3-pyridyl carboxamide-containing spleen tyrosine kinase (SYK) inhibitors

1. A compound of the Formula (I)

or a pharmaceutically acceptable salt thereof, wherein

B is pyridyl or quinolinyl;

wherein B is unsubstituted or substituted by 1 to 3 R 3 moieties, wherein each R 3 moiety is independently selected from the group consisting of C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 fluoroalkyl, C 1 -C 3 hydroxyalkyl, halo, hydroxy, amino, (C 1 -C 3 alkyl)amino, di(C 1 -C 3 alkyl)amino, and E;

wherein E is a 5-membered heteroaryl containing 1 to 3 N atoms, wherein E is unsubstituted or substituted by 1 to 2 moieties independently selected from the group consisting of C 1 -C 3 alkyl;

A is selected from the group consisting of:

wherein

Y is —CH 2 — or —O—;

R 11 and R 12 are independently H or F; and

n′ is 0 or 1; and

wherein

R a and R b are independently H or C 1 -C 6 alkyl;

R c is H, C 1 -C 6 alkyl, C 1 -C 3 fluoroalkyl, C 3 -C 6 cycloalkyl, or —(CH 2 ) r OR 13 ,

wherein R 13 is H or C 1 -C 3 alkyl; and

r is 1 or 2;

R d is H or C 1 -C 6 alkyl,

or R e and R d together with the carbon atom to which they are attached form a group of the formula

wherein p is 1 or 2.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein B is substituted by no more than 2 R 3 moieties, and no more than 1 of said R 3 moieties is E.

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein B is substituted by 1 to 3 R 3 moieties and one 1 of said R 3 moieties is E.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein A is

wherein

Y is —CH 2 — or —O—;

R 11 and R 12 are independently H or F; and

n′ is 0 or 1.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof wherein A is selected from the group consisting of

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof wherein A is selected from the group consisting of

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein A is

R a and R b are independently H or C 1 -C 6 alkyl;

R e is H, C 1 -C 6 alkyl, C 1 -C 3 fluoroalkyl, C 3 -C 6 cycloalkyl, or —(CH 2 ) r OR 13 ,

wherein R 13 is H or C 1 -C 3 alkyl; and

r is 1 or 2;

R d is H or C 1 -C 6 alkyl,

or R c and R d together with the carbon atom to which they are attached form a group of the formula

wherein p is 1 or 2.

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein

R a and R b are H;

R c is H or C 1 -C 6 alkyl; and

R d is H.

9. The compound of claim 1 having the Formula (IA)

or a pharmaceutically acceptable salt thereof, wherein

R 3a is halo, C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, or a 5-membered heteroaryl containing 1 to 3 N atoms;

wherein said heteroaryl of R 3a is unsubstituted or substituted by 1 to 2 moieties selected from the group consisting of C 1 -C 3 alkyl;

R 3b is H, C 1 -C 3 alkyl, halo, or a 5-membered heteroaryl containing 1 to 3 N ring atoms;

wherein said heteroaryl of R 3b is unsubstituted or substituted by 1 to 2 moieties selected from the group consisting of C 1 -C 3 alkyl;

or R 3a and R 3b together with the carbon atoms to which they are attached form a phenyl ring;

R 3c is H, C 1 -C 3 alkyl, halo, or a 5-membered heteroaryl containing 1 to 3 N atoms;

wherein said heteroaryl of R 3c is unsubstituted or substituted by 1 to 2 moieties selected from the group consisting of C 1 -C 3 alkyl;

A is selected from the group consisting of:

wherein R 11 and R 12 are independently H or F; and

wherein

R a and R b are independently H or C 1 -C 6 alkyl;

R c is H, C 1 -C 6 alkyl, C 1 -C 3 fluoroalkyl, C 3 -C 6 cycloalkyl, or —(CH 2 ) r OR 13 ,

wherein R 13 is H or C 1 -C 3 alkyl; and

r is 1 or 2;

R d is H or C 1 -C 6 alkyl.

10. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein

R 3a is C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, or a 5-membered heteroaryl containing 1 to 3 N atoms;

wherein said heteroaryl of R 3a is unsubstituted or substituted by 1 to 2 moieties selected from the group consisting of C 1 -C 3 alkyl;

R 3b is H, C 1 -C 3 alkyl, halo, or a 5-membered heteroaryl containing 1 to 3 N ring atoms;

wherein said heteroaryl of R 3b is unsubstituted or substituted by 1 to 2 moieties selected from the group consisting of C 1 -C 3 alkyl;

R 3c is H, C 1 -C 3 alkyl, halo, or a 5-membered heteroaryl containing 1 to 3 N atoms;

wherein said heteroaryl of R 3c is unsubstituted or substituted by 1 to 2 moieties selected from the group consisting of C 1 -C 3 alkyl.

11. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein the moiety

12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein A selected from the group consisting of

13. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein A is wherein

wherein

R a and R b are independently H or C 1 -C 6 alkyl;

R c is H, C 1 -C 6 alkyl, C 1 -C 3 fluoroalkyl, C 3 -C 6 cycloalkyl, or —(CH 2 ) r OR 13 ,

wherein R 13 is H or C 1 -C 3 alkyl; and

r is 1 or 2;

R d is H or C 1 -C 6 alkyl.

14. The compound of claim 13 or a pharmaceutically acceptable salt thereof,

wherein

R a and R b are H;

R c is H or C 1 -C 6 alkyl; and

R d is H.

15. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

rel-6-{[(1R,2S)-2-aminocyclohexyl]amino}-4-[(6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-[(2-aminoethyl)amino]-4-[(6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

rel-6-{[(1R,2S)-2-aminocyclohexyl]amino}-4-{[6-(2H-1,2,3-triazol-2-yl)pyridin-2-yl]amino}pyridine-3-carboxamide;

rel-6-{[(1R,2S)-2-aminocyclohexyl]amino}-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide;

rel-6-{[(1R,2S)-2-aminocyclohexyl]amino}-4-(quinolin-2-ylamino)pyridine-3-carboxamide;

rel-6-{[(1R,2S)-2-aminocyclohexyl]amino}-4-[(5-fluoro-6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-{[2-aminopropyl]amino}-4-{[4,6-bis(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl]amino}pyridine-3-carboxamide;

6-{[2-aminopropyl]amino}-4-{[6-methyl-5-(1-methyl-1-pyrazol-4-yl)pyridin-2-yl]amino}pyridine-3-carboxamide;

rel-6-{[(1R,2S)-2-aminocyclohexyl]amino}-4-{[6-(trifluoromethyl)pyridin-2-yl]amino}pyridine-3-carboxamide;

6-[(2-aminoethyl)amino]-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-[(2-amino-3,3,3-trifluoropropyl)amino]-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide;

rel-6-{[(3S,4S)-4-aminotetrahydrofuran-3-yl]amino}-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-{[(4-aminotetrahydro-2H-pyran-4-yl)methyl]amino}-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-{[(3-aminotetrahydrofuran-3-yl)methyl]amino}-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-{[2-amino-3-methoxypropyl]amino}-4-[(6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

rel-6-{[(1R,2R)-2-aminocyclohexyl]amino}-4-[(6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-[(2-amino-2-methylbutyl)amino]-4-[(6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-[(2-aminobutyl)amino]-4-[(6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-[(2-amino-1-methylethyl)amino]-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-[(2-aminopentyl)amino]-4-[(6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-[(2-amino-2-cyclopropylethyl)amino]-4-[(6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-[(2-aminoethyl)amino]-4-[(5-bromo-6-methylpyridin-2-yl)amino]pyridine-3-carboxamide;

6-{[2-aminopropyl]amino}-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide; and

rel-6-{[(1S,6S)-6-amino-2,2-difluorocyclohexyl]amino}-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carboxamide.

16. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

17. The pharmaceutical composition of claim 16 , further comprising an additional therapeutic agent.