Pharmaceutical compounds

Abstract

The present invention relates to compounds of Formula (I) that are useful as inhibitors of the activity of the ubiquitin specific protease USP19. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in therapy.

Description

Abstract This invention relates to compounds of formula (I) that can be used as inhibitors of the activity of the ubiquitin-specific protease USP19. The invention also relates to pharmaceutical compositions comprising these compounds, and methods of using these compounds for treatment.

Claims

CLAIMS:

1. A compound of formula (I):whereinR1is optionally substituted C1-C6 alkyl, optionally substituted amino, optionally substituted 3 to 11 membered heterocycloalkyl, optionally substituted aryl, or optionally substituted 5 to 8 membered heteroaryl;R2and R3are each independently selected from H and C1-C6 alkyl, or wherein R2and R3together form C3-C8 cycloalkyl, C3-C8 cycloalkenyl or 3 to 8 membered heterocycloalkyl together with the carbon to which they are attached;M is N or CRawherein Rais H, halo, optionally substituted C3-C8 cycloalkyl, or optionally substituted C1-C6 alkyl;A, D, E and G are absent andX is NR15or CH;Y is CR4or N or absent;Z is CR5, NR6or O;R4is halo, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, 4 to 10 membered fused-ring heterocyclyl, optionally substituted C1-C6 alkylsulfanyl, sulfoxide, sulfone, sulfoximine, optionally substituted amino, optionally substituted 3 to 8 membered heterocycloalkyl, or OR20;wherein R20is optionally substituted C1-C6 alkyl;R5is H, optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, optionally substituted 3 to 8 membered heterocycloalkyl, amido, sulfoximine, CN, halo, C(O)OR21, OR22, or NR23R24; wherein R21is selected from H and C1-C6 alkyl;R22is selected from H and C1-C6 alkyl;R23and R24are independently selected from H and optionally substituted C1-C6 alkyl;R15is H or C1-C6 alkyl; or R4and R5together form 3 to 8 membered heterocycloalkyl or aryl together with Y and Z to which they are attached; or R4and R15together form 5 membered cycloalkyl, heterocycloalkyl, or heteroaryl together with X and Y to which they are attached;R6is H, C1-C6 alkyl, optionally substituted aryl, or C3-C8 cycloalkyl; or A is CR12or N, D is CR7or N, E is CR13or N and G is OR14or N andX is N or C;Y is C;Z is OR20, N, NR11, or O, wherein R11is H, optionally substituted 01-06 alkyl, optionally substituted 03-08 cycloalkyl, optionally substituted aryl, or optionally substituted 5 to 8 membered heteroaryl; wherein R20is H, optionally substituted 01-06 alkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, optionally substituted 3 to 8 membered heterocycloalkyl, amido, sulfoximine, CN, halo, C(O)OR25, OR26, or NR27R28;wherein R25is selected from H and C1 -C6 alkyl;R26is selected from H and C1-C6 alkyl;R27and R28are independently selected from H and C1-C6 alkyl;R7is H, halo, C1 -C6 alkyl, or OR19; wherein R19is optionally substituted C1 -C6 alkyl;R12is H, halo, or C1 -C6 alkyl;R13is H, halo, C1-C6 alkyl, OR16; or NR17R18; wherein R16is optionally substituted C1 -C6 alkyl, R17and R18are independently selected from H and C1-C6 alkyl or wherein R17and R18together form 5 to 6 membered heterocycloalkyl with the nitrogen atom to which they are attached; andR14is H, halo, or C1 -C6 alkyl; or a stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt thereof.

2. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 1 , wherein for each optionally substituted group, each one or more optional substituent is independently selected from alkyl, alkoxy, oxo, halo, cycloalkyl, heterocycloalkyl, aryl, aryl substituted by one or more halo, aryl substituted by halo and alkyl, aryl substituted by halo and alkoxy, heteroaryl, hydroxyl, CR8R9R10, NR8, NR8R9, NHC(O)R8, NHCR8R9R10, NHCH2CR8R9R10and NHCH2C(O)R8, wherein R8, R9and R10are each independently selected from H, halo, hydroxyl, alkyl, cycloalkyl, cycloalkyl substituted by one or more halo or alkyl, heterocycloalkyl substituted by one or more alkyl or oxo, heteroaryl, alkoxy, CH2OH, and CH2CH2OH.

3. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 1 or claim 2, wherein R1is optionally substituted 3 to 11 membered heterocycloalkyl.

4. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein R1is optionally substituted 5 to 8 membered heterocycloalkyl, optionally wherein R1is optionally substituted 5 to 6 membered heterocycloalkyl.

5. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein R1is optionally substituted morpholine, bridged azepane, diazepane, thiomorpholine, pyrrolidine, piperazine, or piperidine.

6. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein R1is optionally substituted piperidine.

7. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 3 to 6, wherein R1is substituted by one or more alkyl, oxo, cycloalkyl, heterocycloalkyl, aryl, aryl substituted by one or more halo, heteroaryl, NR8, NR8R9, NHC(O)R8, NHCR8R9R10, NHCH2CR8R9R10and NHCH2C(O)R8, wherein R8, R9and R10are each independently selected from H, halo, hydroxyl, alkyl, cycloalkyl, cycloalkyl substituted by one or more halo or alkyl, heterocycloalkyl substituted by one or more alkyl or oxo, heteroaryl, and alkoxy.

8. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 3 to 7, wherein R1is substituted by phenyl or phenyl substituted by one or more halo, and wherein R1is optionally substituted with one or more further substituents.

9. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 3 to 8, wherein R1issubstituted by phenyl or phenyl substituted by one or more fluoro, and wherein R1is optionally substituted with one or more further substituents.

10. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 3 to 9, wherein R1is substituted by difluoro-phenyl.11 . The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 3 to 10, wherein R1is substituted by NR8R9, NHC(O)R8, or NHCH2CR8R9R10, and wherein R1is optionally substituted with one or more further substituents.

12. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 2 to 11 , wherein R8, R9, and R10are each independently selected from H, C1-C6 alkyl, fluoro-substituted C1- C6 alkyl, C1 -C6 alkoxy, CH2OH, CH2CH2OH, fluoro-substituted C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1 -C6 alkyl, and pyridine-substituted C1 -C6 alkyl.

13. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 1 or claim 2, wherein R1is optionally substituted C1-C6 alkyl.

14. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 13, wherein each optional substituent is selected from halo, C1-C6 alkoxy, cycloalkyl, and hydroxyl.

15. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 -4, wherein R1is optionally substituted amino.

16. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 15, wherein R1is amino substituted with phenyl substituted by one or more halo, or benzyl substituted by one or more halo.

17. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein R2and R3are each independently H or methyl, or wherein R2and R3together form C3-C6 cycloalkyl, cyclopentenyl or 4 to 6 membered heterocycloalkyl together with the carbon to which they are attached.

18. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein R2and R3are each independently H or methyl, or wherein R2and R3together form cyclopentyl.

19. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein R2and R3together form oxetanyl or oxanyl together with the carbon to which they are attached.

20. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein M is CRa.21 . The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein Rais H, cyclopropyl, CF3or methyl.

22. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein Rais H.

23. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein:A, D, E and G are absent andX is NR15or CH;Y is CR4, N or absent;Z is CR5, NR6or O;R4is halo, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, 4 to 10 membered fused-ring heterocyclyl, or C1-C6 alkylsulfanyl;R5is H, optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, optionally substituted 3 to 8 membered heterocycloalkyl, amido, sulfoximine, CN, or halo; or R4and R5together form 3 to 8 membered heterocycloalkyl or aryl together with Y and Z to which they are attached;R6is H, C1-C6 alkyl, aryl, or C3-C8 cycloalkyl;R15is H or C1-C6 alkyl; or R4and R15together form 5 membered heterocycloalkyl, or heteroaryl together with X and Y to which they are attached, optionally wherein R4and R15together form dihydrothiazole with X and Y to which they are attached; or A is CR12or N, D is CR7or N, E is CR13or N and G is OR14or N andX is N or C;Y is C;Z is CH, N, NR11, or O, wherein R11is H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, or optionally substituted 5 to 8 membered heteroaryl;R7is H, halo, C1-C6 alkyl;R12is H, halo, or C1-C6 alkyl;R13is H, halo, C1-C6 alkoxy, or C1-C6 alkyl; andR14is H, halo, or C1-C6 alkyl; or a stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt thereof.

24. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein:A, D, E and G are absent andX is NH or CH;Y is CR4or N.

25. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein:A, D, E and G are absent andX is NH or CH;Y is CR4or N;Z is CR5, NR6or O;R4is halo, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, 4 to 10 membered fused-ring heterocyclyl, C1-C6 alkylsulfanyl, sulfoxide, sulfone, sulfoximine, optionally substituted amino, or optionally substituted 3 to 8 membered heterocycloalkyl;R5is H, optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, optionally substituted 3 to 8 membered heterocycloalkyl, amido, sulfoximine, CN, or halo; or R4and R5together form 3 to 8 membered heterocycloalkyl or aryl together with Y and Z to which they are attached; andR6is H, C1-C6 alkyl, or C3-C8 cycloalkyl.

26. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 25, wherein Z is CR5or NR6.

27. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 25 or claim 26, wherein R6is H or C1- C6 alkyl.

28. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 27, wherein R4is halo, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, 4 to 10 membered fused-ring heterocyclyl, SMe, sulfoxide, sulfone, sulfoximine, optionally substituted amino, optionally substituted pyrrolidine, optionally substituted piperidine, optionally substituted morpholine, or optionally substituted piperazine.

29. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 28, wherein R4is halo, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, optionally substituted 5 to 8 membered heteroaryl, or 4 to 10 membered fused-ring heterocyclyl.

30. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 29, wherein R5is H.

31. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 30, wherein Y is CR4.

32. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 31 , wherein Y is N.

33. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 32, wherein X is NH.

34. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 32, wherein X is CH.

35. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 34, wherein R4is C1-C6 alkyl, C1-C6 alkyl substituted by one or more halo groups, halo, cycloalkyl, cycloalkyl substituted by one or more C1-C6 alkyl, heteroaryl, heteroaryl substituted by C1-C6 alkyl, dihydrobenzofuran, phenyl, or phenyl substituted by one or more C1-C6 alkyl, C1-C6 alkoxy, or halo.

36. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 35, wherein R4is methyl, CF3, CHF2, chloro, cyclopropyl, methyl substituted cyclopropyl, thiophene, methyl substituted pyrazole, 2,3-dihydrobenzofuran, phenyl, or phenyl substituted by methyl, methoxy, or fluoro.

37. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 36, wherein R4is phenyl or phenyl substituted by methyl, methoxy, or fluoro.

38. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25, 26, 31 , 33 or 34, wherein R4and R5together form 6 membered heterocycloalkyl or aryl together with Y and Z to which they are attached.

39. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25, 26 or 28 to 38, wherein Z is CH.

40. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 38, wherein Z is NR6.41 . The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25 to 37 or 40, wherein R6is H or methyl.

42. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25, 33 or 34, wherein Y is CR4wherein R4is C1 -C6 alkylsulfanyl, optionally SMe, and wherein Z is CR5wherein R5is CN.

43. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 25, 28, 29, 35, 36 or 37, wherein M is N, X is CH, Y is CR4and Z is NH, optionally wherein R4is phenyl.

44. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 to 23, wherein:A is CR12or N, D is CR7or N, E is CR13or N and G is CR14or N andX is N or C;Y is C;Z is CH, N, NR11, or O, wherein R11is H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted aryl, or optionally substituted 5 to 8 membered heteroaryl;R7is H, halo, or C1-C6 alkyl;R12is H, halo, or C1 -C6 alkyl;R13is H, halo, C1-C6 alkoxy, or C1-C6 alkyl; andR14is H, halo, or C1 -C6 alkyl.

45. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 44, wherein Z is CH, N, or NR11.

46. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 44, wherein Z is CH, N, or O.

47. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 44, wherein Z is CH or N.

48. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 47, wherein R7is H, methyl or halo.

49. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 48, wherein R12is H.

50. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 49, wherein D is CR7.51 . The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 50, wherein E is CR13.

52. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 51 , wherein R13is H.

53. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 52, wherein G is CR14.

54. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 53, wherein R14is H.

55. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 54, wherein X is N.

56. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 55, wherein A is CH.

57. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 55, wherein A is N.

58. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 57, wherein R7is halo.

59. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 58, wherein R7is fluoro.

60. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 57, wherein R7is H.

61. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 60, wherein Z is CH.

62. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44 to 60, wherein Z is N.

63. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44, 46 or 48 to 60, wherein Z is O.

64. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44, 45 or 48 to 60, wherein Z is NR11.

65. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44, 45, 48 to 60 or 64, wherein R11is H, C1-C6 alkyl, C3-C6 cycloalkyl, phenyl, or 5 to 7 membered heteroaryl.

66. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44, 45, 48 to 60, 64 or 65, wherein R11is H.

67. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 44, 45, 48 to 60, 64 or 65, wherein R11is methyl.

68. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 to 25, 27 to 29, 35 to 37 or41 , wherein:A, D, E and G are absent;M is CRaor N;X is CH;Y is CR4; and Z is NR6.

69. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 to 25, 28 to 30, 35 to 39 or42, wherein:A, D, E and G are absent;M is CRa;X is NH;Y is CR4; and Z is CR5.

70. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 to 25, 28, 29, 35, 36 or 37, wherein:A, D, E and G are absent;M is CRa;X is NH;Y is CR4; andZ is N.

71. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 to 23, 44, 48, 52, 58, 59 or 60, wherein:X is N;Y is C;Z is N;M is CRa;A and G are each CH;D is CR7; andE is CR13.

72. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 to 23, 44, 48, 58, 59 or 60, wherein:X and Y are each C;Z is O;A, E, G and M are each CH; and D is CR7.73 The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 to 23, 44, 65, 66 or 67, wherein:X and Y are each C;Z is NR11;A, E, G and M are each CH; and D is N.

74. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1 to 23 or 44, wherein: X and Y are each C;Z is NH;E is N; andA, D, G and M are each CH.

75. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein the C1-C6 alkyl is C1-C3 alkyl, optionally methyl.

76. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 12, 14, 23, 35 or 44, wherein the C1-C6 alkoxy is methoxy or 2-methoxyethyl.

77. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, wherein the 01-06 alkylsulfanyl is SMe.

78. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 1 , wherein:A, D, E and G are absent,X is NH or CH;Y is OR4;Z is OR5or NR6;R1is optionally substituted piperidine or piperazine,R2and R3together form cyclopentyl together with the carbon to which they are attached,R4is phenyl,R5is H, andR6is H or methyl, wherein each optional substituent is selected from phenyl, difluoro-phenyl, NHCH3, NHCH2CH3, NHCH(CH3)2, NHC(0)CH3, N(CH3)2, NHCH2CHF2, NHCH2CH2F, NHCH2CH2OH, and NHCH2CH2OCH3.

79. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 1 , whereinA, D, E and G are absent;X is NH or CH;Y is CR4;Z is CR5or NR6;R1is piperidine or piperazine each substituted by difluoro-phenyl and further substituted by amino optionally substituted by one or more C1-C3 alkyl, oxo- substituted C1-C3 alkyl, fluoro-substituted C1-C3 alkyl, CH2CH2OH, C1-C3 alkoxy, fluoro-substituted C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted by C1-C3 alkyl, or pyridine-substituted C1-C3 alkyl;R2and R3are each methyl, or together form cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, oxetanyl or oxanyl together with the carbon to which they are attached;R4is methyl, dihydrobenzofuran, phenyl, phenyl substituted by methyl, phenyl substituted by F, phenyl substituted by OMe, phenyl substituted by SMe, phenyl substituted by OH, or thiophene;R5is H, methyl or CN; andR6is H or methyl.

80. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to claim 1 , wherein X is N or C;Y is C;Z is N, NR11or O, wherein R11is H or methyl;M is CRawherein Rais H, methyl or cyclopropyl;A is C;D is CR7, wherein R7is H, methyl, F, Cl, Br;E is N or CR13, wherein R13is H, Cl or OMe;G is C;R1is piperidine or piperazine each substituted by difluoro-phenyl and further substituted by amino optionally substituted by one or more C1-C3 alkyl, fluoro- substituted C1-C3 alkyl, CH2CH2OH, C1-C3 alkoxy; andR2and R3are each methyl, or together form cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, oxetanyl or oxanyl together with the carbon to which they are attached.

81. A compound selected from:(fl)-6-Phenyl-3-((4-(3-phenylmorpholine-4-carbonyl)piperazin-1-yl)methyl)pyridin- 2(1 H)-one;(fl)-3-((2,2-Dimethyl-4-(3-phenylmorpholine-4-carbonyl)piperazin-1-yl)methyl)-6- phenylpyridin-2(1 H)-one;3-((9-((2S,4fi)-2-(3,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4fi)-2-(3,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)quinolin-2(1 H)-one; / V-((2S,4fl)-2-(2,5-Difluorophenyl)-1-(6-((2-oxo-6-phenyl-1 ,2-dihydropyridin-3- yl)methyl)-6,9-diazaspiro[4.5]decane-9-carbonyl)piperidin-4-yl)acetamide;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1 ,5,7,8-tetrahydro-2H-pyrano[4,3-b]pyridin-2-one;A / -(2,4-Difluorobenzyl)-6-((2-oxo-6-phenyl-1 ,2-dihydropyridin-3-yl)methyl)-6,9- diazaspiro[4.5]decane-9-carboxamide;(fl)-6-Phenyl-3-((9-(4,4,4-trifluoro-2-methylbutanoyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)pyridin-2(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(ethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1-methyl-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(3,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4fi)-2-(3,5-Difluorophenyl)-4-(dimethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-((2-methoxyethyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4fi)-4-(Methylamino)-2-phenylpiperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4 / 7)-2-(2,5-Difluorophenyl)-4-(dimethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;(fl)-3-((9-(2-(2,5-Difluorophenyl)piperazine-1-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-6-phenylpyridin-2(1 H)-one;6-Phenyl-3-((9-((3f?,4 / 3)-3-phenylpiperidine-4-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)pyridin-2(1 H)-one',3-((9-((2S,4fi)-4-((3,3-Difluorocyclobutyl)amino)-2-(2,5-difluorophenyl)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;(S)-6-Phenyl-3-((9-(4,4,4-trifluoro-2-(methoxymethyl)butanoyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)pyridin-2(1 H)-one;(fl)-3-((9-(3-Cyclohexyl-2-methylpropanoyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-6- phenylpyridin-2(1 H)-one;6-Phenyl-3-((9-(3-phenylisonicotinoyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)pyridin- 2(1 H)-one;3-((9-((2S,4fi)-4-((2-Hydroxyethyl)amino)-2-phenylpiperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-2,2- dimethylpiperazin-1 -yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((7-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-4,7- diazaspiro[2.5]octan-4-yl)methyl)-2-phenylpyridin-4(1 H)-one;6-Phenyl-3-((9-((2S,4fl)-2-phenyl-4-((pyridin-2-ylmethyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)pyridin-2(1 H)-one;5-((9-((2S,4R)-2-(3,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(3,4-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;(fl)-3-((9-(2-Methyl-2-phenylpiperazine-1-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(ethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;(fl)-5-((9-(3-(2,5-Difluorophenyl)morpholine-4-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-2-phenylpyridin-4(1 H)-one;(S)-5-((9-(3-(2,5-Difluorophenyl)morpholine-4-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4 / 7)-2-(2,5-Difluorophenyl)-4-(dimethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2SJ4fi)-2-(2,3-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-4-(Methylamino)-2-phenylpiperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-4-(Cyclopropylamino)-2-phenylpiperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;(fl)-5-((9-(2-(2,5-Difluorophenyl)-1 ,4-diazepane-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;(S)-5-((9-(2-(2,5-Difluorophenyl)-1 ,4-diazepane-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(3,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;(fl)-5-((9-(3-(2,5-Difluorophenyl)-1-oxa-4,9-diazaspiro[5.5]undecane-4-carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;(S)-5-((9-(3-(2,5-Difluorophenyl)-1-oxa-4,9-diazaspiro[5.5]undecane-4-carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4R)-2-(2,6-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4R)-2-(2,4-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;3-((9-((3 / ?,5S)-3-(2,5-Difluorophenyl)-5-methylmorpholine-4-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-((2-methoxyethyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((8-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-5,8- diazaspiro[3.5]nonan-5-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((8-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-2-oxa-5,8-diazaspiro[3.5]nonan-5-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-1 ,4- diazaspiro[5.5]undecan-1 -yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4 / 7)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;3-((9-((2S,4 / 7)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((4-((2SJ4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-9-oxa- 1 ,4-diazaspiro[5.5]undecan-1 -yl)methyl)-2-phenylpyridin-4(1 H)-one;3-((4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-2,2- dimethylpiperazin-1 -yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((7-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-4,7- diazaspiro[2.5]octan-4-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4f?)-4-Amino-2-(2,5-difluorophenyl)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((8-((2S,4f?)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-5,8- diazaspiro[3.5]nonan-5-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((8-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-2-oxa- 5,8-diazaspiro[3.5]nonan-5-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-1 ,4- diazaspiro[5.5]undecan-1 -yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-9-oxa- 1 ,4-diazaspiro[5.5]undecan-1 -yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(pyrrolidin-1-yl)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(thiophen-3-yl)pyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(1 -methyl-1 H-pyrazol-5-yl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-methyl-5-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(thiophen-2-yl)pyridin-4(1 H)-one;(fl)-3-((9-(3-Cyclohexyl-2-methylpropanoyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)- 4H-pyrido[1 ,2-a]pyrimidin-4-one;5-((9-((2S,4fi)-4-((2,2-Difluoroethyl)amino)-2-(2,5-difluorophenyl)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-4-Morpholino-2-phenylpiperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2-fluorophenyl)pyridin-4(1 H)-one;5-((9-((2SJ4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(o-tolyl)pyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2-methoxyphenyl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-4H-chromen-4-one;3-((9-((2S,4f?)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-fluoro-4H-chromen-4-one;(fl)-3-((9-(3-Cyclohexyl-2-methylpropanoyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-4H-chromen-4-one;(fl)-3-((9-(3-Cyclohexyl-2-methylpropanoyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-6- fluoro-4H-chromen-4-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2,3-dihydrobenzofuran-7-yl)pyridin-4(1 H)-one;(fl)-3-((9-(2-(2,5-Difluorophenyl)piperazine-1-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-6-fluoro-4H-chromen-4-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(1 -methyl-1 H-pyrazol-3-yl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;1-Cyclopropyl-5-((9-((2S,4fl)-2-(2,5-difluorophenyl)-4-(methylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-methylpyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-5,6-dimethylpyridin-2(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrimido[1 ,2-b]pyridazin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-fluoroquinolin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2-hydroxyphenyl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-methyl-2-propylpyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2SJ4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-5-(trifluoromethyl)pyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(o-tolyl)pyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2,3-dihydrobenzofuran-7-yl)pyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2-methoxyphenyl)pyridin-4(1 H)-one;(fl)-5-((9-(2-(2,5-Difluorophenyl)piperazine-1-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-2-phenylpyridin-4(1 H)-one;(fl)-3-((9-(2-(2,5-Difluorophenyl)piperazine-1-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;5-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(4-fluorophenyl)pyridin-4(1 H)-one;3-((9-((2S,4R)-2-(3,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;5-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(3-fluorophenyl)pyridin-4(1 H)-one;5-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(m-tolyl)pyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(3,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2-methoxyphenyl)pyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(3,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2,3-dihydrobenzofuran-7-yl)pyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(3,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(o-tolyl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-(m-tolyl)pyridin-2(1 H)-one;3-((9-((2S,4 / 7)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-(3-fluorophenyl)pyridin-2(1 H)-one;3-((9-((2S,4 / 7)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-(4-fluorophenyl)pyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(3-Fluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(methylthio)-6-oxo-1 ,6-dihydropyridine-3- carbonitrile;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyrimidin-4(3H)-one;3-((9-((2S,4F?)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1 ,7-naphthyridin-4(1 H)-one;5-((9-((2S,4F?)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1 -carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyrimidin-4(3H)-one;5-((4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1 -carbonyl)-1 ,4- diazaspiro[5.5]undecan-1 -yl)methyl)-2-phenylpyridin-4(1 A7)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1 -carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(thiophen-2-yl)pyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(dimethylamino)piperidine-1 -carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(thiophen-2-yl)pyridin-4(1 H)-one;5-((4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(dimethylamino)piperidine-1 -carbonyl)-1 ,4- diazaspiro[5.5]undecan-1 -yl)methyl)-2-phenylpyridin-4(1 H)-one;3-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2,6-dimethylpyridin-4(1 H)-one;3-((9-((2S,4fi)-4-((2,2-Difluoroethyl)amino)-2-(2,5-difluorophenyl)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4 / - / -pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-((2-methoxyethyl)amino)piperidine-1 - carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4 / - / -pyrido[1 ,2-a]pyrimidin-4-one;3-((4-((2S,5fi)-5-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)piperazin-1- yl)methyl)-6-phenylpyridin-2(1 / - / )-one;(fl)-6-Phenyl-3-((4-(3-phenylmorpholine-4-carbonyl)-9-oxa-1 ,4- diazaspiro[5.5]undecan-1 -yl) methyl)pyridin-2( 1 H)-one;(fl)-3-((4-(3-(4-Fluorophenyl)morpholine-4-carbonyl)-9-oxa-1 ,4- diazaspiro[5.5]undecan-1 -yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((4-((2fl,5R)-5-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)piperazin-1 - yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2-Fluoro-5-methylphenyl)-4-(isopropylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2-Fluoro-5-methoxyphenyl)-4-(isopropylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,5F?)-5-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4F?)-2-(3,5-Difluorophenyl)-4-(isopropylamino)piperidine-1 -carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyrimidin-4(3H)-one;3-((9-((2S,4F?)-2-(2,5-Difluorophenyl)-4-((2-hydroxyethyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4F?)-2-(2,5-Difluorophenyl)-4-((2-hydroxyethyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;A / -((2S,4 / 7)-2-(2,5-Difluorophenyl)-1 -(6-((7-fluoro-4-oxo-4H-pyrido[1 ,2-a]pyrimidin-3- yl)methyl)-6,9-diazaspiro[4.5]decane-9-carbonyl)piperidin-4-yl)acetamide;A / -((2S,4fl)-2-(2,5-Difluorophenyl)-1 -(6-((7-fluoro-4-oxo-4H-pyrido[1 ,2-a]pyrimidin-3- yl)methyl)-6,9-diazaspiro[4.5]decane-9-carbonyl)piperidin-4- y l)cyclopropanecarboxam ide ;3-((9-((2S,4R)-4-((1 ,1-Dioxidothietan-3-yl)amino)-2-phenylpiperidine-1 -carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4R)-4-((2,2-Difluoroethyl)amino)-2-(3,5-difluorophenyl)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(dimethylamino)piperidine-1 -carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1-methyl-2-(thiophen-3-yl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(dimethylamino)piperidine-1 -carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;(S)-6-(2-Methoxyphenyl)-3-((9-(2-phenylpyrrolidine-1 -carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)pyridin-2(1 H)-one;(S)-6-Phenyl-3-((7-(2-phenylpyrrolidine-1-carbonyl)-47-diazaspiro[2.5]octan-4- yl)methyl)pyridin-2(1 H)-one;(S)-6-Phenyl-3-((4-(2-phenylpyrrolidine-1 -carbonyl)-9-oxa-1 ,4- diazaspiro[5.5]undecan-1 -yl) methyl)pyridin-2(1 H)-one;5-((9-((2H,5R)-5-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;(S)-3-((4-(2-(2,5-Difluorophenyl)pyrrolidine-1 -carbonyl)-2,2-dimethylpiperazin-1 - yl)methyl)-6-(1-methyl-1 H-pyrazol-5-yl)pyridin-2(1 H)-one;(S)-3-((2,2-Dimethyl-4-(2-phenylpyrrolidine-1-carbonyl)piperazin-1-yl)methyl)-6- phenylpyridin-2(1 H)-one;(S)-6-Phenyl-3-((8-(2-phenylpyrrolidine-1-carbonyl)-2-oxa-5,8-diazaspiro[3.5]nonan- 5-yl)methyl)pyridin-2(1 H)-one', 3-((4-((1 S,2fl,5fl)-2-(2,5-Difluorophenyl)-8-oxa-3-azabicyclo[3.2.1]octane-3- carbonyl)piperazin-1 -yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((1 S,2fl,5fl)-2-(2,5-Difluorophenyl)-8-oxa-3-azabicyclo[3.2.1]octane-3- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((1 S,2fl,5fl)-2-(2,5-Difluorophenyl)-8-oxa-3-azabicyclo[3.2.1]octane-3- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(2-fluorophenyl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-fluoro-1-methylquinolin-4(1 H)-one;3-((9-((2fl,3R)-3-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,3S)-3-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1 -methyl-2-(1 -methyl-1 H-pyrazol-5-yl)pyridin- 4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-(trifluoromethyl)pyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(trifluoromethyl)pyridin-4(1 H)-one;3-((4-((2fl,3H)-3-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)piperazin-1- yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((4-((2S,3S)-3-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)piperazin-1- yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2fl,3H)-3-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,3S)-3-(2,5-Difluorophenyl)-2-methylmorpholine-4-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;3-((9-((2fl,4R)-4-Amino-2-ethylpiperidine-1-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2f?,4 / ^-2-Ethyl-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-((2-hydroxyethyl)(methyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridin-2(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1 -methyl-2-(1 -methyl-1 H-pyrazol-3-yl)pyridin- 4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(dimethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(thiophen-3-yl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(ethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-hydroxypiperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(dimethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1 -methyl-2-(1 -methyl-1 H-pyrazol-3-yl)pyridin- 4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropyl(methyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-((2-methoxyethyl)(methyl)amino)piperidine-1-carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2- a]pyrimidin-4-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-hydroxypiperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(thiophen-3-yl)pyridin-4(1 H)-one;3-(((S)-4-((2S,4fl)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-2-methylpiperazin-1-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;7-Chloro-3-((9-((2S,4fl)-2-(2,5-difluorophenyl)-4-(isopropylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((4-((2S,4R)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-1 ,4- diazaspiro[5.5]undecan-1-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((4-((2S,4 / 7)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-2,2- dimethylpiperazin-1-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((( / ^-4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-2-methylpiperazin-1-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;5-((9-((2S,4fi)-2-(2,5-difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1-methyl-2-(thiophen-3-yl)pyridin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-((2-hydroxyethyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-((2-hydroxyethyl)(methyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4 / ?)-2-(2,5-Difluorophenyl)-4-(ethyl(methyl)amino)piperidine-1 -carbonyl)-6.9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4 / - / -pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-methyl-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-8-methoxy-4H-pyrido[1 ,2-a]pyrimidin-4-one;5-((9-((2S,4S)-4-Amino-2-phenylpyrrolidine-1-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-2-phenylpyridin-4(1 H)-one;5-((9-((2S,4S)-4-(lsopropylamino)-2-phenylpyrrolidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;3-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7,8-dihydropyrrolo[1 ,2-a]pyrimidin-4(6H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7,8-dihydropyrrolo[1 ,2-a]pyrimidin-4(6H)-one;3-((9-(5-Amino-2',5'-difluoro-[1 ,1'-biphenyl]-2-carbonyl)-6,9-diazaspiro[4.5]decan-6- yl)methyl)-6-phenylpyridin-2(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-2-methyl-4 / - / -pyrido[1 ,2-a]pyrimidin-4- one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-((2-fluoroethyl)amino)piperidine-1-carbonyl)-6.9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;5-((9-((2S,4 / 7)-2-(2,5-Difluorophenyl)-4-((2-fluoroethyl)amino)piperidine-1-carbonyl)-6.9-diazaspiro[4.5]decan-6-yl)methyl)-2-phenylpyridin-4(1 H)-one;7-Fluoro-3-((9-((2S,4S)-4-(isopropylamino)-2-phenylpyrrolidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2SJ4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-methyl-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-2-methyl-4H-pyrido[1 ,2-a]pyrimidin-4- one;4-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1-phenyl-1 ,2-dihydro-3H-pyrazol-3-one;4-((9-((2S,4f?)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-methyl-1-phenyl-1 ,2-dihydro-3H-pyrazol-3-one;7-Chloro-3-((9-((2S,4fl)-2-(2,5-difluorophenyl)-4-(methylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((4-((2S,4f?)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-1 ,4- diazaspiro[5.5]undecan-1-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((4-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(ethylamino)piperidine-1-carbonyl)-1 ,4- diazaspiro[5.5]undecan-1-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;7-Chloro-3-((9-((2S,4fl)-2-(2,5-difluorophenyl)-4-(ethylamino)piperidine-1-carbonyl)- 6,9-diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;6-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-5H-thiazolo[3,2-a]pyrimidin-5-one;6-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-5H-thiazolo[3,2-a]pyrimidin-5-one;7-Fluoro-3-((9-((2S,4fi)-4-((3-methyloxetan-3-yl)amino)-2-phenylpiperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(ethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-methyl-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(ethylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-2-methyl-4H-pyrido[1 ,2-a]pyrimidin-4- one;2-Cyclopropyl-3-((9-((2S,4fl)-2-(2,5-difluorophenyl)-4-(methylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;2-Cyclopropyl-3-((9-((2S,4H)-2-(2,5-difluorophenyl)-4-(isopropylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin- 4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridazin-4(1 H)-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-6-phenylpyridazin-4(1 H)-one;3-((9-((2S,4fi)-4-Amino-2-(2,5-difluorophenyl)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]dec-2-en-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one;7-Bromo-3-((9-((2S,4fl)-2-(2,5-difluorophenyl)-4-(isopropylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;8-Chloro-3-((9-((2S,4fl)-2-(2,5-difluorophenyl)-4-(isopropylamino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-4H-pyrido[1 ,2-a]pyrimidin-4-one;3-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-2-(trifluoromethyl)-4H-pyrido[1 ,2- a]pyrimidin-4-one;3-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-2-(trifluoromethyl)-4H-pyrido[1 ,2- a]pyrimidin-4-one;3-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-(methylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-1 -methyl-1 ,6-naphthyridin-4(1 H)-one;3-((9-((2S,4R)-2-(2,5-Difluorophenyl)-4-((1-methylcyclopropyl)amino)piperidine-1- carbonyl)-6,9-diazaspiro[4.5]decan-6-yl)methyl)-7-fluoro-4H-pyrido[1 ,2-a]pyrimidin-4-one; and5-((9-((2S,4fi)-2-(2,5-Difluorophenyl)-4-(isopropylamino)piperidine-1-carbonyl)-6,9- diazaspiro[4.5]decan-6-yl)methyl)-2-(1-methylcyclopropyl)pyridin-4(1 H)-one; or a stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt thereof.

82. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim that is an inhibitor of USP19, preferably human USP19.

83. A pharmaceutical composition comprising a compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any preceding claim, and a pharmaceutically acceptable carrier or diluent.

84. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1-82 or the pharmaceutical composition according to claim 83 for use in therapy.

85. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any of claims 1-82 or the pharmaceutical composition according to claim 83 for use as a medicament.

86. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any one of claims 1-82 or the pharmaceutical composition according to claim 83 for use in treating muscular atrophy, obesity, insulin resistance, or type II diabetes.

87. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any one of claims 1-82 or the pharmaceutical composition according to claim 83 for use in treating muscular atrophy, cachexia or sarcopenia, wherein the muscular atrophy, cachexia and sarcopenia are associated with or induced by cancer.

88. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any one of claims 1-82 or the pharmaceutical composition according to claim 83 for use in treating cancer, preferably wherein the cancer is breast cancer or neuroblastoma.

89. The compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any one of claims 1-82 or the pharmaceutical composition according to claim 83 for use according to claim 88, wherein the use comprises treating muscular atrophy, cachexia and / or sarcopenia.

90. A method of treating obesity, insulin resistance, type II diabetes, or muscular atrophy, comprising administering to a subject in need thereof an effective amount of acompound, stereoisomer, tautomer, hydrate, N-oxide derivative or pharmaceutically acceptable salt according to any one of claims 1-82 or a pharmaceutical composition according to claim 83.

91. A method of reducing loss of muscle mass in a subject comprising administering to a subject in need thereof an effective amount of a compound, stereoisomer, tautomer, hydrate, / V-oxide derivative or pharmaceutically acceptable salt according to any one of claims 1 -82 or a pharmaceutical composition according to claim 83.

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