Amino-pyridine-containing spleen tyrosine kinase (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:

(i) —C 1 -C 3 alkyl;

(ii) fluoroalkyl;

(iii) —CH 2 OR 1a ,

wherein R 1a is selected from the group consisting of H and C 1 -C 6 alkyl;

(iv) —N(R 1b ) 2 ,

wherein each occurrence of R 1b is selected from the group consisting of H and C 1 -C 3 alkyl, or two R 1b together with the N atom to which they are attached form a group of the formula

 wherein r is 1, 2, 3, or 4;

(v) —O—(C 1 -C 3 alkyl);

(vi) —N(H)C(O)—(C 1 -C 3 alkyl);

(vii) halo;

(viii) H; and

(ix) morpholinyl;

R 2 is —OH, —O—(C 1 -C 3 alkyl), —N(R 2a ) 2 , —N(R 2a )C(O)_R 2b ; or —F;

wherein each occurrence of R 2a is selected from the group consisting of H and C 1 -C 3 alkyl; and

R 2b is C 1 -C 6 alkyl;

R 3 is —CO 2 R 3a , —CH 2 CO 2 R 3a , —CH 2 CH 2 CO 2 R 3a , tetrazole, —C(O)N(R 3b ) 2 , —CH 2 OH, H, halo, —OH C 1 -C 6 alkyl, —O—(C 1 -C 3 alkyl), —N(R 3b ) 2 , —CN, —C(O)N(H)S(O) 2 R 3c , —C(O)—N(H)(R 3d ), —C(O)N(H)C(O)R 3a , —P(O)(OR 3b ) 2 , or —B(OH) 2 ;

wherein R 3a is selected from the group consisting of H and C 1 -C 6 alkyl;

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

wherein R 3c is selected from the group consisting of C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, C 3 -C 6 cycloalkyl, and phenyl, wherein said phenyl is unsubstituted or substituted with one or two C 1 -C 3 alkyl;

wherein R 3d is selected from the group consisting of —CN, —O—(C 1 -C 3 alkyl), and tetrazole;

R 4 is —CO 2 R 4a , —CH 2 CO 2 R 4a , —CH 2 CH 2 CO 2 R 4a , tetrazole, —C(O)N(R 4b ) 2 , —CH 2 OH, H, halo, —OH, C 1 -C 6 alkyl, —O—(C 1 -C 3 alkyl), —N(R 4b ) 2 , —CN, —C(O)N(H)S(O) 2 R 4c , —C(O)—N(H)(R 4d ), —C(O)N(H)C(O)R 4a , —P(O)(OR 4b ) 2 , or —B(OH) 2 ;

wherein R 4a is selected from the group consisting of H and C 1 -C 6 alkyl;

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

wherein R 4c is selected from the group consisting of C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, C 3 -C 6 cycloalkyl, and phenyl, wherein said phenyl is unsubstituted or substituted with one or two C 1 -C 3 alkyl;

wherein R 4d is selected from the group consisting of —CN, —O—(C 1 -C 3 alkyl), and tetrazole;

R 5 is —CO 2 R 5a , —CH 2 CO 2 R 5a , —CH 2 CH 2 CO 2 R 5a , tetrazole, —C(O)N(R 5b ) 2 , —CH 2 OH, H, halo, —OH, C 1 -C 6 alkyl, —O—(C 1 -C 3 alkyl), —N(R 5b ) 2 , —CN, —C(O)N(H)S(O) 2 R 5c , —C(O)—N(H)(R 5d ), —C(O)N(H)C(O)R 5a , —P(O)(OR 5b ) 2 , or —B(OH) 2 ;

wherein R 5a is selected from the group consisting of H and C 1 -C 6 alkyl;

wherein each R 5b is independently selected from the group consisting of H and C 1 -C 3 alkyl;

wherein R 5c is selected from the group consisting of C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, C 3 -C 6 cycloalkyl, and phenyl, wherein said phenyl is unsubstituted or substituted with one or two C 1 -C 3 alkyl;

wherein R 5d is selected from the group consisting of —CN, —O—(C 1 -C 3 alkyl), and tetrazole;

R 6 is selected from the group consisting of:

(i) C 1 -C 6 alkyl;

(ii) C 1 -C 3 fluoroalkyl;

(iii) —O—(C 1 -C 6 alkyl);

(iv) —O—(C 1 -C 3 fluoroalkyl);

(v) —R 6a , wherein R 6a is selected from the group consisting of:

(a) C 3 -C 6 cycloalkyl;

(b) a group of the formula

 wherein m is 1, 2, 3, or 4;

(c) a group of the formula

 where R 6a1 is H, C 1 -C 3 alkyl, or —CH 2 CH 2 NH 2 ; and

(d) a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S;

wherein R 6a is unsubstituted or substituted with 1 to 3 R 6a2 moieties selected from the group consisting of halo and C 1 -C 3 alkyl;

(vi) —O—R 6b ,

wherein R 6b is selected from the group consisting of:

(a) C 3 -C 6 cycloalkyl; and

(b) a group of the formula

 wherein p is 0, 1, or 2, and q is 1, 2, or 3;

wherein R 6b is unsubstituted or substituted with 1 to 2 R 6b1 moieties selected from the group consisting of fluoro and C 1 -C 3 alkyl;

(vii) —N(R 6c ) 2 , wherein each occurrence of R 6c is selected from the group consisting of H and C 1 -C 3 alkyl;

(viii) —N(H)C(O)—(C 1 -C 3 alkyl);

(ix) —N(H)C(O)O—(C 1 -C 3 alkyl);

(x) —NHC(O)—N(R 6d ) 2 , wherein each R 6d is H or C 1 -C 3 alkyl;

(xi) halo; and

(xii) H;

R 7 is H or halo;

R 8 is H or halo;

R 9 is H or halo; and

n is 0, 1, or 2.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein:

R 2 is —OH, —O—(C 1 -C 3 alkyl), or —N(R 2a ) 2 ;

R 3 is —CO 2 R 3a , —CH 2 CO 2 R 3a , —CH 2 CH 2 CO 2 R 3a , tetrazole, —C(O)N(R 3b ) 2 , —CH 2 OH, H, halo, C 1 -C 6 alkyl, —O—(C 1 -C 3 alkyl), or —N(R 3b ) 2 ;

R 4 is —CO 2 R 4a , —CH 2 CO 2 R 4a , —CH 2 CH 2 CO 2 R 4a , tetrazole, —C(O)N(R 4b ) 2 , —CH 2 OH, H, halo, C 1 -C 6 alkyl, —O—(C 1 -C 3 alkyl), or —N(R 4b ) 2 ;

R 5 is —CO 2 R 5a , —CH 2 CO 2 R 5a , —CH 2 CH 2 CO 2 R 5a , tetrazole, —C(O)N(R 5b ) 2 , —CH 2 OH, H, halo, C 1 -C 6 alkyl, —O—(C 1 -C 3 alkyl), and —N(R 5b ) 2 ;

R 6 is selected from the group consisting of:

(i) C 1 -C 6 alkyl;

(ii) C 1 -C 3 fluoroalkyl;

(iii) —O—(C 1 -C 6 alkyl);

(iv) —O—(C 1 -C 3 fluoroalkyl);

(v) —R 6a , wherein R 6a is selected from the group consisting of:

(a) C 3 -C 6 cycloalkyl;

(b) a group of the formula

 wherein m is 1, 2, 3, or 4;

(c) a group of the formula

 where R 6a1 is H, C 1 -C 3 alkyl, or —CH 2 CH 2 NH 2 ; and

(d) a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S;

wherein R 6a is unsubstituted or substituted with 1 to 3 R 6a2 moieties selected from the group consisting of halo and C 1 -C 3 alkyl;

(vi) —O—R 6b ,

wherein R 6b is selected from the group consisting of:

(a) C 3 -C 6 cycloalkyl; and

(b) a group of the formula

 wherein p is 0, 1, or 2, and q is 1, 2, or 3;

wherein R 6b is unsubstituted or substituted with 1 to 2 R 6b1 moieties selected from the group consisting of fluoro and C 1 -C 3 alkyl;

(vii) —N(R 6c ) 2 , wherein each occurrence of R 6c is selected from the group consisting of H and C 1 -C 3 alkyl;

(viii) —N(H)C(O)—(C 1 -C 3 alkyl);

(xi) halo; and

(xii) H.

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

when R 3 is —CO 2 R 3a , —CH 2 CO 2 R 3a , —CH 2 CH 2 CO 2 R 3a , tetrazole, —C(O)N(R 3b ) 2 , or —CH 2 OH; then R 4 is H, halo, C 1 -C 6 alkyl, —O—(C 1 -C 3 alkyl), or —N(R 4b ) 2 , and R 5 is H or halo; and

when R 4 is —CO 2 R 4a , —CH 2 CO 2 R 4a , —CH 2 CH 2 CO 2 R 4a , tetrazole, —C(O)N(R 4b ) 2 , or —CH 2 OH; then R 3 is H, halo, C 1 -C 6 alkyl, —O—(C 1 -C 3 alkyl), or —N(R 3b ) 2 , and R 5 is H or halo.

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

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

6. A compound of the Formula IA or a pharmaceutically acceptable salt thereof

wherein

R 4 is —CO 2 R 4a , —C(O)NH 2 , or —CH 2 OH;

wherein R 4a is selected from the group consisting of H and CH 3 ;

R 5 is H or fluoro;

R 6 is selected from the group consisting of:

(i) C 1 -C 4 alkyl;

(ii) C 1 -C 3 fluoroalkyl;

(iii) —O—(C 1 -C 6 alkyl);

(iv) —R 6a , wherein R 6a is selected from the group consisting of:

(a) C 3 -C 6 cycloalkyl,

(b) a group of the formula

 where R 6a1 is H or —CH 2 CH 2 NH 2 ; and

(c) a 5-membered heteroaryl containing 1 to 3 heteroatoms selected from the group consisting of N, O, and S;

wherein R 6a is unsubstituted or substituted with 1 to 3 R 6a2 moieties selected from the group consisting of halo and C 1 -C 3 alkyl;

(v) —O—R 6b ; and

wherein R 6b is selected from the group consisting of:

(a) C 3 -C 6 cycloalkyl; and

(b) a group of the formula

wherein p is 1 or 2, and q is 1 or 2;

wherein R 6b is unsubstituted; and

R 7 is H or halo.

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein R 4 is —CO 2 R 4a , wherein R 4a is selected from the group consisting of H and CH 3 .

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

C 1 -C 4 alkyl, —CF 3 , —C(H)F 2 , —O—(C 1 -C 3 alkyl), —OCF 3 , C 3 -C 6 cycloalkyl,

and —O—(C 4 -C 6 cycloalkyl).

9. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein R 7 is H or chloro.

10. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein

R 4 is —CO 2 R 4a , —C(O)NH 2 , or —CH 2 OH;

wherein R 4a is selected from the group consisting of H and CH 3 ;

R 5 is H or fluoro;

R 6 is selected from the group consisting of C 1 -C 4 alkyl, —CF 3 , —C(H)F 2 , —O—(C 1 -C 3 alkyl), —OCF 3 , C 3 -C 6 cycloalkyl,

and —O—(C 4 -C 6 cycloalkyl); and

R 7 is H or chloro.

11. The compound of claim 1 , selected from the group consisting of:

5-(5-{6-[(4-tert-butoxypyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(6-{[4-(difluoromethyl)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(6-{[5-chloro-4-(trifluoromethyl)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-{5-[6-({4-[4-(2-aminoethyl)piperazin-1-yl]pyridin-2-yl}amino)-4-methylpyridin-2-yl]-1,3-thiazol-2-yl}-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(piperazin-1-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(4-methyl-1H-pyrazol-1-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(1H-pyrazol-1-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(thiophen-3-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-(5-{4-methyl-6-[(4-methylpyridin-2-yl)amino}pyridin-2-yl]-1,3-thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(6-{[4-(cyclohexyloxy)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(3-methyl-1H-pyrazol-1-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-(5-{6-[(4-cyclobutylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(6-{[4-(cyclobutyloxy)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-(5-{4-methyl-6-[(4-propylpyridin-2-yl)amino]pyridin-2-yl}-1,3-thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-(5-{6-[(4-ethoxypyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(6-{[4-(cyclopentyloxy)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-(5-{6-[(4-ethylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-(5-{6-[(4-cyclohexylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(propan-2-yloxy)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(5-methyl-1,3,4-oxadiazol-2-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(tetrahydrofuran-3-yloxy)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-(5-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(1-methylethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-(5-{6-[(4-tert-butylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

methyl 5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate;

methyl 3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate;

3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

7-fluoro-6-(hydroxymethyl)-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-1,2,3,4-tetrahydronaphthalen-1-ol;

5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide;

methyl 5-hydroxy-5-[5-(4-methyl-6-{[4-(1H-1,2,3-triazol-4-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate;

5-hydroxy-5-[5-(4-methyl-6-{[4-(1H-1,2,3-triazol-4-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(3-bromo-4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(5-bromo-4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(3,5-dibromo-4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-{5-[4-(acetylamino)-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl]-1,3-thiazol-2-yl}-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-[5-(4-amino-6-{[4-(trifluoromethyl)pyri din-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

methyl-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxylate;

5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid;

1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-2,3-dihydro-1H-indene-4-carboxylic acid;

9-hydroxy-9-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-carboxylic acid;

5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulene-1-carboxylic acid;

3-hydroxy-3-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-2,3-dihydro-1H-indene-5-carboxylic acid;

methyl 1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-2,3-dihydro-1H-indene-5-carboxylate;

1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-2,3-dihydro-1H-indene-5-carboxylic acid;

methyl 1-bromo-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate;

1-bromo-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

1-cyano-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-1-methoxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

6-bromo-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-1,2,3,4-tetrahydronaphthalen-1-ol;

5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;

1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-6-(2H-tetrazol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-ol;

5-hydroxy-N-(methylsulfonyl)-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide;

N-(cyclopropylsulfonyl)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide;

5-hydroxy-N-[(4-methylphenyl)sulfonyl]-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide;

N-cyano-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide;

5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-N-[(trifluoromethyl)sulfonyl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide;

5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-N-1H-tetrazol-5-yl-5,6,7,8-tetrahydronaphthalene-2-carboxamide;

5-hydroxy-N-methoxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide;

diethyl {5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}phosphonate;

{5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}phosphonic acid;

{5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}boronic acid;

methyl 5-fluoro-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate;

5-fluoro-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-amino-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-(acetylamino)-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

5-hydroxy-5-(5-{6-[(4-methoxypyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid; and

5-hydroxy-5-(5-{4-methyl-6-[(4-propoxypyridin-2-yl)amino]pyridin-2-yl}-1,3-thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

13. A method of treating asthma comprising administering a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to a patient in need thereof.

14. A method of treating chronic obstructive pulmonary disease, comprising administering a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to a patient in need thereof.

15. The compound of claim 1 which is 5-hydroxy-5-[5-(4-methyl-6-{[4-(piperazin-1-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 which is 5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

17. The compound of claim 1 which is 3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

18. The compound of claim 1 which is 5-{5-[4-(acetylamino)-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl]-1,3-thiazol-2-yl}-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

19. The compound of claim 1 which is 1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-2,3-dihydro-1H-indene-4-carboxylic acid or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1 which is 5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carbonitrile or a pharmaceutically acceptable salt thereof.

21. A compound which is (5R)-5-hydroxy-5-[5-(4-methyl-6-{[4-(piperazin-1-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

22. A compound which is (5R)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

23. A compound which is (5R)-3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

24. A compound which is (5R)-5-{5-[4-(acetylamino)-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl]-1,3-thiazol-2-yl}-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

25. A compound which is (1R)-1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-2,3-dihydro-1H-indene-4-carboxylic acid or a pharmaceutically acceptable salt thereof.

26. A compound which is (5R)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carbonitrile or a pharmaceutically acceptable salt thereof.

27. A compound which is (5R)-5-hydroxy-5-[5-(4-methyl-6-{[4-(piperazin-1-yl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid.

28. A compound which is (5R)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid.

29. A compound which is (5R)-3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid.

30. A compound which is (5R)-5-{5-[4-(acetylamino)-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl]-1,3-thiazol-2-yl}-5-hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid.

31. A compound which is (1R)-1-hydroxy-1-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-2,3-dihydro-1H-indene-4-carboxylic acid.

32. A compound which is (5R)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carbonitrile.

33. A method of treating asthma comprising administering a therapeutically effective amount of the compound of claim 21 or a pharmaceutically acceptable salt thereof to a patient in need thereof.

34. A method of treating asthma comprising administering a therapeutically effective amount of the compound of claim 22 or a pharmaceutically acceptable salt thereof to a patient in need thereof.

35. A method of treating asthma comprising administering a therapeutically effective amount of the compound of claim 23 or a pharmaceutically acceptable salt thereof to a patient in need thereof.

36. A method of treating asthma comprising administering a therapeutically effective amount of the compound of claim 24 or a pharmaceutically acceptable salt thereof to a patient in need thereof.

37. A method of treating asthma comprising administering a therapeutically effective amount of the compound of claim 25 or a pharmaceutically acceptable salt thereof to a patient in need thereof.

38. A method of treating asthma comprising administering a therapeutically effective amount of the compound of claim 26 or a pharmaceutically acceptable salt thereof to a patient in need thereof.