Pyridine compounds, process for their preparation and compositions containing them

1. A compound having the formula:

or a salt, a prodrug, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof;

wherein:

Y 2 is selected independently from —NR 5 ;

R 5 is hydrogen or methyl;

R 1 and R 2 are selected independently from a substituted or an unsubstituted alkyl, cycloalkyl, aryl, or heterocyclyl or heteroaryl comprising at least one heteroatom or heterogroup selected from —O—, —N—, —S—, —CO or —SO 2 , any of which having up to 10 carbon atoms; or

Y 2 R 2 is independently selected from a substituted or an unsubstituted morpholinyl, piperazinyl, piperidinyl, or pyrrolidinyl;

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

R 1 and R 2 are optionally substituted with at least one group independently selected from: 1) an alkyl, an alkoxy, a haloalkyl, a haloalkoxy, —COR 9 , —CO 2 R 8 , —CONR 8 2 , —SO 2 R 9 , —NHSO 2 R 9 , or —SO 2 NR 8 2 , any of which having up to 10 carbon atoms; or 2) halogen, —OCH 2 O—, cyano, or hydroxyl;

R 8 in each occurrence, is selected independently from: 1) an alkyl, a haloalkyl, or an aryl, any of which having up to 10 carbon atoms; or 2) hydrogen;

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

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

or a salt, a prodrug, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof;

wherein:

R 1 is selected from a substituted or an unsubstituted heterocyclyl comprising at least one heteroatom or heterogroup selected from —O—, —N—, —S—, —SO 2 , or —CO, 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 , —CO 2 R 8 , —CONR 8 2 , —SO 2 R 9 , —NHSO 2 R 9 , or —SO 2 NR 8 2 , any of which having up to 10 carbon atoms; or 2) halogen, cyano, —OCH 2 O—, or hydroxyl;

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

R 1 is optionally substituted with at least one group independently selected from: 1) an alkyl, a cycloalkyl, a haloalkyl, or —OCOCH 2 CH 2 CO 2 R 8 , any of which having up to 10 carbon atoms; or 2) hydroxyl.

3. A compound according to claim 2 , wherein:

R 1 is selected from

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

n and m are independently an integer from 0 to 2, inclusive; 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, CONHMe, NHSO 2 Me, SO 2 NH 2 , SO 2 NHMe, SO 2 NMe 2 , CONH 2 , CONMe 2 , CO 2 Me, —OCH 2 O—, or OH.

4. A compound having the formula:

or a salt, a prodrug, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof; wherein:

5. A compound selected from:

[6′-(4-Fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yl]-(4-trifluoromethoxy-phenyl)-amine;

(4-Trifluoromethoxy-phenyl )-[6′-(4-trifluoromethoxy-phenyl )-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yl]-amine;

(6′-Phenyl-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yl )-(4-trifluoro-methoxy-phenyl)-amine;

[6′-(3-Methanesulfonyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yl]-(4-trifluoromethoxy-phenyl)-amine;

4-[6′-(4-Fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-ylamino]-N-methyl-benzenesulfonamide;

1-[4-(4-Hydroxy-6′-phenyl-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-ylamino)-phenyl]-ethanone;

(6-Phenyl-4-pyrrolidin-1-yl-pyridin-2-yl)-(4-trifluoromethoxy-phenyl)-amine;

[6-(4-Fluoro-phenyl)-4-pyrrolidin-1-yl-pyridin-2-yl]-(4-trifluoromethoxy-phenyl)-amine;

N-Methyl-4-[4-pyrrolidin-1-yl-6-(4-trifluoromethoxy-phenyl)-pyridin-2-ylamino]-benzenesulfonamide;

N-Methyl-4-[4-(4-methyl-piperazin-1-yl)-6-(4-trifluoromethoxy-phenylamino)-pyridin-2-yl]-benzenesulfonamide;

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

N-Methyl-4-[4-morpholin-4-yl-6-(4-trifluoromethoxy-phenylamino)-pyridin-2-yl]-benzenesulfonamide;

or any combination thereof;

or a salt, a prodrug, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof.

6. A compound according to claim 4 , wherein:

7. A compound according to claim 5 wherein the compound is 1-[4-(4-hydroxy-6′-phenyl-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-ylamino)-phenyl]-ethanone.

8. A compound according to claim 1 having the formula:

or a salt, a prodrug, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof;

wherein:

R 1 is a substituted heterocyclyl with a single heteroatom wherein the heteroatom is —N—;

m is 0;

n is 1;

R 12 is —COR 9 ;

R 9 is an alkyl having one carbon atom; and

R 1 is substituted with hydroxyl.

9. A compound according to claim 8 , wherein:

R 1 is

X is CH(OH);

m is 0;

n is 1; and

R 12 is COMe.

10. A compound according to claim 8 , having the formula:

or a pharmaceutically acceptable salt, a prodrug, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof.

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the formula:

wherein:

Y 2 is selected independently from —NR 5 ;

R 5 is hydrogen or methyl;

R 1 and R 2 are selected independently from a substituted or an unsubstituted alkyl, cycloalkyl, aryl, or heterocyclyl or heteroaryl comprising at least one heteroatom or heterogroup selected from —O—, —N—, —S—, —CO or —SO 2 , any of which having up to 10 carbon atoms; or

Y 2 R 2 is independently selected from a substituted or an unsubstituted morpholinyl, piperazinyl, piperidinyl, or pyrrolidinyl

R 4 is selected independently from: 1) a substituted or an unsubstituted aryl, or a substituted or an unsubstituted heteroaryl or heterocyclyl comprising at least one heteroatom or heterogroup selected from —O—, —N—, —S—, or —CO, any of which having up to 10 carbon atoms;

wherein any of R 1 or R 2 , is also optionally substituted with at least one group independently selected from: 1) an alkyl, an alkoxy, a haloalkyl, a haloalkoxy, —COR 9 , —CO 2 R 8 , —CONR 8 2 , —SO 2 R 9 , —NHSO 2 R 9 , or —SO 2 NR 8 2 , any of which having up to 10 carbon atoms; or 2) hydroxyl, halogen, —OCH 2 O—, or cyano;

R 8 , in each occurrence, is selected independently from: 1) an alkyl, a haloalkyl, or an aryl, any of which having up to 10 carbon atoms; or 2) hydrogen;

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

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

or a pharmaceutically acceptable salt, a prodrug, a diastereomeric mixture, an enatiomer, a tautomer, or a racemic mixture thereof.

12. The composition as claimed in claim 11 , 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.

13. The composition as claimed in claim 11 , further comprising an agent selected from an immunosuppressive agent, a cytotoxic agent, an anti-inflammatory agent, an antirheumatic agent, a cardiovascular agent, or any combination thereof.

14. The composition as claimed in claim 11 , 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.

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

wherein:

or a pharmaceutically acceptable salt, a prodrug, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof.

16. The composition as claimed in claim 15 , 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.

17. The composition as claimed in claim 15 , further comprising an agent selected from an immunosuppressive agent, a cytotoxic agent, an anti-inflammatory agent, an antirheumatic agent, a cardiovascular agent, or any combination thereof.

18. The composition as claimed in claim 15 , 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.

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

[6′-(4-Fluoro-phenyl )-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yl]-(4-trifluoromethoxy-phenyl)-amine;

(4-Trifluoromethoxy-phenyl)-[6′-(4-trifluoromethoxy-phenyl )-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yl]-amine;

(6′-Phenyl-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yl )-(4-trifluoro-methoxy-phenyl)-amine;

[6′-(3-Methanesulfonyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-yl]-(4-trifluoromethoxy-phenyl)-amine;

4-[6′-(4-Fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-ylamino]-N-methyl-benzenesulfonamide;

1-[4-(4-Hydroxy-6′-phenyl-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-ylamino)-phenyl]-ethanone;

(6-Phenyl-4-pyrrolidin-1-yl-pyridin-2-yl)-(4-trifluoromethoxy-phenyl)-amine;

[6-(4-Fluoro-phenyl)-4-pyrrolidin-1-yl-pyridin-2-yl]-(4-trifluoromethoxy-phenyl)-amine;

N-Methyl-4-[4-pyrrolidin-1-yl-6-(4-trifluoromethoxy-phenyl)-pyridin-2-ylamino]-benzenesulfonamide;

N-Methyl-4-[4-(4-methyl-piperazin-1-yl)-6-(4-trifluoromethoxy-phenylamino)-pyridin-2-yl]-benzenesulfonamide;

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

N-Methyl-4-[4-morpholin-4-yl-6-(4-trifluoromethoxy-phenylamino)-pyridin-2-yl]-benzenesulfonamide;

(4-Fluoro-phenyl)-[6-(4-trifluoromethoxy-phenyl )-pyridin-2-yl]-amine;

or any combination thereof;

or a pharmaceutically acceptable salt, a prodrug, a diastereomeric mixture, an enantiomer, a tautomer, or a racemic mixture thereof.

20. A composition according to claim 19 , 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.

21. The composition as claimed in claim 19 , further comprising an agent selected from an immunosuppressive agent, a cytotoxic agent, an anti-inflammatory agent, an antirheumatic agent, a cardiovascular agent, or any combination thereof.

22. The composition as claimed in claim 19 , 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.

23. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 15 wherein:

24. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 19 wherein the compound is 1-[4-(4-Hydroxy-6′-phenyl-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-ylamino)-phenyl]-ethanone.