4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
The disclosures herein relate to novel compounds of formula wherein R 1 , R 2 , R 3 and R 4 and n are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of inflammation, neurological or psychiatric disorders associated with modulating mGlu5 receptor function.
1. A method for the treatment of a disorder, comprising administering an effective amount of a compound to a subject in need thereof, wherein the compound is selected from the group consisting of the compounds represented by the following formulae:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is halogen, optionally substituted C 1 -C 3 alkyl, cyclopropyl, optionally substituted C 1 -C 3 alkoxy, cyano, hydroxyl, nitro or NH 2 ;
R 2 is H or F;
R 3 is H, halogen, optionally substituted C 1 -C 3 alkyl, optionally substituted C 1 -C 3 alkoxy or cyano;
R 4 is H, halogen, optionally substituted C 1 -C 3 alkyl, optionally substituted C 1 -C 3 alkoxy, or cyano; and
n is 0-3,
wherein the disorder is migraine, dystonia, depression, anxiety or amyotrophic lateral sclerosis (ALS).
2. The method of claim 1 , wherein the disorder is migraine.
3. The method of claim 1 , wherein the disorder is dystonia.
4. The method of claim 1 , wherein the disorder is depression.
5. The method of claim 1 , wherein the disorder is anxiety.
6. The method of claim 1 , wherein the disorder is amyotrophic lateral sclerosis (ALS).
7. The method according to claim 1 wherein R 1 is F, Cl, OMe, CH 2 OMe, Me, fluoromethyl or cyano.
8. The method according to claim 1 wherein R 1 is F, Cl or cyano.
9. The method according to claim 1 wherein R 3 is H, Me, F, Cl or cyano.
10. The method according to claim 1 wherein R 3 is H or F.
11. The method according to claim 1 wherein n is 0 or 1.
12. The method according to claim 1 wherein the compound is selected from the group consisting of:
3-chloro-4-fluoro-5-[6-(pyridin-2-yl)pyrimidin-4-yl]benzonitrile,
3-chloro-5- [6-(pyridin-2-yl)pyrimidin-4-yl]benzonitrile,
6-[6-(3-chloro-5-cyanophenyl)pyrimidin-4-yl]pyridine-3-carbonitrile,
3-methyl-5-[6-(pyridin-2-yl)pyrimidin-4-yl]benzonitrile,
3-chloro-5-[6-(pyridazin-3-yl)pyrimidin-4-yl]benzonitrile,
3-(4,4′-bipyrimidin-6-yl)-5-chlorobenzonitrile,
3-chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile,
5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzene-1,3-dicarbonitrile,
3-chloro-5-[6-(5-methylpyridin-2-yl)pyrimidin-4-yl]benzonitrile,
3-chloro-5-[6-(5-chloropyridin-2-yl)pyrimidin-4-yl]benzonitrile,
5-[6-(pyridin-2-yl)pyrimidin-4-yl]benzene-1,3-dicarbonitrile,
3-chloro-4-fluoro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile,
3-methyl-5-[6-(5-methylpyridin-2-yl)pyrimidin-4-yl]benzonitrile,
3-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]-5-methoxymethyl)benzonitrile, and
3-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]-5-methoxybenzonitrile,
or a pharmaceutically acceptable salt thereof.