2-oxo-piperidinyl derivatives

1. A 2-Oxo-piperidinyl compound of the form according to formula I, or a geometrical isomer, enantiomer, diastereomer or mixture, or a pharmaceutically acceptable salt thereof,

wherein

X is either CH or N; Y is either —NR 4 — or —CH═CH—; with the proviso that X is N when Y is —NR 4 —;

n is an integer selected from 1, 2 or 3; m is 1 or 2;

R 1 is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle, a substituted or unsubstituted C 3-8 cycloalkyl; or R 1 is a —O—R 2 moiety;

R 2 is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl;

R 3 is hydrogen, substituted or unsubstituted C 1-4 alkyl or halogen; and

R 4 is hydrogen or C 1-4 alkyl.

2. The compound according to claim 1 having formula I-A,

wherein

X is either CH or N;

n is an integer selected from 1, 2 or 3; m is 1 or 2;

R 1 is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle, a substituted or unsubstituted C 3-8 cycloalkyl; or R 1 is a —O—R 2 moiety whereby R 2 is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and

R 3 is hydrogen, substituted or unsubstituted C 1-4 alkyl or halogen.

3. The compound according to claim 1 having formula I-B,

wherein

n is an integer selected from 1, 2 or 3; m is 1 or 2;

R 1 is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocycle, a substituted or unsubstituted C 3-8 cycloalkyl; or R 1 is a —O—R 2 moiety; whereby R 2 is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and

R 4 is hydrogen or C 1-4 alkyl.

4. The compound according to claim 1 , wherein R 1 is benzyl, 2-bromobenzyl, tert-butyl, 2-methylpropyl, 2-fluoro-2-methylpropyl, 2-chloro-2,2-difluoroethyl, 2-oxo-2-(pyrrolidin-1-yl)ethyl, 2,2,2-trifluoroethyl, propyl, phenyl, 2-carbamoylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3,4-difluorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-hydroxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxy-phenyl, 2-(methylcarbamoyl)phenyl, 2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl, 2-(pyrrolidin-1-ylcarbonyl)phenyl, 2-(trifluoromethyl)phenyl, 3-(trifluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, cyclohexyl, 4,4-difluorocyclohexyl, pyridin-2-yl, 6-cyanopyridin-2-yl, 3-fluoropyridin-2-yl, 5-fluoropyridin-2-yl, 6-methoxypyridin-2-yl, 6-methylpyridin-2-yl, 6-(4-fluorophenyl)pyridin-2-yl, 6-(propan-2-yloxy)pyridin-2-yl, 6-(1H-pyrazol-1-yl)pyridin-2-yl, 6-trifluoromethylpyridin-2-yl, 6-(cyclobutyloxy)-pyridin-2-yl, 6-(difluoromethoxy)pyridin-2-yl, 6-(2,2,2-trifluoroethoxy)pyridin-2-yl, pyridin-3-yl, 2-fluoropyridin-3-yl, pyridin-4-yl, 4-methoxypyrimidin-2-yl, 4-methyl-1,3-thiazol-2-yl, 4-methyl-1,3-thiazol-5-yl, 1-acetylpiperidin-2-yl, tetrahydro-2H-pyran-3-yl, tetrahydro-2H-pyran-4-yl, tetrahydrofuran-2-yl.

5. The compound according to claim 1 having formula I-C,

wherein

X is either CH or N;

R 1 is a substituted or unsubstituted C 1-4 alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted C 3-6 cycloalkyl; or R 1 is a —O—R 2 moiety;

R 2 is a substituted or unsubstituted C 1-4 -alkyl aryl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; and

R 3 is hydrogen, substituted or unsubstituted C 1-4 alkyl or halogen.

6. The compound according to claim 1 having formula I-D,

wherein

X is either CH or N;

R 1 is a substituted or unsubstituted C 1-4 alkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted C 3-6 cycloalkyl; or R 1 is a —O—R 2 moiety; and

R 2 is a substituted or unsubstituted C 1-4 -alkyl aryl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

7. The compound according to claim 1 having formula I-E,

wherein

X is either CH or N;

R 1 is a substituted or unsubstituted C 1-4 alkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted pyridinyl, a substituted or unsubstituted pyrimidinyl, a substituted or unsubstituted thiazolyl, a substituted or unsubstituted piperidinyl, a substituted or unsubstituted tetrahydropyranyl, a substituted or unsubstituted tetrahydrofuranyl, a substituted or unsubstituted cyclohexyl; or R 1 is a —O—R 2 moiety; and

R 2 is a substituted or unsubstituted benzyl, a substituted or unsubstituted phenyl, or a substituted or unsubstituted pyridinyl.

8. The compound according to claim 1 selected from the group comprising:

(+)-2-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzamide oxalate;

N-methyl-2-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzamide oxalate;

2-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzonitrile oxalate;

2-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}piperidin-3-yl)benzamide oxalate;

1-[2-(2-{3-[2-(trifluoromethyl)phenyl]pyrrolidin-1-yl}ethyl)phenyl]piperidin-2-one oxalate;

1-(2-{2-[3-(2-methoxyphenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(3-methoxyphenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(4-methoxyphenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(2-fluorophenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(2-chlorophenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-[2-(2-{3-[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]pyrrolidin-1-yl}ethyl)phenyl]piperidin-2-one;

(+)-2-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzonitrile oxalate;

(−)-2-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzonitrile oxalate;

1-{2-[2-(3-phenylpyrrolidin-1-yl)ethyl]phenyl}piperidin-2-one;

3-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzonitrile oxalate;

4-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzonitrile oxalate;

(−)-1-[2-(2-{3-[2-(pyrrolidin-1-ylcarbonyl)phenyl]pyrrolidin-1-yl}ethyl)phenyl]piperidin-2-one;

1-(2-{2-[3-(2-methoxyphenyl)piperidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

(+)-1-(2-{2-[3-(2-methoxyphenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

(−)-1-(2-{2-[3-(2-methoxyphenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-[2-(2-{3-[3-(trifluoromethyl)phenyl]pyrrolidin-1-yl}ethyl)phenyl]piperidin-2-one oxalate;

1-(2-{2-[3-(3-fluorophenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-{2-[2-(3-phenylazetidin-1-yl)ethyl]phenyl}piperidin-2-one oxalate;

1-(2-{2-[3-(3-fluorophenyl)piperidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(3-methoxyphenyl)piperidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-{2-[2-(3-phenylpiperidin-1-yl)ethyl]phenyl}piperidin-2-one oxalate;

1-(2-{2-[3-(4-chlorophenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(3-chlorophenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(benzyloxy)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(4-fluorophenyl)azetidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

3-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}azetidin-3-yl)benzonitrile oxalate;

1-(2-{2-[3-(2-fluorophenyl)azetidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-{2-[2-(3-cyclohexylpyrrolidin-1-yl)ethyl]phenyl}piperidin-2-one oxalate;

1-(2-{2-[3-(2-hydroxyphenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one dioxalate;

1-(2-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(4-fluorophenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[(3R)-3-(2,2,2-trifluoroethyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one trifluoroacetate;

1-(2-{2-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

4-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}piperidin-3-yl)benzonitrile oxalate;

(−)-4-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzonitrile oxalate;

(+)-4-(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)benzonitrile oxalate;

1-(2-{2-[3-(2-methoxyphenyl)azetidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(3-fluorophenyl)azetidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(3,4-difluorophenyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(3-methoxyphenyl)azetidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-{2-[2-(3-benzylpyrrolidin-1-yl)ethyl]phenyl}piperidin-2-one oxalate;

1-(2-{2-[3-(2-methoxyphenoxy)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

4-[(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}pyrrolidin-3-yl)oxy]benzonitrile;

1-(2-{2-[3-(tetrahydro-2H-pyran-4-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-{2-[2-(3-benzylazetidin-1-yl)ethyl]phenyl}piperidin-2-one;

1-(2-{2-[3-(pyridin-3-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(4,4-difluorocyclohexyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one trifluoroacetate;

4-[(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}azetidin-3-yl)oxy]benzonitrile oxalate;

1-(2-{2-[3-(2-methylpropyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one trifluoroacetate;

1-{2-[2-(3-propylpyrrolidin-1-yl)ethyl]phenyl}piperidin-2-one trifluoroacetate;

3-[(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}azetidin-3-yl)oxy]benzonitrile;

2-[(1-{2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl}azetidin-3-yl)oxy]benzonitrile;

1-(2-{2-[3-(4-fluorophenoxy)azetidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(3-methoxyphenoxy)azetidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(2-bromobenzyl)azetidin-1-yl]ethyl}phenyl)piperidin-2-one;

4-(1-{2-[2-(2-oxopiperidin-1-yl)pyridin-3-yl]ethyl}pyrrolidin-3-yl)benzonitrile;

1-(2-{2-[3-(4-methyl-1,3-thiazol-5-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(5-bromo-2-methoxyphenoxy)azetidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-{2-[2-(3-phenoxyazetidin-1-yl)ethyl]phenyl}piperidin-2-one oxalate;

1-{2-[2-(3-tert-butylpyrrolidin-1-yl)ethyl]phenyl}piperidin-2-one;

1-(2-{2-[3-(2-methoxyphenoxy)azetidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(2-{2-[3-(2-chloro-2,2-difluoroethyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(3-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one;

1-(3-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

1-(2-{2-[3-(1-acetylpiperidin-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(pyridin-4-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(2-fluoropyridin-3-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(tetrahydrofuran-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(tetrahydrofuran-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

(+)-1-(2-{2-[3-(tetrahydro-2H-pyran-4-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one trifluoroacetate;

(+)-1-(2-{2-[3-(tetrahydro-2H-pyran-4-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(3-{2-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

1-(3-{2-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one;

1-(2-{2-[3-(tetrahydro-2H-pyran-3-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one trifluoroacetate;

1-(2-{2-[3-(6-methoxypyridin-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(5-fluoropyridin-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(3-fluoropyridin-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-(2-{2-[3-(2-fluoro-2-methylpropyl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one;

1-[2-(2-{3-[2-oxo-2-(pyrrolidin-1-yl)ethyl]pyrrolidin-1-yl}ethyl)phenyl]piperidin-2-one;

1-(2-{2-[3-(4-methyl-1,3-thiazol-2-yl)pyrrolidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate;

1-(3-{2-[3-(5-fluoropyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one;

1-(3-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate, isomer A;

(+)-1-(3-{2-[3-(4,4-difluorocyclohexyl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

(−)-1-(3-{2-[3-(4,4-difluorocyclohexyl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

1-(3-{2-[3-(6-methoxypyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one;

1-(3-{2-[3-(6-methoxypyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

1-[3-(2-{3-[6-(propan-2-yloxy)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one oxalate;

1-(3-{2-[(3R)-3-(2,2,2-trifluoroethyl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

6-(1-{2-[2-(2-oxopiperidin-1-yl)pyridin-3-yl]ethyl}pyrrolidin-3-yl)pyridine-2-carbonitrile oxalate;

1-(3-{2-[3-(3-fluoropyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

1-[3-(2-{3-[6-(trifluoromethyl)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one;

1-[3-(2-{3-[(5-fluoropyridin-2-yl)oxy]azetidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one;

1-(3-{2-[3-(4-fluorophenoxy)azetidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

1-(3-{2-[3-(2-fluorophenoxy)azetidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

(−)-1-(3-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one oxalate;

1-(3-{2-[3-(6-methylpyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one;

1-[3-(2-{3-[6-(1H-pyrazol-1-yl)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one oxalate;

1-(3-{2-[3-(4-methoxypyrimidin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one;

1-[3-(2-{3-[6-(4-fluorophenyl)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one;

1-[3-(2-{3-[6-(cyclobutyloxy)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one oxalate;

1-[3-(2-{3-[6-(2,2,2-trifluoroethoxy)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one;

1-[3-(2-{3-[6-(difluoromethoxy)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one; 1-[3-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}-5-(trifluoromethyl)pyridin-2-yl]piperidin-2-one;

1-[3-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}-5-(trifluoromethyl)pyridin-2-yl]piperidin-2-one oxalate; and

1-(5-fluoro-3-{2-[3-(pyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one.

9. A pharmaceutical composition comprising a compound according to claim 1 in combination with a pharmaceutically acceptable diluent or carrier.

10. A method of treating migraine in a subject comprising administering to the subject a therapeutically effective amount of a compound according to claim 1 .

11. The compound according to claim 7 wherein R 2 is benzyl or substituted or unsubstituted phenyl.