Substituted diazine and triazine spleen tyrosine kinease (Syk) inhibitors

1. A compound of the Formula (I)

or a pharmaceutically acceptable salt thereof, wherein

R 1 is selected from the group consisting of H, C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, C 1 -C 3 alkoxy, and C 3 -C 6 cycloalkyl;

R 2 is selected from the group consisting of H, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 fluoroalkyl, halo, and cyano;

R 3 is selected from the group consisting of H, C 1 -C 3 alkyl and halo;

R 4 is selected from the group consisting of H, C 1 -C 3 alkyl, —N(R 4a ) 2 , —N(R 4a )C(O)R 4b , —N(R 4a )C(O)N(R 4a ) 2 ,

each R 4a is independently selected from the group consisting of H and C 1 -C 3 alkyl;

R 4b is C 1 -C 3 alkyl;

C y is a 6-membered heteroaryl selected from the group consisting of:

t is 0, 1, or 2;

each R cy is independently selected from the group consisting of:

A. a group of the formula

wherein

Y is a bond, —N(R e )—, or —O—;

R e is H, C 1 -C 3 alkyl; hydroxyl(C 2 -C 3 ) alkyl;

each R a and R b is independently selected from the group consisting of H, fluoro, hydroxyl, —CH 2 OH, —CH 2 —O—(C 1 -C 3 )alkyl, and C 1 -C 3 alkyl;

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

wherein R 11 is C 1 -C 3 alkyl;

m is 1, 2, 3, or 4; and

r is 0, 1, 2, or 3;

each R c and R d is independently selected from the group consisting of H, fluoro, hydroxyl, —CH 2 OH, —CH 2 —O—(C 1 -C 3 )alkyl, and C 1 -C 3 alkyl;

R f is methyl, —CHF 2 , —CF 3 , —CH 2 SO 2 —(C 1 -C 3 )alkyl, —CH 2 —S(O) 2 N(R h ) 2 , —CH 2 OH, —C(CH 3 ) 2 OH, —CH 2 —O—(C 1 -C 3 )alkyl,

—CO 2 R g , —CON(R h ) 2 , —CH 2 —N(H)—C(O)—(C 1 -C 3 ) alkyl, or CN;

 R g is H or C 1 -C 3 alkyl;

 each R h is independently H or C 1 -C 3 alkyl;

n1 is 0, 1, 2, or 3; and

n2 is 0 or 1;

B. a group of the formula

wherein

D 1 is a 4- to 7-membered heterocyclic ring optionally containing one additional heteroatom selected from the group consisting of N, O, S, S(O), and S(O) 2 ;

each R 10 is independently selected from the group consisting of C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, —CO 2 H, —OH, hydroxyl(C 1 -C 3 )alkyl, —CH 2 OCH 3 , —C(O)—(C 1 -C 3 )alkyl, and —CON(R h ) 2 or wherein when two R 10 moieties are geminally substituted on a common ring carbon atom of D 1 , the two geminally substituted R 10 moieties together with the carbon atom on which they are attached form —C(O)—; and

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

C. a group of the formula

wherein

D 2 is selected from the group consisting of:

(i) a C 5 -C 6 cycloalkyl,

(ii) a 5- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O, S, S(O), and S(O) 2 ;

(iii) a 5- to 6-membered heteroaryl containing 1 to 2 heteroatoms selected from the group consisting of N, O, and S; and

(iv) phenyl;

each R i and R j is independently H or C 1 -C 3 alkyl;

s is 0, 1, 2, or 3; and

Y, R 10 and q are as described above.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is trifluoromethyl.

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

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 and R 3 are both H.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein C y is

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein t is 0 or 1.

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein t is 1.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof,

wherein R cy is a group of the formula

wherein

Y is a bond, —N(R e )—, or —O—;

R e is H, C 1 -C 3 alkyl; hydroxyl(C 2 -C 3 ) alkyl;

each R a and R b is independently selected from the group consisting of H, fluoro, hydroxyl, —CH 2 OH, —CH 2 —O—(C 1 -C 3 )alkyl, and C 1 -C 3 alkyl;

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

wherein R 11 is C 1 -C 3 alkyl;

m is 1, 2, 3, or 4; and

r is 0, 1, 2, or 3;

each R c and R d is independently selected from the group consisting of H, fluoro, hydroxyl, —CH 2 OH, —CH 2 —O—(C 1 -C 3 )alkyl, and C 1 -C 3 alkyl;

R f is methyl, —CHF 2 , —CF 3 , —CH 2 SO 2 —(C 1 -C 3 )alkyl, —CH 2 —S(O) 2 N(R h ) 2 , —CH 2 OH, —C(CH 3 ) 2 OH, —CH 2 —O—(C 1 -C 3 )alkyl,

—CO 2 R g , —CON(R h ) 2 , —CH 2 —N(H)—C(O)—(C 1 -C 3 ) alkyl, or CN;

R g is H or C 1 -C 3 alkyl;

each R h is independently H or C 1 -C 3 alkyl;

n1 is 0, 1, 2, or 3; and

n2 is 0 or 1.

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

Y is —N(R e )—;

R e is H or methyl;

each R a , R b , R c , and R d is independently H, C 1 -C 3 alkyl, hydroxyl, —CH 2 OH, or —CH 2 —O—CH 3 ;

R f is —CO 2 H;

n1 is 1 or 2; and

n2 is 0 or 1.

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

R cy is a group of the formula

11. The compound of claim 1 or a pharmaceutically acceptable salt thereof,

wherein R cy is a group of the formula

wherein

D 1 is a 4- to 7-membered heterocyclic ring optionally containing one additional heteroatom selected from the group consisting of N, O, S, S(O), and S(O) 2 ;

each R 10 is independently selected from the group consisting of C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, —CO 2 H, —OH, hydroxyl(C 1 -C 3 )alkyl, —CH 2 OCH 3 ,

—C(O)—(C 1 -C 3 )alkyl, and —CON(R h ) 2 or wherein when two R 10 moieties are geminally substituted on a common ring carbon atom of D 1 , the two geminally substituted R 10 moieties together with the carbon atom on which they are attached form —C(O)—; and

q is 0, 1, 2, 3, or 4.

12. The compound of claim 11 or a pharmaceutically acceptable salt thereof, wherein R cy is selected from the group consisting of:

wherein p1 is 1, 2, or 3;

p2 is 1 or 2; and

q is 0 or 1.

13. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein R cy is

wherein

p1 is 1 or 2;

q is 1; and

R 10 is —CO 2 H.

14. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound of the Formula (I) has the Formula (IA)

and R cy is as described in claim 1 .

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

N-(3-methyl-5-pyrimidin-5-ylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

N-[3-(2-methoxypyrimidin-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

N-[3-(2-aminopyrimidin-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

N-(3-{2-[(2-methoxyethyl)amino]pyrimidin-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

3-(5-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-2-yl)propanoic acid;

ethyl 3-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-2-yl)propanoate;

ethyl 3-(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrimidin-2-yl)propanoate;

ethyl 3-(5-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-2-yl)propanoate;

2-methyl-2-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propane-1,3-diol;

2-methyl-N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]alanine;

1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}cyclopropanecarboxylic acid;

1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}cyclobutanecarboxylic acid;

1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]proline;

1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]azetidine-2-carboxylic acid

3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}pyrrolidin-2-one;

N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]-beta-alanine;

N-methyl-N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]alanine;

1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]pyrrolidin-3-ol;

4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}butanoic acid;

N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]glycine;

3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propane-1,2-diol;

N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]norvaline;

1,1-difluoro-3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propan-2-ol;

N-(3-{2-[(1,1-dioxidotetrahydrothiophen-3-yl)amino]pyrimidin-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

N-[3-methyl-5-(2-{[(1-methyl-1H-pyrazol-4-yl)methyl]amino}pyrimidin-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

N-{3-methyl-5-[2-(tetrahydrofuran-3-ylamino)pyrimidin-5-yl]phenyl}-4-(trifluoromethyl)pyrimidin-2-amine;

N-(3-{2-[(1,4-dioxan-2-ylmethyl)amino]pyrimidin-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

N-{3-[2-(1,1-dioxidothiomorpholin-4-yl)pyrimidin-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine;

N-(3-methyl-5-{2-[(1-pyridin-2-ylethyl)amino]pyrimidin-5-yl}phenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

5-({[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}methyl)pyrrolidin-2-one;

2-{4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]morpholin-2-yl}ethanol;

4-methyl-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]-1,4-diazepan-5-one;

N-(3-{2-[2-(methoxymethyl)morpholin-4-yl]pyrimidin-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

2-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}ethanesulfonamide;

3-methyl-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]piperidin-3-ol;

3-methyl-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]pyrrolidin-3-ol;

4-methyl-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]piperidin-4-ol;

2-{methyl[5-(3-methyl-5-[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino ethanol;

2,2′-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]imino}diethanol;

N-methyl-N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]glycine;

N-[3-(2-{[2-(1H-imidazol-4-yl)ethyl]amino}pyrimidin-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propan-1-ol;

4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}butan-1-ol;

(1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}cyclopentyl)methanol;

N-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]glycinamide;

O-methyl-N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]serine;

N-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]-beta-alaninamide;

N-{3-[2-(4-acetylpiperazin-1-yl)pyrimidin-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine;

N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]serine;

3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}azepan-2-one;

3-{methyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propane-1,2-diol;

N-methyl-N-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]glycinamide;

N-[2-(1,3-dioxolan-2-yl)ethyl]-N-methyl-5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-amine;

4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]piperazin-2-one;

2-methyl-1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propan-2-ol;

N-[3-methyl-5-(2-{[2-(methylsulfonyl)ethyl]amino}pyrimidin-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

N-(3-{2-[2-(methoxymethyl)piperidin-1-yl]pyrimidin-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]azetidin-3-ol;

3-ethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]piperazin-2-one;

N-[3-methyl-5-(2-{[(1-methyl-1H-imidazol-5-yl)methyl]amino}pyrimidin-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

N-{3-methyl-5-[2-(3-propoxypiperidin-1-yl)pyrimidin-5-yl]phenyl}-4-(trifluoromethyl)pyrimidin-2-amine;

1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]azetidine-2-carboxylic acid;

N-{3-[2-(4-ethylpiperazin-1-yl)pyrimidin-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine;

(2S)-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]piperidine-2-carboxylic acid;

2-methyl-2-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propan-1-ol;

2-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propan-1-ol;

2-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}butan-1-ol;

1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propan-2-ol;

3-hydroxy-4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}butanoic acid;

2-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}ethanol;

N-[3-methyl-5-(2-{[(1-methyl-1H-imidazol-4-yl)methyl]amino}pyrimidin-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

N,N-dimethyl-N-2˜[5˜-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]glycinamide;

N-(3-methyl-5-{2-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]pyrimidin-5-yl}phenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

N-(3-{2-[3-(methoxymethyl)pyrrolidin-1-yl]pyrimidin-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

1,3-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]piperazin-2-one;

N-{3-methyl-5-[2-(4-propyl-1,4-diazepan-1-yl)pyrimidin-5-yl]phenyl}-4-(trifluoromethyl)pyrimidin-2-amine;

N-methyl-N˜3˜-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]-beta-alaninamide;

N-methyl-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]prolinamide;

N-(3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}propyl)acetamide;

5-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}piperidin-2-one;

1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]prolinamide;

1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]piperidin-3-ol;

1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}cyclopentanecarboxylic acid;

3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}pyrrolidin-2-one;

3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}pyrrolidin-2-one;

1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]piperidine-4-carboxylic acid;

2-cyano-N-methyl-N-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]acetamide;

3-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-2-yl)propanoic acid;

N-(3-methyl-5-pyrazin-2-ylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

ethyl 3-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrazin-2-yl]propanoate;

3-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrazin-2-yl]propanoic acid;

ethyl 3-(5-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyrazin-2-yl)propanoate;

3-(5-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyrazin-2-yl)propanoic acid;

ethyl 3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrazin-2-yl]propanoate;

3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrazin-2-yl]propanoic acid;

ethyl 3-(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrazin-2-yl)propanoate;

3-(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrazin-2-yl)propanoic acid;

ethyl 3-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrazin-2-yl)propanoate;

3-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrazin-2-yl)propanoic acid;

ethyl 3-[6-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrazin-2-yl]propanoate;

3-[6-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrazin-2-yl]propanoic acid;

ethyl 3-(6-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyrazin-2-yl)propanoate;

3-(6-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyrazin-2-yl)propanoic acid;

ethyl 3-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrazin-2-yl]propanoate;

3-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrazin-2-yl]propanoic acid;

ethyl 3-(6-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrazin-2-yl)propanoate;

3-(6-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrazin-2-yl)propanoic acid;

ethyl 3-(6-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrazin-2-yl)propanoate;

3-(6-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrazin-2-yl)propanoic acid;

N-(3-methyl-5-pyrimidin-2-ylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

ethyl 3-[6-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]propanoate;

3-[6-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]propanoic acid;

ethyl 3-(6-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyridazin-3-yl)propanoate;

ethyl 3-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]propanoate;

N-(3-methyl-5-pyridazin-3-ylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

N-[3-methyl-5-(6-morpholin-4-ylpyridazin-3-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

1-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]piperidin-4-ol;

1-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]piperidine-4-carboxamide;

3-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]benzoic acid;

4-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]benzoic acid;

2-methyl-2-{[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]oxy}propanoic acid;

1-[2-(dimethylamino)ethyl]-3,3-dimethyl-1-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]urea;

2-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]propan-2-ol;

1-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]piperidine-4-carboxylic acid

N-methyl-N-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]glycine;

3-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridazin-3-yl]propanoic acid;

ethyl 3-(6-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyridazin-3-yl)propanoate;

3-(6-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyridazin-3-yl)propanoic acid;

ethyl 3-(6-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyridazin-3-yl)propanoate;

N-(3-methyl-5-pyridazin-4-ylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

ethyl 3-[6-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-4-yl]propanoate;

3-[6-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-4-yl]propanoic acid;

ethyl 3-(6-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-4-yl)propanoate;

3-(6-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-4-yl)propanoic acid;

N-(3-methyl-5-pyrimidin-4-ylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

ethyl 3-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-4-yl]propanoate;

3-[6-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-4-yl]propanoic acid;

ethyl 3-(6-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrimidin-4-yl)propanoate;

3-(6-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrimidin-4-yl)propanoic acid;

ethyl 3-(6-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-4-yl)propanoate;

3-(6-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-4-yl)propanoic acid;

3-(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrimidin-2-yl)propanoic acid;

ethyl 3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]propanoate;

3-(5-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}pyrimidin-2-yl)propanoic acid;

4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]oxy}cyclohexanecarboxylic acid;

4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]oxy}cyclohexanecarboxylic acid;

4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]oxy}cyclohexanecarboxylic acid;

3-(5-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}pyrimidin-2-yl)propanoic acid;

3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]propanoic acid;

1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}cyclopropanecarboxamide;

trans-4-{[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]methyl}cyclohexanecarboxylic acid;

trans-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethyl}cyclohexanecarboxylic acid; and

rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethyl}-2-methylcyclohexanecarboxylic acid.

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 compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein

R cy is a group of the formula a group of the formula

wherein

D 2 is selected from the group consisting of:

(i) a C 5 -C 6 cycloalkyl,

(ii) a 5- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O, S, S(O), and S(O) 2 ;

(iii) a 5- to 6-membered heteroaryl containing 1 to 2 heteroatoms selected from the group consisting of N, O, and S; and

(iv) phenyl;

each R i and R j is independently H or C 1 -C 3 alkyl; and

s is 0, 1, 2, or 3.

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

and

q is 0, 1, or 2.

19. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is trans-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethyl}cyclohexanecarboxylic acid.

20. The compound of claim 17 or a pharmaceutically acceptable salt thereof, wherein Y is a bond or —N(R e )—, wherein R e is H.