Substituted 1,3-Benzothiazol-2(3H)-Ones and [1,3]Thiazolo[5,4-B]Pyridin-2(IH)-Ones as Positive Allosteric Modulators of MGLUR2

Abstract

The present invention is directed to benzothiazol-one and thiazolo pyridine-one derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

1 . A compound according to Formula I 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is selected from the group consisting of:
 (1) C 1-8 alkyl, 
 (2) (CHR) p C 5-10 heterocyclyl, 
 (3) (CHR) p C 6-10 aryl, 
 (4) (CHR) p C 3-6 cycloalkyl, said alkyl, heterocyclyl, aryl, and cycloalkyl, optionally substituted with 1 to 3 groups of le; 
 
 X represents —CR b —, or —N—; 
 each R 2  is independently selected from the group consisting of: hydrogen, halo, OH, C 1-4 alkyl, C 1-4 alkoxy, CF 3  and —CN; 
 R 3  is selected from the group consisting of: C(O)R, C 6-10  aryl and C 5-10  heterocyclyl, OC 6-10  aryl, OC 5-10  heterocyclyl wherein said aryl and heterocyclyl are optionally substituted with 1 to 3 substituents R a ; 
 each R a  is independently selected from the group consisting of:
 (1) halo, 
 (2) C 1-8 alkyl, 
 (3) C 2-6 alkenyl, 
 (4) C 2-6 alkynyl, 
 (5) C 3-6 cycloalkyl, 
 (6) C 1-6 alkoxy, 
 (7) C 3-6 cycloalkoxy, 
 (8) —CN, 
 (9) —OH, 
 (10) —C(O)—O—R, 
 (11) —C(O)—C 1-6 alkyl, 
 (12) —N(R) 2 , 
 (13) —C(O)—N(R) 2 , 
 (14) —S(O) k —C 1-6 alkyl, wherein k is 0, 1 or 2, 
 (15) —(CH 2 ) p C 6-10 aryl, 
 (16) —(CH 2 ) p C 5-10 heterocyclyl, 
 (17) CF 3 , 
 (18) —C(O)-aryl, 
 (19) —N(R)-aryl, 
 (20) benzyl, 
 (21) benzyloxy, 
 (22) phenoxy, 
 (23) —C(CH 3 ) 2 OR, 
 (24) —SH, 
 (25) —SO 2 N(R)R, 
 (26) —(CH 2 ) p N(R)C(O)N(R)R, 
 (27) —(CH 2 ) p N(R)C(O)C 1-6 alkyl, 
 (28) —(CH 2 ) p N(R)SO 2 N(R)R, and 
 (29) —B(OH) 2 , 
 (30) —OR, 
 (31) —(CH 2 ) p NHC(O)OC 1-6 alkyl, 
 (32) —OC 5-10 heterocyclyl, 
 
 wherein groups (2) to (7), (11), (14) to (16), (18) to (23), and (32) above are optionally substituted with one up to the maximum number of substitutable positions of one or more substituents independently selected from the group consisting of: OH, CN, halo, carboxy, —C(O)—O—C 1-4 alkyl, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino, phenyl and C 5-10  heterocycle, 
 R is selected from the group consisting of: H, (CH 2 ) p C 6-10 aryl and C 1-6 alkyl; 
 R b  and R k  independently represent H or halo; 
 p represents 0-4; 
 and pharmaceutically acceptable salts thereof. 
 
     
     
         2 . The compound according to  claim 1  wherein R 1  is (CHR) p C 3-6 cycloalkyl, —(CH 2 ) p piperidinyl, (CH 2 ) p phenyl, and C 1-6  alkyl, said cycloalkyl, piperidinyl, phenyl and alkyl optionally substituted with 1 to 3 groups of R a . 
     
     
         3 . The compound according to  claim 2  wherein R 1  is optionally substituted (CHR) p C 3-6 cycloalkyl. 
     
     
         4 . The compound according to  claim 3  wherein R 1  is —(CH 2 )pcyclopropyl, said cyclopropyl optionally substituted with 0-2 groups of halo. 
     
     
         5 . The compound according to  claim 2  wherein R 1  is optionally substituted C 1-6  alkyl. 
     
     
         6 . The compound according to  claim 1  wherein R a  is selected from the group consisting of halo, C 1-8 alkyl, C 3-6 cycloalkyl, —OC 5-10 heterocyclyl, C 1-6 alkoxy, C 3-6 cycloalkoxy, —CN, —OH, —C(O)—C 1-6 alkyl, —(CH 2 ) p C 6-10 aryl, —(CH 2 ) p C 5-10 heterocyclyl, CF 3 , —C(O)-aryl, and —(CH 2 ) p NHC(O)OC 1-6 alkyl, said alkyl, aryl and heterocyclyl optionally substituted with 1 to 3 groups of OH, CN, halo, carboxy, —C(O)—O—C 1-4 alkyl, C 1-4 alkyl, C 1-4 -alkoxy, C 1-4 alkylamino, phenyl and C 5-10  heterocycle. 
     
     
         7 . The compound according to  claim 1  wherein R 3  is C 6-10  aryl, C 5-10  heterocyclyl, OC 6-10  aryl or OC 5-10  heterocyclyl optionally substituted with 1 to 3 substituents R a . 
     
     
         8 . The compound according to  claim 7  wherein R 3  is selected from the group consisting of phenyl, pyridyl, benzfuranyl, pyrazinyl, pyrimidinyl, O-phenyl, or O-pyridyl all of which optionally substituted with 1 to 3 groups of R a . 
     
     
         9 . The compound according to  claim 8  wherein R 3  is optionally substituted phenyl or O-phenyl. 
     
     
         10 . The compound according to  claim 8  wherein R 3  is optionally substituted pyridyl or O-pyridyl. 
     
     
         11 . The compound according to  claim 1  represented by Formula Ia 
       
         
           
           
               
               
           
         
       
       wherein X is —CH— or R 1  is selected from —(CH 2 ) p cyclopropyl, —(CH 2 ) p cyclopentyl, —(CH 2 ) p cyclohexyl, —(CH 2 ) p piperidinyl, (CH 2 ) p phenyl, and C 1-6  alkyl, said cyclopropyl, cyclopentyl, cyclohexyl, piperidinyl, phenyl, and alkyl optionally substituted with 1-3 halo, C 1-6  alkyl, CF 3 , —C(O)OC 1-6  alkyl, pyrimidinyl, 2,2-dimethylpropyl and 4,4,4-trifluorobutyl; R a  is selected from the group consisting of CN, halo, OR, CF 3 , —C(CH 3 ) 2 OR, C 1-6  alkyl, (CH 7 ) p morpholinyl, (CH 2 ) p dioxidomorpholinyl, and (CH 2 ) p NHC(O)OC(CH 3 ) 3  and pharmaceutically acceptable salts thereof. 
     
     
         12 . The compound according to  claim 1  represented by Formula Ib 
       
         
           
           
               
               
           
         
       
       wherein X is —CH— or —N, A is pyridyl and R 1  is selected from —(CH 2 ) p cyclopropyl, —(CH 2 ) p cyclopentyl, —(CH 2 ) p cyclohexyl, —(CH 2 ) p piperidinyl, (CH 2 ) p phenyl, and C 1-6  alkyl, said cyclopropyl, cyclopentyl, cyclohexyl, piperidinyl, phenyl, and alkyl optionally substituted with 1-3 halo, C 1-6  alkyl, CF 3 , —C(O)OC 1-6  alkyl, pyrimidinyl, 2,2-dimethylpropyl and 4,4,4-trifluorobutyl; and R a  is selected from the group consisting of CN, halo, OR, CF 3 , —C(CH 3 ) 2 OR, C1-6 alkyl, (CH 2 ) p morpholinyl, (CH 2 ) p dioxidomorpholinyl, and (CH 2 ) p NHC(O)OC(CH 3 ) 3  and pharmaceutically acceptable salts thereof. 
     
     
         13 . The compound according to  claim 1  represented by Formula Ic 
       
         
           
           
               
               
           
         
       
       wherein X is —CH— or —N, A is O-phenyl or O-pyridyl and R 1  is selected from —(CH 2 ) p cyclopropyl, —(CH 2 ) p cyclopentyl, —(CH 2 ) p cyclohexyl, —(CH 2 ) p piperidinyl, (CH 2 ) p phenyl, and C 1-6  alkyl, said cyclopropyl, cyclopentyl, cyclohexyl, piperidinyl, phenyl, and alkyl optionally substituted with 1-3 halo, C 1-6  alkyl, CF 3 , —C(O)OC 1-6  alkyl, pyrimidinyl, 2,2-dimethylpropyl and 4,4,4-trifluorobutyl; R a  is selected from the group consisting of CN, halo, OR, CF 3 , —C(CH 3 ) 2 OR, C 1-6  alkyl, (CH 2 ) p morpholinyl, (CH 2 ) p dioxidomorpholinyl, and (CH 2 ) p NHC(O)OC(CH 3 ) 3  and pharmaceutically acceptable salts thereof. 
     
     
         14 . A compound which is:
 2-(1-{[2,2-difluorocyclopropyl]methyl}-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl)benzonitrile,   1-{[2,2-difluorocyclopropyl]methyl}-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one,   1-{[2,2-difluorocyclopropyl]methyl}-5-(2-methylphenyl)[1,3]thiazolo[5,4-b]pyridin-2(1H)-one,   3-(1-{[2,2-difluorocyclopropyl]methyl}-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl)pyridine-4-carbonitrile,   2-(1-{[2,2-difluorocyclopropyl]methyl}-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl)-5-fluorobenzonitrile,   1-[(2,2-difluorocyclopropyl)methyl]-5-phenyl[1,3]thiazolo[5,4-b]pyridin-2(1H)-one,   5-{5-[(4-acetylpiperazin-1-yl)methyl]-2-methyl phenyl}-1-[(2,2-difluorocyclopropyl)methyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one,   1-{[2,2-difluorocyclopropyl]methyl}-5-[5-(1-hydroxy-1-methylethyl)-2-methylphenyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one,   2-[1-(2,2-dimethylpropyl)-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl]benzonitrile,   1-(2,2-dimethylpropyl)-5-[5-(1-hydroxy-1-methylethyl)-2-methylphenyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one,   1-(2,2-dimethylpropyl)-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl][1,3]thiazolo[5,4-b]pyridin-2(1H)-one,   2-[1-(cyclopropylmethyl)-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl]benzonitrile,   1-(cyclopropylmethyl)-5-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl][1,3]thiazolo[5,4-b]pyridine-2(1H)-one,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)benzonitrile,   3-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)pyridine-4-carbonitrile,   3-{[2,2-difluorocyclopropyl]methyl}-6-(2,3-dihydro-1-benzofuran-5-yl)-1,3-benzothiazol-2(3H)-one,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-6-methylpyridine-3-carbonitrile,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)pyridine-3-carbonitrile,   3-{[2,2-difluorocyclopropyl]methyl}-6-(2-fluoro-5-methylpyridin-3-yl)-1,3-benzothiazol-2(3H)-one,   3-{[2,2-difluorocyclopropyl]methyl}-6-[3-(1-hydroxy-1-methylethyl)phenyl]-1,3-benzothiazol-2(3H)-one,   3-{[2,2-difluorocyclopropyl]methyl}-6-[4-(1,1-dioxidothiomorpholin-4-yl)phenyl]-1,3-benzothiazol-2(3H)-one,   3-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-4-fluorobenzonitrile,   4-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)pyridine-3-carbonitrile,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-5-fluorobenzonitrile,   2-(3-{[2,2-difluoroeyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-6-fluorobenzonitrile,   tert-butyl[3-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)benzyl]carbamate,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-3-fluorobenzonitrile,   3-{[2,2-difluorocyclopropyl]methyl}-6-[3-(morpholin-4-ylmethyl)phenyl]-1,3-benzothiazol-2(3H)-one,   3-{[2,2-difluorocyclopropyl]methyl}-6-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-1,3-benzothiazol-2(3H)-one,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-3,4-difluorobenzonitrile,   3-{[2,2-difluorocyclopropyl]methyl}-difluorophenyl)-1,3-benzothiazol-2(3H)-one,   3-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)pyrazine-2-carbonitrile,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-4-fluorobenzonitrile,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-4-(morpholin-4-ylmethyl)benzonitrile,   3-{[2,2-difluorocyclopropyl]methyl}-difluorophenyl)-1,3-benzothiazol-2(3H)-one,   3-{[2,2-difluorocyclopropyl]methyl}-6-(2,6-difluorophenyl)-1,3-benzothiazol-2(3H)-one,   3-{[2,2-difluorocyclopropyl]methyl}-6-(2-fluorophenyl)-1,3-benzothiazol-2(3H)-one,   3-{[2,2-difluorocyclopropyl]methyl}-6-(2,4-difluorophenyl)-1,3-benzothiazol-2(3H)-one,   2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-3,6-difluorobenzonitrile,   3-{[2,2-difluorocyclopropyl]methyl}-6-[5-(1-hydroxy-1-methylethyl)-2-methylphenyl]-1,3-benzothiazol-2(3H)-one,   2-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   3-(cyclopropylmethyl)-6-phenyl-1,3-benzothiazol-2(3H)-one,   3-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   3-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]pyridine-4-carbonitrile,   2-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]-5-fluorobenzonitrile,   2-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]-3-methoxybenzonitrile,   2-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]-6-methoxybenzonitrile,   3-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]-4-fluorobenzonitrile,   3-(cyclopropylmethyl)-6-(2-fluorophenyl)-1,3-benzothiazol-2(3H)-one,   2-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]-5-(trifluoromethyl)benzonitrile,   2-[3-(cyclopropylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]-6-(trifluoromethyl)benzonitrile,   3-(cyclopropylmethyl)-6-(2,5-difluorophenyl)-1,3-benzothiazol-2(3H)-one,   3-(cyclopropylmethyl)-6-(2-methoxyphenyl)-1,3-benzothiazol-2(3)-one,   3-(cyclopropylmethyl)-6-(2-methylphenyl)-1,3-benzothiazol-2(3H)-one,   3-(cyclopropylmethyl)-6-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-1,3-benzothiazol-2(3H)-one,   2-[3-(2,2-dimethylpropyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   3-(2,2-dimethylpropyl)-6-phenyl-1,3-benzothiazol-2(3H)-one,   3-[3-(2,2-dimethylpropyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   3-(2,2-dimethylpropyl)-6-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-1,3-benzothiazol-2(3H)-one,   3-butyl-6-phenyl-1,3-benzothiazol-2(3H)-one,   3-(cyclopentylmethyl)-6-phenyl-1,3-benzothiazol-2(3H)-one,   2-(2-oxo-3-propyl-2,3-dihydro-1,3-benzothiazol-6-yl)benzonitrile,   2-[2-oxo-3-(3,3,3-trifluoropropyl)-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-(3-butyl-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)benzonitrile,   2-(2-oxo-3-pentyl-2,3-dihydro-1,3-benzothiazol-6-yl)benzonitrile,   2-(3-hexyl-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)benzonitrile,   2-[3-(2-methylpropyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-[2-oxo-3-(4,4,4-trifluorobutyl)-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-[3-(cyclobutylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-[3-(cyclopentylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-[3-(cyclohexylmethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-[3-(4-tert-butyl benzyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-{3-[2-fluoro-5-(trifluoromethyl)benzyl]-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl}benzonitrile,   2-[3-(4-bromo-2-fluorobenzyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   [3-(4-chloro-2-fluorobenzyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-[3-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-[3-(1-cyclopropylethyl)-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   2-{3-[1,2-dimethylpropyl]-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl}benzonitrile,   2-{3-[1-cyclopentylethyl]-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl}benzonitrile,   2-{3-[1-cyclohexylethyl]-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl}benzonitrile,   2-{3-[1-methylbutyl]-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl}benzonitrile,   2-{3-[(1-methylcyclopropyl)methyl]-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl}benzonitrile,   2-{2-oxo-3-[(1-pyrimidin-2-ylpiperidin-4-yl)methyl]-2,3-dihydro-1,3-benzothiazol-6-yl}benzonitrile,   2-[2-oxo-3-(piperidin-4-ylmethyl)-2,3-dihydro-1,3-benzothiazol-6-yl]benzonitrile,   Benzyl 4-{[6-(2-cyanophenyl)-2-oxo-1,3-benzothiazol-3(2H)-yl]methyl}piperidine-1-carboxylate,   2-(7-bronco-3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)benzonitrile,   7-bromo-3-{[2,2-difluorocyclopropyl]methyl}-6-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-1,3-benzothiazol-2(3H)-one,   2-{2-oxo-3-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1,3-benzothiazol-6-yl}benzonitrile,   4-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl}phenoxy)pyridine-2-carbonitrile,   4-(4-cyano-3-{1-[(2,2-difluorocyclopropyl)methyl]-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl}phenoxy)pyridine-2-carbonitrile,   2-({3-[(2,2-difluorocyclopropyl)methyl]-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl}oxy)nicotinonitrile,   3-{[2,2-difluorocyclopropyl]methyl}-6-[(3,5-difluoropyridin-2-yl)oxy]-1,3-benzothiazol-2(3H)-one,   3-{[2,2-difluorocyclopropyl]methyl}-6-[(5-methylpyridin-2-yl)oxy]-1,3-benzothiazol-2(3H)-one,   2-[(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)oxy]benzonitrile,   6-[(3-acetylpyridin-2-yl)oxy]-3-{[2,2-difluorocyclopropyl]methyl}-1,3-benzothiazol-2(3H)-one,   3-{[2,2-difluorocyclopropyl]methyl}-6-(pyridin-2-yloxy)-1,3-benzothiazol-2(3H)-one,   6-[(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)oxy]pyridine-3-carbonitrile,   2-[(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)oxy]pyridine-3-carbonitrile,   2-[(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)oxy]-3-fluorobenzonitrile,   3-[(2,2-difluorocyclopropyl)methyl]-6-{[3-(1-hydroxyethyl)pyridin-2-yl]oxy}-1,3-benzothiazol-2(3H)-one,   or a pharmaceutically acceptable salt thereof.   
     
     
         15 . The compound according to  claim 14  which is:
 2-(1-{[2,2-difluorocyclopropyl]methyl}-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl) benzonitrile; 
 2-[1-(2,2-dimethylpropyl)-2-oxo-1,2-dihydro[1,3]thiazolo[5,4-b]pyridin-5-yl]benzonitrile; 
 2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)benzonitrile; 
 3-[(2,2-difluorocyclopropyl)methyl]-6-{[3-(1-hydroxyethyl)pyridin-2-yl]oxy}-1,3-benzothiazol-2(3H)-one; 
 3-{[2,2-difluorocyclopropyl]methyl}-6-[3-(1,1-dioxidothiomorpholin-4-yl)phenyl]-1,3-benzothiazol-2(3H)-one; 
 2-(3-{[2,2-difluorocyclopropyl]methyl}-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)-4-(morpholin-4-ylmethyl)benzonitrile; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         16 . A pharmaceutical composition comprising a compound according to  claim 1  in combination with a pharmaceutically acceptable carrier. 
     
     
         17 . A method for treating a neurological or psychiatric disorder associated with glutamate dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         18 . The method according to  claim 17  wherein the neurological or psychiatric disorder associated with glutamate dysfunction is schizophrenia.