Substituted 1,3-benzothiazol-2(3H)-ones and [1,3]thiazolo[5,4-B]pyridin-2(1H)-ones as positive allosteric modulators of mGluR2
View Patent ↗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 —(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, wherein each said cyclopropyl, cyclopentyl, cyclohexyl and alkyl is 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;
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 phenyl, pyridyl, —O-phenyl, and —O-pyridyl, wherein each said phenyl, pyridyl, —O-phenyl, and —O-pyridyl are optionally substituted with 1 to 3 R a groups;
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 )pC 6-10 aryl,
(16) —(CH 2 )pC 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 )pN(R)C(O)C 1-6 alkyl,
(28) —(CH 2 )pN(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 C5-10 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 0-1;
and pharmaceutically acceptable salts thereof.
2. The compound according to claim 1 wherein R 1 is —(CH 2 )pcyclopropyl, said cyclopropyl optionally substituted with 0-2 groups of halo.
3. The compound according to claim 1 wherein R 1 is optionally substituted C 1-6 alkyl.
4. 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 )pC 6-10 aryl, —(CH 2 )pC 5-10 heterocyclyl, CF 3 , —C(O)-aryl, and —(CH 2 )pNHC(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.
5. The compound according to claim 1 wherein R 3 is C6-10 aryl, C5-10 heterocyclyl, OC6- 10 aryl or OC 5-10 heterocyclyl optionally substituted with 1 to 3 substituents R a .
6. The compound according to claim 5 wherein R 3 is optionally substituted phenyl or O-phenyl.
7. The compound according to claim 5 wherein R 3 is optionally substituted pyridyl or O-pyridyl.
8. The compound according to claim 1 represented by Formula Ia
wherein X is —CH— or —N, 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.
9. 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.
10. 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, 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.
11. 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-difluorocyclopropyl]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}-6-(2,3-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}-6-(2,5-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(3H)-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-butylbenzyl)-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-bromo-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.
12. The compound according to claim 11 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.
13. A pharmaceutical composition comprising a compound according to claim 1 in combination with a pharmaceutically acceptable carrier.
14. A method for treating schizophrenia in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.