IP Library › Granted Patent US 9,242,984

Granted Patent B2

US 9,242,984 · App. 14/409,133 · Granted Jan 26, 2016

Pyrazolyl derivatives as Syk inhibitors

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Quick Facts

Patent No.: US 9,242,984
App. No.: 14/409,133
Granted: Jan 26, 2016
Kind: B2

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Abstract

The present invention provides novel pyrazole derivatives of formula I which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.

Claims (643)

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

is:

ring a is

ring b is

Y a1 is independently CH or N;

Y b1 and Y b2 are independently CH or N, such that Y a1 and Y b1 are not both simultaneously C or N;

R 1a and R 1b are independently: H, halogen, C 1 -C 3 -alkyl, or C 1 -C 3 -fluoroalkyl;

R 1 is:

halogen;

C 1 -C 6 -alkyl, optionally with one to four substituents selected from: CN, OH, oxo, NH 2 , CF 3 , C 1 -C 3 -alkyl, and C 1 -C 3 -alkoxyl;

(CR a R b ) n CO 2 R c ;

(CR a R b ) n CONR d R e ;

(CHR a ) n NHCONR d R e ;

(CHR a ) n NHCO 2 R c ;

(CHR a ) n NHCOR c ;

(CHR a ) n CONHSO 2 R d ;

(CHR a ) n SO 2 R d ;

(CHR a ) n SO 2 NR d R e ;

(CHR a ) n NHSO 2 R d ;

(CR a R b ) n -heterocyclyl; wherein heterocyclyl is as defined below;

(CHR a ) p —C(O)-heterocyclyl; wherein heterocyclyl is as defined below;

(CR a R b ) n -carbocyclyl; wherein carbocyclyl is as defined below;

CR a (carbocyclyl) 2 ; wherein carbocyclyl is as defined below;

(CR a R b ) n -aryl; wherein aryl is as defined below;

(CR a R b ) n —O-carbocyclyl; wherein carbocyclyl is as defined below;

(CR a R b ) n —O-aryl; wherein aryl is as defined below;

or optionally, R 1 and R 1a , R 1 and R 1b , R 1a and R 1b , when present on adjacent pyrazolyl ring atoms, taken together can form a 5- or 6-membered ring with the atoms to which they are attached; the ring may contain one or two heteroatoms selected from N, O, or S including the nitrogens of the pyrazole ring to which the ring is fused and the ring may be saturated, unsaturated or aromatic and may be optionally substituted with one to three substituents selected from: C 1 -C 3 -alkoxyl and C 1 -C 3 -alkyl;

Heterocyclyl is a 4-, 5-, 6-, or 7-membered monocyclic ring or 8-, 9-, 10-membered bicyclic ring, or 13- or 14-membered tricyclic ring; the monocyclic, bicyclic or tricyclic ring can be saturated, unsaturated or aromatic, containing one to four heteroatoms selected from O, N, or S, the heterocyclyl may optionally be substituted with one to four substituents selected from oxo, halo, hydroxyl, C 1 -C 3 -alkyl, C 2 -C 6 -alkenyl, C 1 -C 3 -alkoxyl, C 3-6 cycloalkyl, (CR a R b ) n CO 2 R c , (CR a R b ) n CONR d R e , (CHR a ) n NHCONR d R e , (CHR a )NHCO 2 R c , and (CHR a ) p —C(O)-heterocyclyl; or alternatively 2 substituents geminally substituted on a common ring carbon atom of said heterocyclyl may together with the common ring carbon atom form a C 3-6 spirocyclic ring;

Carbocyclyl is a 4-, 5-, 6-, 7- or 8-membered monocyclic ring or 8-, 9-, 10-membered bicyclic ring, or 13- or 14-membered tricyclic ring, in which all ring atoms are carbon, at least one ring is saturated or partially unsaturated and that ring being isolated or fused to one or two such rings or to a benzene ring; the carbocyclyl may optionally be substituted with one to four substituents selected from hydroxyl, C 1 -C 3 -alkyl, C 1 -C 3 -alkoxyl, (CR a R b ) n CO 2 R c , (CR a R b ) n CONR d R e , and a spiro-linked —OCH 2 CH 2 O—;

Aryl is a 6-membered monocyclic or 10-membered bicyclic aromatic carbon ring, the aryl may optionally be substituted with one to four substituents selected from hydroxyl, C 1 -C 3 -alkyl, C 1 -C 3 -alkoxyl, (CR a R b ) n CO 2 R c ; and (CR a R b ) n CONR d R e ;

R 2 is H, halogen, C 1 -C 3 -alkyl, C 1 -C 3 -haloalkyl, C 3 -C 7 -cycloalkyl, heterocyclyl, NR d R e , CONR d R e , NHCONR d R e , or NO 2 ;

R 3 is H or C 1 -C 4 -alkyl, C 1 -C 3 -fluoroalkyl, C 1 -C 3 -alkoxyl, optionally substituted with one to three substituents selected from hydroxyl; —O—(CH 2 ) 2 —O—Si(CH 3 ) 3 ; C 3 -C 6 -cycloalkyl and pyridyl;

R 4 is H, halogen, or C 1 -C 3 -alkyl;

R a and R b are independently: H, OH, CN, NH 2 , cyclopropyl, C 1 -C 3 -fluoroalkyl, or C 1 -C 3 -alkyl optionally substituted with hydroxyl;

R c is: H, C 1-6 alkyl, C 3-6 cycloalkyl, -M-R CH , —(CH 2 ) 1-2 —R f , —(CH 2 ) 2 —O—(CH 2 ) 2 —R f , —(CH 2 ) 2 —R g ,

—CHR h OCO 2 R i , or —(CHR h ) 1-2 OC(O)R i ;

R d and R e are independently: H, C 1 -C 3 -alkoxyl or C 1 -C 6 -alkyl, optionally substituted with one to four substituents selected from: CN, OH, oxo, NH 2 , halogen, CO 2 R c , CONH 2 , C 1 -C 3 -alkoxyl, CO 2 R c ; aryl, carbocyclyl, or heterocyclyl, as defined above;

R f is CO 2 R f1 , CN, C(O)N(R f2 ) 2 , —OC(O)R f1 , or C 1-2 alkoxyl;

R f1 is C 1-4 alkyl; and

R f2 is H or C 1-4 alkyl;

R g is OH, C 1-4 alkoxyl, NH 2 , NH(C 1-4 alkyl) or N(C 1-4 alkyl) 2 ;

R h is H or C 1-4 alkyl;

R i is C 1-6 alkyl, C 3-6 cycloalkyl, or phenyl;

M is a bond or —(CH 2 ) 1-3 —;

R CH is (a) aryl, aryl is phenyl or naphthalyl, optionally substituted with one to three groups independently selected from halo, C 1-4 alkyl, or C 1-4 alkoxy; (b) carbocyclyl, carbocyclyl is a 5-, 6- or 7-membered monocyclic carbon ring, that is saturated or partially unsaturated and the carbocyclyl is optionally substituted with one to three substituents independently selected from halo, C 1-4 alkyl, or C 1-4 alkoxy; or (c) a 5- to 6-membered monocyclic heterocyclyl containing one or two heteroatoms independently selected from the group consisting of N and O, and the heterocyclyl is optionally substituted with one or two substituents independently selected from the group consisting of: oxo and C 1-3 alkyl;

n is 0, 1, 2, 3 or 4; and

p is 0 or 1.

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

R 1a and R 1b are independently: H, Cl, F, CH 3 , or CF 3 ;

R 2 is H, or CH 3 ;

R 3 is H, Cl, F, CH 3 , CH(CH 3 ) 2 , cyclopropyl, OCH(CH 3 ) 2 , OCH 3 , OCHFCH 3 , OCH 2 CH 2 OH, CHF 2 , or CF 3 ;

R 4 is H, Cl or F; and all other substituents are as defined in claim 1 .

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein rings a and b are defined as follows:

a) Y a1 is N; and Y b1 and Y b2 are CH;

b) Y b1 is N; and Y a1 and Y b2 are CH;

c) Y a1 and Y b2 are N; and Y b1 is CH; or

d) Y b1 and Y b2 are N; and Y a1 is CH;

and all other substituents are as defined in claim 1 .

4. The compound of claim 2 having the Formula Ia

wherein rings a and b are defined as follows:

a) Y b1 and Y b2 are N; and Y a1 is CH; or

b) Y a1 and Y b2 are N; and Y b1 is CH;

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 4 , wherein R 1 is H; C 1 -C 6 -alkyl, optionally with one or more substituent selected from the group consisting of: CN, OH, oxo, NH 2 , CF 3 , C 1 -C 3 -alkyl, and C 1 -C 3 -alkoxyl; (CR a R b ) n CO 2 R c ; (CR a R b ) n CONR d R e ; (CR a R b ) n -heterocyclyl; or (CR a R b ) n -carbocyclyl; or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 having the Formula Ia(i)

wherein rings a and b are defined as follows:

a) Y a1 is N; and Y b1 is CH; or

b) Y b1 is N; and Y a1 is CH;

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein R 1 is H; C 1 -C 6 -alkyl, optionally with one or more substituent selected from the group consisting of: CN, OH, oxo, NH 2 , CF 3 , C 1 -C 3 -alkyl, and C 1 -C 3 -alkoxyl; (CR a R b ) n CO 2 R c ; (CR a R b ) n CONR d R e ; (CR a R b ) n -heterocyclyl; or (CR a R b ) n -carbocyclyl.

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein R 1 is H; C 1 -C 6 -alkyl, optionally with one or more substituent selected from the group consisting of: CN, OH, oxo, NH 2 , CF 3 , CH 3 and OCH 3 ; (CR a R b ) n CO 2 R c ; (CR a R b ) n CONH 2 ; (CR a R b ) n -heterocyclyl; or (CR a R b ) n -carbocyclyl; R a and R b are independently H, CH 3 , or OH; and n is 0, 1, 2, 3 or 4.

9. The compound of claim 2 having the Formula Ib

wherein rings a and b are defined as follows:

a) Y a1 is N; and Y b1 is CH; or

b) Y b1 is N; and Y a1 is CH;

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9 or a pharmaceutically salt thereof, wherein R 1 is H; C 1 -C 6 -alkyl, optionally with one or more substituent selected from the group consisting of: CN, OH, oxo, NH 2 , CF 3 , C 1 -C 3 -alkyl, and C 1 -C 3 -alkoxyl; (CR a R b ) n CO 2 R c ; (CR a R b ) n CONR d R e ; (CR a R b ) n -heterocyclyl; or (CR a R b ) n -carbocyclyl.

11. The compound of claim 2 , wherein the compound of Formula I has the Formula Ic or Id

wherein rings a and b are defined as follows:

a) Y a1 is N; and Y b1 and Y b2 is CH;

b) Y b1 is N; and Y a1 and Y b2 are CH; or

c) Y b1 and Y b2 are N; and Y a1 is CH;

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 11 or a pharmaceutically acceptable salt thereof, wherein R 1 is H; C 1 -C 6 -alkyl, optionally with one or more substituent selected from the group consisting of: CN, OH, oxo, NH 2 , CF 3 , C 1 -C 3 -alkyl, or C 1 -C 3 -alkoxyl; (CR a R b ) n CO 2 R c ; (CR a R b ) n CONR d R e ; (CR a R b ) n -heterocyclyl; or (CR a R b ) n -carbocyclyl.

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

N-(3-methyl-5-(pyrazolo[1,5-a]pyridin-3-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

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

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

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

N-[3-(1-cyclohex-2-en-1-yl-1H-pyrazol-4-yl)-5-methylphenyl]-4-(trifluoromethyl)-pyrimidin-2-amine;

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

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

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

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

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

tert-butyl 4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}-pyridin-2-yl)-1H-pyrazole-1-carboxylate;

4-methyl-6-(1H-pyrazol-4-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

4-methyl-6-(1-methyl-1H-pyrazol-4-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

4-methyl-6-[1-(3-methylbutyl)-1H-pyrazol-4-yl]-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

6-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

ethyl 3-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]propanoate;

ethyl 3-(4-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1H-pyrazol-1-yl)propanoate;

3-(4-{6-[(4-methylpyridin-2-yl)amino]pyridin-2-yl}-1H-pyrazol-1-yl)propanoic acid;

3-[4-(6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]propanoic acid;

3-(4-{4-methyl-6-[(4-methylpyridin-2-yl)amino]pyridin-2-yl}-1H-pyrazol-1-yl)propanoic acid;

3-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]propanoic acid;

3-(4-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1H-pyrazol-1-yl)propanoic acid;

ethyl 3-(4-{6-[(4-methylpyridin-2-yl)amino]pyridin-2-yl}-1H-pyrazol-1-yl)propanoate;

ethyl 3-[4-(6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]propanoate;

ethyl 3-(4-{6-[(5-chloro-4-methylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1H-pyrazol-1-yl)propanoate;

ethyl 3-(4-{4-methyl-6-[(4-methylpyridin-2-yl)amino]pyridin-2-yl}-1H-pyrazol-1-yl)propanoate;

3-(4-{6-[(5-chloro-4-methylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1H-pyrazol-1-yl)propanoic acid;

5R-{[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one;

5S-{[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one;

tert-butyl [4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]acetate;

[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]acetic acid;

4R-{1R-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethyl}pyrrolidin-2-one;

4R-{1 S-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethyl}pyrrolidin-2-one;

4S-{1R-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethyl}pyrrolidin-2-one;

4R-{[4-(6-{[4-(difluoromethyl)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1H-pyrazol-1-yl]methyl}pyrrolidin-2-one;

4S-{1S-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethyl}pyrrolidin-2-one;

4S-{[4-(6-{[4-(difluoromethyl)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1H-pyrazol-1-yl]methyl}pyrrolidin-2-one;

4-{[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]methyl}pyrrolidin-2-one;

3-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyrimidin-2-yl)-1H-pyrazol-1-yl]propanoic acid;

6-methyl-2-(1H-pyrazol-4-yl)-N-[4-(trifluoro-methyl)pyridin-2-yl]pyrimidin-4-amine;

6-methyl-2-pyrazolo[1,5-a]pyridin-3-yl-N-[4-(trifluoro-methyl)pyridin-2-yl]pyrimidin-4-amine;

N-[2-methyl-6-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl]-4-(trifluoro-methyl)pyrimidin-2-amine;

N-[2-methyl-6-(1H-pyrazol-4-yl)pyridin-4-yl]-4-(trifluoro-methyl)pyrimidin-2-amine;

6-methyl-2-(1-methyl-1H-pyrazol-5-yl)-N-[4-(trifluoro-methyl)pyridin-2-yl]pyrimidin-4-amine;

6-methyl-2-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]-N-[4-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine;

3-(4-(3-((4-methoxypyrimidin-2-yl)amino)-5-methylphenyl)-1H-pyrazol-1-yl)propanoic acid;

ethyl 3-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanoate;

ethyl 3-(4-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanoate;

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

3-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanoic acid;

3-(4-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanamide;

3-(4-{3-[(5-chloro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanamide;

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

3-[4-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]propanamide;

3-(4-{3-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)propanamide;

3-(4-{3-[(5-fluoro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanamide;

3-(4-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)propanamide;

3-(4-{3-[(5-chloro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanamide;

3-(4-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanamide;

3-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanamide;

5R or 5S-[(4-{3-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5-[(4-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5-[(4-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5-[(4-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5-[(4-{3-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5-[(4-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5R or 5S-[(4-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5R-[(4-{3-[(5-chloro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5R-{[4-(3-methyl-5-{[4-(1-methylethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one;

5R-[(4-{3-[(5-fluoro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5R-[(4-{3-[(5-chloro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

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

5S-[(4-{3-[(5-chloro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5S-{[4-(3-methyl-5-{[4-(1-methylethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one;

5S-[(4-{3-[(5-fluoro-4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5R-[(4-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5S-[(4-{3-[(5-chloro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

5R or 5S-[(4-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)methyl]-1,3-oxazolidin-2-one;

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

N-(3-methyl-5-pyrazolo[1,5-b]pyridazin-3-ylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

N-[3-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

N-(3-methyl-5-pyrazolo[1,5-a]pyrimidin-3-ylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

N-[3-(3,5-dimethyl-1H-pyrazol-4-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

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

3-(4-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-H-pyrazol-1-yl)propanoic acid;

ethyl 3-(4-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanoate;

ethyl 3-(4-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)propanoate;

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

3-(4-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)propanoic acid;

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

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

N-[3-(1H-indazol-3-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine;

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

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

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

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

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

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

1-{3-[4-(3-methyl-5-{[4-(trifluoro-methyl)pyrimidin-2-yl]amino}-phenyl)-1H-pyrazol-1-yl]-propyl}imidazolidin-2-one;

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

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

N-{3-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-5-methyl-phenyl}-4-(trifluoro-methyl)pyrimidin-2-amine;

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

N-(3-{1-[2-(4,4-dimethyl-1,3-oxazolidin-3-yl)-2-oxoethyl]-1H-pyrazol-4-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine;

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

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

N-[3-(1-{2-[(3R,5S)-3,5-dimethyl-morpholin-4-yl]-2-oxoethyl}-1H-pyrazol-4-yl)-5-methylphenyl]-4-(trifluoromethyl)-pyrimidin-2-amine;

N-[3-(1-{2-[(3R,5R)-3,5-dimethylmorpholin-4-yl]-2-oxoethyl}-1H-pyrazol-4-yl)-5-methylphenyl]-4-(trifluoromethyl)-pyrimidin-2-amine;

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

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

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

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

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

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

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

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

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

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

N-{3-[1-(2-azetidin-1-yl-2-oxoethyl)-1H-pyrazol-4-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine;

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

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

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

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

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

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

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

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

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

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

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

3-[4-(3-{[4-(2-hydroxyethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]propanamide;

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

3-(4-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanamide;

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

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

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

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

3-methyl-5R or 5S-{[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one;

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

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

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

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

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

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

4-{1-hydroxy-2-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]ethyl}benzoic acid;

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

N-{3-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazol-4-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine;

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

tert-butyl 4-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]piperidine-1-carboxylate;

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

6-[1-(methoxyacetyl)-1H-pyrazol-4-yl]-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

3-[4-(4-methyl-6-{[4-(trifluoro-methyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]propan-1-ol;

3-[4-(4-methyl-6-{[4-(trifluoro-methyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]propanamide;

2-[4-(4-methyl-6-{[4-(trifluoro-methyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]acetamide;

1-{3-[4-(4-methyl-6-{[4-(trifluoro-methyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]propyl}imidazolidin-2-one;

6-[1-(1,4-dioxan-2-ylmethyl)-1H-pyrazol-4-yl]-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

N-(2-methoxy-1,1-dimethylethyl)-2-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}-pyridin-2-yl)-1H-pyrazol-1-yl]-acetamide;

6-(1-{2-[(3R,5S)-3,5-dimethylmorpholin-4-yl]-2-oxoethyl}-1H-pyrazol-4-yl)-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

4-methyl-6-[1-(3-morpholin-4-ylpropyl)-1H-pyrazol-4-yl]-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

4-methyl-6-[1-(oxetan-2-ylmethyl)-1H-pyrazol-4-yl]-N-[4-(trifluoromethyl)-pyridin-2-yl]pyridin-2-amine;

2-{2-[4-(4-methyl-6-{[4-(trifluoromethyl)-pyridin-2-yl]amino}-pyridin-2-yl)-1H-pyrazol-1-yl]-ethoxy}ethanol;

6-[1-(3-aminopropyl)-1H-pyrazol-4-yl]-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

6-[1-(cyclopropyl-methyl)-1H-pyrazol-4-yl]-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

6-[1-(2,2-diethoxyethyl)-1H-pyrazol-4-yl]-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

4-methyl-6-[1-(1-methylethyl)-1H-pyrazol-4-yl]-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine;

2-[4-(4-methyl-6-{[4-(trifluoro-methyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethanol;

4-[4-(4-methyl-6-{[4-(trifluoro-methyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid;

methyl 4-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]-1,2,3,4-tetrahydro-naphthalene-1-carboxylate;

4-{1-hydroxy-2-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethyl}-benzoic acid;

methyl 4-{1-hydroxy-2-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethyl}-benzoate;

tert-Butyl 4-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate;

[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}-pyridin-2-yl)-1H-pyrazol-1-yl]-acetonitrile;

(S) methyl 3-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazo(-1-yl]-L-alaninate;

2-(4-(3-methyl-5-((4-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)-1H-pyrazol-1-yl)-1-phenylethanol;

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

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

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

Cis-4-hydroxy-4-{[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}cyclohexanecarboxylic acid;

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

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

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

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

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

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

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

1-fluoro-3-({3-[1-(3-fluoro-2-hydroxy-propyl)-1H-pyrazol-4-yl]-5-methylphenyl}-[4-(trifluoromethyl)-pyrimidin-2-yl]amino)propan-2-ol;

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

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

(2R)-2-hydroxy-3-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanoic acid;

(2S)-2-hydroxy-3-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanoic acid;

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

(2S)-2-hydroxy-3-[4-(3-{[4-(2-hydroxyethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]propanamide;

(2S)-2-hydroxy-3-(4-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)propanamide;

(2S)-2-hydroxy-3-(4-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)propanamide;

(2S)-3-(4-{3-[(4-cyclopropylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)-2-hydroxypropanamide;

(2S)-2-hydroxy-3-[4-(3-methyl-5-{[4-(1-methylethoxy)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanamide;

(2S)-3-(4-{3-[(4-tert-butylpyrimidin-2-yl)amino]-5-methylphenyl}-1H-pyrazol-1-yl)-2-hydroxypropanamide;

(2S)-3-[4-(3-{[4-(1-fluoroethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanamide;

(2S)-2-hydroxy-3-[4-(3-methyl-5-{[4-(1-methylethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanamide;

(2S)-2-hydroxy-3-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]-N-[3-(2-oxopyrrolidin-1-yl)propyl]propanamide;

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

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

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

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

(2S)-2-hydroxy-3-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]propanamide;

4-{1-hydroxy-2-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethyl}benzamide;

(R or S)-2-hydroxy-3-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanamide;

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

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

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

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

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

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

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

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

4-[4-(3-{[4-(2-hydroxyethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]cyclohexanecarboxamide;

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

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

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

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

2-methyl-2-(4-{3-methyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1H-pyrazol-1-yl)propanamide;

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

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