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 here, 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:
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, cyano and
n is 0-3.
2. The compound of claim 1 wherein R 1 is F, Cl, OMe, CH 2 OMe, Me, fluoromethyl or cyano.
3. The compound of claim 1 wherein R 1 is F, Cl or cyano.
4. The compound of claim 1 wherein R 3 is H, Me, F, Cl or cyano.
5. The compound of claim 1 wherein R 3 is H or F.
6. The compound of claim 1 wherein n is 0 or 1.
7. The compound of 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.
8. A pharmaceutical composition comprising the compound of claim 1 .
9. A method of producing the compound of claim 1 , the method comprising coupling a reagent of formula (X):
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 ; and
R 2 is H or F;
with a 2-pyridyl stannane reagent (Stille coupling) or 2-pyridyl organozinc reagent (Negishi coupling) to form an aryl-aryl bond.