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 compound of formula (4):
or a pharmaceutically acceptable salt thereof, wherein
R 1 is F, Cl, OMe, CH 2 OMe, Me, fluoromethyl or cyano;
R 2 is H or F;
and
R 3 is H, Me, F, Cl or cyano.
2. The compound according to claim 1 , wherein R 1 is F, Cl or cyano.
3. The compound according to claim 1 , wherein R 3 is H or F.
4. The compound according to claim 1 which 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-(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,
3-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]-5-methoxybenzonitrile,
or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1 which is 3-chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 1 which is 5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzene-1,3-dicarbonitrile or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 1 which is 3-chloro-5-[6-(5-methylpyridin-2-yl)pyrimidin-4-yl]benzonitrile or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 1 which is 3-chloro-5-[6-(5-chloropyridin-2-yl)pyrimidin-4-yl]benzonitrile or a pharmaceutically acceptable salt thereof.
9. A method for the treatment of migraine, dystonia, depression, anxiety or amyotrophic lateral sclerosis (ALS) comprising administering an effective amount of a compound according to claim 1 to a subject in need thereof.
10. The method according to claim 9 , wherein the disorder is migraine.
11. The method according to claim 9 , wherein the disorder is dystonia.
12. The method according to claim 9 , wherein the disorder is depression.
13. The method according to claim 9 , wherein the disorder is anxiety.
14. The method according to claim 9 , wherein the disorder is amyotrophic lateral sclerosis (ALS).
15. The method according to claim 12 , wherein the depression is treatment-resistant depression.