IP Library › Granted Patent US 7,935,703
Granted Patent B2
US 7,935,703 · App. 12/160,959 · Granted May 3, 2011

Piperazines and piperidines as Mglur5 potentiators

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Quick Facts
Patent No.
US 7,935,703
App. No.
12/160,959
Granted
May 3, 2011
Kind
B2
Abstract

Compounds of Formula I or pharmaceutically acceptable salts or solvates thereof: wherein Ar 1 , Ar 2 , A, X, Y, m, n and R 1 , R 2 , R 3 , R 4 and R 5 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.

Claims (90)

1. 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-dichlorophenyl)-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-(3methyl-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-phenyp-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-thiazo-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-(thiazo-4-ylmethoxy)-ethanone.

2. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or excipient.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 17, 2008
From: SLASSI, ABDELMALIK; ISAAC, METHVIN; ARORA, JALAJ; BROWN, DEAN
To: ASTRAZENECA AB
Reel/Frame 021699/0973 →