Oxazolidinone compounds and their use as metabotropic glutamate receptor potentiators

1. A compound according to Formula I:

wherein:

R 1 is an optionally substituted phenyl group having one or more independently selected R 6 substituents;

R 2 is selected from the group consisting of H, F, Cl, Br, I, alkyl and alkylhalo substituents;

R 6 is independently selected from the group consisting of H, hydroxy, F, Cl, Br, I, nitro, CN, oxo, alkyl, alkylhalo, O-alkyl, O-alkylhalo, alkenyl, O-alkenyl, alkynyl, O-alkynyl, cycloalkyl, alkylene-cycloalkyl, O-cycloalkyl, O-alkyl-cycloalkyl, heterocycloalkyl, alkylene-heterocycloalkyl, O-heterocycloalkyl, O-alkylene-heterocycloalkyl, aryl, alkylenearyl, O-aryl, O-alkylenearyl, heteroaryl, alkyleneheteroaryl, O-heteroaryl, O-alkyleneheteroaryl, alkyleneOR 4 , O-alkyleneOR 4 , (CO)R 3 , O(CO)R 3 , alkyleneO(CO)R 3 , alkylene(CO)R 3 , O-alkylene(CO)R 3 , CO 2 R 4 , alkyleneCO 2 R 3 , O-alkyleneCO 2 R 3 , alkylenecyano, O-alkylenecyano, NR 4 R 5 , alkyleneNR 4 R 5 , O-alkyleneNR 4 R 5 , (CO)NR 4 R 5 , alkylene(CO)NR 4 R 5 , O—(CO)NR 4 R 5 , O-alkylene(CO)NR 4 R 5 , NR 4 (CO)R 3 , alkyleneNR 4 (CO)R 3 , O-alkyleneNR 4 (CO)R 3 , NR 4 (CO)NR 4 R 13 , alkyleneNR 4 (CO)NR 4 R 5 , SR 4 , alkyleneSR 5 , O-alkyleneSR 4 , (SO)R 3 , alkylene(SO)R 3 , O-alkylene(SO)R 3 , SO 2 R 3 , alkyleneSO 2 R 3 , O-alkyleneSO 2 R 3 , (SO 2 )NR 4 R 5 , alkylene(SO 2 )NR 4 R 5 , O-alkylene(SO 2 )NR 7 R 8 , NR 7 (SO 2 )R 8 , alkyleneNR 7 (SO 2 )R 8 , O-alkyleneNR 4 (SO 2 )R 5 , NR 4 (SO 2 )NR 4 R 5 , alkyleneNR 4 (SO 2 )NR 4 R 5 , O-alkyleneNR 4 (SO 2 )NR 4 R 5 , NR 4 (CO)OR 5 , alkylNR 4 (CO)OR 5 , O-alkylNR 4 (CO)OR 5 , SO 3 R 4 and any cyclic moiety may be further substituted with a substituent selected from the group consisting of alkyl, O-alkyl or haloalkyl;

R 3 is independently selected from the group consisting of H, hydroxy, alkyl, alkylhalo, O-alkyl, O-alkylhalo, alkenyl, O-alkenyl, alkynyl, O-alkynyl, cycloalkyl, O-cycloalkyl, alkylenecycloalkyl, O-alkylene-cycloalkyl, heterocycloalkyl, O-heterocycloalkyl, alkyleneheterocycloalkyl, O-alkyleneheterocycloalkyl, aryl, O-aryl, alkylenearyl, O-alkylenearyl, heteroaryl, O-heteroaryl, alkyleneheteroaryl, O-alkyleneheteroaryl and any cyclic moiety may be further substituted with a substituent selected from the group consisting of alkyl, halo, haloalkyl O-alkyl, aryl, alkylenearyl, heteroaryl, alkyleneheteroaryl, and any cyclic moiety may be further substituted with a substituent selected from the group consisting of halo, alkyl, O-alkyl, haloalkyl, O-haloalkyl and NR 4 R 5 ;

R 4 and R 5 are independently selected from the group consisting of H, alkyl, alkylhalo, alkenyl, alkynyl, cycloalkyl, alkylenecycloalkyl, heterocycloalkyl, alkyleneheterocycloalkyl, aryl, alkylenearyl, heteroaryl, and alkyleneheteroaryl, NR 7 R 8 , alkyleneNR 7 R 8 , OR 7 , alkyleneOR 7 , and any cyclic moiety may be further substituted with a substituent selected from the group consisting of alkyl, halo, haloalkyl O-alkyl, O-haloalkyl, aryl, alkylenearyl, heteroaryl, alkyleneheteroaryl; R 7 and R 8 are independently selected from the group consisting of H and alkyl;

Y is —CH 2 —; and

m is 1, and

n is 0, 1, 2, 3 or 4;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 wherein R 2 is H, Cl or F, or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 2 wherein R 2 is Cl, or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 1 selected from the group consisting of:

3-Biphenyl-4-ylmethyl-5-(R)-phenyl)-oxazolidin-2-one;

4′-(2-Oxo-5-(R)-phenyl-oxazolidin-3-ylmethyl) biphenyl-3-carboxylic acid (2-dimethylamino-ethyl)-amide;

3-[4′-(4-Methyl-piperazine-1-carbonyl)-biphenyl-4-ylmethyl]-5-(R)-phenyl-oxazolidin-2-one;

3-[3′-(4-Methyl-piperazine-1-carbonyl)-biphenyl-4-ylmethyl]-5-(R)-phenyl-oxazolidin-2-one;

4′-(2-Oxo-5-(R)-phenyl-oxazolidin-3-ylmethyl) biphenyl-4-carboxylic acid (2-dimethylamino-ethyl)-amide;

4′-[5-(4-Fluorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid (2-dimethylamino-ethyl)-amide;

5-(4-Fluorophenyl)-3-(2′-morpholin-4-ylmethyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

4′-[5-(4-Fluorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid;

5-(4-Fluorophenyl)-3-[3′-(4-methyl-piperazine-1-carbonyl)-biphenyl-4-ylmethyl]-oxazolidin-2-one;

3-(4′-Dimethylamino methyl-biphenyl-4-ylmethyl)-5-(4-fluorophenyl)-oxazolidin-2-one;

4′-[5-(4-Fluorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid (2-dimethylamino-ethyl)-methyl-amide;

4′-[5-(4-Fluorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid (2-hydroxyethyl)-amide;

4′-[5-(4-Fluorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid ethylamine;

4′-[5-(R)-(4-Chlorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid (2-dimethylamino-ethyl)-amide;

3′-(2-oxo-5-(R)-phenyl-oxazolidin-3-ylmethyl)-biphenyl-3-carboxylic acid (2-dimethylamino-ethyl)-amide;

4′-(2-oxo-5-(R)-phenyl-oxazolidin-3-ylmethyl)-biphenyl-4-carboxylic acid (1-benzyl-pyrrolidin-3-(S)-yl)-amide;

4′-[5-(S)-(4-Fluorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid (2-dimethylamino-ethyl)-methyl-amide;

4′-[5-(R)-(4-Fluorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid (2-dimethylamino-ethyl)-methyl-amide;

5-(R)-(4-Chlorophenyl)-3-(2′-morpholin-4-ylmethyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

4′-[5-(R)-(4-Chlorophenyl)-2-oxo-oxazolidin-3-yl methyl]-biphenyl-3-carboxylic acid (2-dimethylamino-ethyl)-methyl-amide;

3-[4′-(4-Methyl-piperazin-1-ylmethyl)-biphenyl-4-yl methyl]-5-phenyl-oxazolidin-2-one;

5-(4-Fluorophenyl)-3-[3′-(4-methyl-piperazin-1-ylmethyl)-biphenyl-4-ylmethyl]-oxazolidin-2-one;

5-(4-Fluorophenyl)-3-(3′-morpholin-4-yl methyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(4-Fluorophenyl)-3-(3′-piperazin-1-ylmethyl)-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(3′-diethylaminomethyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(3′-{[dimethylaminoethyl)-methylamino]-methyl} biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(3′-piperidin-1-yl methyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(3′-morpholin-4-yl methyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-[3′-(4-methyl-piperazin-1-ylmethyl)-biphenyl-4-ylmethyl]-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(3′-dimethylaminomethyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(3′-piperazin-1-ylmethyl)-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(2′-dimethylaminomethyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(2′-{[(2-dimethylaminoethyl)-methyl-amino]-methyl}-biphenyl-4-yl methyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(2′-(4-methyl-piperazin-1-yl methyl)-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-[2′-(3-(S)-dimethylamino-pyrrolidin-1-yl methyl)-1-biphenyl-4-ylmethyl]-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(2′-piperidin-1-yl methyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-[2′-(3-(R)-dimethylamino-pyrrolidin-1-yl methyl)-1-biphenyl-4-ylmethyl]-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(2′-piperazin-1-yl methyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(4′-dimethylaminomethyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(4′-{[(2-dimethylamino ethyl)-methyl-amino]-methyl}-biphenyl-4-yl methyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(4′-morpholin-4-yl methyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(4′-piperidin-1-yl methyl-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-[4′-(4-methyl-piperazin-1-yl methyl)-biphenyl-4-ylmethyl)-oxazolidin-2-one;

5-(R)-(4-Chlorophenyl)-3-(4′-piperazin-1-yl methyl-biphenyl-4-ylmethyl)-oxazolidin-2-one, and

5-(4-Fluorophenyl)-3-(3′-hydroxymethyl-biphenyl-4-ylmethyl)-oxazolidin-2-one

or a pharmaceutically acceptable salt of any foregoing compound.

5. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier or excipient.

6. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 4 and a pharmaceutically acceptable carrier or excipient.