Pyrimidine compounds, process for their preparation and compositions containing them

1. A compound having the formula:

or a salt thereof;

wherein:

R 4 is selected from a substituted or an unsubstituted heterocyclyl comprising at least one heteroatom or heterogroup selected from —O—, —NH—, —S—, or, any of which having up to 10 carbon atoms;

n and m are independently an integer from 0 to 3, inclusive;

R 11 and R 12 , in each occurrence, are selected independently from: 1) an alkyl, an alkoxy, a haloalkyl, a haloalkoxy, —COR 9 , —CONR 8 2 , —CO 2 R 8 , —SO 2 R 9 , —SR 8 , —NHSO 2 R 9 , or —SO 2 NR 8 2 , any of which having up to 10 carbon atoms; or 2) halogen, hydroxyl, or —OCH 2 O—; and

R 4 is optionally substituted with at least one group independently selected from: 1) an alkyl, —COR 9 , —CO 2 R 8 , —CONR 8 2 , —SO 2 R 9 , or —SO 2 NR 10 2 , any of which having up to 10 carbon atoms; or 2) hydroxyl;

R 8 , in each occurrence, is selected independently from: 1) an alkyl, a haloalkyl, or an aryl having up to 6 carbon atoms; or 2) hydrogen;

R 9 , in each occurrence, is selected independently from an alkyl, a haloalkyl, an aryl, or a heterocyclyl or a heteroaryl comprising at least one heteroatom selected from —O— or —N—, any of which having up to 10 carbon atoms; and

R 10 , in each occurrence, is selected independently from: 1) an alkyl, an aryl, or a heterocyclyl comprising at least one heteroatom selected from —O— or —N—, any of which having up to 10 carbon atoms; or 2) hydrogen.

2. A compound according to claim 1 , wherein:

R 4 is selected from

 wherein X is selected from CH 2 , O, NH, NMe, NEt, S, SO 2 , or CH(OH); and

R 11 and R 12 , in each occurrence, are selected independently from OCF 3 , OMe, Cl, F, SO 2 Me, CF 3 , Me, COMe, SMe, CONHMe, NHSO 2 Me, SO 2 NH 2 , SO 2 NHMe, SO 2 NMe 2 , CONH 2 , CONMe 2 , CO 2 Me, CO 2 H, —OCH 2 O—, or OH.

3. A compound according to claim 1 selected from:

1-[2-(3-Chloro-4-methoxy-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-(4-trifluoromethoxy-phenyl)-amine;

4-[4-(4-Hydroxy-piperid in-1-yl)-6-phenyl-pyrimid in-2-ylamino]-N-methylbenzenesulfonamide;

1-{4-[4-(4-Hydroxy-piperid in-1-yl)-6-phenyl-pyrimid in-2-ylamino]-phenyl}-ethanone hydro chloride;

1-[2-(3-Chloro-4-hydroxy-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

1-[2-(3-Fluoro-4-methoxy-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

1-(6-Phenyl-2-phenylamino-pyrimidin-4-yl)-piperidin-4-ol;

(3-Chloro-4-methoxy-phenyl)-(4-phenyl-6-thiomorpholin-4-yl-pyrimidin-2-yl)-amine;

Benzo[1,3]dioxol-5-yl-(4-phenyl-6-thiomorpholin-4-yl-pyrimidin-2-yl)-amine;

(3-Fluoro-4-methoxy-phenyl)-(4-phenyl-6-thiomorpholin-4-yl-pyrimidin-2-yl)-amine;

2-Chloro-4-(4-phenyl-6-thiomorpholin-4-yl-pyrimidin-2-ylamino)-phenol;

(3-Chloro-4-methoxy-phenyl)-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-amine;

Benzo[1,3]dioxol-5-yl-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-amine;

(3-Fluoro-4-methoxy-phenyl)-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-amine;

2-Chloro-4-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-phenol;

1-[6-Phenyl-2-(3-trifuoromethyl-phenylamino)-pyrimidin-4-yl]-piperidin-4-ol;

Benzo[1,3]dioxol-5-yl-[4-(4-fluoro-phenyl)-6-morpholin-4-yl-pyrimidin-2-yl]-amine;

1-[2-Benzo[1,3]dioxol-5-ylamino)-6-phenyl-pyrimid in-4-yl]-piperdin-4-ol;

[4-(4-Fluoro-phenyl)-6-morpholin-4-yl-pyrimidin-2-yl]-(3-trifluoromethyl-phenyl)-amine

(4-Fluoro-phenyl)-[4-(4-fluoro-phenyl)-6-morpholin-4-yl-pyrimidin-2-yl]amine;

1-[2-(4-Chloro-3-trifluoromethyl-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-(3-trifluoromethyl-phenyl)-amine;

N-{4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimid in-2-ylamino]-phenyl}-methanesulfonamide;

N-[4-(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-phenyl]-methanesulfonamide hydrochloride;

4-[4-(4-Fluoro-phenyl)-6-(4-hydroxy-piperid in-1-yl)-pyrimidin-2-ylamino]-N, N-dimethyl-benzenesulfonamide;

4-[4-(4-Fluoro-phenyl)-6-(4-hydroxy-piperidin-1-yl)-pyrimidin-2-ylamino]-benzenesulfonamide;

4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-N, N-dimethyl-benzenesulfonamide;

4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimid in-2-ylamino]-benzenesulfonamide;

4-[4-(4-Fluoro-phenyl)-6-(4-hydroxy-piperidin-1-yl)-pyrimidin-2-ylamino]-N-methyl-benzenesulfonamide;

4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-benzamide;

4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimid in-2-ylamino]-N-methyl-benzamide;

N-Methyl-4-(4-morpholin-4-yl-6-phenyl-pyrimid in-2-ylamino)-benzenesulfonamide;

N-Methyl-4-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-benzamide;

3-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-benzamide;

1-{3-[4-(4-Hydroxy-piperid in-1-yl)-6-phenyl-pyrimid in-2-ylamino]-phenyl}-ethanone;

3-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-N-methyl-benzamide;

N-Methyl-3-(4-morpholin-4-yl-6-phenyl-pyrimid in-2-ylamino)-benzamide;

1-[4-(4-Morpholin-4-yl-6-phenyl-pyrimid in-2-ylamino)-phenyl]-ethanone;

3-(4-Morpholin-4-yl-6-phenyl-pyrimid in-2-ylamino)-benzamide;

1-[3-(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-phenyl]-ethanone;

3-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamina]-benzenesulfonamide;

3-(4-Morpholin-4-yl-6-phenyl-pyrimid in-2-ylamino)-benzenesulfonamide;

1-{4-[4-(4-Fluoro-phenyl)-6-morpholin-4-yl-pyrimid in-2-ylamino]-phenyl}-ethanone;

1-{4-[4-(4-Fluoro-phenyl)-6-(4-hydroxy-piperidin-1-yl)-pyrimidin-2-ylamino]-phenyl}-ethanone;

1-[6-Phenyl-2-(4-trifluoromethoxy-phenylamino)-pyrimidin-4-yl]-piperid in-4-ol;

(3-Chloro-4-methoxy-phenyl)-(4-phenyl-6-piperazin-1-yl-pyrimidin-2-yl)-amine;

Succinic acid mono-{1-[2-(3-chloro-4-methoxy-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-yl}ester;

(3-Chloro-4-methoxy-phenyl)-[4-(4-ethyl-piperazin-1-yl)-6-phenyl-pyrimid in-2-yl]-amine;

(3-Chloro-4-methoxy-phenyl)-[4-(4-methyl-piperazin-1-yl)-6-phenyl-pyrimidin-2-yl]-amine;

[4-(1,1-Dioxo-1-lambda-6-thiomorpholin-4-yl)-6-phenyl-pyrimidin-2-yl]-(3-fluoro-4-methoxy-phenyl)-amine;

1-[2-(4-Methanesulfonyl-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

[4,6-Bis-(4fluoro-phenyl)-pyrimidin-2-yl]-(4-trifluoromethoxy-phenyl)-amine;

[4-(3-Methanesulfonyl-phenyl)-6-morpholin-4-yl-pyrimidin-2-yl]-(4-trifluoromethoxyphenyl)-amine;

1-{4-[4-(4-Hydroxy-piperid in-1-yl)-6-phenyl-pyrimid in-2-ylamino]-phenyl}-ethanone;

1-[2-(4-methylsulfanyl-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol; or any combination thereof;

or a salt thereof.

4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected from:

wherein:

R 4 is selected from a substituted or an unsubstituted heterocyclyl comprising at least one heteroatom or heterogroup selected from —O—, —NH—, —S—, or, any of which having up to 10 carbon atoms;

n and m are independently an integer from 0 to 3, inclusive;

R 4 is optionally substituted with at least one group independently selected from: 1) an alkyl, —COR 9 , —CO 2 R 8 , —CONR 8 2 , —SO 2 R 9 , or, —SO 2 NR 10 2 any of which having up to 10 carbon atoms; or 2) hydroxyl;

R 8 , in each occurrence, is selected independently from: 1) an alkyl, a haloalkyl, or an aryl having up to 6 carbon atoms; or 2) hydrogen;

R 9 , in each occurrence, is selected independently from an alkyl, a haloalkyl, an aryl, or a heterocyclyl or a heteroaryl comprising at least one heteroatom selected from —O— or —N—, any of which having up to 10 carbon atoms; and

R 10 , in each occurrence, is selected independently from: 1) an alkyl, an aryl, or a heterocyclyl comprising at least one heteroatom selected from —O— or —N—, any of which having up to 10 carbon atoms; or 2) hydrogen;

R 11 and R 12 , in each occurrence, are selected independently from: 1) an alkyl, an alkoxy, a haloalkyl, a haloalkoxy, —COR 9 , —CONR 8 2 , —CO 2 R 8 , SO 2 R 9 , SR 8 , NHSO 2 R 9 , or —SO 2 NR 8 2 , any of which having up to 10 carbon atoms; or 2) halogen, hydroxyl, or —OCH 2 O—;

or a pharmaceutically acceptable salt thereof.

5. The composition as claimed in claim 4 , wherein the composition is in the form of a tablet, a capsule, a cachet, a powder, a granule, a solution, a suspension, an emulsion, a bolus, a lozenge, a suppository, a pessary, a tampon, a cream, a gel, a paste, a foam, a spray, an aerosol, a microcapsule, a liposome, a transdermal patch, a pastille, a paste, or a mouthwash.

6. A pharmaceutical composition according to claim 4 comprising pharmaceutically acceptable carrier and a compound selected from:

1-[2-(3-Chloro-4-methoxy-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-(4-trifluoromethoxy-phenyl)-amine;

4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimid in-2-ylamino]-N-methylbenzenesulfonamide;

1-{4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-phenyl}-ethanone hydro chloride;

1-[2-(3-Chloro-4-hydroxy-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

1-[2-(3-Fluoro-4-methoxy-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

1-(6-Phenyl-2-phenylamino-pyrimidin-4-yl)-piperidin-4-ol;

(3-Chloro-4-methoxy-phenyl)-(4-phenyl-6-thiomorpholin-4-yl-pyrimidin-2-yl)-amine;

Benzo[1,3]dioxol-5-yl-(4-phenyl-6-thiomorpholin-4-yl-pyrimidin-2-yl)-amine;

(3-Fluoro-4-methoxy-phenyl)-(4-phenyl-6-thiomorpholin-4-yl-pyrimidin-2-yl)-amine;

2-Chloro-4-(4-phenyl-6-thiomorpholin-4-yl-pyrimidin-2-ylamino)-phenol;

(3-Chloro-4-methoxy-phenyl)-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-amine;

Benzo[1,3]dioxol-5-yl-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-amine;

(3-Fluoro-4-methoxy-phenyl)-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-amine;

2-Chloro-4-(4-morpholin-4-yl-6-phenyl-pyrimid in-2-ylamino)-phenol;

1-[6-Phenyl-2-(3-trifluoromethyl-phenylamino)-pyrimidin-4-yl]-piperidin-4-ol;

Benzo[1,3]dioxol-5-yl-[4-(4-fluoro-phenyl)-6-morpholin-4-yl-pyrimidin-2-yl]-amine;

1-[2-(Benzo[1,3]dioxol-5-ylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

[4-(4-Fluoro-phenyl)-6-morpholin-4-yl-pyrimidin-2-yl]-(3-trifluoromethyl-phenyl)-amine;

(4-Fluoro-phenyl)-[4-(4-fluoro-phenyl)-6-morpholin-4-yl-pyrimidin-2-yl]-amine;

1-[2-(4-Chloro-3-trifluoromethyl-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-yl)-(3-trifluoromethyl-phenyl)-amine;

N-{4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimid in-2-ylamino]-phenyl}-methanesulfonamide;

N-[4-(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-phenyl]-methanesulfonamide hydrochloride;

4-[4-(4-Fluoro-phenyl)-6-(4-hydroxy-piperidin-1-yl)-pyrimidin-2-ylamino]-N,N-dimethyl-benzenesulfonamide;

4-[4-(4-Fluoro-phenyl)-6-(4-hydroxy-piperid in-1-yl)-pyrimidin-2-ylamino]-benzenesulfonamide;

4-[4-(4-Hydroxy-piperid in-1-yl)-6-phenyl-pyrimidin-2-ylamino]-N, N-dimethyl-benzenesulfonamide;

4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-benzenesulfonamide;

4-[4-(4-Fluoro-phenyl)-6-(4-hydroxy-piperidin-1-yl)-pyrimidin-2-ylamino]-N-methyl-benzenesulfonamide;

4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-benzamide;

4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-N-methyl-benzamide;

N-Methyl-4-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-benzenesulfonamide;

N-Methyl-4-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-benzamide;

3-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-benzamide;

1-{3-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-phenyl}-ethanone;

3-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimid in-2-ylamino]-N-methyl-benzamide;

N-Methyl-3-(4-morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-benzamide;

1-[4-(4-Morpholin-4-yl-6-phenyl-pyrimid in-2-ylamino)-phenyl]-ethanone;

3-(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-benzamide;

1-[3-(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-phenyl]-ethanone;

3-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-benzenesulfonamide;

3-(4-Morpholin-4-yl-6-phenyl-pyrimidin-2-ylamino)-benzenesulfonamide;

1-{4-[4-(4-Fluoro-phenyl)-6-morpholin-4-yl-pyrimidin-2-ylamino]-phenyl}-ethanone;

1-{4-[4-(4-Fluoro-phenyl)-6-(4-hydroxy-piperidin-1-yl)-pyrimidin-2-ylamino]-phenyl}-ethanone;

1-[6-Phenyl-2-(4-trifluoromethoxy-phenylamino)-pyrimidin-4-yl]-piperidin-4-ol;

(3-Chloro-4-methoxy-phenyl)-(4-phenyl-6-piperazin-1-yl-pyrimidin-2-yl)-amine;

Succinic acid mono-{1-[2-(3-chloro-4-methoxy-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-yl}ester;

(3-Chloro-4-methoxy-phenyl)-[4-(4-ethyl-piperazin-1-yl)-6-phenyl-pyrimid in-2-yl]-amine;

(3-Chloro-4-methoxy-phenyl)-[4-(4-methyl-piperazin-1-yl)-6-phenyl-pyrimidin-2-yl]-amine;

[4-(1,1-Dioxo-1-lambda-6-thiomorpholin-4-yl)-6-phenyl-pyrimidin-2-yl]-(3-fluoro-4-methoxy-phenyl)-amine;

1-[2-(4-Methanesulfonyl-phenylamino)-6-phenyl-pyrimidin-4-yl]-piperidin-4-ol;

[4,6-8 is-(4-fluoro-phenyl)-pyrimidin-2-yl]-(4-trifluoromethoxy-phenyl)-amine;

[4-(3-Methanesulfonyl-phenyl)-6-morpholin-4-yl-pyrimidin-2-yl]-(4-trifluoromethoxy-phenyl)-amine;

1-{4-[4-(4-Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidin-2-ylamino]-phenyl}-ethanone;

1-[2-(4-methylsulfanyl-phenylamino)-6-phenyl-pyrimid in-4-yl]-piperidin-4-ol;

or any combination thereof;

or a pharmaceutically acceptable salt thereof.

7. The composition as claimed in claim 6 , further comprising:

optionally, a pharmaceutically acceptable auxiliary;

optionally, a pharmaceutically acceptable preservative;

optionally, a pharmaceutically acceptable excipient;

optionally, a pharmaceutically acceptable diluent; and

optionally, a pharmaceutically acceptable solvate.

8. The composition as claimed in claim 6 , wherein the composition is in the form of a tablet, a capsule, a cachet, a powder, a granule, a solution, a suspension, an emulsion, a bolus, a lozenge, a suppository, a pessary, a tampon, a cream, a gel, a paste, a foam, a spray, an aerosol, a microcapsule, a liposome, a transdermal patch, a pastille, a paste, or a mouthwash.

9. The compound of claim 3 wherein the compound is 1-{4-[4-(4Hydroxy-piperidin-1-yl)-6-phenyl-pyrimidine-2-ylamino]-phenyl)-ethanone.