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 2:
or a 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; and
Q is an optionally substituted pyridyl or pyrazyl group.
2. The compound according to claim 1 which is a compound of formula 3:
or a 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; and
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.
3. The compound according to claim 1 which is a compound of formula 4:
or a 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; and
R 3 is H, halogen, optionally substituted C 1 -C 3 alkyl, optionally substituted C 1 -C 3 alkoxy or cyano.
4. The compound according to claim 1 which is a compound of formula 5:
or a 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 5 is H, D, halogen, optionally substituted C 1 -C 3 alkyl or cyano; and
R 6 is H, D, halogen, optionally substituted C 1 -C 3 alkyl or cyano.
5. The compound according to claim 1 , wherein R 1 is F, Cl, OMe, CH 2 OMe, Me, fluoromethyl or cyano.
6. The compound according to claim 1 , wherein R 1 is F, Cl or cyano.
7. The compound according to claim 2 , wherein R 3 is H, Me, F, Cl or cyano.
8. The compound according to claim 2 , wherein n is 0 or 1.
9. The compound according to claim 4 , wherein R 5 and R 6 are independently H, D or F.
10. 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-methyl-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
3-chloro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
3-chloro-4-fluoro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
3-chloro-4-fluoro-5-[4-(1H-pyrazol-1-yl)pyridin-2-yl]benzonitrile;
3-chloro-4-fluoro-5-[2-(1H-pyrazol-1-yl)pyridin-4-yl]benzonitrile;
3-chloro-4-fluoro-5-[6-(4-fluoro-1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
3-methyl-5-{6-[( 2 H 3 )-1H-pyrazol-1-yl]pyrimidin-4-yl}benzonitrile;
3-chloro-5-{6-[( 2 H 3 )-1H-pyrazol-1-yl]pyrimidin-4-yl}benzonitrile;
3-chloro-4-fluoro-5-{6-[( 2 H 3 )-1H-pyrazol-1-yl]pyrimidin-4-yl}benzonitrile;
3-(fluoromethyl)-5-[6-(1H-pyrazol-1-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; and
3-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]-5-methoxybenzonitrile;
or a salt thereof.
11. The compound according to claim 1 which is selected from the group consisting of:
3-methyl-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
3-chloro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
3-chloro-4-fluoro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
3-chloro-4-fluoro-5-[4-(1H-pyrazol-1-yl)pyridin-2-yl]benzonitrile;
3-chloro-4-fluoro-5-[2-(1H-pyrazol-1-yl)pyridin-4-yl]benzonitrile;
3-chloro-4-fluoro-5-[6-(4-fluoro-1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
3-methyl-5-{6-[( 2 H 3 )-1H-pyrazol-1-yl]pyrimidin-4-yl}benzonitrile;
3-chloro-5-{6-[( 2 H 3 )-1H-pyrazol-1-yl]pyrimidin-4-yl}benzonitrile;
3-chloro-4-fluoro-5-{6-[( 2 H 3 )-1H-pyrazol-1-yl]pyrimidin-4-yl}benzonitrile; and
3-(fluoromethyl)-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile;
or a salt thereof.
12. A pharmaceutical composition comprising a compound according to claim 1 .