IP Library Granted Patent US 9,422,267
Granted Patent B2
US 9,422,267 · App. 14/141,003 · Granted Aug 23, 2016

Fused pyrimidine compounds and use thereof

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Quick Facts
Patent No.
US 9,422,267
App. No.
14/141,003
Granted
Aug 23, 2016
Kind
B2
Abstract

The present invention provides fused pyrimidine compounds of the general Formula (I): or a salt thereof, wherein the variables are as defined in the specification. Fused pyrimidine compounds of the general Formula (I) are provided as kinase inhibitors, such as multi-kinase inhibitors. In one aspect, fused pyrimidine compounds of the general Formula (I) are provided as IGF-IR inhibitors. The compounds may be used in a method of treating cancer. Pharmaceutical compositions containing a fused pyrimidine compounds of the general Formula (I) and a pharmaceutically acceptable carrier are also provided, as are kits containing a fused pyrimidine compound of the general Formula (I) or salt thereof and instructions for use, e.g., in a method of treating cancer.

Claims (474)

1. A compound of the formula (I):

or a salt or N-oxide thereof, wherein:

D is hydrogen; unsubstituted C 1 -C 6 alkyl; C 1 -C 6 alkyl substituted by 1 to 5 substituents independently selected from the group consisting of hydroxy, heteroaryl, and heteroaryl substituted by C 1 -C 6 alkyl; unsubstituted aryl; unsubstituted heteroaryl; heteroaryl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl; unsubstituted C 3 -C 8 cycloalkyl; unsubstituted heterocyclyl; or heterocyclyl substituted by 1 to 5 substituents independently selected from unsubstituted acyl, acyl substituted by amino, C 1 -C 6 alkyl and oxo; wherein the heteroaryl of D is selected from the group consisting of pyridyl, pyrimidyl, pyrazinyl, thiazolyl, oxazolyl, pyrazolyl, furanyl and thiadiazolyl, and the heterocyclyl of D is selected from the group consisting of pyrrolidinyl and piperidinyl;

E is unsubstituted 5-membered heteroaryl or 5-membered heteroaryl substituted by 1 to 4 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl;

each j, k, m, and n is independently 0 or 1;

each R A1 , R A2 , R A3 , R A4 , R A5 , R A6 , R A7 , R A8 , R A9 and R A10 , where present, is independently hydrogen, unsubstituted C 1 -C 6 alkyl, halo, hydroxy, or taken together with a geminal R A(1-10) group and the carbon to which they are attached to form a carbonyl moiety or a thiocarbonyl moiety;

R D is hydrogen;

X is O or S;

R Z is hydrogen, or unsubstituted C 1 -C 6 alkyl;

each R Z1 and R Z2 is independently hydrogen, or unsubstituted C 1 -C 6 alkyl;

each R Z3 , R Z4 , R Z5 , R Z6 , R Z7 and R Z8 , where present, is independently hydrogen, unsubstituted C 1 -C 6 alkyl, halo, hydroxy, —OR 1 , —O—C 1 -C 6 alkylene-P(O)(OH) 2 , —OC(O)R 8 , unsubstituted tetrazolyl, tetrazolyl substituted by C 1 -C 6 alkyl, or is taken together with a geminal R Z(3-8) group and the carbon to which they are attached to form a carbonyl moiety;

each R 1 is independently unsubstituted C 1 -C 6 alkyl;

each R 8 is independently unsubstituted C 1 -C 6 alkyl.

2. The compound of claim 1 , or a salt or N-oxide thereof, wherein each of j and k is 0.

3. The compound of claim 2 , or a salt or N-oxide thereof, wherein each of R A1 , R A2 , R A3 , R A4 , R A5 and R A6 is hydrogen.

4. The compound of claim 2 , or a salt or N-oxide thereof, wherein each of R A1 and R A2 is independently C 1 -C 6 alkyl; and each of R A3 , R A4 , R A5 and R A6 is hydrogen.

5. The compound of claim 4 , or a salt or N-oxide thereof, wherein each of R A1 and R A2 is methyl.

6. The compound of claim 2 , or a salt or N-oxide thereof, wherein each of R A3 and R A4 is independently C 1 -C 6 alkyl; and each of R A1 , R A2 , R A5 and R A6 is hydrogen.

7. The compound of claim 6 , or a salt or N-oxide thereof, wherein each of R A3 and R A4 is methyl.

8. The compound of claim 2 , or a salt or N-oxide thereof, wherein each of R A5 and R A6 is independently C 1 -C 6 alkyl; and each of R A1 , R A2 , R A3 and R A4 is hydrogen.

9. The compound of claim 8 , or a salt or N-oxide thereof, wherein each of R A5 and R A6 is methyl.

10. The compound of claim 2 , or a salt or N-oxide thereof, wherein each of R A1 , R A2 , R A5 and R A6 is hydrogen.

11. The compound of claim 2 , or a salt or N-oxide thereof, wherein each of R A5 and R A6 is hydrogen.

12. The compound of claim 2 , or a salt or N-oxide thereof, wherein R A3 and R A4 are taken together with the carbon to which they are attached to form a carbonyl moiety; and each of R A1 , R A2 , R A5 and R A6 is hydrogen.

13. The compound of claim 2 , or a salt or N-oxide thereof, wherein R A3 and R A4 are taken together with the carbon to which they are attached to form a thiocarbonyl moiety; and each of R A1 , R A2 , R A5 and R A6 is hydrogen.

14. The compound of claim 2 , or a salt or N-oxide thereof, wherein each of R A3 and R A4 is independently halogen; and each of R A1 , R A2 , R A5 and R A6 is hydrogen.

15. The compound of claim 14 , or a salt or N-oxide thereof, wherein each of R A3 and R A4 is fluorine.

16. The compound of claim 2 , or a salt or N-oxide thereof, wherein R A3 is halogen; and each of R A1 , R A2 , R A4 , R A5 and R A6 is hydrogen.

17. The compound of claim 16 , or a salt or N-oxide thereof, wherein R A3 is fluorine.

18. The compound of claim 2 , or a salt or N-oxide thereof, wherein each of R A1 , R A2 , R A3 , R A4 , R A5 and R A6 is independently hydroxy or hydrogen.

19. The compound of claim 18 , or a salt or N-oxide thereof, wherein one of R A1 , R A2 , R A3 , R A4 , R A5 and R A6 is hydroxy.

20. The compound of claim 18 , or a salt or N-oxide thereof, wherein two of R A1 , R A2 , R A3 , R A4 , R A5 and R A6 are hydroxy.

21. The compound of claim 1 , or a salt or N-oxide thereof, wherein j is 1 and k is 0.

22. The compound of claim 21 , or a salt or N-oxide thereof, wherein each of R A1 , R A2 , R A3 , R A4 , R A5 , R A6 , R A7 and R A8 is hydrogen.

23. The compound of claim 1 , or a salt or N-oxide thereof, wherein each of j and k is 1.

24. The compound of claim 23 , or a salt or N-oxide thereof, wherein each of R A1 , R A2 , R A3 , R A4 , R A5 , R A6 , R A7 , R A8 , R A9 and R A10 is hydrogen.

25. The compound of claim 1 , or a salt or N-oxide thereof, wherein each of m and n is 0.

26. The compound of claim 25 , or a salt or N-oxide thereof, wherein each of R Z1 , R Z2 , R Z3 and R Z4 is hydrogen.

27. The compound of claim 1 , or a salt or N-oxide thereof, wherein m is 1 and n is 0.

28. The compound of claim 27 , or a salt or N-oxide thereof, wherein each of R Z1 , R Z2 , R Z3 and R Z4 is hydrogen.

29. The compound of claim 27 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is hydrogen.

30. The compound of claim 27 , or a salt or N-oxide thereof, wherein R Z5 is hydroxy; and R Z6 is hydrogen.

31. The compound of claim 27 , or a salt or N-oxide thereof, wherein R Z3 is hydroxy; and R Z4 is hydrogen.

32. The compound of claim 27 , or a salt or N-oxide thereof, wherein R Z5 is OR 1 ; and R Z6 is hydrogen.

33. The compound of claim 32 , or a salt or N-oxide thereof, wherein R Z5 is methoxy.

34. The compound of claim 27 , or a salt or N-oxide thereof, wherein R Z5 is halogen; and R Z6 is hydrogen.

35. The compound of claim 34 , or a salt or N-oxide thereof, wherein R Z5 is fluorine.

36. The compound of claim 27 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is independently unsubstituted C 1 -C 6 alkyl.

37. The compound of claim 36 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is methyl.

38. The compound of claim 27 , or a salt or N-oxide thereof, wherein R Z5 is unsubstituted tetrazolyl or tetrazolyl substituted by C 1 -C 6 alkyl; and R Z6 is hydrogen.

39. The compound of claim 38 , or a salt or N-oxide thereof, wherein R Z5 is tetrazolyl substituted by C 1 -C 6 alkyl.

40. The compound of claim 27 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is independently halogen.

41. The compound of claim 40 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is fluorine.

42. The compound of claim 27 , or a salt or N-oxide thereof, wherein R Z5 is —O—C 1 -C 6 alkylene-P(O)(OH) 2 ; and R Z6 is hydrogen.

43. The compound of claim 27 , or a salt or N-oxide thereof, wherein R Z5 is —OC(O)R 8 ; and R Z6 is hydrogen.

44. The compound of claim 27 , or a salt or N-oxide thereof, wherein R Z5 and R Z6 are taken together with the carbon to which they are attached to form a carbonyl moiety.

45. The compound of claim 1 , or a salt or N-oxide thereof, wherein each of m and n is 1.

46. The compound of claim 45 , or a salt or N-oxide thereof, wherein each of R Z3 , R Z4 , R Z5 , R Z6 , R Z7 and R Z8 is hydrogen.

47. The compound of claim 1 , or a salt or N-oxide thereof, wherein X is O.

48. The compound of claim 1 , or a salt or N-oxide thereof, wherein X is S.

49. The compound of claim 1 , or a salt or N-oxide thereof, wherein R Z is hydrogen.

50. The compound of claim 1 , or a salt or N-oxide thereof, wherein R Z is unsubstituted C 1 -C 6 alkyl.

51. The compound of claim 50 , or a salt or N-oxide thereof, wherein R Z is methyl.

52. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is hydrogen.

53. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted C 1 -C 6 alkyl or C 1 -C 6 alkyl substituted by 1 to 5 substituents independently selected from the group consisting of hydroxy, heteroaryl, and heteroaryl substituted by C 1 -C 6 alkyl.

54. The compound of claim 53 , or a salt or N-oxide thereof, wherein D is methyl.

55. The compound of claim 53 , or a salt or N-oxide thereof, wherein D is hydroxyethyl.

56. The compound of claim 53 , or a salt or N-oxide thereof, wherein D is methyl substituted with unsubstituted oxazolyl, oxazolyl substituted by C 1 -C 6 alkyl, unsubstituted pyrazolyl, pyrazolyl substituted by C 1 -C 6 alkyl, unsubstituted furanyl, furanyl substituted by C 1 -C 6 alkyl, unsubstituted thiazolyl, or thiazolyl substituted by C 1 -C 6 alkyl.

57. The compound of claim 56 , or a salt or N-oxide thereof, wherein D is methyl substituted with oxazol-2-yl, pyrazol-5-yl, 1-methylpyrazol-5-yl, furan-2-yl, or thiazol-2-yl.

58. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted phenyl.

59. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted pyridyl or pyridyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

60. The compound of claim 59 , or a salt or N-oxide thereof, wherein D is unsubstituted pyridyl.

61. The compound of claim 59 , or a salt or N-oxide thereof, wherein D is pyridyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

62. The compound of claim 59 , or a salt or N-oxide thereof, wherein D is selected from the group consisting of 3-pyridyl and 6-fluoro-3-pyridyl.

63. The compound of claim 59 , or a salt or N-oxide thereof, wherein D is selected from the group consisting of 6-hydroxypyridin-3-yl, 6-aminopyridin-3-yl, 6-(methylthio)pyridin-3-yl, and 6-ethoxypyridin-3-yl.

64. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted pyrimidyl or pyrimidyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

65. The compound of claim 64 , or a salt or N-oxide thereof, wherein D is unsubstituted pyrimidyl.

66. The compound of claim 65 , or a salt or N-oxide thereof, wherein D is pyrimid-5-yl.

67. The compound of claim 64 , or a salt or N-oxide thereof, wherein D is pyrimidyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

68. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted pyrazinyl or pyrazinyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

69. The compound of claim 68 , or a salt or N-oxide thereof, wherein D is pyrazin-2-yl.

70. The compound of claim 68 , or a salt or N-oxide thereof, wherein D is pyrazinyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

71. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted thiazolyl or thiazolyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

72. The compound of claim 71 , or a salt or N-oxide thereof, wherein D is unsubstituted thiazolyl.

73. The compound of claim 71 , or a salt or N-oxide thereof, wherein D is substituted thiazolyl substituted by 1 to 3 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

74. The compound of claim 73 , or a salt or N-oxide thereof, wherein D is 5-chlorothiazol-2-yl.

75. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted thiadiazolyl or thiadiazolyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

76. The compound of claim 75 , or a salt or N-oxide thereof, wherein D is unsubstituted thiadiazolyl.

77. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted C 3 -C 8 cycloalkyl.

78. The compound of claim 1 , or a salt or N-oxide thereof, wherein D is unsubstituted heterocyclyl or heterocyclyl substituted by 1 to 5 substituents independently selected from unsubstituted acyl, acyl substituted by amino, C 1 -C 6 alkyl and oxo.

79. The compound of claim 78 , or a salt or N-oxide thereof, wherein D is unsubstituted pyrrolidin-3-yl or pyrrolidin-3-yl substituted by 1 to 5 substituents independently selected from unsubstituted acyl, acyl substituted by amino, C 1 -C 6 alkyl and oxo.

80. The compound of claim 79 , or a salt or N-oxide thereof, wherein D is 1-acetylpyrrolidin-3-yl.

81. The compound of claim 78 , or a salt or N-oxide thereof, wherein D is unsubstituted piperidin-3-yl or piperdin-3-yl substituted by 1 to 5 substituents independently selected from unsubstituted acyl, acyl substituted by amino, C 1 -C 6 alkyl and oxo.

82. The compound of claim 81 , or a salt or N-oxide thereof, wherein D is 1-(2-amino-2-methylpropanoyl)piperidin-3-yl.

83. The compound of claim 81 , or a salt or N-oxide thereof, wherein D is 1-isopropylpiperidin-3-yl.

84. The compound of claim 1 , or a salt or N-oxide thereof, wherein E is an unsubstituted 5-membered heteroaryl.

85. The compound of claim 1 , or a salt or N-oxide thereof, wherein E is unsubstituted pyrazolyl or pyrazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl.

86. The compound of claim 85 , or a salt or N-oxide thereof, wherein E is pyrazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl.

87. The compound of claim 86 , or a salt or N-oxide thereof, wherein E is selected from the group consisting of 5-cyclopropylpyrazol-3-yl, 5-cyclopentylpyrazol-3-yl, 5-(isopropyl)pyrazol-3-yl, 3-cyclopropylpyrazol-5-yl, 3-cyclopentylpyrazol-5-yl and 3-(isopropyl)pyrazol-5-yl.

88. The compound of claim 86 , or a salt or N-oxide thereof, wherein E is selected from the group consisting of 5-hydroxypyrazol-3-yl, 5-(2-hydroxypropan-2-yl)pyrazol-3-yl, 5-(1-hydroxypropan-2-yl)pyrazol-3-yl, 5-(2-hydroxycyclopropyl)pyrazol-3-yl, and 1-hydroxy-5-isopropylpyrazol 3-yl.

89. The compound of claim 1 , or a salt or N-oxide thereof, wherein E is unsubstituted imidazolyl or imidazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl.

90. The compound of claim 1 , or a salt or N-oxide thereof, wherein E is unsubstituted-isoxazolyl or isoxazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl.

91. The compound of claim 1 , or a salt or N-oxide thereof, wherein E is unsubstituted oxazolyl or oxazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl.

92. The compound of claim 1 , or a salt or N-oxide thereof, wherein E is unsubstituted thiazolyl or thiazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl.

93. A compound, or a salt thereof, wherein the compound is selected from the group consisting of:

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyridin-3-yl)pyrrolidine-2-carboxamide;

1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)azetidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrazin-2-yl)pyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrimidin-5-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)piperidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-hydroxypyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-3-hydroxypyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(3-isopropylisoxazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)piperidine-2-carboxamide;

1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)piperidine-2-carboxamide;

1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-methylpyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-methoxypyrrolidine-2-carboxamide;

1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrrolidin-3-yl)pyrrolidine-2-carboxamide;

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-N-(pyrimidin-4-yl)pyrrolidine-2-carboxamide;

1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(piperidin-3-yl)pyrrolidine-2-carboxamide;

N-(1-(2-amino-2-methylpropanoyl)piperidin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(5-chlorothiazol-2-yl)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxypyrrolidine-2-carboxamide;

N-(6-aminopyridin-3-yl)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-hydroxy-N-(pyridin-3-yl)pyrrolidine-2-carboxamide;

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-fluoro-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-(1-methylcyclopropyl)-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4,4-dimethylpyrrolidine-2-carboxamide

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxy-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-(5-methyl-2H-tetrazol-2-yl)pyrrolidine-2-carboxamide;

4-fluoro-N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

4,4-difluoro-N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

3-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)-1H-pyrazole-5-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(1-isopropylpiperidin-3-yl)pyrrolidine-2-carboxamide;

2-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)oxazole-5-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-(1-hydroxycyclopropyl)-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

2-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)thiazole-5-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((2-isopropyl-1H-imidazol-5-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-5,5-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-7,7-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-5,7-dihydrospiro[cyclopenta[d]pyrimidine-6,1′-cyclopropan]-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,6-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(6,6-difluoro-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-5,7-dihydrospiro[cyclopenta[d]pyrimidine-6,2′-oxiran]-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6-thioxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(((1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl)oxy)methyl)phosphonic acid;

1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl isobutyrate;

2-fluoro-5-(1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamido)pyridine 1-oxide;

2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxide;

2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidine 3-oxide;

N-(6-hydroxypyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-oxo-1,6-dihydropyridin-3-yl)pyrrolidine-2-carboxamide;

1-(5-hydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

1-(5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

1-(4-((5-hydroxy-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrimidin-4-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(5-(2-hydroxypropan-2-yl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

3-(2-(2-(6-fluoropyridin-3-ylcarbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)-5-isopropyl-1H-pyrazole 2-oxide;

N-(6-fluoropyridin-3-yl)-1-(4-(1-hydroxy-5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-(methylthio)pyridin-3-yl)pyrrolidine-2-carboxamide;

N-(6-ethoxypyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-oxopyrrolidine-2-carboxamide;

N-(1-acetylpyrrolidin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(2-hydroxyethyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carbothioamide;

N-(2-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(furan-2-ylmethyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-((1H-pyrazol-5-yl)methyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-((1-methyl-1H-pyrazol-5-yl)methyl)pyrrolidine-2-carboxamide;

1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(oxazol-2-ylmethyl)pyrrolidine-2-carboxamide;

1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-ylmethyl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(5-(1-hydroxypropan-2-yl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(4-(5-(2-hydroxycyclopropyl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

1-(6-fluoro-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(6-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(7-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-y77l)pyrrolidine-2-carboxamide;

N-(6-fluoropyridin-3-yl)-1-(7-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide; and

N-(2-ethoxypyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide.

94. A compound, or a salt thereof, wherein the compound is selected from the group consisting of:

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)azetidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)azetidine-2-carboxamide;

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrazin-2-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrazin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrimidin-5-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrimidin-5-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)piperidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)piperidine-2-carboxamide;

(2R,4R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-hydroxypyrrolidine-2-carboxamide;

(2S,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-hydroxypyrrolidine-2-carboxamide;

(2R,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-hydroxypyrrolidine-2-carboxamide;

(2S,4R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-hydroxypyrrolidine-2-carboxamide;

(2R,3R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-3-hydroxypyrrolidine-2-carboxamide;

(2S,3S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-3-hydroxypyrrolidine-2-carboxamide;

(2R,3S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-3-hydroxypyrrolidine-2-carboxamide;

(2S,3R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-3-hydroxypyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-(3-isopropylisoxazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-(3-isopropylisoxazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)piperidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)piperidine-2-carboxamide;

(R)-1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)piperidine-2-carboxamide;

(S)-1-(4-(5-cyclopentyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)piperidine-2-carboxamide;

(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-methylpyrrolidine-2-carboxamide;

(S)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-methylpyrrolidine-2-carboxamide;

(2R,4R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-methoxypyrrolidine-2-carboxamide;

(2S,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-methoxypyrrolidine-2-carboxamide;

(2R,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-methoxypyrrolidine-2-carboxamide;

(2S,4R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-methoxypyrrolidine-2-carboxamide;

(R)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((R)-pyrrolidin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((S)-pyrrolidin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((S)-pyrrolidin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((R)-pyrrolidin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-N-(pyrimidin-4-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-2-methyl-N-(pyrimidin-4-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((R)-piperidin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((S)-piperidin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((S)-piperidin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N—((R)-piperidin-3-yl)pyrrolidine-2-carboxamide;

(R)—N—((R)-1-(2-amino-2-methylpropanoyl)piperidin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N—((S)-1-(2-amino-2-methylpropanoyl)piperidin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N—((S)-1-(2-amino-2-methylpropanoyl)piperidin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N—((R)-1-(2-amino-2-methylpropanoyl)piperidin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2R,4R)—N-(5-chlorothiazol-2-yl)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxypyrrolidine-2-carboxamide;

(2S,4S)—N-(5-chlorothiazol-2-yl)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxypyrrolidine-2-carboxamide;

(2R,4S)—N-(5-chlorothiazol-2-yl)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxypyrrolidine-2-carboxamide;

(2S,4R)—N-(5-chlorothiazol-2-yl)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxypyrrolidine-2-carboxamide;

(R)—N-(6-aminopyridin-3-yl)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-aminopyridin-3-yl)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2R,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-hydroxy-N-(pyridin-3-yl)pyrrolidine-2-carboxamide;

(2S,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-hydroxy-N-(pyridin-3-yl)pyrrolidine-2-carboxamide;

(2R,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-hydroxy-N-(pyridin-3-yl)pyrrolidine-2-carboxamide;

(2S,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-hydroxy-N-(pyridin-3-yl)pyrrolidine-2-carboxamide;

(2R,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-fluoro-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

(2S,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-fluoro-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

(2R,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-fluoro-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

(2S,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-fluoro-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((5-(1-methylcyclopropyl)-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((5-(1-methylcyclopropyl)-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4,4-dimethylpyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4,4-dimethylpyrrolidine-2-carboxamide;

(2R,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxy-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

(2S,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxy-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

(2R,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxy-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

(2S,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-methoxy-N-(1,2,4-thiadiazol-5-yl)pyrrolidine-2-carboxamide;

(2R,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-(5-methyl-2H-tetrazol-2-yl)pyrrolidine-2-carboxamide;

(2S,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-(5-methyl-2H-tetrazol-2-yl)pyrrolidine-2-carboxamide;

(2R,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-(5-methyl-2H-tetrazol-2-yl)pyrrolidine-2-carboxamide;

(2S,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)-4-(5-methyl-2H-tetrazol-2-yl)pyrrolidine-2-carboxamide;

(2R,4R)-4-fluoro-N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2S,4S)-4-fluoro-N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2R,4S)-4-fluoro-N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2S,4R)-4-fluoro-N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-4,4-difluoro-N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)-4,4-difluoro-N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-3-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)-1H-pyrazole-5-carboxamide;

(S)-3-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)-1H-pyrazole-5-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2R,4R)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(1-isopropylpiperidin-3-yl)pyrrolidine-2-carboxamide;

(2S,4S)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(1-isopropylpiperidin-3-yl)pyrrolidine-2-carboxamide;

(2R,4S)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(1-isopropylpiperidin-3-yl)pyrrolidine-2-carboxamide;

(2S,4R)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(1-isopropylpiperidin-3-yl)pyrrolidine-2-carboxamide;

(R)-2-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)oxazole-5-carboxamide;

(S)-2-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)oxazole-5-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((5-(1-hydroxycyclopropyl)-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((5-(1-hydroxycyclopropyl)-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2R,4R)—N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2S,4S)—N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2R,4S)—N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2S,4R)—N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-((1-isopropyl-1H-imidazol-4-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-2-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)thiazole-5-carboxamide;

(S)-2-((2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)thiazole-5-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((2-isopropyl-1H-imidazol-5-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((2-isopropyl-1H-imidazol-5-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-5,5-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-5,5-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-7,7-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-7,7-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,6-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,6-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(6,6-difluoro-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(6,6-difluoro-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6-thioxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6-thioxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7,8,9-tetrahydro-5H-cyclohepta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(2R,4R)-(((1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl)oxy)methyl)phosphonic acid;

(2S,4S)-(((1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl)oxy)methyl)phosphonic acid;

(2R,4S)-(((1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl)oxy)methyl)phosphonic acid;

(2S,4R)-(((1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl)oxy)methyl)phosphonic acid;

(2R,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl isobutyrate;

(2S,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl isobutyrate;

(2R,4S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl isobutyrate;

(2S,4R)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-5-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-3-yl isobutyrate

(R)-2-fluoro-5-(1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamido)pyridine 1-oxide;

(S)-2-fluoro-5-(1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamido)pyridine 1-oxide;

(R)-2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxide;

(S)-2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxide;

(R)-2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidine 3-oxide;

(S)-2-(2-((6-fluoropyridin-3-yl)carbamoyl)pyrrolidin-1-yl)-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidine 3-oxide;

(R)—N-(6-hydroxypyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-hydroxypyridin-3-yl)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-oxo-1,6-dihydropyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-oxo-1,6-dihydropyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-((R)-5-hydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-((S)-5-hydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-((S)-5-hydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-((R)-5-hydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-((5R,7R)-5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-((5R,7S)-5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-((5S,7R)-5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-((5S,7S)-5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-((5R,7R)-5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-((5R,7S)-5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-((5S,7R)-5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-((5S,7S)-5,7-dihydroxy-4-((5-isopropyl-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-((5-hydroxy-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-((5-hydroxy-1H-pyrazol-3-yl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-hydroxypyridin-3-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrimidin-4-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrimidin-4-yl)pyrrolidine-2-carboxamide;

(2R,4R)—N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2R,4S)—N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2S,4R)—N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2S,4S)—N-(6-fluoropyridin-3-yl)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(2R,4R)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(2R,4S)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(2S,4R)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide;

(2S,4S)-4-hydroxy-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-yl)pyrrolidine-2-carboxamide

(R)—N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-aminopyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(2-hydroxypropan-2-yl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(2-hydroxypropan-2-yl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-3-(2-(2-(6-fluoropyridin-3-ylcarbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)-5-isopropyl-1H-pyrazole 2-oxide;

(S)-3-(2-(2-(6-fluoropyridin-3-ylcarbamoyl)pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)-5-isopropyl-1H-pyrazole 2-oxide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-(1-hydroxy-5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-(1-hydroxy-5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-(methylthio)pyridin-3-yl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-(methylthio)pyridin-3-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-ethoxypyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(6-ethoxypyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-oxopyrrolidine-2-carboxamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-4-oxopyrrolidine-2-carboxamide;

(R,R)—N-(1-acetylpyrrolidin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R,S)—N-(1-acetylpyrrolidin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,R)—N-(1-acetylpyrrolidin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,S)—N-(1-acetylpyrrolidin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(2-hydroxyethyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(2-hydroxyethyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carbothioamide;

(S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carbothioamide;

(R)—N-(2-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(2-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(furan-2-ylmethyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-(furan-2-ylmethyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-((1H-pyrazol-5-yl)methyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S)—N-((1H-pyrazol-5-yl)methyl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-((1-methyl-1H-pyrazol-5-yl)methyl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-((1-methyl-1H-pyrazol-5-yl)methyl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(oxazol-2-ylmethyl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(oxazol-2-ylmethyl)pyrrolidine-2-carboxamide;

(R)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-ylmethyl)pyrrolidine-2-carboxamide;

(S)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(thiazol-2-ylmethyl)pyrrolidine-2-carboxamide;

(R,R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(1-hydroxypropan-2-yl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R,S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(1-hydroxypropan-2-yl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(1-hydroxypropan-2-yl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(1-hydroxypropan-2-yl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R,R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(2-hydroxycyclopropyl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R,S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(2-hydroxycyclopropyl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,R)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(2-hydroxycyclopropyl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-(2-hydroxycyclopropyl)-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R,R)-1-(6-fluoro-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(R,S)-1-(6-fluoro-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(S,R)-1-(6-fluoro-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(S,S)-1-(6-fluoro-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(6-fluoropyridin-3-yl)pyrrolidine-2-carboxamide;

(R,R)—N-(6-fluoropyridin-3-yl)-1-(6-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R,S)—N-(6-fluoropyridin-3-yl)-1-(6-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,R)—N-(6-fluoropyridin-3-yl)-1-(6-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,S)—N-(6-fluoropyridin-3-yl)-1-(6-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R,R)—N-(6-fluoropyridin-3-yl)-1-(7-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R,S)—N-(6-fluoropyridin-3-yl)-1-(7-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,R)—N-(6-fluoropyridin-3-yl)-1-(7-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(S,S)—N-(6-fluoropyridin-3-yl)-1-(7-hydroxy-4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide;

(R)—N-(2-ethoxypyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide; and

(S)—N-(2-ethoxypyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide.

95. The compound of claim 1 , wherein the compound is of the formula (I-A):

or a salt or N-oxide thereof.

96. The compound of claim 95 , or a salt or N-oxide thereof, wherein each of R A1 , R A2 , R A3 , R A4 , R A5 and R A6 is independently hydrogen, unsubstituted C 1 -C 6 alkyl, halo, or taken together with a geminal R A(1-6) group and the carbon to which they are attached to form a carbonyl moiety or a thiocarbonyl moiety.

97. The compound of claim 95 , or a salt or N-oxide thereof, wherein each of R A1 , R A2 , R A3 , R A4 , R A5 and R A6 is independently hydroxy or hydrogen.

98. The compound of claim 95 , or a salt or N-oxide thereof, wherein each of R Z1 , R Z2 , R Z3 and R Z4 is hydrogen.

99. The compound of claim 98 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is hydrogen.

100. The compound of claim 98 , or a salt or N-oxide thereof, wherein R Z5 is hydroxy or —OR 1 ; and R Z6 is hydrogen.

101. The compound of claim 95 , or a salt or N-oxide thereof, wherein R Z3 is hydroxy; and R Z4 is hydrogen.

102. The compound of claim 95 , or a salt or N-oxide thereof, wherein R Z5 is —OR 1 ; and R Z6 is hydrogen.

103. The compound of claim 102 , or a salt or N-oxide thereof, wherein R Z5 is methoxy.

104. The compound of claim 95 , or a salt or N-oxide thereof, wherein R Z5 is halogen and R Z6 is hydrogen.

105. The compound of claim 104 , or a salt or N-oxide thereof, wherein R Z5 is fluorine.

106. The compound of claim 95 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is independently unsubstituted C 1 -C 6 alkyl.

107. The compound of claim 104 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is methyl.

108. The compound of claim 95 , or a salt or N-oxide thereof, wherein R Z5 is unsubstituted tetrazolyl or tetrazolyl substituted by C 1 -C 6 alkyl; and R Z6 is hydrogen.

109. The compound of claim 108 , or a salt or N-oxide thereof, wherein R Z5 is tetrazolyl substituted by C 1 -C 6 alkyl.

110. The compound of claim 95 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is independently halogen.

111. The compound of claim 110 , or a salt or N-oxide thereof, wherein each of R Z5 and R Z6 is fluorine.

112. The compound of claim 95 , or a salt or N-oxide thereof, wherein R Z5 is —O—C 1 -C 6 alkylene-P(O)(OH) 2 ; and R Z6 is hydrogen.

113. The compound of claim 95 , or a salt or N-oxide thereof, wherein R Z5 is —OC(O)R 8 ; and R Z6 is hydrogen.

114. The compound of claim 95 , or a salt or N-oxide thereof, wherein R Z5 and R Z6 are taken together with the carbon to which they are attached to form a carbonyl moiety.

115. The compound of claim 95 , or a salt or N-oxide thereof, wherein R Z is hydrogen or methyl.

116. The compound of claim 95 , or a salt or N-oxide thereof, wherein D is unsubstituted pyridyl, pyridyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl; unsubstituted pyrimidyl, pyrimidyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl; unsubstituted pyrazinyl, or pyrazinyl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

117. The compound of claim 116 , or a salt or N-oxide thereof, wherein D is selected from the group consisting of 6-fluoro-3-pyridyl, 3-pyridyl, pyrimid-5-yl and pyrazin-2-yl.

118. The compound of claim 95 , or a salt or N-oxide thereof, wherein D is unsubstituted C 1 -C 6 alkyl or C 1 -C 6 alkyl substituted by 1 to 5 substituents independently selected from the group consisting of hydroxy, heteroaryl, and heteroaryl substituted by C 1 -C 6 alkyl.

119. The compound of claim 118 , or a salt or N-oxide thereof, wherein D is methyl.

120. The compound of claim 118 , or a salt or N-oxide thereof, wherein D is methyl substituted with unsubstituted oxazolyl, oxazolyl substituted by C 1 -C 6 alkyl, unsubstituted pyrazolyl, pyrazolyl substituted by C 1 -C 6 alkyl, unsubstituted furanyl, furanyl substituted by C 1 -C 6 alkyl, unsubstituted thiazolyl, or thiazolyl substituted by C 1 -C 6 alkyl.

121. The compound of claim 120 , or a salt or N-oxide thereof, wherein D is methyl substituted with oxazol-2-yl, pyrazol-5-yl, 1-methylpyrazol-5-yl, furan-2-yl, or thiazol-2-yl.

122. The compound of claim 95 , or a salt or N-oxide thereof, wherein D is unsubstituted piperdin-3-yl or piperdin-3-yl substituted by 1 to 5 substituents independently selected from unsubstituted acyl, acyl substituted by amino.

123. The compound of claim 122 , or a salt or N-oxide thereof, wherein D is 1-(2-amino-2-methylpropanoyl)piperidin-3-yl.

124. The compound of claim 122 , or a salt or N-oxide thereof, wherein D is 1-isopropylpiperidin-3-yl.

125. The compound of claim 95 , or a salt or N-oxide thereof, wherein D is unsubstituted thiazolyl or thiazolyl substituted by 1 to 3 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

126. The compound of claim 95 , or a salt or N-oxide thereof, wherein D is unsubstituted thiadiazolyl or thiadiazolyl substituted by 1 to 3 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl.

127. The compound of claim 95 , or a salt or N-oxide thereof, wherein D is unsubstituted pyrrolidin-3-yl or pyrrolidin-3-yl substituted by 1 to 5 substituents independently selected from unsubstituted acyl, acyl substituted by amino.

128. The compound of claim 95 , or a salt or N-oxide thereof, wherein E is unsubstituted pyrazolyl, pyrazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl; unsubstituted isoxazolyl, isoxazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl; unsubstituted imidazolyl, imidazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl; unsubstituted oxazolyl, oxazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl; unsubstituted thiazole thiazolyl, or thiazolyl substituted by 1 to 3 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by hydroxy, unsubstituted C 3 -C 8 cycloalkyl, and C 3 -C 8 cycloalkyl substituted by hydroxy or C 1 -C 6 alkyl.

129. The compound of claim 128 , or a salt or N-oxide thereof, wherein E is selected from the group consisting of 5-cyclopropylpyrazol-3-yl, 5-cyclopentylpyrazol-3-yl, 5-(isopropyl)pyrazol-3-yl, 3-cyclopropylpyrazol-5-yl, 3-cyclopentylpyrazol-5-yl, 3-(isopropyl)pyrazol-5-yl, and 3-(isopropyl)isoxazol-5-yl.

130. The compound of claim 128 , or a salt or N-oxide thereof, wherein E is selected from the group consisting of 5-hydroxypyrazol-3-yl, 5-(2-hydroxypropan-2-yl)pyrazol-3-yl, 5-(1-hydroxypropan-2-yl)pyrazol-3-yl, 5-(2-hydroxycyclopropyl)pyrazol-3-yl, and 1-hydroxy-5-isopropylpyrazol-3-yl.

131. A pharmaceutical composition comprising a compound of claim 1 , or a salt or N-oxide thereof, and a pharmaceutically acceptable carrier.

132. A kit comprising a compound of claim 1 , or an N-oxide thereof, or a pharmaceutically acceptable salt thereof.

133. A pharmaceutical composition comprising a compound of claim 93 , or a salt thereof, and a pharmaceutically acceptable carrier.

134. A kit comprising a compound of claim 93 , or a pharmaceutically acceptable salt thereof.

135. A pharmaceutical composition comprising a compound of claim 94 , or a salt thereof, and a pharmaceutically acceptable carrier.

136. A kit comprising a compound of claim 94 , or a pharmaceutically acceptable salt thereof.

137. A pharmaceutical composition comprising a compound of claim 95 , or a salt or N-oxide thereof, and a pharmaceutically acceptable carrier.

138. A kit comprising a compound of claim 95 , or an N-oxide thereof, or a pharmaceutically acceptable salt thereof.

Assignments (3)
RELEASE OF SECURITY INTEREST Recorded Sep 28, 2016
From: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
To: MEDIVATION PROSTATE THERAPEUTICS, INC.; MEDIVATION TECHNOLOGIES, INC.
Reel/Frame 040181/0177 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 25, 2016
From: CHAKRAVARTY, SARVAJIT; RAI, ROOPA; GREEN, MICHAEL JOHN
To: MEDIVATION TECHNOLOGIES, INC.
Reel/Frame 038105/0824 →
CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Sep 4, 2015
From: MEDIVATION TECHNOLOGIES, INC.
To: JPMORGAN CHASE BANK, N.A., AS ADMINISTRATIVE AGENT
Reel/Frame 036553/0925 →