, pyridinyl, pyridazinyl, 1H-pyrazolyl, 1H-pyrrolyl, 4H-pyrazolyl, 4H-imidazolyl, imidazo[1,2-a]pyrimidinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, 1H-imidazolyl, 3-oxo-2H-pyridazinyl, 1H-2-oxo-pyrimidinyl, 1H-2-oxo-pyridinyl, 2,4(1H,3H)-dioxo-pyrimidinyl, and 1H-2-oxo-pyrazinyl, each optionally substituted with 1, 2, 3, or 4 independently selected R 7 . 
     
     
         5 . The compound of  claim 1 , or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein Q 1  is selected from: 
       
         
           
           
               
               
           
         
       
       and
 each m is independently 0, 1, 2, or 3. 
 
     
     
         6 . The compound of  claim 1 , or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein R T1  and R T2  are both H; R 1  is H; and R 2  is H, —CN, Br, C 1-3  alkyl, or cyclopropyl. 
     
     
         7 . The compound of  claim 1 , or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein R 3  and R 4  are each independently selected from the group consisting of H, F, Cl, and C 1-3  alkyl. 
     
     
         8 . The compound of  claim 1 , or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein one of R 5  and R 6  is H; and the other of R 5  and R 6  is selected from the group consisting of H, —OH, —CN, Cl, F, methyl, ethyl, CF 3 , CH 2 F, and —OCH 3 . 
     
     
         9 . The compound of  claim 1 , or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein each of R 7  and R 7a  is independently selected from the group consisting of C 1-4  alkyl, C 1-4  fluoroalkyl, oxo, —OH, C 1-4  alkoxy, and C 1-4  haloalkoxy; wherein the C 1-4  alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents each independently selected from halogen, OH, C 1-4  alkoxy, —NH 2 , —NH(C 1-4  alkyl), —N(C 1-4  alkyl) 2 , azetidin-1-yl, pyrrolidin-1-yl, and pyridin-1-yl. 
     
     
         10 . A compound of  claim 1  selected from:
 4-[4-(4,6-dimethylpyrimidin-5-yl)-3-methylphenoxy]furo[3,2-c]pyridine; 
 2-(4,6-dimethylpyrimidin-5-yl)-5-(furo[3,2-c]pyridin-4-yloxy)benzonitrile; 
 5-[2-fluoro-4-(furo[3,2-c]pyridin-4-yloxy)phenyl]-4,6-dimethylpyridazin-3(2H)-one; 
 5-[4-(furo[3,2-c]pyridin-4-yloxy)phenyl]-4,6-dimethylpyridazin-3(2H)-one; 
 (+)-5-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-4,6-dimethylpyridazin-3(2H)-one; 
 (−)-5-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-4,6-dimethylpyridazin-3(2H)-one; 
 5-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-4,6-dimethylpyridazin-3(2H)-one; 
 (+)-5-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-6-methylimidazo[1,2-a]pyrazine; 
 (−)-5-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-6-methylimidazo[1,2-a]pyrazine; 
 5-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-6-methylimidazo[1,2-a]pyrazine; 
 4-[4-(4,6-dimethylpyrimidin-5-yl)-3-fluorophenoxy]furo[3,2-c]pyridine; 
 4-[4-(4,6-dimethylpyrimidin-5-yl)phenoxy]furo[3,2-c]pyridine; 
 (−)-6-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-1,5-dimethylpyrazin-2(1H)-one; 
 (+)-6-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-1,5-dimethylpyrazin-2(1H)-one; 
 6-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-1,5-dimethylpyrazin-2(1H)-one; 
 6-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-1,5-dimethylpyrimidin-2(1H)-one; 
 4-[4-(4,6-dimethylpyrimidin-5-yl)-2-fluorophenoxy]furo[3,2-c]pyridine; 
 5-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-2,4,6-trimethylpyridazin-3(2H)-one; 
 5-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-4-methylpyridazin-3(2H)-one; 
 (+)-4-[4-(3,5-dimethylpyridazin-4-yl)-3-methylphenoxy]furo[3,2-c]pyridine; 
 (−)-4-[4-(3,5-dimethylpyridazin-4-yl)-3-methylphenoxy]furo[3,2-c]pyridine; 
 4-[4-(3,5-dimethylpyridazin-4-yl)-3-methylphenoxy]furo[3,2-c]pyridine; 
 4-[4-(3,5-dimethyl-6-oxo-1,6-dihydropyridazin-4-yl)phenoxy]furo[3,2-c]pyridine-3-carbonitrile; 
 (−)-4-[4-(3,5-dimethylpyridazin-4-yl)-3-methoxyphenoxy]furo[3,2-c]pyridine; 
 (+)-4-[4-(3,5-dimethylpyridazin-4-yl)-3-methoxyphenoxy]furo[3,2-c]pyridine; 
 4-[4-(3,5-dimethylpyridazin-4-yl)-3-methoxyphenoxy]furo[3,2-c]pyridine; 
 6-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-1,5-dimethylpyrimidine-2,4(1H,3H)-dione; 
 (−)-6-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-1,5-dimethylpyrimidine-2,4(1H,3H)-dione; 
 (+)-6-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-1,5-dimethylpyrimidine-2,4(1H,3H)-dione; and 
 6-[4-(furo[3,2-c]pyridin-4-yloxy)phenyl]-1,5-dimethylpyrimidine-2,4(1H,3H)-dione, 
 or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide. 
 
     
     
         11 . A pharmaceutical composition comprising a compound according to  claim 1  or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, and a pharmaceutically acceptable carrier. 
     
     
         12 . A method for treating a disorder in a human, which method comprises administering to said human a therapeutically effective amount of a compound according to  claim 1  or an N-oxide thereof or a pharmaceutically acceptable salt of said compound or said N-oxide, wherein the disorder is selected from schizophrenia, cognitive impairment, attention deficit hyperactivity disorder (ADHD), impulsivity, compulsive gambling, overeating, autism spectrum disorder, mild cognitive impairment (MCI), age-related cognitive decline, dementia, restless leg syndrome (RLS), Parkinson's disease, Huntington's chorea, anxiety, depression, major depressive disorder (MDD), treatment-resistant depression (TRD), bipolar disorder, chronic apathy, anhedonia, chronic fatigue, post-traumatic stress disorder, seasonal affective disorder, social anxiety disorder, post-partum depression, serotonin syndrome, substance abuse and drug dependence, drug abuse relapse, Tourette's syndrome, tardive dyskinesia, drowsiness, excessive daytime sleepiness, cachexia, inattention, a movement disorder, a therapy-induced movement disorder, migraine, systemic lupus erythematosus (SLE), hyperglycemia, atherosclerosis, dislipidemia, obesity, diabetes, sepsis, post-ischemic tubular necrosis, renal failure, hyponatremia, resistant edema, narcolepsy, hypertension, congestive heart failure, postoperative ocular hypotonia, sleep disorders, and pain.