Tetrazole compounds and their use as metabotropic glutamate receptor antagonists

1. A compound according to formula I

wherein

X 3 and X 4 are selected from N and C, such that when X 3 is N, X 4 is C and when X 3 is C, X 4 is N;

P is selected from aryl and heteroaryl;

if m=1 then R 1 is attached to P via a carbon atom on ring P at the meta-position of the ring P relative to the attachment point of P at X 3 , and if m=2 then R 1 is attached to P via carbon atoms on ring P at the 2-, and 5-positions of the ring P;

R 1 is selected from the group consisting of hydroxy, halo, nitro, C 1-6 alkylhalo, OC 1-6 alkylhalo, C 1-6 alkyl, OC 1-6 alkyl, C 2-6 alkenyl, OC 2-6 alkenyl, C 2-6 alkynyl, OC 2-6 alkynyl, C 0-6 alkylC 3-6 cycloalkyl, OC 0-6 alkylC 3-6 cycloalkyl, C 0-6 alkylaryl, OC 0-6 alkylaryl, CHO, (CO)R 5 , O(CO)R 5 , O(CO)OR 5 , O(CNR 5 )OR 5 , C 1-6 alkylOR 5 , OC 2-6 alkylOR 5 , C 1-6 alkyl(CO)R 5 , OC 1-6 alkyl(CO)R 5 , C 0-6 alkylCO 2 R 5 , OC 1-6 alkylCO 2 R 5 , C 0-6 alkylcyano, OC 2-6 alkylcyano, C 0-6 alkylNR 5 R 6 , OC 2-6 alkylNR 5 R 6 , C 1-6 alkyl(CO)NR 5 R 6 , OC 1-6 alkyl(CO)NR 5 R 6 , C 0-6 alkylNR 5 (CO)R 6 , OC 2-6 alkylNR 5 (CO)R 6 , C 0-6 alkylNR 5 (CO)NR 5 R 6 , C 0-6 alkylSR 5 , OC 2-6 alkylSR 5 , C 0-6 alkyl(SO)R 5 , OC 2-6 alkyl(SO)R 5 , C 0-6 alkylSO 2 R 5 , OC 2-6 alkylSO 2 R 5 , C 0-6 alkyl(SO 2 )NR 5 R 6 , OC 2-6 alkyl(SO 2 )NR 5 R 6 , C 0-6 alkylNR 5 (SO 2 )R 6 , OC 2-6 alkylNR 5 (SO 2 )R 6 , C 0-6 alkylNR 5 (SO 2 )NR 5 R 6 , OC 2-6 alkylNR 5 (SO 2 )NR 5 R 6 , (CO)NR 5 R 6 , O(CO)NR 5 R 6 , NR 5 OR 6 , C 0-6 alkylNR 5 (CO)OR 6 , OC 2-6 alkylNR 5 (CO)OR 6 , SO 3 R 5 and a 5- or 6-membered ring containing one or more atoms independently selected from the group consisting of C, N, O and S;

X 1 is selected from the group consisting of C 2-3 alkyl, C 2-3 alkenyl, NR 3 , O, S, CR 3 R 4 , SO, SO 2

X 2 is selected from the group consisting of a bond, CR 3 R 4 , O, S, NR 3 , SO, SO 2

R 3 and R 4 are independently selected from a group consisting of hydrogen, hydroxy, C 1-6 alkyl, C 0-6 alkylcyano, oxo, ═NR 5 , ═NOR 5 , C 1-4 alkylhalo, halo, C 1-4 alkylC 3-7 cycloalkyl, C 3-7 cycloalkyl, O(CO)C 1-4 alkyl, (CO)C 1-4 alkyl, C 1-4 alkyl(SO)CO 0-4 alkyl, C 1-4 alkyl(SO 2 )C 0-4 alkyl, (SO)C 0-4 alkyl, (SO 2 )C 0-4 alkyl, OC 1-4 alkyl, C 1-4 alkylOR 5 and C 0-4 alkylNR 5 R 6 ;

Q is either selected from triazole, piperazine, and imidazole, or else, Q is any other 4-, 5-, 6-, or 7-membered heterocyclic ring containing one or more heteroatoms selected from N, O and S and is fused to a triazole ring;

R 2 is selected from the group consisting of hydroxy, C 0-6 alkylcyano, ═NR 5 , ═O, ═NOR 5 , C 1-4 alkylhalo, halo, C 1-6 alkyl, C 3-6 cycloalky, C 0-6 alkylaryl, C 0-6 alkylheteroaryl, C 0-6 alkycycloalkyl, C 0-6 alkylheterocycloalkyl, OC 1-4 alkyl, OC 0-6 alkylaryl, O(CO)C 1-4 alkyl, (CO)OC 1-4 alkyl, C 0-4 alkyl(S)C 0-4 alkyl, C 1-4 alkyl(SO)C 0-4 alkyl, C 1-4 alkyl(SO 2 )C 0-4 alkyl, (SO)C 0-4 alkyl, (SO 2 )C 0-4 alkyl, C 1-4 alkylOR 5 , C 0-4 alkylNR 5 R 6 and a 5- or 6-membered ring containing one or more atoms independently selected from C, N, O and S, which ring may optionally be fused with a 5- or 6-membered ring containing one or more atoms independently selected from the group consisting of C, N and O and wherein said ring and said fused ring may be substituted by one or more A; and

any C 1-6 alkyl, aryl, or heteroaryl defined under R 1 , R 2 and R 3 may be substituted by one or more A; and

A is selected from the group consisting of hydrogen, hydroxy, halo, nitro, oxo, C 0-6 alkylcyano, C 0-4 alkylC 3-6 cycloalky, C 1-6 alkyl, OC 1-6 alkyl, C 1-6 alkylhalo, OC 1-6 alkylhalo, C 2-6 alkenyl, C 0-3 alkylaryl, C 0-6 alkylOR 5 , OC 2-6 alkylOR 5 , C 1-6 alkylSR 5 , OC 2-6 alkylSR 5 , (CO)R 5 , O(CO)R 5 , OC 2-6 alkylcyano, OC 1-6 alkylCO 2 R 5 , O(CO)OR 5 , OC 1-6 alkyl(CO)R 5 , C 1-6 alkyl(CO)R 5 , NR 5 OR 6 , C 0-6 NR 5 R 6 , OC 2-6 alkylNR 5 R 6 , C 0-6 alkyl(CO)NR 5 R 6 , OC 1-6 alkyl(CO)NR 5 R 6 , OC 2-6 alkylNR 5 (CO)R 6 , C 0-6 alkylNR 5 (CO)R 6 , C 0-6 alkylNR 5 (CO)NR 5 R 6 , O(CO)NR 5 R 6 , C 0-6 alkyl(SO 2 )NR 5 R 6 , OC 2-6 alkyl(SO 2 )NR 5 R 6 , C 0-6 alkylNR 5 (SO 2 )R 6 , OC 2-6 alkylNR 5 (SO 2 )R 6 ; SO 3 R 5 , C 1-6 alkylNR 5 (SO 2 )NR 5 R 6 , OC 2-6 alkyl(SO 2 )R 5 , C 0-6 alkyl(SO 2 )R 5 , C 0-6 alkyl(SO)R 5 , OC 2-6 alkyl(SO)R 5 and a 5- or 6-membered ring containing one or more atoms independently selected from the group consisting of C, N, O and S;

R 5 and R 6 are independently selected from, H, C 1-6 alkyl, C 3-7 cycloalkyl and aryl

and salts and hydrates thereof

m is selected from 1 or 2

p is selected from 0, 1, 2, 3 or 4

or a salt or hydrate thereof;

provided that the compound is not

1-(2-benzothiazolyl)-4-[[5-(5-methyl-2-furanyl)-2H-tetrazol-2-yl]acetyl-piperazine,

1-(4-acetylphenyl)-4-[[5-(5-methyl-2-furanyl)-2H-tetrazol-2-yl]acetyl]-piperazine, or

5-(5-methyl-2-furanyl)-N-(2-phenyl-2H-benzotriazol-5-yl)-2-acetamide.

2. A compound according to claim 1 wherein X 3 is N and X 4 is C.

3. A compound according to claim 1 wherein P is aryl.

4. A compound according to claim 3 wherein P is phenyl.

5. A compound according to claim 1 wherein R 1 is selected from halo, C 1-6 alkyl, —OC 1-6 alkyl, C 0-6 alkylcyano.

6. A compound according to claim 5 wherein, R 1 is selected from Cl, F, cyano and methyl.

7. A compound according to claim 1 wherein X 1 is CR 3 R 4 .

8. A compound according to claim 7 wherein X 2 is selected from CR 3 R 4 , O, S and NR 3 .

9. A compound according to claim 1 wherein Q is either selected from triazole and piperazine, or else Q is any other 4-, 5-, 6-, or 7-membered heterocyclic ring containing one or more heteroatoms selected from N, O and S and is fused to a triazole ring.

10. A compound according to claim 1 wherein Q is triazole.

11. A compound according to claim 1 wherein X 2 is a bond.

12. A compound according to claim 1 wherein Q is piperazine.

13. A compound according to claim 1 wherein Q is a 5-, 6-, or 7-membered heterocyclic ring, other than triazole or piperazine, and is fused to a triazole ring.

14. A compound according to claim 1 wherein R 2 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkylhalo, C 3-7 cylcoalkyl, C 0-6 alkylaryl, C 0-6 alkylheteroaryl, O(CO)C 1-4 alkyl.

15. A compound according to claim 1 wherein R 2 is a 5- or 6-membered ring containing one or more atoms independently selected from C, N, O and S, which ring may optionally be fused with a 5- or 6-membered ring containing one or more atoms independently selected from the, group consisting of C, N and O and wherein said ring and said fused ring may be substituted by one or more A.

16. A compound according to claim 1 wherein A is selected from the group consisting of halo, —OC 1-6 alkyl, C 0-6 NR 5 R 6 , C 1-6 alkylhalo.

17. A compound according to claim 1 selected from:

Ethyl 4-{[2-(3-chlorophenyl)-2H-tetrazol-5-yl]methyl}piperazine-1-carboxylate,

4-[2-(5-Chloro-2-fluoro-phenyl)-2H-tetrazol-5-ylmethyl]-piperazine-1-carboxylic acid ethyl ester,

4-(2-m-Tolyl-2H-tetrazol-5-ylmethyl]-piperazine-1-carboxylic acid ethyl ester,

4-[2-(3-Iodo-phenyl)-2H-tetrazol-5-ylmethyl]-piperazine-1-carboxylic acid ethyl ester,

4-[2-(3-Cyano-phenyl)-2H-tetrazol-5-ylmethyl]-piperazine-1-carboxylic acid ethyl ester,

4-[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethyl]-piperazine 1-carboxylic acid ethyl ester,

4-[5-({[2-(3-chlorophenyl)-2H-tetrazol-5-yl]methyl}thio)-4-cyclopropyl-4H-1,2,4-triazol-3-yl]pyridine,

4-[5-({[1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}thio)-4-cyclopropyl-4H-1,2,4-triazol-3-yl]pyridine,

Ethyl 4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,

4-{5-[2-(5-Chloro-2-fluoro-phenyl)-2H-tetrazol-5-ylmethylsulfanyl]-4-methyl-4-H [1,2,4]triazol-3-yl}-pyridine,

4-{5-[2-(5-Chloro-2-fluoro-phenyl)-2H-tetrazol-5-ylmethylsulfanyl]-4-cyclopropyl-4H-[1,2,4]triazol-3-yl}-pyridine,

4-(5-{1-[2-(5-Chloro-2-fluoro-phenyl)-2H-tetrazol-5-yl]-ethylsulfanyl}-4-methyl-4H-[1,2,4]triazol-3-yl)-pyridine,

4-(5-{1-[2-(5-Chloro-2-fluoro-phenyl)-2H-tetrazol-5-yl]-ethylsulfanyl}-4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridine,

4-{1-[2-(5-Chloro-2-fluoro-phenyl)-2H-tetrazol-5-yl]-ethyl}-piperazine-1-carboxylic acid ethyl ester,

4-[4-Cyclopropyl-5-(2-m-tolyl-2H-tetrazol-5-ylmethylsulfanyl)-4H-[1,2,4]triazol-3-yl]-pyridine,

4-{4-Cyclopropyl-5-[1-(2-m-tolyl-2H-tetrazol-5-yl)-ethylsulfanyl]-4H-[1,2,4]triazol-3-yl}-pyridine,

4-{4-Methyl-5-[1-(2-m-tolyl-2H-tetrazol-5-yl)-ethylsulfanyl]-4H-[1,2,4]triazol-3-yl }-pyridine,

3-[5-(4-Cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-tetrazol-2-yl]-benzonitrile,

3-{5-[1-(4-Cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethyl]-tetrazol-2-yl}-benzonitrile

3-{5-[1-(4-Methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethyl]-tetrazol-2-yl}-benzonitrile4-{4-Cyclopropyl-5-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethylsulfanyl]-4H-[1,2,4]triazol-3-yl}-pyridine,

4-(4-Cyclopropyl-5-{1-[2-(2-fluoro-5-methyl-plenyl)-2H-tetrazol-5-yl]-ethylsulfanyl}-4H-[1,2,4]triazol-3-yl)-pyridine,

4-(5-{1-[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethylsulfanyl}-4-methyl-4H-[1,2,4]triazol-3-yl)-pyridine,

Methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-(2-m-tolyl-2H-tetrazol-5-ylmethyl)-amine,

Methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-[1-(2-m-tolyl-2H-tetrazol-5-yl)-ethyl]-amine,

[2-(3-Chloro-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

{1-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5′-ylmethyl]-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

{1-[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

[2-(3-Iodo-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

{1-[2-(3-Iodo-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

Methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-(2-m-tolyl-2H-tetrazol-5-ylmethyl)-amine,

Methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-[1-(2-m-tolyl-2H-tetrazol-5-yl)-ethyl]-amine,

[2-(3-Chloro-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

{1-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl-5-pyridin-4yl -4H-[1,2,4]triazol-3-yl)-amine,

{1-[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amine,

8-{1-]2-(3-Iodo-phenyl)-2H-tetrazol-5-yl]-ethyl}-3-pyridin-4-yl-5,6,7,8-tetrahydro -[1,2,4]triazolo[4,3-a]pyrimidine,

8-{1-[2-(3-Iodo-phenyl)-2H-tetrazol-5-yl]-ethyl}-3-pyridin-4-yl-5,6,7,8-tetrahydro -[1,2,4]triazolo[4,3-a]pyrimidine,

3-Pyridin-4-yl-8-(2-m-tolyl-2H-tetrazol-5-yl methyl)-5,6,7,8-tetrahydro-4H-1,2,3a, 8-tetraaza-azulene,

3-Pyridin-4-yl-8-[1-(2-m-tolyl-2H-tetrazol-5-yl)-ethyl]-5,6,7,8-tetrahydro-4H-1,2,3a, 8-tetraaza-azulene,

8-[2-(3-Chloro-phenyl)-2H-tetrazol-5-ylmethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3a, 8-tetraaza-azulene,

8-{1-(2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-ethyl}-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3a, 8-tetraaza-azulene,

8-[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3a, 8-tetraaza-azulene,

8-{1-[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethyl}-3-pyridin-4-yl5,6,7,8-tetra-hydro-4H-1,2,3a, 8-tetraaza-azulene,

8-[2-(3-Iodo-phenyl)-2H-tetrazol-5-ylmethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H -1,2,3a,8-tetraaza-azulene,

8-{1-[2-(3-Iodo-phenyl)-2H-tetrazol-5-yl]-ethyl}-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3a,8-tetraaza-azulene,

4-(5-{[2-(3-chlorophenyl)-2H-tetrazol-5-yl]methoxy}-4-methyl-4H-1,2,4-triazol-3-yl)pyridine,

4-(5-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethoxy}-4-methyl-4H-1,2,4-triazol-3-yl)pyridine,

4-[4-Methyl-5-(2-m-tolyl-2H-tetrazol-5-ylmethoxy)-4H-[1,2,4]triazol-3-yl]-pyridine,

4-{4-Methyl-5-[1-(2-m-tolyl-2H-tetrazol-5-yl)-ethoxy]-4H-[1,2,4]triazol-3-yl }-pyridine,

4-{5-[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethoxy]-4-methyl-4H-[1,2,4]triazol-3-yl}-pyridine,

4-(5-{1-[2-(2-Fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazol-3-yl)-pyridine,

4-{5-[2-(3-Chloro-phenyl)-2H-tetrazol-5-ylmethoxy]-4-cyclopropyl-4H-[1,2,4]triazol-3-yl}-pyridine,

4-(5-{1-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridine,

4-[4-Cyclopropyl-5-(2-m-tolyl-2H-tetrazol-5-ylmethoxy)-4H-(1,2,4]triazol-3-yl-]-pyridine,

4-{4-Cyclopropyl-5-[1-(2-m-tolyl-2H-tetrazol-5-yl)-ethoxy]-4H-[1,2,4]triazol-3-yl}-pyridine,

4-{4-Cyclopropyl-5-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol5-ylmethoxyl4H-[1,2,4]triazol-3-yl) -pyridine,

4-(4-Cyclopropyl-5-{1-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethoxy)-4H-[1,2,4]triazol-3-yl)-pyridine,

4-{5-[2-(3-iodo-phenyl)-2H-tetrazol-5-yl methoxy]-4-methyl-4H-[1,2,4]triazol-3-yl}-pyridine,

4-(5-(1-[2-(3-iodo-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazol-3-yl)-pyridine,

4-{4-Cyclopropyl-5-[2-(3-iodo-phenyl)-2H-tetrazol-5-ylmethoxy]-4H-[1,2,4]triazol-3-yl }-pyridine,

4-(4-Cyclopropyl-5-{1-[2-(3-iodo-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4H-[1,2,4)triazol-3-yl)-pyridine,

3-[5-(4-Methyl-5-pyridin-4-yl-4H-[1,2,4]tetrazol-3-yloxymethyl)-tetrazol-2-yl]-benzonitrile

3-{5-[1-(4-Methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yloxy)-ethyl]-tetrazol-2-yl}-benzonitrile,

3-[5-(4-Cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yloxymethyl)-tetrazol-2-yl]-benzonitrile,

3-{5-[1-(4-Cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yloxy)-ethyl]-tetrazol-2-yl}-benzonitrile,

3-(5-{[Methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amino]-methyl}-tetrazol-2-yl)-benzonitrile,

3-(5-{1-[Methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-amino]-ethyl}-tetrazol-2-yl)-benzonitrile,

3-[5-(3-Pyridin-4-yl-6,7-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrimidin-8-ylmethyl)-tetrazol-2-yl]-benzonitrile,

3-{5-[1-(3-Pyridin-4-yl-6,7-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrimidin-8-yl)-ethyl)-tetrazol-2-yl }-benzonitrile,

3-[5-(3-Pyridin-4-yl-4,5,6,7-tetrahydro- 1,2,3a,8-tetraaza-azulen-8-ylmethyl)-tetrazol-2-yl]-benzonitrile,

3-[5-[1-(3-Pyridin-4-yl-4,5,6,7-tetrahydro-1,2,3a,8-tetraaza-azulen-8-yl)-ethyl]-tetrazol-2-yl }-benzonitrile,

(R) & (S)-4-(5-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethoxy}-4-methyl-4H- 1,2,4-triazol-3-yl)pyridine,

2-(3-chloro-phenyl)-5-[(triphenyl-λ 5 -phosphanyl)-methyl]-2H-tetrazole hydrobromide,

4-(5-{2-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-vinyl}-4-ethyl-4H-[1,2,4]triazol-3-yl)-pyridine,

1-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-2-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-ethanol,

2-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-1-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-ethanol,

4-(5-{2-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-vinyl}-4-ethyl-4H-[1,2,4]triazol-3-yl)-pyridine,

3-[4-Methyl-5-({[2-(3-methylphenyl)-2H-tetrazol-5-yl]methyl}thio)-4H-1,2,4-triazol-3-yl]benzonitrile,

5-({[5-(3,5-Difluorophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]thio}methyl)-2-(3-methylphenyl)-2H-tetrazole,

3-[4-Methyl-5-({1-[2-(3-methylphenyl)-2H-tetrazol-5-yl]ethyl)thio)-4H-1,2,4-triazol-3-yl]benzonitrile,

5-(1-{[5-(3,5-Difluorophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]thio}ethyl)-2-(3-methylphenyl)-2H-tetrazole,

6-(4-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazin-1-yl)nicotinonitrile,

3-(4-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazin-1-yl)pyrazine-2-carbonitrile,

2-(4-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazin-1-yl)nicotinonitrile,

1-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}-4-(3-nitropyridin-2-yl)piperazine,

8-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}-3-(3,5-difluorophenyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,

8-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl-}-3-(4-methoxyphenyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,

3-(2-Chloro-6-methoxypyridin-4-yl)-8-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,

8-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}-3-(2-methoxypyridin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,

8-{[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]methyl}-3-(2-methoxypyridin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,

3-(5-{[3-(2-Methoxypyridin-4-yl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrimidine-8(5H)-yl]methyl}-2H-tetrazol-2-yl)benzonitrile,

3-(2-Methoxypyridin-4-yl)-8-{1-[2-(3-iodophenyl)-2H-tetrazol-5-yl]ethyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,

3-(5-{1-[3-(2-Methoxypyridin-4-yl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrimidin-8(5H)-yl]ethyl}-2H-tetrazol-2-yl)benzonitrile,

3(5-{[3-(2-Methoxypyridin-4-yl)-5,6,7,8-tetrahydro-9H-[1,2,4]triazolo[4,3-a][1,3]diazepin-9-yl]methyl}-2H-tetrazol-2-yl)benzonitrile,

3-(5-{[3-(2,6-Dimethoxypyrimidin-4-yl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrimidin-8(5H)-yl]methyl}-2H-tetrazol-2-yl)benzonitrile,

(R) 3-(5-(1-[3-(2-Methoxypyridin-4-yl)-6,7-dihydro[1,2,4]triazolo]4,3-a]pyrimidin-8(5H)-yl]ethyl}-2H-tetrazol-2-yl)benzonitrile,

(S) 3-(5-(1-[3-(2-Methoxypyridin-4-yl)-6,7-dihydro [1,2,4]triazolo[4,3-a]pyrimidin-8(5H)-yl]ethyl}-2H-tetrazol-2-yl)berizonitrile,

(R) Ethyl 4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl)piperazine-1-carboxylate,

(S) Ethyl 4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,

(R) Ethyl 4-{1-[2-(5-chloro-2-fluorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,

(S) Ethyl 4-{1-[2-(5-chloro-2-fluorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,

(R) 6-(4-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazin-1-yl)nicotinonitrile,

(S) 6-(4-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazin-1-yl)nicotinonitrile,

(R) 3-(4-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazin- 1-yl)pyrazine-2-carbonitrile

(S) 3-(4-{1-[2-(3-Chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazin-1-yl)pyrazine-2-carbonitrile,

4-(5-{(S)-1-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazol-3-yl)-pyridine,

2-(3-Chloro-phenyl)-5-{(R)-1-[5-(3,5-difluoro-phenyl)-4-methyl-4H-(1,2,4]triazol-3-yloxy]-ethyl)-2H-tetrazole,

3-(5-{(R)-1-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazol-3-yl)-pyridine,

4-(5-{2-[5-(3-Chlorophenyl)-2H-tetrazol-2-yl]propyl}-4-methyl-4H- 1,2,4-triazol-3-yl)pyridine,

4-(5-{(R)-1-[2-(3-Chloro-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazol-3-yl)-pyridine,

2-(3-chlorophenyl)-5-[1-methyl-2-phenylvinyl]-2H-tetrazole, and

2-({1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl)ethyl}thio)-imidazo[4,5-b]pyridine.

18. A pharmaceutical composition comprising as active ingredient a therapeutically effective, amount of the compound of claim 1 , in association with one or more of a pharmaceutically acceptable diluent, excipient and/or inert carrier.

19. A compound according to claim 4 wherein R 1 is selected from halo, C 1-6 alkyl, —OC 1-6 alkyl, C 0-6 alkylcyano.

20. A compound according to claim 19 wherein Q is triazole or piperazine.

21. A compound according to claim 20 wherein R 2 is selected from the group consisting of C 1-6 alkyl, C 1-6 alkylhalo, C 3-7 cylcoalkyl, C 0-6 alkylaryl, C 0-6 alkylheteroaryl, and O(CO)C 1-4 alkyl.

22. A compound according to claim 21 wherein R 2 is pyridine.