Thiazole-substituted aminoheteroaryls as Spleen Tyrosine Kinase inhibitors

1. A compound of the Formula (I)

or a pharmaceutically acceptable salt thereof, wherein

the moiety

is selected from the group consisting of:

R 3 is selected from the group consisting of

(a) C 1 -C 3 alkyl;

(b) C 1 -C 3 alkoxy; and

(c) halo;

X is N or C(H);

the subscript r is 0 or 1;

R 4 is selected from the group consisting of:

ring C y is a mono- or bicyclic carbocyclic ring system containing 4 to 12 carbon atoms;

ring C A is phenyl or C 3 -C 6 cycloalkyl;

R 5 is —C(O)OR A or —C(O)NH 2 ;

R 6 is C 1 -C 3 alkyl or halo;

R 7 is H or C 1 -C 3 alkyl;

R 8 is H or F;

R 9 is H or OH;

the subscript s is 0 or 1;

the subscript t is 0, 1, 2, 3, 4, or 5;

R A is independently selected from the group consisting of:

(a) H;

(b) C 1 -C 8 alkyl;

(c) a group of the formula -M-R CH , wherein

M is a bond or —(CH 2 ) n3 —, wherein the subscript n3 is 1 or 2;

R CH is (a) aryl or C 3 -C 6 cycloalkyl optionally substituted with 1-3 groups independently selected from halo, C 1 -C 4 alkyl, or C 1 -C 4 alkoxy; or (b) a 5- to 6-membered monocyclic heterocycle containing 1 or 2 heteroatoms independently selected from the group consisting of N and O, wherein said heterocycle of R CH is optionally substituted with 1 or 2 groups independently selected from the group consisting of oxo and C 1-3 alkyl;

(d) a group of the formula —(CH 2 ) n3 —R m or —(CH 2 ) 2 —O—(CH 2 ) 2 —R m wherein R m is —CO 2 R m1 , —C(O)N(R m2 ) 2 , or —O(CO)R m1 ;

R m1 is C 1 -C 4 alkyl; and

R m2 is H or C 1 -C 4 alkyl;

(e) a group of the formula —(CH 2 ) 2 —R n ,

R n is —OH, —O—(C 1 -C 4 alkyl), —O—(CH 2 ) 2 —O—(C 1 -C 4 alkyl), —NH 2 , —N(H)(C 1 -C 4 alkyl) or —N(C 1 -C 4 alkyl) 2 ;

(f) a group of the formula

wherein

R o is H or C 1 -C 4 alkyl; and

R p is C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, or phenyl; and,

(g) a group of the formula

wherein R o and R p are as set forth above.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein X is C(H).

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein X is N.

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

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

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

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof wherein C y is cyclobutyl, cyclohexyl, tetrahydronapthyl, or dihydroindenyl.

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

C y is cyclohexyl;

R 5 is —C(O)OR A ;

R 6 is methyl;

the subscript s is 1; and

the subscript t is 0, 1, or 2.

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

C y is cyclobutyl; and

the subscripts s and t are both 0.

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

11. The compound of claim 10 or a pharmaceutically acceptable salt thereof wherein C A is phenyl.

12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 5 is —C(O)OR A .

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

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

1,1,1-trifluoro-2-{5-[3-methyl-5-(thieno[3,2-d]pyrimidin-4-ylamino)phenyl]-1,3-thiazol-2-yl}propan-2-ol;

5-hydroxy-5-(5-(6-((2-methoxy-1,7-naphthyridin-6-yl)amino)-4-methylpyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid;

4-(1-(5-(6-(furo[3,2-b]pyridin-5-ylamino)-4-methylpyridin-2-yl)thiazol-2-yl)-1-hydroxyethyl)benzoic acid;

4-(1-(5-(6-((1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-4-methylpyridin-2-yl)thiazol-2-yl)-1-hydroxyethyl)benzoic acid;

4-hydroxy-2,2-dimethyl-4-(5-(3-methyl-5-((4-methylfuro[3,2-d]pyrimidin-2-yl)amino)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid;

4-((5-(3-([1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-5-methylphenyl)thiazol-2-yl)methyl)benzoic acid;

4-hydroxy-2,2-dimethyl-4-(5-{3-methyl-5-[(6-methyl-1,7-naphthyridin-8-yl)amino]phenyl}-1,3-thiazol-2-yl)cyclohexanecarboxylic acid;

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

1-hydroxy-1-{5-[3-methyl-5-([1,2,4]triazolo[1,5-a]pyridin-2-ylamino)phenyl]-1,3-thiazol-2-yl}-2,3-dihydro-1H-indene-5-carboxylic acid;

4-(1-hydroxy-1-{5-[3-methyl-5-([1,2,4]triazolo[1, 5-a]pyridin-2-ylamino)phenyl]-1,3-thiazol-2-yl}ethyl)benzoic acid; and

4-(1-hydroxy-1-{5-[3-methyl-5-([1,2,4]triazolo[1, 5-a]pyridin-2-ylamino)phenyl]-1,3-thiazol-2-yl}ethyl)benzoic acid;

or a pharmaceutically acceptable salt thereof.

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