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1. (WO2017147700) INHIBITORS OF WDR5 PROTEIN-PROTEIN BINDING
Nota: Texto obtenido mediante procedimiento automático de reconocimiento óptico de caracteres.
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Claims:

1. A compound of Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof:


(I)

wherein:

R1 is a heterocycloalkyl that is unsubstituted or substituted with one or more substituents selected from halo, Ci-6alkyl, Ci-6fiuoroalkyl, C3-iocycloalkyl, OR4, SR4, NR5R6, Ci-galkyleneOR4, Ci-6alkyleneSR4 and Ci-6alkyleneNR5R6, provided that R1 comprises at least one basic nitrogen atom;

R2 is selected from C6-ioaryl and heteroaryl, and R2 is unsubstituted or substituted with one or more substituents selected from halo, Ci-6alkyl, Ci-6fluoroalkyl, =0, =S, OR7, SR7 and NR8R9;

R3 is selected from Ce-io ryl, heteroaryl and heterocycloalkyl, and R3 is unsubstituted or substituted with one or more substituents selected from halo, CN, Ci-6alkyl, Ci_ efluoroalkyl, =0, =S, OR10, SR10, S02R10, NRnR12, R13, Ci-6alkyleneR13, Ci. salkenyleneR13, OCi-6alkyleneR13, SCi-6alkyleneR13,
Ci. salkyleneOR10, Ci-6alkyleneSR10, OCi-6alkyleneNRnR12, SCi-6alkyleneNRnR12, OCi. salkyleneOR10, SCi-6alkyleneOR10, OCi-6alkyleneSR10, SCi-6alkyleneSR10, C(0)OR10, C(S)OR10, C(S)NRnR12 and C(0)NRnR12;

R4 is selected from H, Ci-6alkyl Ci-6fluoroalkyl, C(0)Ci-6alkyl and C(0)d. 6fluoroalkyl;

R5 and R6 are independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, heterocycloalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OCi-6alkyl, C(0)NHCi_

6alkyl, S02Ci-6alkyl, S02HNCi-6alkyl, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl and Ci-6alkyleneC3-6cycloalkyl, or R5 and R6 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents selected from halo, CN, OH, Ci-6alkyl OCi-6alkyl, Ci-6fiuoroalkyl, OCi-efluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)NHCi-6alkyl, S02Ci-6alkyl, S02HNCi-6alkyl, Ci.6alkyleneOCi-6alkyl, Ci-6alkyleneC6-ioaryl, Ci. 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl and Ci-6alkyleneC3-6cycloalkyl;

R7 is selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6fluoroalkyl and C(0)Ci_ ealkyl;

R8 and R9 are independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci_ 6fluoroalkyl and C(0)Ci-6alkyl, or R8 and R9 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents selected from halo, OH, CN, Ci-6alkyl OCi-6alkyl, Ci-6fluoroalkyl and OCi-6fluoroalkyl;

R10 is selected from H, Ci-6alkyl, Ci.6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, heteroaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and is unsubstituted or substituted with one or more substituents selected from halo, CN, OR14, SR14, NR15R16, Ci-6alkyl, C(0)R14, C(0)OR14, C(0)NR15R16, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-ioaryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-loaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci_

6alkyleneheterocycloalkyl, Ci-6alkyleneR14, Ci-6alkyleneOR14, Ci-6alkyleneSR14 and Ci-6alkyleneNR15R16;

R11 and R12 are each independently selected from H, Ci-ioalkyl, Ci-iofluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(O)C3-i0cycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C(0)OCi-6alkyl, C(0)OCi-6fluoroalkyl, C(O)OC6-i0aryl, C(O)OC3-i0cycloalkyl, C(0)Oheteroaryl, C(0)Oheterocycloalkyl,

C(0)NHCi-6alkyl, C(0)NHCi-6fluoroalkyl, C(0)NHC6-ioaryl, C(0)NHC3- locycloalkyl, C(0)NHheteroaryl, C(0)NHheterocycloalkyl, S02Ci-6alkyl, S02Ci_ 6fluoroalkyl, S02C6-ioaryl, S02C3-iocycloalkyl, S02heteroaryl, S02heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl, C6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and each of R11 and R12 are independently unsubstituted or substituted with one or more substituents selected from halo, CN, OR14, SR14, NR15R16, Ci-6alkyl, C(0)R14, C(0)OR14, C(0)NR15R16, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3- locycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR14, Ci-6alkyleneOR14, Ci-galkyleneSR14 and Ci-6alkyleneNR15R16, or

R11 and R12 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents independently selected from halo, CN, OR14, SR14, NR15R16, Ci-6alkyl, C(0)R14, C(0)OR14, C(0)NR15R16, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneR14, Ci-6alkyleneOR14, Ci-6alkyleneSR14 and Ci. 6alkyleneNR15R16;

R13 is selected from C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(0)C3- locycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl and C6-ioaryl, and R13 is unsubstituted or substituted with one or more substituents independently selected from halo, CN, OR14, SR14, NR15R16, Ci-galkyl, C(0)R14, C(0)OR14, C(0)NR15R16, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR14, Ci-galkyleneOR14, Ci-6alkyleneSR14 and Ci-6alkyleneNR15R16,

R14 is selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl and Ci-6alkyleneheterocycloalkyl, and R14 is unsubstituted or substituted with one or more substituents selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, OH, SH, OCi-galkyl, OC^fluoroalkyl, SCi-6alkyl, SC^fluoroalkyl, NH2, NHCi-6alkyl, N(Ci-6alkyl)(Ci-6alkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi. salkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci-6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-ioaryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-loaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci_

6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci-6alkyleneNHCi-6alkyl and Ci_ salkyleneNiCi-galky iCi-galkyl);

R15 and R16 are each independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, Ci_ 6alkyleneC6-ioaryl, Ci.6alkyleneC3.iocycloalkyl and Ci-6alkyleneheterocycloalkyl and each of R15 and R16 is unsubstituted or substituted with one or more substituents independently selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, OH, SH, OCi-6alkyl, OCi-gfluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci. salkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci-6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci_ 6alkyleneNHCi-6alkyl and Ci-6alkyleneN(Ci-6alkyl)(Ci-6alkyl), or

R15 and R16 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents selected from halo, CN, Ci-6alkyl, Ci-6fiuoroalkyl, OH, SH, OCi-6alkyl, OCi-gfluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci. 6alkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci.6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci_ 6alkyleneNHCi-6alkyl and Ci^alkyleneNi i-ealkylXCi-ealkyl);

X1 and X2 are each independently selected from CR17 and N;

R17 is selected from H, F, Ci-6alkyl and Ci-6fiuoroalkyl;

A is F, and

all alkyl and alkylene groups are optionally fluorosubstituted.

2. The compound of claim 1, wherein R1 is a heterocycloalkyl that is unsubstituted or substituted with one, two or three substituents selected from halo, Ci_ 6alkyl, Ci-6fluoroalkyl, NR5R6 and Ci-6alkyleneNR5R6, provided that R1 comprises at least one basic nitrogen atom.

3. The compound of claim 1 or 2, wherein R1 is a heterocycloalkyl that is substituted with one or two substituents selected from halo, Ci-6alkyl and NR5R6, provided that R1 comprises at least one basic nitrogen atom.

4. The compound of claim 3, wherein R1 is a heterocycloalkyl that is substituted with one or two substituents selected from Ci-6alkyl and NR5R6, provided that R1 comprises at least one basic nitrogen atom.

5. The compound of claim 4, wherein R1 is selected from:


. The compound of claim 5, wherein R1 is selected from:


7. The compound of claim 6, wherein R1 is selected from:


8. The compound of any one of claims 1 to 7, wherein R2 is selected from Ce-loaryl and heteroaryl, and R2 is unsubstituted or substituted with one, two or three substituents selected from halo, Ci-6alkyl, Ci-6fluoroalkyl, =0, OR7, SR7 and NR8R9.

9. The compound of claim 8, wherein R2 is selected from C6-ioaryl and heteroaryl, and R2 is unsubstituted or substituted with one, two or three substituents selected from halo, Ci-6alkyl, Ci-6fluoroalkyl, =0 and NR8R9.

10. The compound of claim 9, wherein R2 is selected from C6-ioaryl and heteroaryl, and R2 is unsubstituted or substituted with one or two substituents selected from halo, Ci-6alkyl, Ci-6fluoroalkyl and =0.

1 1. The compound of claim 10, wherein R2 is selected from:


tautomer thereof.

The compound of claim 11 , wherein R2 is selected from:


13. The compound of any one of claims 1 to 12, wherein R3 is selected from Ce-loaryl, heteroaryl and heterocycloalkyl, and R3 is substituted with one, two or three substituents selected from halo, CN, Ci-6alkyl, Ci.6fluoroalkyl, OR10, NRnR12, R13, Ci-6alkyleneR13, OCi-6alkyleneR13, Ci-6alkyleneNRnR12, Ci-6alkyleneOR10, OCi. 6alkyleneNRnR12, OCi-6alkyleneOR10, C(0)OR10 and C(0)NRnR12.

14. The compound of claim 13, wherein R3 is selected from C6-ioaryl, heteroaryl and heterocycloalkyl, and R3 is substituted with one or two substituents selected from halo, CN, Ci-galkyl, Ci-6fluoroalkyl, OR10, NRnR12, R13, Ci-6alkyleneR13, OCi. salkyleneR13,
Ci-6alkyleneOR10, OCi.6alkyleneNRnR12 and OCi-6alkyleneOR10.

15. The compound of claim 14, wherein R3 is selected from C6-ioaryl, heteroaryl and heterocycloalkyl, and R3 is unsubstituted or substituted with one or two substituents selected from halo, CN, Ci-6alkyl, OR10, NRnR12, R13 and OCi. 6alkyleneR13.

16. The compound of claim 15, wherein R3 is heteroaryl, and R3 is substituted with one substituent selected from halo, CN, Ci-6alkyl, OR10, NRnR12, R13 and OCi_ 6alkyleneR13.

17. The compound of claim 16, wherein R3 is heteroaryl, and R3 is substituted with one substituent selected from R13

18. The compound of any one of claims 1 to 17, wherein R5 and R6 are independently selected from H, Ci-6alkyl and heterocycloalkyl.

19. The compound of claim 18, wherein R5 and R6 are independently selected from H and Ci-6alkyl.

20. The compound of any one of claims 1 to 19, wherein R5 and R6 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one, two or three substituents selected from halo and Ci-6alkyl.

21. The compound of claim 20, wherein R and R together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted.

22. The compound of any one of claims 1 to 21, wherein R10 is selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, heteroaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl.

23. The compound of claim 22, wherein R10 is selected from H, Ci-6alkyl, Ci_ 6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC3-iocycloalkyl and Ci_ 6alkyleneheterocycloalkyl.

24. The compound of claim 23, wherein R10 is selected from H, Ci-6alkyl, Ci_ 6fluoroalkyl, heterocycloalkyl and Ci-6alkyleneC3-iocycloalkyl.

25. The compound of claim 24, wherein R10 is selected from Ci-6alkyl and Ci_ 6fluoroalkyl.

26. The compound of any one or claims 1 to 25, wherein R11 and R12 are each independently selected from H, Ci-ioalkyl, Ci-iofluoroalkyl, C(0)Ci-6alkyl, C3-locycloalkyl, heterocycloalkyl, heteroaryl, C6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl.

27. The compound of claim 26, wherein R11 and R12 are each independently selected from H, Ci-ioalkyl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC3-locycloalkyl and Ci-6alkyleneheterocycloalkyl.

28. The compound of claim 27, wherein R11 and R12 are each independently selected from H, Ci-ioalkyl and C3-iocycloalkyl.

29. The compound of any one of claims 1 to 28, wherein R11 and R12 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted.

30. The compound of any one of claims 1 to 29, wherein R13 is selected from C(0)Ci-6alkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl and C6-ioaryl.

31. The compound of claim 30, wherein R13 is selected from C3-iocycloalkyl and heterocycloalkyl.

32. The compound of claim 31, wherein R13 is heterocycloalkyl.

33. The compound of any one of claims 1 to 32, wherein X1 and X2 are each independently selected from CR17 and N, in which R17 is selected from H and Ci_ 6alkyl.

34. The compound of claim 33, wherein both of X1 and X2 are CR17, in which R17 is H.

35. The compound of claim 33, wherein one of X1 and X2 is CR17 and the other of X1 and X2 is N, in which R17 is H.

36. The compound of claim 1 having the Formula (la), or a pharmaceutically acceptable salt and/or solvate thereof:

(la)

R18 is a heterocycloalkyl that is unsubstituted or substituted with one or more substituents selected from halo, Ci-6alkyl, Ci-6fluoroalkyl, C3-iocycloalkyl, OR21, SR21, NR22R23, Ci-galkyleneOR21, Ci-6alkyleneSR21 and Ci-6alkyleneNR22R23, provided that R18 comprises at least one basic nitrogen atom;;

R19 is selected from C6-ioaryl and heteroaryl, and R19 is unsubstituted or substituted with one or more substituents selected from halo, Ci-6alkyl, Ci-6fluoroalkyl, =0, =S, OR24, SR24 and NR25R26;

R20 is selected from H, halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, OR27, SR27, S02R27, NR28R29, R30, Ci-6alkyleneR30, Ci-6alkenyleneR30, OCi-6alkyleneR30, SCi-6alkyleneR30, Ci-6alkyleneNR28R29, Ci-6alkyleneOR27, Ci-6alkyleneSR27, OCi-6alkyleneNR28R29, SCi-6alkyleneNR28R29, OCi-6alkyleneOR27, SCi-6alkyleneOR27, OCi-6alkyleneSR27, SCi-6alkyleneSR27, C(0)OR27, C(S)OR27, C(S)NR28R29 and C(0)NR28R29;

R21 is selected from H, Ci-6alkyl Ci-6fluoroalkyl, C(0)Ci-6alkyl and C(0)Ci_ 6fluoroalkyl;

R22 and R23 are independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, heterocycloalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OCi-6alkyl, C(0)NHCi_ 6alkyl, S02Ci-6alkyl, S02HNCi-6alkyl, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl and Ci-6alkyleneC3-6cycloalkyl, or R22 and R23 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents selected from halo, CN, OH, Ci-6alkyl OCi-6alkyl, Ci-6fiuoroalkyl, OCi-sfiuoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)NHCi-6alkyl, S02Ci-6alkyl, S02HNCi-6alkyl, Ci.6alkyleneOCi-6alkyl, Ci-ealkyleneCe-ioaryl, Ci. 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl and Ci-6alkyleneC3-6cycloalkyl;

R24 is selected froni H, Ci-6alkyl, Ci-6fluoroalkyl and C(0)Ci-6alkyl;

R25 and R26 are independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl and C(0)Ci_ 6alkyl, or R25 and R26 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents selected from halo, OH, CN, Ci-6alkyl OCi-6alkyl, Ci-6fiuoroalkyl and OCi-6fluoroalkyl;

R27 is selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, heteroaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-ealkyleneCe-ioaryl, Ci-6alkyleneheteroaryl and Ci_6alkyleneheterocycloalkyl, and is unsubstituted

31 31 32 33 or substituted with one or more substituents selected from halo, OR , SR , NR R , Ci-6alkyl, C(0)R31, C(0)OR31, C(0)NR32R33, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR31, Ci-galkyleneOR31, Ci-6alkyleneSR31 and Ci-6alkyleneNR32R33;

R28 and R29 are each independently selected from H, Ci.i0alkyl, Ci.iofluoroalkyl, C(0)Ci-6alkyl, C(O)C6-i0aryl, C(0)C3-iocycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C(0)OCi-6alkyl, C(0)OCi-6fluoroalkyl, C(O)OC6-i0aryl, C(O)OC3-i0cycloalkyl, C(0)Oheteroaryl, C(0)Oheterocycloalkyl, C(0)NHCi-6alkyl, C(0)NHCi-6fluoroalkyl, C(O)NHC6-i0aryl, C(0)NHC3-iocycloalkyl,

C(0)NHheteroaryl, C(0)NHheterocycloalkyl, S02Ci-6alkyl, S02Ci-6fluoroalkyl, S02C6-ioaryl, S02C3-iocycloalkyl, S02heteroaryl, S02heterocycloalkyl, C3-locycloalkyl, heterocycloalkyl, heteroaryl, C6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and each of R28 and R29 are independently unsubstituted or substituted with one or more substituents selected from halo, CN, OR31, SR31, NR32R33, Ci-6alkyl, C(0)R31, C(0)OR31, C(0)NR32R33, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3- locycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR31, Ci-6alkyleneOR31, Ci-galkyleneSR31 and Ci-6alkyleneNR32R33, or

R and R together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents independently selected from halo, CN, OR31, SR31, NR32R33, C1-6alkyl, C(0)R31, C(0)OR31, C(0)NR32R33, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneR31, Ci-6alkyleneOR31, Ci-6alkyleneSR31 and Ci_ 6alkyleneNR32R33;

R30 is selected from C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(0)C3- locycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl and C6-ioaryl, and R30 is unsubstituted or substituted with

31 31 32 33 one or more substituents independently selected from halo, CN, OR , SR , NR R , Ci-galkyl, C(0)R31, C(0)OR31, C(0)NR32R33, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR31, Ci-galkyleneOR31, Ci-6alkyleneSR31 and Ci-6alkyleneNR32R33,

R31 is selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3.iocycloalkyl and Ci. 6alkyleneheterocycloalkyl, and R31 is unsubstituted or substituted with one or more substituents selected from halo, CN, Ci-6alkyl, Ci-6fiuoroalkyl, OH, SH, OCi-6alkyl, OCi-gfluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci. salkyl), C(0)Ci-6alkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci-6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-i0aryl, heteroaryl, C3- locycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci-6alkyleneNHCi-6alkyl and Ci-ealkyleneNi i-ealkylXCi-ealkyl);

R32 and R33 are each independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, Ci-6alkyleneC6-ioaryl, Ci_ 6alkyleneC3-iocycloalkyl and Ci-6alkyleneheterocycloalkyl and each of R15 and R16 is unsubstituted or substituted with one or more substituents independently selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, OH, SH, OCi-6alkyl, OCi-6fluoroalkyl, SCi. salkyl, SC^fluoroalkyl, NH2, NHCi-6alkyl, N(Ci-6alkyl)(Ci-6alkyl), C(0)Ci-6alkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci-6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-ioaryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci_ 6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci-6alkyleneNHCi-6alkyl and Ci_ 6alkyleneN(Ci-6alkyl)(Ci-6alkyl), or

R32 and R33 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents selected from halo, CN, Ci-6alkyl, Ci-6fiuoroalkyl, OH, SH, OCi-6alkyl, OCi-gfluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci. salkyl), C(0)Ci-6alkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci-6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-i0aryl, heteroaryl, C3- locycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci-6alkyleneNHCi-6alkyl and Ci-6alkyleneN(Ci-6alkyl)(Ci-6alkyl);

X3 and X4 are each independently selected from CR34 and N;

R34 is selected from H, Ci-6alkyl and Ci-6fluoroalkyl;

A2 is F; and

alkyl and alkylene groups are optionally fluorosubstituted.

37. The compound of claim 1 having the Formula (lb), or a pharmaceutically acceptable salt and/or solvate thereof:

(lb)

wherein:

R35 is selected from phenyl, C5-6heteroaryl and C5-6heterocycloalkyl, and R35 is substituted with one substituents selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, =0, =S, OR40, SR40, S02R40, NR41R42, R43, Ci-6alkyleneR43, Ci-6alkenyleneR43, OCi. salkyleneR43, SCi-6alkyleneR43, Ci-6alkyleneNR41R42, Ci-6alkyleneOR40, Ci. salkyleneSR40, OCi-6alkyleneNR41R42, SCi-6alkyleneNR41R42, OCi-6alkyleneOR40, SCi. salkyleneOR40, OCi-6alkyleneSR40, SCi-6alkyleneSR40, C(0)OR40, C(S)OR40, C(S)NR41R42 and C(0)NR41R42;

R36 is selected from CF2H and CF3;

R37 is selected from H and CH3;

R38 and R39 are independently selected from H and CH3

R40 is selected from H, Ci-6alkyl, Ci.6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, heteroaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and is unsubstituted or substituted with one to three substituents selected from halo, CN, OR44, SR44, NR45R46, Ci-6alkyl, C(0)R44, C(0)OR44, C(0)NR45R46, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-ioaryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-loaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci_

6alkyleneheterocycloalkyl, Ci-6alkyleneR44, Ci-6alkyleneOR44, Ci-6alkyleneSR44 and Ci-6alkyleneNR45R46;

R41 and R42 are each independently selected from H, Ci-ioalkyl, Ci-iofluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(O)C3-i0cycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C(0)OCi-6alkyl, C(0)OCi-6fluoroalkyl, C(0)OC6-ioaryl, C(0)OC3-iocycloalkyl, C(0)Oheteroaryl, C(0)Oheterocycloalkyl, C(0)NHCi-6alkyl, C(0)NHCi-6fluoroalkyl, C(O)NHC6-i0aryl, C(0)NHC3- locycloalkyl, C(0)NHheteroaryl, C(0)NHheterocycloalkyl, S02Ci-6alkyl, S02Ci_ 6fluoroalkyl, S02C6-ioaryl, S02C3-iocycloalkyl, S02heteroaryl, S02heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl, C6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and each of R and R are independently unsubstituted or substituted with one to three substituents selected from halo, CN, OR44, SR44, NR45R46, Ci-6alkyl, C(0)R44, C(0)OR44, C(0)NR45R46, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3- locycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR44, Ci-6alkyleneOR44, Ci-galkyleneSR44 and Ci-6alkyleneNR45R46, or

R41 and R42 together with the nitrogen atom to which they are attached form a 3-6 membered heterocycle that is unsubstituted or substituted with one to three substituents independently selected from halo, CN, OR44, SR44, NR45R46, Ci-6alkyl, C(0)R44, C(0)OR44, C(0)NR45R46, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneR44, Ci-6alkyleneOR44, Ci-6alkyleneSR44 and Ci. 6alkyleneNR45R46;

R43 is selected from C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(0)C3- locycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl and C6-ioaryl, and R43 is unsubstituted or substituted with one to three substituents independently selected from halo, CN, OR44, SR44, NR45R46, Ci-galkyl, C(0)R44, C(0)OR44, C(0)NR45R46, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR44, Ci-galkyleneOR44, Ci-6alkyleneSR44 and Ci-6alkyleneNR45R46;

R44 is selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl and Ci-6alkyleneheterocycloalkyl, and R44 is unsubstituted or substituted with one to three substituents selected from halo, CN, Ci-6alkyl, Ci-6fiuoroalkyl, OH, SH, OCi-galkyl, OCi-6fluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci-6alkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi_ salkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci-6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-ioaryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-loaryl, Ci-6alkyleneC3.iocycloalkyl, Ci-6alkyleneheteroaryl, Ci.

6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci-6alkyleneNHCi-6alkyl and Ci_ 6alkyleneN(Ci-6alkyl)(Ci^alkyl);

R45 and R46 are each independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, Ci_ 6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl and Ci-6alkyleneheterocycloalkyl and each of R45 and R46 is unsubstituted or substituted with one to three substituents independently selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, OH, SH, OCi-6alkyl, OCi-gfluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci. salkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci.6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci_ 6alkyleneNHCi-6alkyl and Ci-6alkyleneN(Ci-6alkyl)(Ci-6alkyl), or

R45 and R46 together with the nitrogen atom to which they are attached form a 3-6 membered heterocycle that is unsubstituted or substituted with one to three substituents selected from halo, CN, Ci-6alkyl, Ci-6fiuoroalkyl, OH, SH, OCi-6alkyl, OCi-gfluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci. salkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci.6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci_ 6alkyleneNHCi-6alkyl and Ci-6alkyleneN(Ci-6alkyl)(Ci-6alkyl).

In some embodiments, R35 is selected from phenyl, pyrimidinyl, pyridinyl, dihydropyridine, pyrrolyl and dihydropyrrolyl, each of which is substituted with one substituent selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, =0, =S, OR40, SR40, S02R40, NR41R42, R43, Ci-galkyleneR43, Ci-6alkenyleneR43, OCi-6alkyleneR43, SCi. salkyleneR43, Ci-6alkyleneNR41R42, Ci-6alkyleneOR40, Ci-6alkyleneSR40, OCi. 6alkyleneNR41R42, SCi-6alkyleneNR41R42, OCi-6alkyleneOR40, SCi-6alkyleneOR40, OCi. 6alkyleneSR40, SCi-6alkyleneSR40, C(0)OR40, C(S)OR40, C(S)NR41R42 and C(0)NR41R42.

38. The compound of claim 37, wherein R is substituted with one substitutent selected from Ci-6alkyl, Ci-6fluoroalkyl, OR40, NR41R42, R43, Ci-6alkyleneR43, OCi. salkyleneR43, Ci-6alkyleneNR41R42, Ci-6alkyleneOR40, OCi-6alkyleneNR41R42, OCi. salkyleneOR40, C(0)OR40 and C(0)NR41R42.

39. The compound of claim 38, wherein R35 is substituted with R43 or Ci_ 6alkyleneR43 wherein R43 is selected from C5-6cycloalkyl, Cs-eheterocycloalkyl, C5-6heteroaryl and phenyl, and R43 is unsubstituted or substituted with one to three substituents independently selected from halo and Ci-6alkyl.

40. The compound of claim 39, wherein R43 is C6-heterocycloalkyl. In some embodiments, R43 is selected from piperazinyl, morpholinyl, thiomorpholinyl, pyranyl, thiopyranyl, 2,3-dihydropyranyl, tetrahydropyranyl, 1,4-dihydropyridinyl, 1 ,4-dioxanyl, 1,3-dioxanyl, dioxanyl, homopiperidinyl, 2,3,4,7-tetrahydro-lH-azepinyl, homopiperazinyl, 1,3-dioxepanyl, 4,7-dihydro-l,3-dioxepinyl, and hexamethylene oxidyl.

41. The compound of claim 40, wherein R43 is morpholinyl, optionally substituted with one or two Me.

42. The compound of claim 37, wherein R35 is selected from:


wherein R is the subsituent.

The compound of claim 37, wherein the compound of Formula lb is selected

975

976

or a pharmaceutically acceptable salt and/or solvate thereof.

44. The compound of claim having the Formula (Ic) or a pharmaceutically acceptable salt and/or solvate thereof:


(Ic)

wherein:

R is selected from phenyl, Cs-eheteroaryl and Cs-eheterocycloalkyl, and R is substituted with one substituents selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, =0, =S, OR53, SR53, S02R53, NR54R55, R56, Ci-6alkyleneR56, Ci-6alkenyleneR56, OCi. salkyleneR56, SCi-6alkyleneR56, Ci-6alkyleneNR54R55, Ci-6alkyleneOR53, Ci. salkyleneSR53, OCi-6alkyleneNR54R55, SCi-6alkyleneNR54R55, OCi-6alkyleneOR53, SCi. salkyleneOR53, OCi-6alkyleneSR53, SCi-6alkyleneSR53, C(0)OR53, C(S)OR53, C(S)NR54R55 and C(0)NR54R55;

R48, R49 and R50 are independently selected from H, F, CF3 and CF2H, provided that at least one of R48, R49 and R50 is not H;

R and R are independently selected from H and CH3

R53 is selected from H, Ci-6alkyl, Ci.6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, heteroaryl, Ci-6alkyleneC3.iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and is unsubstituted or substituted with one to three substituents selected from halo, CN, OR57, SR57, NR58R58, Ci-galkyl, C(0)R57, C(0)OR57, C(0)NR58R59, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-ioaryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-loaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci_

6alkyleneheterocycloalkyl, Ci-6alkyleneR57, Ci-6alkyleneOR57, Ci-6alkyleneSR57 and Ci-6alkyleneNR58R59;

R54 and R55 are each independently selected from H, Ci-ioalkyl, Ci-iofluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(O)C3-i0cycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C(0)OCi-6alkyl, C(0)OCi-6fluoroalkyl, C(0)OC6-ioaryl, C(0)OC3-iocycloalkyl, C(0)Oheteroaryl, C(0)Oheterocycloalkyl, C(0)NHCi-6alkyl, C(0)NHCi-6fluoroalkyl, C(O)NHC6-i0aryl, C(0)NHC3- locycloalkyl, C(0)NHheteroaryl, C(0)NHheterocycloalkyl, S02Ci-6alkyl, S02Ci. 6fluoroalkyl, S02C6-ioaryl, S02C3-iocycloalkyl, S02heteroaryl, S02heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl, C6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and each of R54 and R55 are independently unsubstituted or substituted with one to three substituents selected from halo, CN, OR57, SR57, NR58R58, Ci-6alkyl, C(0)R57, C(0)OR57, C(0)NR58R59, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3- locycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR57, Ci-6alkyleneOR57, Ci-galkyleneSR57 and Ci-6alkyleneNR58R59, or

R54 and R55 together with the nitrogen atom to which they are attached form a 3-6 membered heterocycle that is unsubstituted or substituted with one to three substituents independently selected from halo, CN, OR57, SR57, NR58R58, Ci-6alkyl, C(0)R57, C(0)OR57, C(0)NR58R59, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR , Ci_ salkyleneOR57, Ci-6alkyleneSR57 and Ci-6alkyleneNR58R59;

R56 is selected from C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(0)C3- locycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl and C6-ioaryl, and R56 is unsubstituted or substituted with one to three substituents independently selected halo, CN, OR57, SR57, NR58R58, Ci_ salkyl, C(0)R57, C(0)OR57, C(0)NR58R59, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR57, Ci-galkyleneOR57, Ci-6alkyleneSR57 and Ci-6alkyleneNR58R59;

R57 is selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl and Ci-6alkyleneheterocycloalkyl, and R57 is unsubstituted or substituted with one to three substituents selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, OH, SH, OCi-galkyl, OCi-6fluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci-6alkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi_ 6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci-6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-ioaryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-loaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci_

6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci-6alkyleneNHCi-6alkyl and Ci_ 6alkyleneN(Ci-6alkyl)(Ci-6alkyl); and

R58 and R59 are each independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, Ci_ 6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl and Ci-6alkyleneheterocycloalkyl and each of R58 and R59 is unsubstituted or substituted with one to three substituents independently selected from halo, CN, Ci-6alkyl, Ci-6fluoroalkyl, OH, SH, OCi-6alkyl, OCi-gfluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci. salkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci.6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci_ 6alkyleneNHCi-6alkyl and Ci-6alkyleneN(Ci-6alkyl)(Ci-6alkyl), or

R58 and R59 together with the nitrogen atom to which they are attached form a 3-6 membered heterocycle that is unsubstituted or substituted with one to three substituents selected from halo, CN, Ci-6alkyl, Ci-6fiuoroalkyl, OH, SH, OCi-6alkyl, OCi-gfluoroalkyl, SCi-6alkyl, SCi-6fluoroalkyl, NH2, NHCi-6alkyl, N(Ci.6alkyl)(Ci. salkyl), C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OH, C(0)OCi-6alkyl, C(0)NH2, C(0)NHCi-6alkyl, C(0)N(Ci.6alkyl)(Ci-6alkyl), S02Ci-6alkyl, S(0)Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-locycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneOH, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneSH, Ci-6alkyleneSCi-6alkyl, Ci-6alkyleneNH2, Ci_ 6alkyleneNHCi-6alkyl and Ci-6alkyleneN(Ci-6alkyl)(Ci-6alkyl).

45. The compound of claim 44, wherein R47 is selected from phenyl, pyrimidinyl, pyridinyl, dihydropyridine, pyrrolyl and dihydropyrrolyl, each of which is substituted with one substituent selected from halo, CN, Ci-6alkyl, Ci-6fiuoroalkyl, =0, =S, OR53, SR53, S02R53, NR54R55, R56, Ci-6alkyleneR56, Ci-6alkenyleneR56, OCi-6alkyleneR56, SCi. salkyleneR56, Ci-6alkyleneNR54R55, Ci-6alkyleneOR53, Ci-6alkyleneSR53, OCi. 6alkyleneNR54R55, SCi-6alkyleneNR54R55, OCi-6alkyleneOR53, SCi-6alkyleneOR53, OCi. salkyleneSR53, SCi-6alkyleneSR53, C(0)OR53, C(S)OR53, C(S)NR54R55 and C(0)NR54R55.

46. The compound of claim 45, wherein R47 is substituted with one substitutent selected from Ci-6alkyl, Ci-6fluoroalkyl, OR53, NR54R55, R56, Ci-6alkyleneR56, OCi. salkyleneR56, Ci-6alkyleneNR54R55, Ci-6alkyleneOR53, OCi-6alkyleneNR54R55, OCi. salkyleneOR53, C(0)OR53 and C(0)NR54R55.

47. The compound of claim 46, wherein R47 is substituted with R56 or Ci_ 6alkyleneR56 wherein R56 is selected from C5-6cycloalkyl, Cs-eheterocycloalkyl, C5-6heteroaryl and phenyl, and R56 is unsubstituted or substituted with one to three substituents independently selected from halo and Ci-6alkyl.

48. The compound of claim 47, wherein R is C6-heterocycloalkyl.

49. The compound of claim 48, wherein R56 is selected from piperazinyl, morpholinyl, thiomorpholinyl, pyranyl, thiopyranyl, 2,3-dihydropyranyl, tetrahydropyranyl, 1,4-dihydropyridinyl, 1,4-dioxanyl, 1,3-dioxanyl, dioxanyl, homopiperidinyl, 2,3,4,7-tetrahydro-lH-azepinyl, homopiperazinyl, 1,3-dioxepanyl, 4,7-dihydro-l,3-dioxepinyl, and hexamethylene oxidyl.

50. The compound of claim 48, wherein R56 is morpholinyl, optionally substituted with one or two Me.

51. The compound of any one of claims 44 to 50, wherein R47 is selected from:


, wherein R is the subsituent.

52. The compound of any one of claims 44 to 51, wherein R , R and R are located on the phenyl ring as follows:


and R are independently selected from H and F..

53. The compound of claim 44, selected from:

The compound of Formula I of claim 1, selected from:

4-fluoro-N-[4-fluoro-2-(4-methylpiperazin- 1 -yl)-5-[3-(morpholin-4- ylmethyl)phenyl] phenyl] -3 ,5 -dimethylbenzamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-[3-(mo holin-4-ylmethyl)phenyl]phenyl]- 6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxarnide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-(2-mo holin-4-ylpyrirnidin-5-yl)phenyl]-6- oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxarnide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-(6-mo holin-4-ylpyridin-3-yl)phenyl]-6- oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxarnide;

N-[5-(l ,3-benzodioxol-5-yl)-4-fluoro-2-(4-methylpiperazin- 1 -yl)phenyl] -6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[2-[(3R)-3,4-dimethylpiperazin-l-yl]-4-fluoro-5-(2-mo holin-4-ylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[2-[(3S)-3,4-dimethylpiperazin-l-yl]-4-fluoro-5-(2-mo holin-4-ylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-(2^yn-olidin-l-ylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-(cyclopropylamino)pyrimidin-5-yl]-4-fluoro-2-(4-methylpiperazin-l-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-(cyclohexylamino)pyrimidin-5-yl]-4-fluoro-2-(4-methylpiperazin-l-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2-ethoxypyrimidin-5-yl)-4-fluoro-2-(4-methylpiperazin-l-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-(2-methylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[6-(cyclohexylamino)pyridin-3-yl]-4-fluoro-2-(4-me1hylpiperazin-l-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 -(2-hydroxypyrimidin-5 -yl)-2-(4-methylpiperazin- 1 -yl)phenyl] -6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2-cyanopyrimidin-5-yl)-4-fluoro-2-(4-methylpiperazin-l-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-[2-(2,2,2-trifluoroe1hoxy)pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-pyrimidin-5-ylphenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2,4-dime1hoxypyrimidin-5-yl)-4-fluoro-2-(4-methylpiperazin-l-yl)phenyl]-6-

oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(difluoromethyl)-N- [4-fluoro-2-(4-methylpiperazin- 1 -yl)-5 -(2-ηιοφ1ιο1ίη-4-ylpyrimidin-5 -yl)phenyl] -6-oxo- 1 H-pyridine-3 -carboxamide;

N-[2-[3-(dimethylamino)pyrrolidin-l^

yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(3,6-dihydro-2H-pyran-4-yl)-4-fluoro-2-(4-methylpiperazin-l-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -3-methylbenzamide;

6-acetamido-N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -4-(tafluoromethyl)pyridine-3 -carboxamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,5-dimethylbenzamide;

N-[4-fluoro-5-(4-moφholin-4-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-[6-(oxan-4-yloxy)pyridin-3-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2-cyanopyrimidin-5-yl)-4-fluoro-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(6-moφholin-4-ylpyridin-3-yl)-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-me lpyrimidin-5-yl)-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(difluorome l)-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3S,5R)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxarnide;

N-[4-fluoro-5-pyridin-3-yl-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-pyridin-4-yl-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[2-[(3R)-3-(dimethylamino)pyrrolidin- 1 -yl] -4-fluoro-5-(2-mo holin-4-ylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[2-[(3S)-3-(dimethylamino)pynOlidm^

5- yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-(dimethylamino)pyrimidin-5-yl] -4-fluoro-2-(4-methylpiperazin- 1 -yl)phenyl] - 6- oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-[6-(mo holin-4-ylmethyl)pyridin-3-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -3 -(trifluoromethyl)- lH-pyrazole-4-carboxamide;


yl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine-3-carboxamide;

N-(3 '-((cyclopentylamino)methyl)-6-fluoro-4-(4-methylpiperazin- 1 -yl)- [ 1 , 1 '-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine-3-carboxamide;


yl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine-3-carboxamide;

N-(4-fluoro-2-(4-methylpiperazin-l-yl)-5-(2-moφholinopyridin-4-yl)phenyl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine-3-carboxamide;

N-(4-fluoro-2-(4-methylpiperazin-l-yl)-5-(5-(moφholinomethyl)pyridin-3-yl)phenyl)-6-oxo-4-(trifluoromethyl)- 1 ,6-dihydropyridine-3-carboxamide;

N-(4-fluoro-2-(4-methylpiperazin-l-yl)-5-(5-(((tetrahydro-2H-pyran-4-yl)amino)methyl)pyridin-3-yl)phenyl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine- 3-carboxamide;

(R)-N-(4-fluoro-2-(4-methylpiperazin- 1 -yl)-5 -(5 -(((tetrahydrofuran-3 -

yl)amino)methyl)pyridin-3-yl)phenyl)-6-oxo

3-carboxamide;


biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine-3-carboxamide;

(S)-N-(4-(3 ,4-dimethylpiperazin- 1 -yl)-6-fluoro-3 '-(mo holinomethyl)- [1,1 -biphenyl] -3-yl)-6-oxo-4-(trifluoromethyl)- 1 ,6-dihydropyridine-3-carboxamide;

N-(6-fluoro-3Η™οφ^1ίηοηΐ6 1)-4-(^5 S)-3,4,5 -trimethylpiperazin- 1 -yl)- [1,1 -biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine-3-carboxamide;


biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine-3-carboxamide;

N-[4-fluoro-2-(4-methylpiperazin-l-yl)-5-(2-moφholin-4-ylpyridin-4-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

2-(difluoromethyl)-N-(5-(2-((2S,6R)-2,6-dimethylmoφholino)pyrimidin-5-yl)-2-((S)-3,4-dimethylpiperazin-l-yl)-4-fluorophenyl)-4-fluorobenzamide;

N-[5-(l,3-benzodioxol-5-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(mfluoromethyl)-lH-pyridine-3-carboxarnide;

N-[5-(6-acetamidopyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(mfluoromethyl)-lH-pyridine-3-carboxarnide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrirnidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -4-methoxy-6-oxo- 1 H-pyridine-3 -carboxamide;

N-[5-[2-(cyclopropylmethoxy)pyridin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-[(cyclohexylamino)methyl]phenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(3-cWoro-4-moφholin-4-ylphenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[5-(3,4-dihydro-2H-l,5-benzodioxepin-7-yl)-4-fluoro-2-[(3R,5S)-3,4,5-

trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2,3-dihydro-l,4-benzodioxin-6-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(4-methyl-2,3-dihydro-l,4-benzoxazin-7-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2-acetamidopyrimidin-5-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(l-phenyl-3,6-dihydro-2H-pyridin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]benzamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3-methoxybenzamide;

3,5-dichloro-N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- lH-pyridazine-3 -carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]furan-2-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]pyridine-3-carboxamide;

N-[4-fluoro-5 2-moφholin-4-ylpyridin-4-yl)-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[6-(2-methoxyethoxy)pyridin-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoΓO-5-(3-moφholin-4-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -2-methoxybenzamide;

2-οωοΓθ-4-ΑυοΓθ-Ν-[4-ΑυοΓθ-5-(2^οφΗο1ίη-4^^ήηιίά-η-5^1)-2-[(3Κ,58)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

5-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -3 -methoxybenzamide;

N-[4-fluoro-5-[4-(2-methoxyethoxy)phenyl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[5-chloro-6-(2-methylpropoxy)pyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[3-chloro-4-(cyclopropylmethoxy)phenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[5-(3,6-dihydro-2H-pyran-4-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]-5-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl] -3 -(trifluoromethyl)- 1 H-pyrazole-4-carboxamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-

dimethylpiperazin-l-yl]phenyl]-3,5-dimethylbenzamide;

N-[5-(3-chloro-5-cyano-4-hydroxyphenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(5-cyano-6-phenylmethoxypyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamide;

N-[5-(4-cyanophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[6-(oxan-4-yloxy)pyridin-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(3-cyanophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-(dimethylamino)pyrimidin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(5,6-dime1hoxypyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -1,3 -benzodioxole-4-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -4-methoxybenzamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5-(3-fluoro-5-moφholin-4-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- lH-pyridine-3 -carboxamide;

2-chloro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

2-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-

trimethylpiperazin-l-yl]phenyl]-3-methoxybenzamide;

3,4-difluoro-N-[4-fluoro-5 2-mo holin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5 4-methoxyphenyl)-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[4-(cyclopropylmethoxy)phenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 4^yrrolidin-l-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

3-acetamido-N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methylindazole-3-carboxamide;

N-[4-fluoro-5-(4-moφholin-4-ylphenyl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-1 -methylindazole-3 -carboxamide;

N-[4-fluoro-5-[3-[[methyl(oxetan-3-yl)amino]methyl]phenyl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[3-[(4-fluoropiperidin-l-yl)methyl]phenyl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[2-(3,4,6,7,9,9a-hexahydro-lH-pyrazino[2, 1 -c] [ 1 ,4] oxazin-8-yl)-4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methylpyrazole-4-carboxamide;

N-[4-fluoro-5-(4-moφholin-4-ylphenyl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-1 -methylpyrazole-4-carboxamide;

N-[5-(5-cyano-6-hydroxypyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l- yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

Ν-[4-ΑυοΓθ-5-(3-ΑυοΓθ-4^οφΗο1ίη-4^1ρΗ^1)-2-[(3Κ,58)-3,4,5-ηιηΐ6^1ρίρ6Γ3ζίη-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[5-[3-(cyclopropylmethoxy)phenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

3 dime lamino)-N-[4-fluoro-5 2-mo holin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -1,3 -oxazole-4-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(4-moφholin-4-ylphenyl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(2-propan-2-yloxypyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[5 -(6-cyanopyridin-3 -yl)-4-fluoro-2-[(3R,5 S)-3,4,5 -trimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(6-cyano-5-methylpyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2-cyanopyridin-4-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-methoxy-6-(trifluoromethyl)pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-methoxy-6-methylpyridin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-[6-methoxy-5-(trifluoromethyl)pyridin-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-cyano-N-[4-fluoro-5-(2-moφholin-4-yl yrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-methoxypyridine-3-carboxamide;

3-chloro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

2,6-dichloro-N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

3-cωoΓO-2-fluoΓO-N-[4-fluoΓO-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[5-[6-(dimethylamino)pyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

tert-butyl 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5 S)-3,4,5-trimethylpiperazin-l -yl]phenyl] -3,6-dihydro-2H-pyridine- 1 -carboxylate;

N-[4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]-5-[4- (trifluoromethyl)phenyl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]-5-[4-(trifluoromethoxy)phenyl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5-phenyl-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(4-chlorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -[(4-methoxyphenyl)methyl] -3,6-dihydro-2H-pyridin-4-yl] -2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(6-methylpyridazin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-

yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(2-methylpropyl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[l-(cyclopropylmethyl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2 (3R,5S)-3,4,5-trime lpiperazin-l-yl]-5-[l-(3,3,3-trifluoropropyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[(4-fluorophenyl)methyl]-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 1-^yridin-3-ylme1hyl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2 (3R,5S)-3,4,5-trime lpiperazin -yl]-5 1 thiophen-3-ylmethyl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[5-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(6-hydroxypyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-piperazin-l-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazm yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

3-cωoro-5-fluoro-N-[4-fluoro-5 2-mo holin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

3,5-difluoro-N-[4-fluoro-5-(2-mo holin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-

trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5 2 (2R,6S)-2,6-dime lmo holin-4-yl]pyrirnidin-5-yl]-2-[(3S,5R)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2 (3R,5S)-3,4,5-trime lpiperazin^-yl]-5 1 l,3-thiazol-2-ylmethyl)- 3,6-dihydro-2H^yridin-4-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 -[ 1 -[(2-methyl- 1 ,3 -oxazol-5 -yl)methyl] -3 ,6-dihy dro-2H-pyridin-4-yl] -2- [(3R,5S)-3,4,5-mmethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -[(1 -methylpyrazol-4-yl)methyl] -3,6-dihydro-2H-pyridin-4-yl] -2- [(3R,5S)-3,4,5-mmethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -[(4-moφholin-4-ylphenyl)methyl] -3,6-dihydro-2H-pyridin-4-yl] -2- [(3R,5S)-3,4,5-mmethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[[4-(4-methylpiperazin-l-yl)phenyl]methyl]-3,6-dihydro-2H-pyridin- 4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(oxan-4-ylmethyl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

3,5-dichloro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3-(dimethylamino)pyrrolidin- 1 -yl] phenyl] benzamide;

3,5-dichloro-N-[4-fluoro-5-(4-moφholin-4-ylphenyl)-2-[(3R)-3-(dimethylamino)pyrrolidin- 1 -yl] phenyl] benzamide;

N-[5-(5-cyano-6-moφholin-4-ylpyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(5-methyl-6-mo holin-4-yl yridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2,3-dihydro-lH-pyrrolo[2,3-b]pyridin-5-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2 (3R,5S)-3,4,5-trime lpiperazin -yl]-5 5 trifluoromethyl)pyridin-3-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[5-(tert-butylcarbamoyl)pyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

3-chloro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-5-(trifluoromethyl)benzamide;

3- fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-5-(trifluoromethyl)benzamide;

N-[4-fluoro-5-(4-moφholin-4-ylphenyl)-2-[(3R)-3-(dimethylan^ino)pyn·olidin-l-yljphenyl] - 1 H-pyrazole-4-carboxamide;

N-[4-fluoro-5-(5-methylpyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(5-carbamoylpyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2 (3R,5S)-3,4,5-trime lpiperazin -yl]-5 5 trifluoromethyl)pyridin-3-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-4-methyl-l,3-thiazole-2-carboxamide;

2-[(dimethylarrino)methyl]-N-[4-fluor^^

3,4-dimethylpiperazin- 1 -yl] phenyl] -1,3 -thiazole-4-carboxamide;

4- chloro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] - lH-pyrazole-3 -carboxamide;

Ν-[4-ΑυοΓθ-5-(2^οφηο1ίη-4^^ήΓτύάώ^

1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

Ν-[4-ΑυοΓθ-5-(2^οφηο1ίη-4^^ή ^η-5^

1 -yl] phenyl] -3 -(trifluoromethyl)- lH-pyrazole-4-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -3 -(trifluoromethyl)benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1- yl]phenyl]-4-(trifluoromethyl)pyrimidine-5-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -4-(trifluoromethyl)- 1 ,3 -thiazole-5 -carboxamide;

2- fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-5-(trifluoromethyl)benzamide;

3- fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-5-methoxybenzamide;

3,5-dichloro-N-[4-fluoro-5-(4-moφholin-4-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methylpyrazole-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-lH-pyrazole-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-2-methyl-l,3-thiazole-4-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-2-methyl-l,3-thiazole-5-carboxamide;

N-[5-(6-acetamidopyridin-3-yl)-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2-cyanopyrimidin-5-yl)-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l- yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-2-methyl-4-(trifluoromethyl)-l,3-thiazole-5-carboxamide;

3,5-dichloro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]benzamide;

N-[4-fluoro-5-(3-fluoro-4-moφholin-4-ylphe yl)-2-[(3R)-3,4-dime1hylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2 (2R,6S)-2,6-dime lmo holin-4-yl]pyrirnidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-5-[2 4-me1hyl-l,4-diazepan-l-yl)pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2-(trifluoromethyl)benzamide;

N-[4-fluoro-5 4-moφholin-4-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[5-(5-cyanopyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(5-chloropyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2-cyclohexyloxypyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -[2-(4-methoxyphenyl)acetyl] -3,6-dihydro-2H-pyridin-4-yl] -2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[6-(2-methoxyethoxy)pyridin-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5-(2^yrrolidin-l-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -3 -(trifluoromethyl)thiophene-2-carboxamide;

3,5-ώοΜθΓθ-4-ΑυοΓθ-Ν-[4-ΑυοΓθ-5-(2^οφΗο1ίη-4^1ρ^ηιίώη-5^1)-2-[(3Κ,58)-3,4,5-trimethylpiperazin-l-yl]phenyl]benzamide;

2,3-dichloro-N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[4-fluoro-5-[3-[[methyl(oxetan-3-yl)amino]methyl]phenyl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[5-(5-ethoxypyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(MuoΓomethyl)-N-[4-fluoΓO-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

N-[5-(6-acetamidopyridin-3-yl)-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)- 1 -methyl-6-oxopyridine-3 -carboxamide;

N-[5-(2-cyanopyrimidin-5-yl)-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)- 1 -methyl-6-oxopyridine-3 -carboxamide;

N-[5-[6-(dimethylamino)pyridin-3-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[5-cyano-6-(dimethylamino)pyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[6-(dimethylamino)-5-fluoropyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(5-chloro-6-moφholin-4-ylpyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2,3-dihydro-[l,4]dioxino[2,3-b]pyridin-7-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

2-(difluoromethyl)-N-(2-((S)-3,4-dimethylpiperazin-l-yl)-4-fluoro-5-(2-((S)-2-methylmoφholino)pyrimidin-5-yl)phenyl)-4-fluorobenzan^ide;

N-[4-fluoro-5 -(2-moφholin-4-ylpyrimidin-5 -yl)-2-(3 ,3 ,4-trimethylpiperazin- 1 -yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2-moφholin-4-ylpyridin-4-yl)-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5 4^yrrolidin-l-ylphenyl)-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[5-[4-(cyclopropylmethoxy)phenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

2,3-difluoro-N-[4-fluoro-5 2-mo holin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

2-chloro-4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]benzamide;

N-[5-(l-cyclopentyl-3,6-dihydro-2H-pyridin-4-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -[ 1 -(4-methoxyphenyl)ethyl] -3,6-dihydro-2H-pyridin-4-yl] -2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(l-butan-2-yl-3,6-dihydro-2H-pyridin-4-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(6-moφholin-4-ylpyridin-3-yl)-2-[(3R)-3-(dimethylamino)pyrrolidin-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5^iperidin-4-yl-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo- 4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(6-hydroxypyridin-3-yl)-2-[(3R)-3-(dimethylamino)pyrrolidin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R)-3- (dimethylamino)pyrrolidin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyrii^ carboxamide;

N-[4-fluoro-5-(6-moφholin-4-ylpyridin-3-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-propan-2-yloxypyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(2,3-dihydro-[l,4]dioxino[2,3-b]pyridin-7-yl)-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5 1 l-methylpiperidin-4-yl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[l-(2,2-dimethylpropanoyl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[l-(2,2-dimethylpropanoyl)piperidin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 l^yrirnidin-2-yl-3,6-dihydro-2H-pyridin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2 (2R,6S)-2,6-dime lmo holin-4-yl]pyrirnidin-5-yl]-2-[(3S,5R)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(3-fluoro-4-moφholin-4-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[4-fluoro-5-(l-methylsulfonyl-2,5-dihydropyrrol-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

3,5-dichloro-N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

2-chloro-N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -4-fluorobenzamide;

N-[5-(l-acetyl-3,6-dihydro-2H-pyridin-4-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

ethyl 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5 S)-3,4,5-trimethylpiperazin-l -yl]phenyl] -3,6-dihydro-2H-pyridine- 1 -carboxylate;

2-methylpropyl 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine- 1 -carboxylate;

N-[5-[ 1 -(3,3-dimethylbutanoyl)-3,6-dihydro-2H-pyridin-4-yl] -4-fluoro-2-[(3R,5 S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[l-(3,3-dimethylbutanoyl)piperidin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(6-fluoropyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[2-[4-(dimethylamino)piperidin-l-yl]-4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[2-[4-[2-(dime1hylan^ino)ethyl] i erazin-l-yl]-4-fluoro-5-(2-mo holin-4-ylpyrimidin-5 -yl)phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[2-[2-[(dimethylan^ino)methyl]mo holin-4-yl]-4-fluoro-5-(2-mo holin-4-ylpyrimidin-5 -yl)phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5-(6^yrrolidin-l-ylpyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(5-cyano-6-pyrrolidin-l-ylpyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamide;

N-[5-(2,2-difluoro-l,3-benzodioxol-5-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

3-οωοΓθ-4-ΑυοΓθ-Ν-[4-ΑυοΓθ-5-(2^οφΗο1ίη-4^^ήηιίάίη-5^1)-2-[(3Κ,58)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

3-chloro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-5-methoxybenzamide;

3-οωοΓθ-2,4-ώΑυοΓθ-Ν-[4-ΑυοΓθ-5-(2^οφΗο1ίη-4^1ρ^ηιί(ϋη-5^1)-2-[(3Κ,58)-3,4,5-trimethylpiperazin-l-yl]phenyl]benzamide;

N-[4-fluoro-5-(l-methyl-3,6-dihydro-2H-pyridin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-5-(2-moφholin-4-ylpyrimidin-5 -yl)phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[5-(6-cyano-4-methylpyridin-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(l-pyridin-2-yl-3,6-dihydro-2H-pyridin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 1 5-me lpyrirnidin-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 6 (2R,6S)-2,6-dimethylmo holin-4-yl]pyridin-3-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2 (2R,6S)-2,6-dime lmo holin-4-yl]pyrirnidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -(6-methoxypyrimidin-4-yl)-3,6-dihydro-2H-pyridin-4-yl] -2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 1 5-chloropyrirnidin-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

ethyl 2-[4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridin-l-yl]pyrimidine-4-carboxylate;

N-[4-fluoro-2-[3-(methylamino)pyrrolidin-l-yl]-5-(2-moφholin-4-ylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[2-[3-[(dimethylamino)methyl]pyrrolidin- 1 -yl] -4-fluoro-5-(2-moφholin-4-ylpyrimidin-5 -yl)phenyl] -6-oxo-4-(trifluoromethyl)- 1 Hφyridine-3-carboxamide;

N-[4-fluoro-5-[2-(4-methylpiperazin-l-yl)pyrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3-hydroxy-5-(trifluoromethyl)benzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -3 -hydroxybenzamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -3 -hydroxy quinoline-4-carboxamide;

Ν-[4-ΑυοΓθ-5-(2^οφηο1ίη-4^^ή ^^^

1 -yl] phenyl] - 1 -methyl-3 -(trifluoromethyl)pyrazole-4-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-3-(trifluoromethyl)pyrazole-4-carboxamide;

N-[5 1 dimethylcarbamoyl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 1-^yn-olidine-l-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 -[ 1 -(4-methylpiperazine- 1 -carbonyl)-3 ,6-dihy dro-2H-pyridin-4-yl] -2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

phenyl 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5 S)-3,4,5-trimethylpiperazin-l -yl]phenyl] -3,6-dihydro-2H-pyridine- 1 -carboxylate;

N-[4-fluoro-5-[l-[(2R,6S)-2,6-dimethyloxan-4-yl]-3,6-dihydro-2H-pyridin-4-yl]-2- [(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-4-hydroxy-2-(trifluoromethyl)benzamide;

2,3-difluoro-N-[4-fluoro-5-(2-mo holin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-5-hydroxybenzamide;

N-[5-[2-(cyclobutylmethoxy)pyridin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-(2,2-dimethylpropoxy)pyridin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-

carboxamide;

N-[5-[2-(diethylarrino)pyrimidin-5-yl]-4-fl^

1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

3- fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

3,4,5-trifluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

2-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -6-(trifluoromethyl)benzamide;

4- fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

3,5-dichloro-N-[4-fluoro-2-[3-(methylamino)pyrrolidin-l-yl]-5-(2-moφholin-4-ylpyrimidin-5 -yl)phenyl] benzamide;

N-[4-fluoro-5-[6-(4-methylpiperazin-l-yl)pyridin-3-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-[4-(4-methylpiperazin-l-yl)phenyl]-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-2-[3-[methyl(propyl)amino]pyrrolidin-l-yl]-5-(2-moφholin-4-ylpyrimidin-5 -yl)phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

3,5-dichloro-N-[4-fluoro-2-[3-[methyl ropyl)anlino]pyrrolidin-l-yl]-5-(2-mo holin-4-ylpyrimidin-5-yl)phenyl]benzamide;

N-[5-[l-[2-(dime lamino)acetyl]-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-[4-[5-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]pyrimidin-2-yl]piperazin-l-yl]-4- oxobutanoic acid;

N-[4-fluoro-5 2-moφholin-4-yl yrimidin-5-yl)-2 (3R,4R)-3 dime lan^ino)-4-fluoropyrrolidin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R,4R)-3-(dime1hylamino)-4-fluoropyrrolidin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-2-mo holin-4-yl-5-(2-piperazin-l-ylpyrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,4R)-3-(dime1hylan^ino)-4-fluoropyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R,4R)-3-(dime1hylamino)- 4-fluoropyrrolidin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(6-hydroxypyridin-3-yl)-2-[(3R,4R)-3-(dimethylamino)-4-fluoropyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide; tert-butyl 4-[2-fluoro-5-[[l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine- 1 -carboxylate;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -4-(difluoromethyl)-6-oxo- 1 H-pyridine-3-carboxamide;

l-ethyl-N-[4-fluoro-5-(2-mo holin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

4-fluoro-N-[4-fluoro-5-[2-(4-methylpiperazin-l-yl)pyrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(tafluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-[6-(4-methylpiperazin-l-yl)pyridin-3-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

2,3-dichloro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-

dimethylpiperazin-l-yl]phenyl]benzarnide;

N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-(2,2,6,6-tetramefliylm^ 4-yl)pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxarrd

N-[4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]-5-[2-(2,2,6,6-tetramethylmo holin-4-yl)pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromet^^ pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-5-(trifluoromethyl)-lH-pyrazole-3-carboxamide;

tert-butyl 5-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH^yriine-3-carbonyl]amino]-4-[(3R,5 S)-3,4,5-trimethylpiperazin-l -yljphenyl] -3,6-dihydro-2H-pyridine- 1 -carboxylate;

tert-butyl 3-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH^yriine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,5-dihydropyrrole-l-carboxylate; tert-butyl 3-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH^yriine-3-carbonyl]amino]-4- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate;

tert-butyl 5-[2-fluoro-5-[[l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carbonyl]armno]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H pyridine- 1 -carboxylate;

tert-butyl 3-[2-fluoro-5-[[l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,5-dihydropyrrole-l-carboxylate;

tert-butyl 3-[2-fluoro-5-[[l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate;

N-[4-fluoro-2 (3R,5S)-3,4,5-trime lpiperazin -yl]-5 l,2,3,64etrahydropyridin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH^yriine-3-carboxamide;

N-[5 2,5-dihydro-lH^yrrol-3-yl)-4-fluoro-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH^yriine-3-carboxarnide;

N-[5-(8-azabicyclo[3.2.1]oct-2-en-3-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-(6-moφholin-4-ylpyridin-3-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

N-[5 2-butan-2-yloxypyridin-4-yl)-4-fluoro-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2 (3R,4R)-3 dime lan^ino)-4-methoxypyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-(l-pyrirnidin-2-yl-3,6-dihydro-2H-pyridin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(l-pyrimidin-2-yl-2,5-dihydropyrrol-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(8-pyrirnidin-2-yl-8-azabicyclo[3.2.1]oct-2-en-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(3R)-3-methylmo holin-4-yl]pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-[(3R)-3-methylmo holin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-yl-l,4,5,6-tetrahydropyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmoφholin-4-yl]pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[6-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyridin-3-yl]-2-[(3R)-3,4-

dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxopyridine-3 -carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(lR,4R)-5-methyl-2,5-diazabicy clo[2.2.1 ]heptan-2-yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2 (3R,4R)-3 e l(me l)an^ino]- 4-fluoropyn-olidin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3- [e1hyl(methyl)amino]pyrrolidin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine- 3- carboxamide;

N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2 (3R,4R)-3 e l(me l)an^ino]- 4- fluoropyrrolidin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-propan-2-ylmoφholin-4-yl]pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-[(2R)-2-propan-2-ylmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-(2,2-dimethylmo holin-4-yl)pyrimidin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[5-[2-(2,2-dimethylmo holin-4-yl)pyrimidin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-7-(trifluoromethyl)-[l,2,4]triazolo[4,3-a]pyridine-6-carboxamide;

N-[5-[2-(7-azabicyclo[2.2.1]heptan-7-yl)pyrimidin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5R)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-(3-fluoro-4-moφholin-4-ylphenyl)-2-[(3R,5R)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5R)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-[2-[(2R,6S)-2,6-dimethylmo holin-4-yl]pyrimidin-5-yl]-2-[(3R,5R)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(3-fluoro-4-moφholin-4-ylphenyl)-2-[(3R,5R)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,4R)-3-[e l(me l)amino]-4-methoxypyrrolidin- 1 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-[me l-[(3R)-oxolan-3-yl]amino]pyrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5 2 me l-[(3R)-oxolan-3-yl]amino]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,5-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[4-fluoro-5-[l-(6-methoxypyrimidin-4-yl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(5-methoxypyrimidin-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 1 5-fluoropyrirnidin-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[ 1 -(4,6-dimethylpyrimidin-2-yl)-3,6-dihydro-2H-pyridin-4-yl] -4-fluoro-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 1 5-fonnylpyrirnidin-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2 me l(oxan-4-yl)amino]pyrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5 2 me l(oxan-4-yl)amino]pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 1 dimethylcarbamoyl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

ethyl 5-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5 S)-3,4,5-trimethylpiperazin-l -yljphenyl] -3,6-dihydro-2H-pyridine- 1 -carboxylate;

N-[4-fluoro-5 1-^yn-olidine-l-carbonyl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(5-methoxypyrimidin-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 1 5-me lpyrirnidin-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 1 5-fluoropyrirnidin-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-4-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

4-fluoro-N-[4-fluoro-5-[2 4-me lpiperazin-l-yl)pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[5 2 dime lamino)pyrimidin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]-5-[2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] pyrimidin-5 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-[2-(4-me1hylpiperazin-l-yl)pyrimidin-5-yl]-2-[(3R,5R)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4- (difluorome l)-N-[4-fluoro-5-[2-[(2R,6S)-2,6-dime lmoφholin-4-yl]pyrin^idin- 5- yl] -2-[(3R)-3,4-dimethylpiperazin- 1 -yl]phenyl] -1 -methyl-6-oxopyridine-3-carboxamide;

N-[4-fluoro-5-(6-moφholin-4-ylpyridazin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

4 difluorome l)-N-[4-fluoro-5 2 (2R,6S)-2,6-dime lmoφholin-4-yl]pyrin^idin- 5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2 (2R)-2-me lmoφholin-4-yl]pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH^yridine-3-carboxamide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5R)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[4-fluoro-5 2 (2R)-2-me lmo holin-4-yl]pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2 (3R)-3,4-dime lpiperazin-l-yl]-5-[2-[(2R)-2-methylmoφholin-4-yl]pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH^yridine-3-carboxamide;

N-[4-fluoro-5 2 (2R)-2-me lmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 l^yrirnidin-2-yl-3,6-dihydro-2H-pyridin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5-[4-[(4-fluorophenyl)methyl]piperazin-l-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(4-pyrimidin-2-ylpiperazin-l-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[5-(hydroxymethyl)pyrimidin-2-yl]-3,6-dihydro-2H-pyridin-4-yl]-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4- (difluorome l)-N-[4-fluoro-5-[2-[(2R,6S)-2,6-dime lmoφholin-4-yl]pyrin^idin- 5- yl]-2-[(3S)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide; 4-(difluoromethyl)-N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmorpholin-4-yl] pyrimidin-5 -yl] phenyl] -6-oxo- lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2 (2R)-2-me lmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH^yridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methyln ^holin-4-yl] pyrimidin-5 -yl] phenyl] -6-oxo- lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-methylsulfonylpyrimidin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

4-fluoro-N-[4-fluoro-5-[2-(4-methyl-l,4-diazepan-l-yl)pyrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-(2-piperazin-l-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-(6-moφholin-4-ylpyridin-3-yl)-2-[(3R)-3,4-dimethylpiperazin-1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-(difluoromethyl)-N-[4-fluoro-5-[6-(oxan-4-yloxy)pyridin-3-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

N-[5-[l-(5-cyanopyrimidin-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[l-[5-[(dimethylamino)methyl]pyrimidin-2-yl]-3,6-dihydro-2H-pyridin-4-yl]-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[5-(moφholin-4-ylmethyl)pyrimidin-2-yl]-3,6-dihydro-2H-pyridin- 4-yl]-2-[(3R,5S)-3,4,5-trime lpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[5-[(4-methylpiperazin-l-yl)methyl]pyrimidin-2-yl]-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4- (trifluoromethyl)-lH-pyridine-3-carboxamide;

2-methylpropyl 5-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-

carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine- 1 -carboxylate;

N-[4-fluoro-5 1 5-fonnylpyrirnidin-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(MuoΓomethyl)-N-[4-fluoΓO-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-6-oxo-lH-pyridine-3-carboxamide;

4- (difluoromethyl)-N-[4-fluoro-5-(6-moφholin-4-ylpyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[5-(hydroxymethyl)pyrimidin-2-yl]-3,6-dihydro-2H-pyridin-5-yl]-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[l-[5-[(dimethylamino)methyl]pyrimidin-2-yl]-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[5-(moφholin-4-ylmethyl)pyrimidin-2-yl]-3,6-dihydro-2H-pyridin- 5- yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[5-[(4-methylpiperazin-l-yl)methyl]pyrimidin-2-yl]-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4- (trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3S)-3-(dime lamino)pyrrolidin-l-yl]-5-[2-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-[(2R,6S)-2,6-dime lmoφholin-4-yl]pyrirnidin-5-yl]-2-[(3S)-3- [e1hyl(methyl)amino]pyrrolidin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine- 3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-yl yrimidin-5-yl)-2-[(3R)-3-(diethylamino) yrrolidin-1 -yl] phenyl] -6-oxo-4-(mfluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrin^idin-5-yl)-2-[(3R)-3-[methyl(propan-2-y^aminolpyn-olidin-l-ylJphenylJ-e-oxo^-^rifluoromethy^-lH-pyridine-S-carboxamide;

N-[4-fluoro-5-[6-[(2R,6S)-2,6-dimethylmo holin-4-yl]pyridin-3-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-[6-[(2R,6S)-2,6-dimethylmo holin-4-yl]pyridin-3-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

4-fluoro-N-[4-fluoro-5-[6-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyridin-3-yl]-2-[(3R)-3,4-dime1hylpiperazin-l-yl]phenyl]-2-(trifluoromethyl)benzamide;

N-[4-fluoro-5-[2-(4-hydroxy-4-methylpiperidin-l-yl)pyrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-(4-hydroxy-4-methylpiperidin-l-yl)pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3S)-3-(dime lamino)pyrrolidin-l-yl]-5-[2-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyrin^idin-5-yl]phenyl]-l-methyl-6-oxo-4- (trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-[2-[(2R,6S)-2,6-dime lmoφholin-4-yl]pyrirnidin-5-yl]-2-[(3S)-3-[ethyl(methyl)amino] pyrrolidin- 1 -yl]phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3-(diethylamino)pyrrolidin-1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrirnidin-5-yl)-2-[(3R)-3-[methyl(propan-2-yl)armno]pyrrolidin-l-yl]phenyl]-l-methyl-6-oxo-4-(mfluoromethyl)pyridine-3-

carboxamide;

4-fluoro-N-[4-fluoro-5-[2 (2R,6S)-2,6-dime lmoφholin-4-yl] yrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl]phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-[2 (2R,6S)-2,6-dime lmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2-(trifluorome1hyl)benzamide;

4-fluoro-N-[4-fluoro-5-[6-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyridin-3-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2-(trifluorome1hyl)benzamide;

N-[4-fluoro-2 (3R)-3,4-dime lpiperazin-l-yl]-5-[6-[(2R)-2-methylmo holin-4-yl]pyridin-3 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-[6-[(2R)-2-methylmoφholin-4-yl]pyridin-3-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-(4-cyclopropylpiperazin-l-yl)pyrimidin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

4-(difluoromethyl)-N-[4-fluoro-5-(3-fluoro-4-moφholin-4-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxarnide;

N-[4-fluoro-5-[l-(5-methoxypyrimidin-2-yl)-2,5-dihydropyrrol-3-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(6-methoxypyrimidin-4-yl)-2,5-dihydropyrrol-3-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(5-me lpyrirnidin-2-yl)-2,5-dihydropyrrol-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(5-fluoropyrimidin-2-yl)-2,5-dihydropyrrol-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(pyrrolidine-l-carbonyl)-2,5-dihydropyrrol-3-yl]-2-[(3R,5S)-3,4,5- trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(pyrazine-2-carbonyl)-2,5-dihydropyrrol-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

2-methylpropyl 3-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,5-dihydropyrrole-l-carboxylate;

N-[4-fluoro-5 1 5-fonnylpyrirnidin-2-yl)-2,5-dihydropyrrol-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(l-methylpyrazol-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 4-cyano-l,3-thiazol-2-yl)-4-fluoro-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 5-cyano-l,3-thiazol-2-yl)-4-fluoro-2 (3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-(3-fluoro-4-moφholin-4-ylphenyl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-(3-fluoro-4-moφholin-4-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxopyridine-3 -carboxamide;

N-[4-fluoro-2 (3R)-3,4-dime lpiperazin-l-yl]-5-[2-[(2R)-2-methylmo holin-4-yl]pyrimidin-5-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5 2 (2R)-2-me lmo holin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

4-fluoro-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmoφholin-4-yl] pyrimidin-5 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-[2-[(2R)-2-me1hylmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-2-(trifluoromethyl)benzamide;

N-[5-[2-(4-cyclopropylpiperazin-l-yl)pyrimidin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

N-[5-[2-(4-cyclopropylpiperazin-l-yl)pyrimidin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmorpholin-4-yl] pyrimidin-5 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[5-[l-[5-[(dimethylarrino)methyl]pyrirm

2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl]phenyl] -6-oxo-4-(trifluoromethyl)- 1H-pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -[5-(moφholin-4-ylmethyl)pyrimidin-2-yl] -2,5-dihydropyrrol-3-yl] -2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-[5-[(4-methylpiperazin-l-yl)methyl]pyrimidin-2-yl]-2,5-dihydropyrrol-3 -yl] -2-[(3R,5 S)-3 ,4,5 -trimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmoφholin-4-yl] pyrimidin-5 -yl] phenyl] - 1 -methyl-6-oxopyridine-3-carboxamide;

4-(difluorome l)-N-[4-fluoro-5-[2-[(2R)-2-me lmoφholin-4-yl]pyrimidin-5-yl]-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4- (difluorome l)-N-[4-fluoro-5-[2-[(2R,6S)-2,6-dime lmoφholin-4-yl]pyrin^idin- 5- yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3aR,6aR)-2,3,3a,4,6,6a-hexahy dro- 1 H-pyrrolo [2,3 -c] pyrrol -5-yl]phenyl] -6-oxo-4-(trifluoromethyl)- 1H-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-piperazin- 1 -ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-5-[2-(4-propan-2-ylpiperazin-l-yl)pyrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-[2-(4-propan-2-ylpiperazin-l-yl)pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2-(trifluoromethyl)benzamide;

N-[4-fluoro-5-[2-(4-propan-2-ylpiperazin-l-yl)pyrimidin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyriume-3-carboxamide;

N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[2-[(3R)-3-methylmo holin-4-yl]pyrimidin-5-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2 (3R)-3-methylmo holin-4-yl]pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

(1-methylcyclobutyl) 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine- 1 -carboxylate;

(1-methylcyclobutyl) 5-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine- 1 -carboxylate;

(1-methylcyclobutyl) 3-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,5-dihydropyrrole-l-carboxylate;

N-[4-fluoro-5-(6-moφholin-4-ylpyriώn-2-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 -(6-moφholin-4-ylpyrazin-2-yl)-2-[(3R,5 S)-3 ,4,5 -trimethylpiperazin- 1 -yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(difluorome l)-N-[4-fluoro-5-[2-[(3R)-3-methylmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-

carboxamide;

N-[4-fluoro-5 2-moφholin-4-yl yrimidin-5-yl)-2-[(3aR,6aR)-l- ro yl-2,3,3a,4,6,6a-hexahydropyn^oloP^-clpyrrol-S-yllphenyll-e-oxo^-^fluoromethy^-lH-pyridine-S-carboxamide;

N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2 (3aR,6aR)-l-methyl-2,3,3a,4,6,6a-hexahydropyn^oloP^-clpyrrol-S-yllphenyll-e-oxo^-^fluoromethy^-lH^yridine-S-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-(3-fluoro-4-moφholin-4-ylphenyl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,4,5-tetramethylpiperazin-4-ium- 1 -yl]phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3-carboxamide;

4 difluoromethyl)-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmc^holin-4-yl] pyrimidin-5 -yl] phenyl] - 1 -methyl-6-oxopyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2 (2R)-2-me lmoφholin-4-yl]pyrimidin-5-yl]-2- [(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

N-(cyclopropylmethyl)-2-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-l,3-thiazole-4-carboxamide;

N-(cyclopropylmethyl)-2-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-N-methyl-l,3-thiazole-4-carboxamide;

N-cyclohexyl-2-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-l,3-thiazole-4-carboxamide;

N-cyclohexyl-2-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-N-methyl-l,3-

thiazole-4-carboxamide;

N-[4-fluoro-5-[4-(moφholine-4-carbonyl)-l,3-thiazol-2-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 4 4-me lpiperazine-l-carbonyl) ,3-thiazol-2-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

(3-methyloxetan-3-yl) 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine- 1 -carboxylate;

(3-methyloxetan-3-yl) 5-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine- 1 -carboxylate;

(3-methyloxetan-3-yl) 3-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]arnino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,5-dihydropyrrole-l-carboxylate;

Ν-[4-ΑυοΓθ-5 5 ηιοφ1ιο1ίη-4^1ηΐ6 1)ύιίορ1ΐ6η-2^1]-2-[(3Κ,58)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]-5-thiophen-2-ylphenyl]-6-ox 4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]-5-thiophen-3-ylphenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[5-(moφholin-4-ylmethyl)thiophe -3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-5-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-(cyclopropylmethyl)-2-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3- carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-l,3-thiazole-5-carboxamide;

N-(cyclopropylmethyl)-2-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-N-methyl-l,3-thiazole-5-carboxamide;

N-cyclohexyl-2-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-l,3-thia^^ carboxamide;

N-cyclohexyl-2-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-N-methyl-l,3-thiazole-5-carboxamide;

N-[4-fluoro-5-[5-(moφholine-4-carbonyl)-l,3-thiazol-2-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 5 4-me lpiperazine-l-carbonyl) ,3-thiazol-2-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

5-amino-4-fluoro-N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[5-[l-(6-cyclopropylpyridazin-3-yl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 1-(6-ethylpyridazin-3-yl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[6-(oxan-4-yloxy)pyridin-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-methoxy-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-6-methoxy-4-(trifluoromethyl)pyridine-3-carboxamide;

4- (difluoromethyl)-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[6-[(2R)-2-methylmoφholin-4-yl]pyridin-3-yl]phenyl]-6-oxo-lH-pyridine-3-carboxan^ide;

4 difluorome l)-N-[4-fluoro-5 6-[(2R)-2-methylmoφholin-4-yl]pyridin-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH^yridine-3-carboxamide;

4 difluoromethyl)-N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[6-[(2R)-2-methylmoφholin-4-yl]pyridin-3-yl]phenyl]-6-oxo-lHφyridine-3-carboxan^ide;

4 difluorome l)-N-[4-fluoro-5 6-[(2R)-2-methylmoφholin-4-yl]pyridin-3-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH^yridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 6 (2R,6S)-2,6-dimethylmoφholin-4-yl]pyridin-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

5- an^ino-4-fluoro-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-5-yl)-2-[(3aR,6aR)-l-ethyl-2,3,3a,4,6,6a-hexahydropyn-oloP^-clpyrrol-S-ylJphenylJ-e-oxo^-^fluoromethy^-lH-pyridine-S-carboxamide;

4 difluorome l)-N-[4-fluoro-5 6 (2R,6S)-2,6-dimethylmoφholin-4-yl]pyridin-3-yl] -2-[(3 S)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo- lH-pyridine-3 -carboxamide;

4 difluorome l)-N-[4-fluoro-5-[6-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyridin-3-yl]-2-[(3S)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4 difluoromethyl)-N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[6-[(2R)-2-methylmoφholin-4-yl]pyridin-3-yl]phenyl]-l-me1hyl-6-oxopyridine-3-carboxan^ide;

4-(difluoromethyl)-N-[4-fluoro-5-[6-[(2R)-2-methylmoφholin-4-yl]pyridin-3-yl]-2- [(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5-[6-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyridin-3-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[6-[(2R)-2-methylmoφholin-4-yl]pyridin-3-yl]phenyl]-l-me1hyl-6-oxopyridine-3-carboxan^ide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3-[methyl(2,2,2-trifluoroethyl)amino] pyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

4-(difluorome l)-N-[4-fluoro-5-[2-[(3R)-3-me lmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxarnide;

N-(cyclopropylmethyl)-4-[2-fluoro-5-[[l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l,3-thiazole-2-carboxamide;

N-(cyclopropylmethyl)-4-[2-fluoro-5-[[l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-N-methyl-l,3-thiazole-2-carboxamide;

N-cyclohexyl-4-[2-fluoro-5-[[l-me1hyl-6-oxo-4-(trifluoromethyl)pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l,3-thiazole-2-carboxamide;

N-cyclohexyl-4-[2-fluoro-5-[[l-me1hyl-6-oxo-4-(trifluoromethyl)pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-N-methyl-l,3-thiazole-2-carboxamide;

N-[4-fluoro-5-[2-(moφholine-4-carbonyl)-l,3-thiazol-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5-[2-(4-me lpiperazine-l-carbonyl)-l,3-thiazol-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

4-fluoro-N-[4-fluoro-5-(4-piperazin-l-ylphenyl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-2-(trifluoromethyl)benzarnide;

4-fluoro-N-[4-fluoro-5-(6-piperazin-l-ylpyridin-3-yl)-2-[(3R)-3,4-dimethylpiperazin-1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-(cyclopropylmethyl)-4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-l,3-thiazole-2-carboxamide;

N-(cyclopropylmethyl)-4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-N-methyl-l,3-thiazole-2-carboxamide;

N-cyclohexyl-4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-l,3-thiazole-2-carboxamide;

N-cyclohexyl-4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-N-methyl-l,3-thiazole-2-carboxamide;

N-[4-fluoro-5-[2-(moφholine-4-carbonyl)-l,3-thiazol-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2 4-me lpiperazine-l-carbonyl)-l,3-thiazol-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[2-(cyclohexylamino)pyrimidin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-(methylamino)pyrimidin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiper^ 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[5-(2-cyanopyrimidin-4-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 2 dime lamino)pyrimidin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-

carboxamide;

N-[4-fluoro-2-[4-(methylan^ino) i eridin-l-yl]-5-(2-moφholin-4-yl yrimidin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 6 (2R)-2-methylmoφholin-4-yl]pyridin-3-yl]-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

N-[5-[6-(cyclopropylmethoxy)pyridin-3-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-l-methyl-6-oxopyridine-3-carboxamide;

N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmo

yl]pyrimidin-5-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxami

4-fluoro-N-[4-fluoro-5-[2 (2R)-2-me lmoφholin-4-yl]pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-(2-piperazin-l-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-(6-moφholin-4-ylpyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[4-fluoro-5-(6^iperazin-l-ylpyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(4-piperazin-l-ylphenyl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(3-carbamoyl-4-fluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(4-carbamoyl-3-fluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(3-carbamoyl-4-fluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-6-oxo-lH-pyridine-3-carboxamide;

N-[5-(4-carbamoyl-3-fluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-6-oxo-lH-pyridine-3-carboxamide;

2-fluoro-5-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)benzoyl]amino]-4-[(3R)-3,4- dimethylpiperazin-l-yl]phenyl]benzamide;

2-fluoro-4-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)benzoyl]amino]-4-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]benzamide;

2-fluoro-5-[2-fluoro-5 [4-fluoro-2 trifluoromethyl)benzoyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] benzamide;

N-[5-[2-(4-tert-butylpiperazin-l-yl)pyrinidin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

N-[5-[2-(2,2-dimethylmo holin-4-yl)pyrimidin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

N-[5-[2-(2,2-dimethylmo holin-4-yl)pyrimidin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

N-[5-[2-[4-(cyclopropylmethyl)piperazin-l-yl]pyrimidin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

N-[2-(4-cyclopropylpiperazin-l-yl)-4-fluoro-5-(2-moφholin-4-ylpyrin^idin-5-yl)phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(5-fluoro-6-oxo-lH-pyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

benzyl N-[5-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]pyridin-3-yl]carbamate;

N-[4-fluoro-5-(5-fluoro-l-methyl-6-oxopyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -(4-methoxybenzoyl)-3,6-dihydro-2H-pyridin-4-yl] -2-[(3R,5 S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-oxo-l,3-dihydropyrrolo[2,3-b]pyridin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(l-methyl-2-oxopyridin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l- yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(l-methyl-6-oxopyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 1 cyclohexanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(mfluoromethyl)-lH-pyridine-3-carboxamide;

tert-butyl N-[l-[2-[(3,5-dicWorobenzoyl)amino]-5-fluoro-4-(2-moφholin-4-ylpyrimidin-5 -yl)phenyl] pyrrolidin-3 -yl] -N-methylcarbamate;

3,5-dichloro-N-[4-fluoro-2-[3-[3-methoxypropyl(methyl)amino]pyrrolidin-l-yl]-5-(2-moφholin-4-ylpyrimidin-5-yl)phenyl]benzan^ide;

N-[4-fluoro-2-[3-[3-methoxypropyl(methyl)amino]pyrrolidin-l-yl]-5-(2-moφholin-4-ylpyrimidin-5 -yl)phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5-[ 1 -(pyrazine-2-carbonyl)-3,6-dihydro-2H-pyridin-4-yl] -2-[(3R,5 S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(mfluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3- [methyl(methylsulfonyl)amino]pyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3- [methyl(methylsulfonyl)amino]pyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,4R)-3-methoxy-4-[2-methoxyethyl(methyl)amino] pyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1H-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R,4R)-3-fluoro-4-[2-methoxyethyl(methyl)amino] pyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1H-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3-[2-methoxyethyl(methyl)amino] pyrrolidin- 1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- 1H- pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-yl yrimidin-5-yl)-2-[(3R,4R)-3-fluoro-4-[2-methoxyethyl(methyl)amino] pyrrolidin- 1 -yl] phenyl] - 1 -methyl -6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3-[2-methoxyethyl(methyl)amino] pyrrolidin- 1 -yl] phenyl] - 1 -methyl -6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[4-fluoro-5-(6-methylsulfonylpyridin-3-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(mfluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-(methanesulfonamido)pyrirnidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[l-(5-cyanopyrimidin-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(l-methylsulfonyl-3,6-dihydro-2H-pyridin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(l-methylsulfonyl-3,6-dihydro-2H-pyridin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3- [cyclopropylmethyl(methyl)aniino]pyrrolidin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-5-yl)-2-[(3R)-3-[cyclopropylmethyl(methyl)amino]pyrrolidin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[5-[l-(5-cyanopyrimidin-2-yl)-2,5-dihydropyrrol-3-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-

carboxamide;

N-[5-(3-carbamoyl-4-fluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[5-(4-carbamoyl-3-fluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

N-[5-(3-carbamoyl-4-fluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-l-methyl-6-oxopyridine-3-carboxamide;

N-[5-(4-carbamoyl-3-fluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-l-methyl-6-oxopyridine-3-carboxamide;

N-[4-fluoro-2 (3R)-3,4-dime lpiperazin-l-yl]-5-[2-[(2R)-2-methylmo holin-4-yl]pyrimidin-4-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2 (2R)-2-methylmo holin-4-yl]pyrimidin-4-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(4-carbamoyl-3-fluorophenyl)-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-6-oxo-lH-pyridine-3-carboxamide;

N-[5-(3-carbamoyl-4-fluorophenyl)-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-6-oxo-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 3-fluoro-4-(methylcarbamoyl)phenyl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5-[4-fluoro-3-(methylcarbamoyl)phenyl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxarnide;

N-[4-fluoro-5-(4-moφholin-4-ylpyrimidin-2-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

propan-2-yl 3-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,5-dihydropyrrole-l-carboxylate; propan-2-yl 5-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]- 4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate;

propan-2-yl 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]- 4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate;

N-[4-fluoro-5-[3-fluoro-4-(methylcarbamoyl)phenyl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[4-fluoro-3-(methylcarbamoyl)phenyl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 3-fluoro-4 methylcarbamoyl)phenyl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 4-fluoro-3 methylcarbamoyl)phenyl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

4 difluoromethyl)-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(3R)-3-methyln ^holin-4-yl] pyrimidin-5 -yl] phenyl] - 1 -methyl-6-oxopyridine-3-carboxamide;

N-[4-fluoro-2-[(3R)-3,4-dime lpiperazin-^^

yl]pyrimidin-5-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxami

N-[4-fluoro-5-(6-fluoropyridin-2-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[6-(trifluoromethyl)pyridin-2-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-5-[2 (2R)-2-me lmoφholin-4-yl]pyrimidin-5-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,5-dimethylbenzamide;

4-(Difluoromethyl)-N-(4-fluoro-5 -(1 -(pyrrolidine- 1 -carbonyl)-2,5 -dihydro- 1 H-pyrrol- 3- yl)-2-((3S,5R)-3,4,5-trimethylpiperazin- 1 -yl)phenyl)-6-oxo- 1 ,6-dihydropyridine-3-carboxamide;

4- fluoro-N-[4-fluoro-5-[2-(4-hydroxy-4-me1hylpiperidin-l-yl)pyrimidin-5-yl]-2-[(3R)-3,4-dime1hylpiperazin-l-yl]phenyl]-2-(trifluoromethyl)berizarnide;

4-fluoro-N-[4-fluoro-5-(2-moφholin-4-yl yrimidin-4-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[5-[l-(5-cyano-l,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

Ν-[4-ΑυοΓθ-5-(2-ηιοφ1ιο1ίη-4^1-1,3-ίηί3ζο1-4^1)-2-[(3Κ,58)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2-moφholin-4-yl ,3-thiazol-4-yl)-2 (3R)-3,4-dime lpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2-moφholin-4-yl ,3-thiazol-5-yl)-2 (3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-yl-l,3-thiazol-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2-moφholin-4-yl-l,3-thiazol-4-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2-moφholin-4-yl-l,3-thiazol-5-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4 difluoromethyl)-N-[4-fluoro-5-(2-moφholin-4-yl-l,3-thiazol-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4 difluoromethyl)-N-[4-fluoro-5-(2-moφholin-4-yl-l,3-thiazol-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

2,4-difluoro-5 2-fluoro-5 [4-fluoro-2 trifluorome l)benzoyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-N-(2,4,4-trimethylpentan-2-yl)benzamide;

2,4-difluoro-5 2-fluoro-5 [4-fluoro-2 trifluorome l)benzoyl]amino]-4-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -N-(2,4,4-trimethylpentan-2-yl)benzamide;

N-[5 2,4-difluoro-5-(2,4,4-trimethylpentan-2-ylcarbamoyl)phenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-

pyridine-3-carboxamide;

4-(difluoromethyl)-N-[5-[2,4-difluoro-5-(2,4,4-trimethylpentan-2-ylcarbamoyl)phenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo- 1 H-pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(3R)-3-methylmorpholin-4-yl] pyrimidin-5 -yl] phenyl] -6-oxo- lH-pyridine-3-carboxamide

(S)-4-(Sifluoromethyl)-N-(2-(3,4-&methylpip^

1 -carbonyl)-2,5-dihydro- lH-pyrrol-3-yl)phenyl)-6-oxo- 1 ,6-dihydropyridine-3-carboxamide;

1-Methylcyclobutyl 3-(5-(4-(difluoromethyl)-6-oxo-l,6-dihydropyridine-3-carboxamido)-2-fluoro-4-((3S,5R)-3,4,5 rimethylpiperazin-l-yl)phenyl)-2,5-dihydro-lH-pyrrole-1 -carboxylate;

1-Methylcyclobutyl (S)-3-(5-(4-(difluoromethyl)-6-oxo-l,6-dihydropyridine-3-carboxamido)-4-(3,4-dimethylpiperazin-l-yl)-2-fluorophenyl)-2,5-dihydro-lH-pyrrole- 1 -carboxylate;

N-[5-(5-carbamoyl-2,4-difluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[5-(5-carbamoyl-2,4-difluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -4-(difluoromethyl)-6-oxo- 1 H-pyridine-3-carboxamide;

2,4-difluoro-5 2-fluoro-5 [4-fluoro-2 trifluorome l)benzoyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]benzamide;

2,4-difluoro-5 2-fluoro-5 [4-fluoro-2 trifluorome l)benzoyl]amino]-4-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]benzamide;

4-fluoro-N-[4-fluoro-5-[2-(4-hydroxy-4-methylpiperidin-l-yl)pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2-(trifluoromethyl)benzamide;

3,3-Difluorocyclobutyl 3-(5-(4-(difluoromethyl)-6-oxo-l,6-dihydropyridine-3-carboxamido)-2-fluoro-4-((3S,5R)-3,4,5 rimethylpiperazin-l-yl)phenyl)-2,5-dihydro-lH-pyrrole-1 -carboxylate;

3,3-Difluorocyclobutyl (S)-3-(5-(4-(difluoromethyl)-6-oxo-l,6-dihydropyridine-3- carboxamido)-4-(3,4-dimethylpiperazin-l-yl)-2-fluorophenyl)-2,5-dihydro-lH-pyrrole- 1 -carboxylate;

(S)-N-(5-(l-(2-cyanopyrimidin-5-yl)-l,2,3,6-tetrahydropyridin-4-yl)-2-(3,4-dimethylpiperazin- 1 -yl)-4-fluorophenyl)-4-(difluoromethyl)-6-oxo- 1 ,6-dihydropyridine-3-carboxamide;

N-[4-fluoro-5 2 (2R)-2-me lmo holin-4-yl]pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5 2 4½droxy-4-methylpiperidin-l-yl)pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[5-[l-(4-cyano-l,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(l,3-oxazol-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamid

4-(difluoromethyl)-N-[4-fluoro-5-(l-pyrimidin-2-yl-3,6-dihydro-2H-pyridin-5-yl)-2 [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-[l-(5-methoxypyrimidin-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 1 5-formylpyrimidin-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-[l-(6-methoxypyrimidin-4-yl)-3,6-dihydro-2H-pyridin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

ethyl 5-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl]amino]-2-fluoro-4-[(3R,5 S)-3,4,5-trimethylpiperazin-l -yl]phenyl] -3,6-dihydro-2H-pyridine- 1 - carboxylate;

4-fluoro-N-[4-fluoro-5 l-pyrimidin-2-yl-3,6-dihydro-2H-pyridin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-[l-(5-formylpyrimidin-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yljphenyl] -2-(trifluoromethyl)benzamide;

(1-methylcyclobutyl) 4-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl]amino]-2-fluoro-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate;

N-[5-(4-carbamoyl-3-fluorophenyl)-4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-l-methyl-6-oxopyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 3-fluoro-4 methylcarbamoyl)phenyl]-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

2 difluorome l)-4-fluoro-N-[4-fluoro-5 2-mo holin-4-ylpyrin^idin-5-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] benzamide;

2 difluorome l)-4-fluoro-N-[4-fluoro-5 2-mo holin-4-ylpyrin^idin-4-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] benzamide;

2,6-difluoro-4-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)benzoyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]benzamide;

2,6-difluoro-4-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)benzoyl]amino]-4-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]benzamide;

N-[5-(4-carbamoyl-3,5-difluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- lH-pyridine-3 -carboxamide;

N-[5-(4-carbamoyl-3,5-difluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -4-(difluoromethyl)-6-oxo- 1 H-pyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(3R)-3-methylmoφholin-4-yl] pyrimidin-5 -yl] phenyl] -2-(trifluoromethyl)benzamide;

N-[4-fluoro-5-[2-(4-propan-2-ylpiperazin-l-yl)pyrimidin-5-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[5 2 2,2-dimethylmo holin-4-yl) yrimidin-5-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-4-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

4-(MuoΓomethyl)-N-[4-fluoΓO-5-(2-moφholin-4-ylpyrimidin-4-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

2,3-difluoro-4-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)benzoyl]amino]-4

3,4,5-trimethylpiperazin-l-yl]phenyl]-N-(2,4,4-trimethylpentan-2-yl)benzamide;

2,3-difluoro-4 2-fluoro-5 [4-fluoro-2 trifluorome l)benzoyl]amino]-4-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -N-(2,4,4-trimethylpentan-2-yl)benzamide;

2,3-difluoro-4 2-fluoro-5 [4-fluoro-2 trifluoromethyl)benzoyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]benzamide;

2,3-difluoro-4 2-fluoro-5 [4-fluoro-2 trifluoromethyl)benzoyl]amino]-4-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]benzamide;

N-[5-[2,3-Muoro-4-(2,4,4-trimethylpentan-2-ylcarbamoyl)phenyl]-4-fluoro-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-(4-carbamoyl-2,3-difluorophenyl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[4-fluoro-5-(6-moφholin-4-ylpyridin-2-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-(6-moφholin-4-ylpyridin-2-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-5-(6-moφholin-4-ylpyridin-2-yl)-2-[(3R)-3,4-dimethylpiperazin-1 -yl] phenyl] -2-(trifluoromethyl)benzamide;

propan-2-yl 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carbonyl]amino]- 4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,3,6,7-tetrahydroazepine-l-carboxylate;

N-[4-fluoro-5-(l-methylbenzimidazol-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-(3-methylbenzimidazol-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 l,3-benzothiazol-4-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 l,3-benzothiazol-5-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5 l,3-benzothiazol-6-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 l-methylbenzimidazol-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxopyridine-3 -carboxamide;

4 difluorome l)-N-[4-fluoro-5-(3-methylbenzimidazol-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxopyridine-3 -carboxamide;

N-[5-(l,3-benzothiazol-4-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-l-methyl-6-oxopyridine-3-carboxamide;

N-[5-(l,3-benzothiazol-5-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-l-methyl-6-oxopyridine-3-carboxamide;

N-[5-(l,3-benzothiazol-6-yl)-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-l-methyl-6-oxopyridine-3-carboxamide;

N-[5-[l-(5-cyano-l,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-6-oxo-lH-pyridine-3-carboxamide;

N-[5-[ 1 -(5-cyano- 1 ,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-4-yl] -4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-(difluoromethyl)-6-oxo- lH-pyridine-3 -carboxamide;

N-[5-[l-(5-cyano-l,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-6-oxo-lH-pyridine-3-carboxamide;

N-[5-[l-(5-cyano-l,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-(difluoromethyl)-6-oxo- lH-pyridine-3 -carboxamide;

N-[5-[l-(5-cyano-l,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

N-[5-[ 1 -(5-cyano- 1 ,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-4-yl] -4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-fluoro-2-(trifluoromethyl)benzamide;

N-[4-fluoro-5-[2-[(2R)-2-methylmo holin-4-yl]pyrimidin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(difluorome l)-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5-[2-[(2R)-2-methylmo holin-4-yl]pyrimidin-4-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxo-4-(trifluoromethyl)pyridine-3 -carboxamide;

N-[4-fluoro-5-[2-(oxan-4-yloxy)pyrimidin-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

N-[5-[l-(5-cyano-l,3-1hiazol-2-yl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyrimidin-4-yl]-2-[(3S,5R)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[2-[(2R,6S)-2,6-dimethylmoφholin-4-yl]pyrimidin-4-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo-4-(tafluoromethyl)- 1 H-pyridine-3-carboxamide;

(1-methylcyclobutyl) 4-[2-fluoro-5-[[6-oxo-4-(trifluoromethyl)-lH-pyridine-3-

carbonyl]amino]-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,3,6,7-tetrahy droazepine- 1 -carboxylate;

N-[5-[ 1 -(5-cyano- 1 ,3-thiazol-2-yl)-2,3,6,7-tetrahydroazepin-4-yl] -4-fluoro-2-[(3R,5 S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[l-(2-c anopyrimidin-4-yl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

(3,3-difluorocyclobutyl) 4-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl]amino]-2-fluoro-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate;

(3,3-difluorocyclobutyl) 4-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl] amino] -2-fluoro-4-[(3R)-3,4-dimethylpiperazin- 1 -yljphenyl] -3,6-dihydro-2H-pyridine- 1 -carboxylate;

(3,3-difluorocyclobutyl) 5-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl]amino]-2-fluoro-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate;

(3,3-difluorocyclobutyl) 5-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl] amino] -2-fluoro-4-[(3R)-3,4-dimethylpiperazin- 1 -yl]phenyl] -3,6-dihydro-2H-pyridine- 1 -carboxylate;

(3,3-difluorocyclobutyl) 5-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)berizoyl]amino]-4-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -3 ,6-dihy dro-2H-pyridine- 1 -carboxylate;

(3,3-difluorocyclobutyl) 4-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)berizoyl]amino]-4-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -3 ,6-dihy dro-2H-pyridine- 1 -carboxylate;

N-[5-[l-(2-cyanopyrimidin-4-yl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-(difluoromethyl)-6-oxo- lH-pyridine-3 -carboxamide;

N-[5-[l-(2-cyanopyrimidin-4-yl)-3,6-dihydro-2H-pyridin-4-yl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-

carboxamide;

N-[5-[4-(cyclohexylcarbamoyl)-3,5-difluorophenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluorome1hyl)-lH-pyridine-3-carboxamide;

N-[5-[4-[(2,2-dime1hylcyclohexyl)carbamoyl]-3,5-difluorophenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[4-(cyclopropylmethylcarbamoyl)-3,5-difluorophenyl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

Ν-[4-ΑυοΓθ-5-[2-(ηιοφ1ιο1ίη-4^1ηΐ6 1)-1,3-ύιί3ζο1-4^1]-2-[(3Κ,58)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[l-(2-moφholin-4-ylethyl)pyrazol-4-yl]-2-[(3R)-3,4-dimethylpiperazin-1 -yl] phenyl] -6-oxo-4-(trifluoromethyl)- lH-pyridine-3 -carboxamide;

4 difluorome l)-N-[4-fluoro-5-[l-(2-moφholin-4-ylethyl)pyrazol-4-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxopyridine-3 -carboxamide;

N-[4-fluoro-5-[l-(2-moφholin-4-ylethyl)pyrazol-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-[l-(2-moφholin-4-yle1hyl)pyrazol-4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-4-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxarnide;

N-[4-fluoro-5-(6-moφholin-4-ylpyridin-2-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxarnide;

4-(difluoromethyl)-N-[4-fluoro-5-(2-moφholin-4-ylpyrimidin-4-yl)-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

4-(difluoromethyl)-N-[4-fluoro-5-(6-moφholin-4-ylpyridin-2-yl)-2-[(3R)-3,4-

dimethylpiperazin- 1 -yl] phenyl] -6-oxo- 1 H-pyridine-3-carboxamide;

2-(difluoromethyl)-4-fluoro-N-[4-fluoro-5-(2-mo holin-4-ylpyrimidin-5-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]benzamide;

propan-2-yl 4-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl]amino]-2-fluoro- 4-[(3R,5S)-3,4,5 rimethylpiperazin-l-yl]phenyl]-2,3,6,7-tetrahydroazepine-l-carboxylate;

propan-2-yl 4-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl]amino]-2-fluoro-4-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate; propan-2-yl 5 -[5-[ [4-(difluoromethyl)-6-oxo- 1 H-pyridine-3 -carbonyl] amino] -2-fluoro- 4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate;

propan-2-yl 5 -[5-[ [4-(difluoromethyl)-6-oxo- 1 H-pyridine-3 -carbonyl] amino] -2-fluoro-4-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate; propan-2-yl 4-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)benzoyl]amino]-4-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate;

propan-2-yl 5-[2-fluoro-5-[[4-fluoro-2-(trifluoromethyl)benzoyl]amino]-4-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-3,6-dihydro-2H-pyridine-l-carboxylate;

(1-methylcyclobutyl) 4-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl]amino]-2-fluoro-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,3,6,7-tetrahy droazepine- 1 -carboxylate;

(3,3-difluorocyclobutyl) 4-[5-[[4-(difluoromethyl)-6-oxo-lH-pyridine-3-carbonyl]amino]-2-fluoro-4-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-2,3,6,7-tetrahy droazepine- 1 -carboxylate;

N-[5-[ 1 -(5-cyano- 1 ,3-thiazol-2-yl)-2,3,6,7-tetrahydroazepin-4-yl] -4-fluoro-2-[(3R,5 S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-4-(difluoromethyl)-6-oxo-lH-pyridine-3-carboxamide;

N-[5-[4-(cyclohexylcarbamoyl)-3-fluorophenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[4-[cyclopropylmethyl(methyl)carbamoyl]-3-fluorophenyl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[4-[(4,4-difluorocyclohexyl)carbamoyl]-3-fluorophenyl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[5-[4-(cyclopropylmethylcarbamoyl)-3-fluorophenyl]-4-fluoro-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4-fluoro-N-[4-fluoro-2-[(3R)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmc^holin-4-yl] pyrimidin-4-yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[2-[(3R)-3-methylmc^holin-4-yl] pyrimidin-5 -yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-2-[(3S)-3,4-dimethylpiperazin-l-yl]-5-[2-[(2R)-2-methylmoφholin-4-yl] pyrimidin-4-yl] phenyl] -2-(trifluoromethyl)benzamide;

4-fluoro-N-[4-fluoro-5-[2 (2R,6S)-2,6-dime lmoφholin-4-yl]pyrin^idin-4-yl]-2-[(3R)-3,4-dimethylpiperazin- 1 -yl]phenyl] -2-(trifluoromethyl)benzamide;

N-[5-[l-(2-cyanopyrimidin-4-yl)-3,6-dihydro-2H-pyridin-5-yl]-4-fluoro-2-[(3R)-3,4-dimethylpiperazin- 1 -yl] phenyl] -4-(difluoromethyl)-6-oxo- lH-pyridine-3 -carboxamide;

4-((1ίΑυοΓοηΐ6 1)-Ν-[4-ΑυοΓθ-5-[4-(ηιοφ^1ίη-4^1ηΐ6 1)-1,3-ύιί3ζο1-2^1]-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

N-[4-fluoro-5-(6^iperazin-l-ylpyridin-2-yl)-2-[(3R)-3,4-dimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5 2 (2R,6S)-2,6-dime lmo holin-4-yl]pyrirnidin-4-yl]-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxo-4-(trifluoromethyl)pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2 (2R,6S)-2,6-dime lmoφholin-4-yl]pyrin^idin-

4-yl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2 (2R,6S)-2,6-dime lmoφholin-4-yl]pyrimidin- 4-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5 2-moφholin-4-ylpyrimidin-4-yl)-2-[(3R,5S)-3,4,5-trimethylpiperazin- 1 -yl] phenyl] - 1 -methyl-6-oxopyridine-3 -carboxamide;

N-[5-[4 (2,2-dimethylcyclohexyl)carbamoyl]-3-fluorophenyl]-4-fluoro-2-[(3R,5S)- 3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5-[5-(moφholin-4-ylmethyl)-l,3-thiazol-2-yl]-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

4 difluorome l)-N-[4-fluoro-5-[2-(moφholin-4-ylmethyl)-l,3-thiazol-4-yl]-2- [(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-l-methyl-6-oxopyridine-3-carboxamide;

N-[4-fluoro-5-[4-(moφholin-4-ylmethyl)-l,3-thiazol-2-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

N-[4-fluoro-5-[5-(moφholin-4-ylmethyl)-l,3-thiazol-2-yl]-2-[(3R,5S)-3,4,5-trimethylpiperazin-l-yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide;

2 difluorome l)-N-(5 2 (2S,6R)-2,6-dime lmo holino)pyrin^idin-5-yl)-4-fluoro-2-((3S,5R)-3,4,5-trimethylpiperazin-l-yl)phenyl)-4-fluorobenzamide;

2-(difluoromethyl)-4-fluoro-N-(4-fluoro-5-(2-((S)-2-methylmo holino)pyrimidin-5-yl)-2-((3S,5R)-3,4,5-trimethylpiperazin-l-yl)phenyl)benzamide;

2- (difluoromethyl)-4-fluoro-N-(4-fluoro-5-(2-((R)-2-methylmo holino)pyrimidin-5^ yl)-2-((3S,5R)-3,4,5-trimethylpiperazin-l-yl)phenyl)benzamide,

3- (difluoromethyl)-N-(5-(2-((2S,6R)-2,6-dimethylmo holino)pyrimidin-5-yl)-4- fluoro-2-((3S,5R)-3,4,5 rimethylpiperazin-l-yl)phenyl)-5-fluoropicolinamide;

3-(difluoromethyl)-5-fluoro-N-(4-fluoro-5-(2-morpholinopyrimidin-5-yl)-2- ((3S,5R)-3,4,5-trimethylpiperazin-l-yl)phenyl)picolinamide;

(S)-3-(difluoromethyl)-N-(2-(3,4-dimethylpiperazin-l-yl)-4-fluoro-5-(2- mo holinopyrinlidin-4-yl)phenyl)-5-fluoropicolinamide;

3-(difluoromethyl)-5-fluoro-N-(4-fluoro-5-(2-((R)-2- methylmorpholino)pyrimidin-4-yl)-2-((3S,5R)-3,4,5-trimethylpiperazin-l- yl)phenyl)picolinamide;

3-(difluoromethyl)-N-(5-(2-((2S,6R)-2,6-dimethylmorpholino)pyrimidin-4-yl)-4- fluoro-2-((3S,5R)-3,4,5-trimethylpiperazin-l-yl)phenyl)-5-fluoropicolinamide;

N-(4'-(cyclohexyl(methyl)carbamoyl)-3',5',6-trifluoro-4-((3S,5R)-3,4,5- trimethylpiperazin- 1 -yl)- [ 1 , 1 '-biphenyl] -3-yl)-6-oxo-4-(trifluoromethyl)- 1,6- dihydropyridine-3-carboxamide;

N-(4'-(cyclopen†yl(methyl)carbamoyl)-3',5',6-trifluoro-4-((3S,5R)-3,4,5- trimethylpiperazin- 1 -yl)- [ 1 , 1 '-biphenyl] -3-yl)-6-oxo-4-(trifluoromethyl)- 1,6- dihydropyridine-3-carboxamide;

6-oxo-N-(3',5',6-trifluoro-4'-(((R)-tetrahydrofuran-3-yl)carbamoyl)-4-((3S,5R)- 3,4,5 -trimethylpiperazin- 1 -yl)-[ 1 , 1 '-biphenyl] -3-yl)-4-(trifluoromethyl)- 1,6- dihydropyridine-3-carboxamide;

3-(difluoromethyl)-N-(5-(2-((2S,6R)-2,6-dimethylmorpholino)pyrimidin-5-yl)-4- fluoro-2-((3S,5R)-3,4,5-trimethylpiperazin-l-yl)phenyl)-5-fluoropicolinamide; and

3-(difluoromethyl)-5-fluoro-N-(4-fluoro-5-(2-morpholinopyrimidin-5-yl)-2- ((3S,5R)-3,4,5-trimethylpiperazin-l-yl)phenyl)picolinamide;

or a pharmaceutically acceptable salt and/or solvate thereof.

55. A pharmaceutical composition comprising one or more compounds of Formula (I) of any one of claims 1 to 54, or a pharmaceutically acceptable salt, and/or solvate thereof, and a pharmaceutically acceptable carrier and/or diluent.

56. The pharmaceutical composition of claim 55 further comprising an additional therapeutic agent.

57. A method of treating one or more diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners comprising administering an effective amount of one or more compounds of any one of claims 1 to 54, or a pharmaceutically acceptable salt, and/or solvate thereof, to a subject in need thereof.

58. The method of claim 57, wherein the disease, disorder or condition is a neoplastic disorder.

59. The method of claim 58, wherein the neoplastic disorder is cancer.

60. The method of claim 59, wherein the cancer is selected from solid cancer and leukemias.

61. The method of claim 59, wherein the cancer is selected from leukaemia, lymphoma, non-Hodgkin's lymphoma, Burkitt lymphoma, MLL-fusion lymphoma, primary effusion leukemia and multiple myeloma.

62. The method of claim 59, wherein the cancer is selected from leukemia, melanoma, lung cancer, bladder cancer, colon cancer, brain cancer, ovarian cancer, breast cancer, prostate cancer, neuroblastoma and kidney cancer.

63. The method of claim 59, wherein the cancer is selected from leukemia, bladder cancer, prostate cancer, brain cancer and neuroblastoma.

64. The method of claim 59, wherein the cancer is selected from bladder cancer, acute myeloid leukemia (AML), gliomas, glioblastomas and MYCN-amplified neuroblastoma.