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US 2010/0144710 A1Published application
Piperazine and Piperidine MGLUR5 Potentiators
AssigneeAstraZeneca AB
InventorsJalaj Arora, Methvin Isaac, Abdelmalik Slassi, Louise Edwards, Satheesh Nair, Fupeng Ma
Life of this patent
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Abstract
Compounds of Formula I or pharmaceutically acceptable salts or solvates thereof, wherein A, B, D, Ar1, Ar2, R2, R3, R4, a, m and n are defined in the specification, methods for the use thereof, processes for making and pharmaceutical compositions containing the same.
Claims13
A compound of Formula:
- wherein:
- Ar1 is selected from the group consisting of aryl and heteroaryl, substituted with a CN group at the position alpha to the link with group B, further optionally-substituted with one or more substituents selected from the group consisting of alkyl, haloalkyl and halo;
- Ar2 is selected from the group consisting of aryl and heteroaryl, optionally substituted with one or more substituents selected from the group consisting of halo, alkyl, haloalkyl, alkoxy, haloalkoxy, NR5R6, O-alkylene-aryl, O-alkylene-heteroaryl, O-alkylene-O-alkyl, O-cycloalkyl, O-heterocycloalkyl, wherein any cyclic group may be further substituted with one or more substituents selected from the group consisting of alkyl and halo;
- A is selected from the group consisting of C and N;
- B is a bond when A is N and is group NR when A is C;
- D is selected from the group consisting of NR1 and O;
- a is selected from the group consisting of 0 and 1;
- m is selected from the group consisting of 1 and 2;
- n is selected from the group consisting of 1, 2, 3 and 4;
- R, R2, R3, R5 and R6 are independently selected from the group consisting of H and alkyl;
- R1 is selected from the group consisting of H, alkyl, COR, CO2R and SO2R;
- and
- R4 is selected from the group consisting of H, halo, CN, alkyl, haloalkyl, CH2OR and CO2R,
- or a pharmaceutically acceptable salt, hydrate, solvate, optical isomer, or combination thereof.
11 more elements
A compound selected from the group consisting of:
- 2-{4-[2-(4-Butoxy-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(4-Butoxy-phenyl)-acetyl]-piperazin-1-yl}-benzonitrile;
- 4-[2-(4-Butoxy-phenyl)-acetyl]-3,4,5,6-tetrahydro-2H-[1,2]bipyrazinyl-3′-carbonitrile;
- 2-{4-[2-(4-Hydroxy-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(4-Ethoxy-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(4-Butoxy-phenyl)-acetyl]-[1,4]diazepan-1-yl}-nicotinonitrile;
- 2-(4-Butoxy-phenyl)-1-[4-(3-chloro-pyridin-2-yl)-piperazin-1-yl]-ethanone;
- 2-{4-[2-(4-Isopropoxy-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-(4-{2-[(4-Bromo-phenyl)-methyl-amino]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-{4-[2-(Methyl-p-tolyl-amino)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(4-Phenoxy-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-[4-(2-Phenoxy-acetyl)-piperazin-1-yl]-nicotinonitrile;
- 2-{4-[2-(4-Butyl-phenoxy)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 3-{4-[2-(4-Butoxy-phenyl)-acetyl]-piperazin-1-yl}-pyridine-2-carbonitrile;
- 2-{4-[2-(4-Benzyloxy-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(4-Propoxy-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-(4-{2-[4-(Tetrahydro-furan-3-yloxy)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-{4-[2-(4-Nitro-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-(4-{2-[4-(2-Methoxy-ethoxy)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-{4-[2-(4-Phenethyloxy-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 3-{4-[2-(4-Butoxy-phenyl)-acetyl]-piperazin-1-yl}-isonicotinonitrile;
- 2-{4-[2-(4-Butoxy-phenyl)-acetyl]-piperazin-1-yl}-6-trifluoromethyl-nicotinonitrile;
- 2-{4-[2-(6-Chloro-pyridin-3-yl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{1-[2-(4-Butoxy-phenyl)-acetyl]-piperidin-4-ylamino}-nicotinonitrile;
- 2-({1-[2-(4-Butoxy-phenyl)-acetyl]-piperidin-4-yl}-methyl-amino)-nicotinonitrile;
- 2-(4-Butoxy-phenyl)-1-[4-(3-ethylamino-pyridin-2-yl)-piperazin-1-yl]-ethanone;
- 2-{4-[2-(5-Butoxy-pyridin-2-yl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(4-Butylamino-phenyl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(4-Butyl-phenylamino)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-(4-{2-[4-(Butyl-methyl-amino)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-(4-{2-[(4-Butyl-phenyl)-methyl-amino]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-(4-{2-[(6-Butoxy-pyridin-3-yl)-methyl-amino]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-(4-{2-[4-(Pyridin-4-ylmethoxy)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-{4-[2-(6-Butoxy-pyridin-3-ylamino)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(6-Butoxy-pyridin-3-yl)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 2-{4-[2-(4-Butoxy-phenylamino)-acetyl]-piperazin-1-yl}-nicotinonitrile;
- 4-{2-[(4-Butyl-phenyl)-methyl-amino]-acetyl}-3,4,5,6-tetrahydro-2H-[1,2]bipyrazinyl-3′-carbonitrile;
- 2-((R)-4-{2-[(4-Butyl-phenyl)-methyl-amino]-acetyl}-3-methyl-piperazin-1-yl)-nicotinonitrile;
- 2-((S)-4-{2-[(4-Butyl-phenyl)-methyl-amino]-acetyl}-3-methyl-piperazin-1-yl)-nicotinonitrile;
- 2-(4-{2-[(4-Butyl-phenyl)-methyl-amino]-acetyl}-2-methyl-piperazin-1-yl)-nicotinonitrile;
- 2-(4-{2-[(4-Butyl-phenyl)-methyl-amino]-acetyl}-[1,4]diazepan-1-yl)-nicotinonitrile;
- 2-(4-{2-[(4-Butyl-phenyl)-methyl-amino]-propionyl}-piperazin-1-yl)-nicotinonitrile;
- N-(4-Butyl-phenyl)-N-{2-[4-(3-cyano-pyridin-2-yl)-piperazin-1-yl]-2-oxo-ethyl}-methanesulfonamide;
- N-(4-Butyl-phenyl)-N-[2-(3′-cyano-2,3,5,6-tetrahydro-[1,2]bipyrazinyl-4-yl)-2-oxo-ethyl]-methanesulfonamide;
- 2-(4-{2-[4-(Pyridin-2-ylmethoxy)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-(4-{2-[4-(Pyridin-3-ylmethoxy)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-(4-{2-[4-(Thiazol-2-ylmethoxy)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile;
- 2-(4-{2-[4-(4-Methyl-thiazol-2-ylmethoxy)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile, and
- 2-(4-{2-[4-(Thiazol-5-ylmethoxy)-phenyl]-acetyl}-piperazin-1-yl)-nicotinonitrile
- or a pharmaceutically acceptable salt, hydrate, solvate or optical isomer, of any foregoing compound.
47 more elements
9-11. (canceled)
Dependencies are inferred from the claim text.