Heteroaryl substituted tetrazole modulators of metabotrophic glutamate receptor-5

1. A compound represented by Formula (I):

or a pharmaceutically acceptable salt thereof, wherein

X is phenyl and Y is 2-pyridyl

X is optionally substituted with 1-7 independent halogen, —CN, NO 2 , —C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —OR 1 , —NR 1 R 2 , —C(═NR 1 )NR 2 R 3 , —N(═NR 1 )NR 2 R 3 , —NR 1 COR 2 , —NR 1 CO 2 R 2 , —NR 1 SO 2 R 4 , —NR 1 CONR 2 R 3 , —SR 4 , —SOR 4 , —SO 2 R 4 , —SO 2 NR 1 R 1 R 2 , —COR 1 , —CO 2 R 1 , —CONR 1 R 2 , —C(═NR 1 )R 2 , or —C(═NOR 1 )R 2 substituents, wherein optionally two substituents are combined to form a cycloalkyl or heterocycloalkyl ring fused to X; wherein the —C 1-6 alkyl substituent, cycloalkyl ring, or heterocycloalkyl ring each optionally is further substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —O(heteroaryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), or —N(C 0-6 alkyl)(aryl) groups;

R 1 , R 2 , and R 3 each independently is —C 0-6 alkyl, —C 3-7 cycloalkyl, or aryl; any of which is optionally substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), —N(C 0-6 alkyl)(aryl) substituents;

R 4 is —C 1-6 alkyl, —C 3-7 cycloalkyl, or aryl; optionally substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), —N(C 0-6 alkyl)(aryl) substituents;

A is a bond;

Y is optionally substituted with 1-7 independent halogen, —CN, NO 2 , —C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —OR 5 , —NR 5 R 6 , —C(═NR 5 )NR 6 R 7 , —N(═NR 5 )NR 6 R 7 , —NR 5 COR 6 , —NR 5 CO 2 R 6 , —NR 5 SO 2 R 8 , —NR 5 CONR 6 R 7 , —SR 8 , —SOR 8 , —SO 2 R 8 , —SO 2 NR 5 R 6 , —COR 5 , —CO 2 R 5 , —CONR 5 R 6 , —C(═NR 5 )R 6 , or —C(═NOR 5 )R 6 substituents, wherein optionally two substituents are combined to form a cycloalkyl or heterocycloalkyl ring fused to Y; wherein the —C 1-6 alkyl substituent, cycloalkyl ring, or heterocycloalkyl ring each optionally is further substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(CO 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —O(heteroaryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), or —N(C 0-6 alkyl)(aryl) groups;

R 5 , R 6 , and R 7 each independently is C 0-6 alkyl, —C 3-7 cycloalkyl, or aryl; any of which is optionally substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), —N(C 0-6 alkyl)(aryl) substituents;

R 8 is —C 1-6 alkyl, —C 3-7 cycloalkyl, or aryl; optionally substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), —N(C 0-6 alkyl)(aryl) substituents;

B is a bond;

R 9 and R 10 each independently is —C 0-6 alkyl, C 3-7 cycloalkyl, or aryl; any of which is optionally substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), —N(C 0-6 alkyl)(aryl) substituents; and any N is optionally an N-oxide.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof wherein

Y is 2-pyridyl optionally substituted with 1-4 independent halogen, —CN, NO 2 , —C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —OR 5 , —NR 5 R 6 , —C(═NR 5 )NR 6 R 7 , —N(═NR 5 )NR 6 R 7 , —NR 5 COR 6 , —NR 5 CO 2 R 6 , —NR 5 SO 2 R 8 , —NR 5 CONR 6 R 7 —SR 8 , —SOR 8 , —SO 2 R 8 , —SO 2 NR 5 R 6 , —COR 5 , —CO 2 R 5 , —CONR 5 R 6 , —C(═NR 5 )R 6 , or —C(═NOR 5 )R 6 substituents, wherein optionally two substituents are combined to form a cycloalkyl or heterocycloalkyl ring fused to Y; wherein the —C 1-6 alkyl substituent, cycloalkyl ring, or heterocycloalkyl ring each optionally is further substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), or —N(C 0-6 alkyl)(aryl) groups.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof wherein

X is phenyl optionally substituted with 1-5 independent halogen, —CN, NO 2 , —C 1-6 alkyl, —OR 1 , —NR 1 R 2 , —C(═NR 1 )NR 2 R 3 , —N(═NR 1 )NR 2 R 3 , —NR 1 COR 2 , —NR 1 CO 2 R 2 , —NR 1 SO 2 R 4 , —NR 1 CONR 2 R 3 , —SR 4 , —SOR 4 , —SO 2 R 4 , —SO 2 NR 1 R 2 , —COR 1 , —CO 2 R 1 , —CONR 1 R 2 , —C(═NR 1 )R 2 , or —C(═NOR 1 )R 2 substituents, wherein optionally two substituents are combined to form a cycloalkyl or heterocycloalkyl ring fused to X; wherein the —C 1-6 alkyl substituent, cycloalkyl ring, or heterocycloalkyl ring each optionally is further substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), or —N(C 0-6 alkyl)(aryl) groups.

4. The compound according to claim 3 , or a pharmaceutically acceptable salt thereof, wherein

Y is 2-pyridyl optionally substituted with 1-4 independent halogen, —CN, NO 2 , —C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —OR 5 , —NR 5 R 6 , —C(═NR 5 )NR 6 R 7 , —N(═NR 5 )NR 6 R 7 , —NR 5 COR 6 , —NR 5 CO 2 R 6 , —NR 5 SO 2 R 8 , —NR 5 CONR 6 R 7 , —SR 8 , —SOR 8 , —SO 2 R 8 , —SO 2 NR 5 R 6 , —COR 5 , —CO 2 R 5 , —CONR 5 R 6 , —C(═NR 5 )R 6 , or —C(═NOR 5 )R 6 substituents, wherein optionally two substituents are combined to form a cycloalkyl or heterocycloalkyl ring fused to Y; wherein the —C 1-6 alkyl substituent, cycloalkyl ring, or heterocycloalkyl ring each optionally is further substituted with 1-5 independent halogen, —CN, —C 1-6 alkyl, —O(C 0-6 alkyl), —O(C 3-7 cycloalkyl), —O(aryl), —N(C 0-6 alkyl)(C 0-6 alkyl), —N(C 0-6 alkyl)(C 3-7 cycloalkyl), or —N(C 0-6 alkyl)(aryl) groups.

5. The compound according to claim 1 , consisting of:

2-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]pyridine;

3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile;

2-[5-(3-bromophenyl)-2H-tetrazol-2-yl]pyridine;

2-[5-(3-chlorophenyl)-2H-tetrazol-2-yl]pyridine;

3-(2-pyridin-2-yl-2H-tetrazol-5-yl)benzonitrile;

2-[2-(3,5-difluorophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-methoxyphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-trifluoromethylphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-iodophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-bromophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-Methylmercaptophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(4-fluorophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-fluorophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(2-methoxyphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-ethylphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-methylphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3,5-dichlorophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(2-chlorophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(4-methoxyphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3,5-dimethylphenyl)-2H-tetrazol-5-yl]pyridine;

3-[5-(6-methylpyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile;

3-[5-(4-methylpyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile;

3-[5-(4-methylpyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile;

2-[2-(3-isopropylphenyl)-2H-tetrazol-5-yl]pyridine;

2-{2-[3-(trifluoromethoxy)phenyl]-2H-tetrazol-5-yl}pyridine;

2-[2-(3-ethoxyphenyl)-2H-tetrazol-5-yl]pyridine;

2-{2-[3-methoxy-5-(trifluoromethyl)phenyl]-2H-tetrazol-5-yl}pyridine;

3-[5-(5-methylpyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile;

3-[5-(3-methylpyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile;

2-[2-(3,4-dimethylphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3,4,5-trichlorophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(2,5-dichlorophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3,4-difluorophenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-chloro-4-methylphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(2,3-dichlorophenyl)-2H-tetrazol-5-yl]pyridine;

2-{2-[3-methyl-5-(trifluoromethyl)phenyl]-2H-tetrazol-5-yl}pyridine;

2-[2-(3-bromo-4-methylphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3-chloro-4-iodophenyl)-2H-tetrazol-5-yl]pyridine;

2-{2-[3-fluoro-5-(trifluoromethyl)phenyl]-2H-tetrazol-5-yl}pyridine;

2-[2-(2,3-dihydro-1 H-inden-5-yl)-2H-tetrazol-5-yl]pyridine;

2-[2-(1,3-dihydro-2-benzoftiran-5-yl)-2H-tetrazol-5-yl]pyridine;

2-[2-(4-methoxy-2-naphthyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(1 -naphthyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(3,5-dimethoxyphenyl)-2H-tetrazol-5-yl]pyridine;

2-[2-(4-phenoxyphenyl)-2H-tetrazol-5-yl]pyridine;

3-[5-(3-fluoro-pyridin-2-yl)-tetrazol-2-yl]-benzonitrile

3-[5-(1-methyl-1H-pyrazol-3-yl)-tetrazol-2-yl]-benzonitrile

3-[5-(5-hydroxy-pyridin-2-yl)-tetrazol-2-yl]-benzonitrile

3-[5-(5-bromo-pyridin-2-yl)-tetrazol-2-yl]-5-fluoro-benzonitrile

2-[2-(3-nitrophenyl)-2H-tetraazol-5-yl]pyridine

2-{2-[4-(allyloxy)-3-methoxyphenyl]-2H-tetraazol-5-yl}pyridine

2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenol

2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl ethylcarbamate

2-[2-(4-bromo-3-methoxyphenyl)-2H-tetraazol-5-yl]pyridine

[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenoxy]acetonitrile

2-bromo-5-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

3-(5-pyridin-2-yl-2H-tetraazol-2-yl)aniline

3-fluoro-5-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

2-{2-[3-bromo-5-(trifluoromethyl)phenyl]-2H-tetraazol-5-yl}pyridine

3-(5-pyridin-2-yl-2H-tetraazol-2-yl)-5-(trifluoromethyl)benzonitrile

3-nitro-5-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

3-amino-5-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

3-chloro-5-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

2-[2-(3-cyano-5-fluorophenyl)-2H-tetraazol-5-yl]-1-hydroxypyridinium

5-(5-pyridin-2-yl-2H-tetrazol-2-yl)isophthalonitrile

2-{5-[3-chloro-5-(pyridin-3-yloxy)phenyl]-2H-tetraazol-2-yl}pyridine

2-[5-(3-bromo-5-chlorophenyl)-2H-tetraazol-2-yl]pyridine

3-chloro-5-(2-pyridin-2-yl-2H-tetraazol-5-yl)benzonitrile

3-methyl-5-(2-pyridin-2-yl-2H-tetraazol-5-yl)benzonitrile

[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]methanol

[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]acetonitrile

N-methyl-3-(5-pyridin-2-yl-2H-tetraazol-2-yl)aniline

2-methoxy-N-[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]aniline

2-[2-(3-fluoro-5-iodophenyl)-2H-tetraazol-5-yl]pyridine

2-{[3-flouro-5-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenoxy]methyl}benzonitrile

4-chloro-2-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

2-[2-(2,4-dichlorophenyl)-2H-tetraazol-5-yl]pyridine

2-[2-(5-chloro-2-methoxyphenyl)-2H-tetraazol-5-yl]pyridine

3-[5-(5-methoxy-pyridin-2-yl)-tetrazol-2-yl]-benzonitrile

4-bromo-3-fluoro-5-[5-(3-fluoro-pyridin-2-yl)-tetrazol-2-yl]-benzonitrile

3-{3-[5-(4,5-dibromo-1H-imidazol-2-yl)-tetrazol-2-yl]-5-fluoro-phenoxy}-pyridine

N-phenyl-N-[4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]amine

N-phenyl-N-[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]amine

2-{2-[3-(3-methoxyphenoxy)phenyl]-2H-tetraazol-5-yl}pyridine

2-{2-[3-methoxy-4-(3H-1□ 5 ,2,3,4-tetraazol-1-ylmethyl)phenyl]-2H-tetraazol-5-yl}pyridine

2-[2-(4-bromo-3-fluorophenyl)-2H-tetraazol-5-yl]pyridine

2-{2-[3,5-bis(trifluoromethyl)phenyl]-2H-tetraazol-5-yl}pyridine

2-{2-[4-bromo-3-(trifluoromethyl)phenyl]-2H-tetraazol-5-yl}pyridine imethyl 5-(5-pyridin-2-yl-2H-tetrazol-2-yl)isophthalate

2-[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenoxy]ethylamine

2-[2-(2,6-dichlorophenyl)-2H-tetraazol-5-yl]pyridine

[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]acetic acid

2-[2-(3-iodo-4-methylphenyl)-2H-tetraazol-5-yl]pyridine

2-[2-(4-chloro-3-methylphenyl)-2H-tetraazol-5-yl]pyridine

2-[2-(1,3-benzodioxol-5-yl)-2H-tetraazol-5-yl]pyridine

2-{2-[2-chloro-5-(trifluoromethyl)phenyl]-2H-tetraazol-5-yl}pyridine

2-chloro-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

2-[2-(4-bromo-3-methylphenyl)-2H-tetraazol-5-yl]pyridine

2-[2-(3,4-dichlorophenyl)-2H-tetraazol-5-yl]pyridine

2-[2-(3-chloro-4-fluorophenyl)-2H-tetraazol-5-yl]pyridine

2-[2-(3-fluoro-4-methylphenyl)-2H-tetraazol-5-yl]pyridine

1-[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]ethanol

1-[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]ethanone

[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]methanol

2-[2-(3-phenoxyphenyl)-2H-tetraazol-5-yl]pyridine

2-{2-[3-(benzyloxy)phenyl]-2H-tetraazol-5-yl}pyridine

2-{2-[3-(methylsulfonyl)phenyl]-2H-tetraazol-5-yl}pyridine

N-[3-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]acetamide

2-[2-(3-isopropylphenyl)-2H-tetrazol-5-yl]pyridine

2-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

2-(2-phenyl-2H-tetraazol-5-yl)pyridine

[2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]acetonitrile

2-[2-(3-methoxy-4-methylphenyl)-2H-tetraazol-5-yl]pyridine

2-[2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]succinonitrile

2-[2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]propane-1,2,3-tricarbonitrile

2-[2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]propanenitrile

2-{cyano[2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)methyl}benzonitrile

2-{2-[4-(methylthio)phenyl]-2H-tetraazol-5-yl}pyridine

2 {2-[4-(trifluoromethoxy)phenyl]-2H-tetraazol-5-yl}pyridine

4-((5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

2-[2-(4-chlorophenyl)-2H-tetraazol-5-yl]pyridine

2-[2-(3,5-ditert-butylphenyl)-2H-tetraazol-5-yl]pyridine

2-fluoro-5-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

2-{2-[4-(bromomethyl)-3-methoxyphenyl]-2H-tetraazol-5-yl}pyridine

2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzoic acid

2-[2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]ethanamine

1-nitroso-6-(5-pyridin-2-yl-2H-tetraazol-2-yl)indoline

2-[2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)phenyl]propan-2-ol

2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzamide

2-methoxy-4-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

3-bromo-6-(5-pyridin-2-yl-2H-tetraazol-2-yl)-1H-indole

6-(5-pyridin-2-yl-2H-tetraazol-2-yl)-1H-indole

6-(5-pyridin-2-yl-2H-tetraazol-2-yl)-1H-indole-1-carbonitrile

6-(5-pyridin-2-yl-2H-tetraazol-2-yl)-1H-indole-3-carbonitrile

3-methoxy-5-(5-pyridin-2-yl-2H-tetraazol-2-yl)benzonitrile

3-[5-(1H-imidazol-2-yl)-2H-tetraazol-2-yl]-5-methylbenzonitrile

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising: a therapeutically effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.