Back to results
US 2009/0023711 A1Published application
Piperazines and Piperidines as Mglur5 Potentiators
AssigneeAstraZeneca AB
InventorsAbdelmalik Slassi, Methvin Isaac, Jalaj Arora, Dean Brown
Life of this patent
Estimating the term…
Abstract
Compounds of Formula I or pharmaceutically acceptable salts or solvates thereof: wherein Ar1, Ar2, A, X, Y, m, n and R1, R2, R3, R4 and R5 are as described in the specification, processes for their preparation, pharmaceutical formulations comprising them and their use in therapy, particularly in the therapy of neurological and psychiatric disorders associated with glutamate dysfunction.
Claims13
A compound of Formula I or a pharmaceutically acceptable salt or solvate thereof:
- wherein:
- Ar1 is selected from the group consisting of phenyl and pyridyl, which may be substituted with up to 4 substituents independently selected from the group consisting of alkyl, halo, haloalkyl and CN;
- Ar2 is selected from the group consisting of phenyl and heteroaryl, which may be substituted with up to 4 substituents independently selected from the group consisting of alkyl, halo and haloalkyl;
- A is selected from the group consisting of C(O), C(S) and S(O)2;
- X is selected from the group consisting of O and S;
- Y is selected from the group consisting of C and N;
- m is selected from the group consisting of 1 and 2;
- n is selected from the group consisting of 1 and 2;
- R1 is selected from the group consisting of H and alkyl,
- R2, R3, R4 and R5 are independently selected from the group consisting of H and alkyl;
- with the proviso that the compound is not 1-[(benzyloxy)acetyl]-4-(4-chlorophenyl)piperazine, 1-[(benzyloxy)acetyl]-4-(2-methoxyphenyl)piperazine, 1-[(benzyloxy)acetyl]-4-(4-methoxyphenyl)piperazine, 1-[(benzyloxy)acetyl]-4-(3-chlorophenyl)piperazine, or 2-benzyloxy-1-[4-(3-methyl-pyridin-2-yl)-piperazin-1-yl]-ethanone.
8 more elements
A compound selected from the group consisting of:
- 2-benzyloxy-1-[4-(4-fluorophenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2-chloro-5-trifluoro methyl-phenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(3,5-dichloro-pyridin-4-yl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(5-chloro-2-methyl-phenyl)-piperazin-1-yl]-ethanone,
- 4-[4-(2-benzyloxyacetyl)-piperazin-1-yl]-benzonitrile,
- 2-benzyloxy-1-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(3,5-dichloromethyl phenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2,4-dichloro phenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-(4-p-tolyl-piperazin-1-yl)-ethanone,
- 2-benzyloxy-1-[4-(2-chlorophenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-(4-phenyl-piperazin-1-yl)-ethanone,
- 2-benzyloxy-1-(4-pyridin-2-yl-piperazin-1-yl)-ethanone,
- 2-benzyloxy-1-(3-methyl-4phenyl-piperazin-1-yl)-ethanone,
- 2-benzyloxy-1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2-trifluoromethyl-phenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(5-ethynyl-pyridin-2-yl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2-fluorophenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(6-methyl-pyridin-2-yl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2,5-dichlorophenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-ethanone,
- 2-[4-(2-benzyloxy-acetyl)-piperazin-1-yl]-nicotinonitrile,
- 1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-2-(4-fluoro-benzyloxy)-propan-1-one,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(4-fluoro-benzyloxy)-propan-1-one,
- 1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-2-(3-methyl-3H-imidazol-4-ylmethoxy)-propan-1-one,
- 1-[4-(2,4-chloro-phenyl)-piperazin-1-yl]-2-(3-methyl-3H-imidazol-4-ylmethoxy)-propan-1-one,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(pyridin-2-ylmethyloxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(pyridin-4-ylmethyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(pyridin-4-ylmethyloxy)-ethanone,
- 2-benzyloxy-1-[4-(4-fluoro-2-chloro-phenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(pyridin-2-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(pyridin-3-ylmethoxy)-ethanone,
- 1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-2-(pyridin-2-ylmethoxy)-ethanone,
- 1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-2-(pyridin-3-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(3-fluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(4-fluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(2-fluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(2,3-difluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(2,4-difluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(2,5-difluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(2,6-difluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(3,4-difluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(3,5-difluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-2-(2-fluoro-benzyloxy)-ethanone,
- 1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-2-(4-fluoro-benzyloxy)-ethanone,
- 2-(2,4-difluoro-benzyloxy)-1-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2,4-dichloro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-ethanone,
- 2-benzyloxy-1-[4-(2,4-dichloro-phenyl)-[1,4]diazepan-1-yl]-ethanone,
- 1-[4-(3-chloro-pyridin-4-yl)-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(5-chloro-pyridin-2-yl)-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-2-methyl-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(1-pyridin-4-yl-ethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-3-methyl-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-2-methyl-piperazin-1-yl]-2-(pyridin-2-ylmethoxy)-ethanone,
- 1-[(R)-4-(2,4-dichloro-phenyl)-2-methyl-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[(S)-4-(2,4-dichloro-phenyl)-2-methyl-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(4-chloro-phenyl)-piperazin-1-yl]-2-(pyridin-2-ylmethoxy)-ethanone,
- 1-[4-(4-chloro-phenyl)-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(5-methyl-pyridin-2-yl)-piperazin-1-yl]-2-(pyridin-2-ylmethoxy)-ethanone,
- 1-[4-(5-fluoro-pyridin-2-yl)-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-2-methyl-piperazin-1-yl]-2-(pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(3-methyl-pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(3-fluoro-pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(3-fluoro-pyridin-4-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(thiazol-4-ylmethoxy)-ethanone,
- 1-[4-(5-chloro-pyridin-2-yl)-piperazin-1-yl]-2-(thiazol-4-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(thiazol-5-ylmethoxy)-ethanone,
- 1-[4-(5-chloro-pyridin-2-yl)-piperazin-1-yl]-2-(thiazol-5-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(thiazol-2-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(thiazol-5-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(thiazol-2-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(2-methyl-thiazol-4-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(2-methyl-thiazol-4-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(4-methyl-thiazol-5-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(pyrazin-2-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(pyrimidin-4-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(pyrimidin-4-ylmethoxy)-ethanone,
- 1-[4-(5-chloro-pyridin-2-yl)-piperazin-1-yl]-2-(pyrimidin-4-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(thiophen-2-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(thiophen-2-ylmethoxy)-ethanone,
- 1-[4-(5-chloro-pyridin-2-yl)-piperazin-1-yl]-2-(thiophen-2-ylmethoxy)-ethanone,
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(thiophen-3-ylmethoxy)-ethanone,
- 1-[4-(2-chloro-4-fluoro-phenyl)-piperazin-1-yl]-2-(thiophen-3-ylmethoxy)-ethanone,
- 1-[4-(5-chloro-pyridin-2-yl)-piperazin-1-yl]-2-(thiophen-3-ylmethoxy)-ethanone, and
- 1-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-2-(thiazol-4-ylmethoxy)-ethanone.
85 more elements
7-9. (canceled)
A compound of Formula I or a pharmaceutically acceptable salt or solvate thereof:
- wherein:
- Ar1 is phenyl which may be substituted with up to 4 substituents independently selected from the group consisting of alkyl, halo, haloalkyl and CN;
- Ar2 is pyridyl, which may be substituted with up to 4 substituents independently selected from the group consisting of alkyl, halo and haloalkyl;
- A is C(O);
- X is O;
- Y is N;
- m is 1;
- n is 1;
- R1 is H and
- R2, R3, R4 and R5 are H.
7 more elements
Dependencies are inferred from the claim text.