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1. WO2020160192 - COMPOSÉS ET LEURS UTILISATIONS

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

Claims

1. A compound having the structure Formula I:

Formula I,

where

R1 is H, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C10 carbocyclyl;

Z1 is CR2 or N;

R2 is H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, or optionally substituted C2-C9 heteroaryl;

X1 is N or CH, and X2 is C-R7; or X1 is C-R7, and X2 is N or CH;

R7 is optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C1-C6 alkoxy, optionally substituted amino, optionally substituted sulfone, optionally substituted sulfonamide, optionally substituted carbocyclyl having 3 to 6 atoms, or optionally substituted heterocyclyl having 3 to 6 atoms;

X3 is N or CH;

X4 is N or CH;

G is optionally substituted C3-C10 carbocyclyl, C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, or optionally substituted C2-C9 heteroaryl,

or a pharmaceutically acceptable salt thereof.

2. A compound having the structure of Formula II:

A-L-B

Formula II,

wherein

L is a linker;

B is a degradation moiety; and

A has the structure of Formula III:

Formula III,

wherein

R1 is H, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C10 carbocyclyl;

Z1 is CR2 or N;

R2 is H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, or optionally substituted C2-C9 heteroaryl;

X1 is N or CH, and X2 is C-R7ʹʹ; or X1 is C-R7ʹʹ, and X2 is N or CH;


, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C1-C6 alkoxy, optionally substituted amino, optionally substituted sulfone, optionally substituted sulfonamide, optionally substituted carbocyclyl having 3 to 6 atoms, or optionally substituted heterocyclyl having 3 to 6 atoms;

R7ʹ is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C10 carbocycylyl;

X3 is N or CH;

X4 is N or CH;


, optionally substituted C3-C10 carbocyclyl, C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, or optionally substituted C2-C9 heteroaryl;

Gʹ is optionally substituted C3-C10 carbocyclylene, C2-C9 heterocyclylene, optionally substituted C6-C10 arylene, or optionally substituted C2-C9 heteroarylene; and

A1 is a bond between A and the linker,

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 or 2, wherein R1 is H, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, or optionally substituted C3-C10 carbocyclyl.

4. The compound of claim 3, wherein R1 is H.

5. The compound of claim 3, wherein R1 is optionally substituted C1-C6 alkyl.

2H2H

CH3 2H CH

6. The compound of claim 5, wherein R1 is , , 3 ,
,

7. The compound of claim 6, wherein R1 is optionally substituted C2-C6 alkenyl.

8. The compound of claim 7, wherein R1 is
, , , or


.

9. The compound of claim 8, wherein R1 is optionally substituted C3-C10 carbocyclyl.

10. The compound of claim 9, wherein R1 is
.

CH3

11. The compound of claim 3, wherein R1 is H or .

12. The compound of claim 11, wherein R1 is H.

CH3

13. The compound of claim 11, wherein R1 is .

14. The compound of any one of claims 1 to 13, wherein Z1 is N.

15. The compound of any one of claims 1 to 13, wherein Z1 is CR2.

16. The compound of claim 15, wherein R2 is H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C10 carbocyclyl, or optionally substituted C6-C10 aryl.

17. The compound of claim 16, wherein R2 is H, halogen, or optionally substituted C1-C6 alkyl.

18. The compound of claim 17, wherein R2 is H,
.

19. The compound of any one of claims 2 to 18, wherein X1 is N and X2 is C-R7ʹʹ.

20. The compound of any one of claims 2 to 18, wherein X1 is CH and X2 is C-R7ʹʹ.

21. The compound of any one of claims 2 to 18, wherein X1 is C-R7ʹʹ and X2 is N.

22. The compound of any one of claims 2 to 18, wherein X1 is C-R7ʹʹ and X2 is CH.

23. The compound of any one of claims 2 to 22, wherein R7ʹʹ is optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted carbocyclyl having 3 to 6 atoms, or optionally substituted heterocyclyl having 3 to 6 atoms.

24. The compound of claim 23, wherein R7ʹʹ is optionally substituted C1-C6 alkyl.

25. The compound of claim 24, wherein R7ʹʹ is
, , , or


.

26. The compound of claim 23, wherein R7ʹʹ is optionally substituted C1-C6 heteroalkyl.

27. The compound of claim 23, wherein R7ʹʹ is optionally substituted C1-C6 alkoxy or optionally substituted amino.

28. The compound of claim 26 or 27, wherein R7ʹʹ is–NR3R4 or–OR4, where R3 is H or optionally substituted C1-C6 alkyl, and R4 is optionally substituted C1-C6 alky.

29. The compound of claim 28, wherein R7ʹʹ is–NR3R4.

30. The compound of claim 29, wherein X1 is N and X2 is C-NR3R4.

31. The compound of claim 29, wherein X1 is C-NR3R4 and X2 is N.

32. The compound of claim 28, wherein R7 is -OR4.

33. The compound of claim 32, wherein X1 is N and X2 is C-OR4.

34. The compound of claim 32, wherein X1 is C-OR4 and X2 is N.

35. The compound of any one of claims 28 to 34, wherein R3 is H.

36. The compound of any one of claims 28 to 35, wherein R3 is
, , ,

,


38. The compound of claim 23, wherein R7ʹʹ is optionally substituted carbocyclyl having 3 to 6 atoms.

39. The compound of claim 38, wherein R7ʹʹ is
, , , ,

40. The compound of claim 23, wherein R7ʹʹ is optionally substituted heterocyclyl having 3 to 6 atoms.

42. The compound of claim 23, wherein R7ʹʹ is optionally substituted sulfone or optionally substituted sulfonamide.

43. The compound of claim 42, wherein R7ʹʹ is
.

O

N

46. The compound of claim 45, wherein R7ʹʹ
, or .

G'

47. The compound of any one of claims 2 to 46, wherein Gʹʹ is A1

.

48. The compound of claim 47, wherein Gʹ is optionally substituted C6-C10 arylene or optionally substituted C2-C9 heteroarylene.

49. The compound of claim 48, wherein Gʹ is optionally substituted C6-C10 arylene.

50. The compound of claim 49, wherein

wherein

each of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is, independently, H, A1, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally

substituted -O-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl, hydroxyl, thiol, or optionally substituted amino; or RG1ʹ and RG2ʹ, RG2ʹ and RG3ʹ, RG3ʹ and RG4ʹ, and/or RG4ʹ and RG5ʹ, together with the carbon atoms to which each is

attached, combine to form
and


is optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl, any of which is optionally substituted with A1,

wherein one of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is A1, or
is substituted with A1.

51. The compound of claim 50, wherein each of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is, independently, H, A1, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted -O-C3-C6 carbocyclyl, or optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl; or RG1ʹ and RG2ʹ, RG2ʹ and RG3ʹ, RG3ʹ and RG4ʹ, and/or RG4ʹ and RG5ʹ, together with the carbon atoms to which

each is attached, combine to form
and


is optionally substituted C2-C9 heteroaryl or optionally substituted C2-C9 heterocyclyl, any of which is optionally substituted with A1,

wherein one of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is A1, or
is substituted with A1.

52. The compound of claim 51, wherein each of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is, independently, H, A1, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted -O-C3-C6 carbocyclyl, or optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl.

.

53. The compound of claim 52, wherein each of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is,

54. The compound of claim 53, wherein each of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is,

55. The compound of claim 54, wherein each of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is,

.

56. The compound of claim 55, wherein RG3ʹ is A1.

O CH

57. The compound of claim 55, wherein RG1ʹ is H; RG2ʹ is 3 ; RG3ʹ is A1; RG4ʹ is O CH3 ; and RG5ʹ is H.

O CH

58. The compound of claim 55, wherein RG1ʹ is H; RG2ʹ is 3 ; RG3ʹ is A1; RG4ʹ is H;

O CH

59. The compound of claim 55, wherein RG1ʹ is H; RG2ʹ is 3 ; RG3ʹ is A1; RG4ʹ is Cl or F; and RG5ʹ is H.

60. The compound of claim 55, wherein RG1ʹ is H; RG2ʹ is
; RG3ʹ is A1; RG4ʹ is H; and RG5ʹ is H.

O

CH

61. The compound of claim 55, wherein RG1ʹ is H; RG2ʹ is 3 ; RG3ʹ is A1; RG4ʹ is

62. The compound of claim 51, wherein RG1ʹ and RG2ʹ, RG2ʹ and RG3ʹ, RG3ʹ and RG4ʹ, and/or

RG4ʹ and RG5ʹ, together with the carbon atoms to which each is attached, combine to form
; and

M

is optionally substituted C2-C9 heterocyclyl, which is optionally substituted with A1,

wherein one of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is A1, or
is substituted with A1.

63. The compound of claim 51, wherein RG1ʹ and RG2ʹ, RG2ʹ and RG3ʹ, RG3ʹ and RG4ʹ, and/or

RG4ʹ and RG5ʹ, together with the carbon atoms to which each is attached, combine to form
; and


is optionally substituted C2-C9 heteroaryl, which is optionally substituted with A1,

wherein one of RG1ʹ, RG2ʹ, RG3ʹ, RG4ʹ, and RG5ʹ is A1, or
is substituted with A1.

64. The compound of claim 62, wherein

wherein RG6ʹ is H, A1, or optionally substituted C1-C6 alkyl.

CH3

66. The compound of claim 64 or 65, wherein RG6ʹ is H, A1, or .

67. The compound of claim 66, wherein RG6ʹ is H.

68. The compound of claim 48, wherein Gʹ is optionally substituted C2-C9 heteroarylene.

69. The compound of claim 68, wherein

,

wherein

each of RG7ʹ, RG8ʹ, RG9ʹ, RG10ʹ, and RG11ʹ is, independently, H, A1, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally

substituted -O-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl, hydroxyl, thiol, or optionally substituted amino; or RG7ʹ and RG8ʹ, RG8ʹ and RG9ʹ, RG9ʹ and RG10ʹ, and/or RG10ʹ and RG11ʹ, together with the carbon atoms to which each is

attached, combine to form
and


is optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or C2-C9 heterocyclyl, any of which is optionally substituted with A1,

wherein one of RG7ʹ, RG8ʹ, RG9ʹ, RG10ʹ, and
is substituted with A1.

70. The compound of claim 69, wherein each of RG7ʹ, RG8ʹ, RG9ʹ, RG10ʹ, and RG11ʹ is, independently, H, A1, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted -O-C3-C6 carbocyclyl, or optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl.

71. The compound of claim 69 or 70, wherein

O CH

72. The compound of any one of claims 69 to 71, wherein RG7ʹ is H; RG8ʹ is 3 ; RG9ʹ is A1; and RG11ʹ is H.

73. The compound of claim 68, wherein Gʹ is

,

wherein

each of RG12ʹ, RG13ʹ, and RG14ʹ is, independently, H, A1, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted -O-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl, hydroxyl, thiol, or optionally substituted amino; or RG12ʹ and RG14ʹ, together with the carbon

atoms to which each is attached, combine to form
; and


is optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl, any of which is optionally substituted with A1,

M

wherein one of RG12ʹ, RG13ʹ, and RG14ʹ is A1; or is substituted with A1.

R7'

N

A1

74. The compound of any one of claims 2 to 22, wherein R7ʹʹ is .

75. The compound of claim 74, wherein Gʹʹ is optionally substituted C6-C10 aryl or optionally substituted C2-C9 heteroaryl.

76. The compound of claim 75, wherein Gʹʹ is optionally substituted C6-C10 aryl.

77. The compound of claim 76, wherein

wherein

each of RG1, RG2, RG3, RG4, and RG5 is, independently, H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally

substituted -O-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl, hydroxyl, thiol, or optionally substituted amino; or RG1 and RG2, RG2 and RG3, RG3 and RG4, and/or RG4 and RG5, together with the carbon atoms to which each is attached, combine to form optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl.

78. The compound of claim 77, wherein each of RG1, RG2, RG3, RG4, and RG5 is,

independently, H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted -O-C3-C6 carbocyclyl, or optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl; or RG1 and RG2, RG2 and RG3, RG3 and RG4, and/or RG4 and RG5, together with the carbon atoms to which each is attached, combine to form optionally substituted C2-C9 heteroaryl or optionally substituted C2-C9 heterocyclyl.

79. The compound of claim 78, wherein each of RG1, RG2, RG3, RG4, and RG5 is,

independently, H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted -O-C3-C6 carbocyclyl, or optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl.

80. The compound of claim 79, wherein each of RG1, RG2, RG3, RG4, and RG5 is,

O O S CH3.

81. The compound of claim 80, wherein each of RG1, RG2, RG3, RG4, and RG5 is,

82. The compound of claim 81, wherein each of RG1, RG2, RG3, RG4, and RG5 is,

independently,

83. The compound of claim 82, wherein two or more of RG1, RG2, RG3, RG4, and RG5 is H.

84. The compound of claim 83, wherein RG1 is H; RG2 is
;

85. The compound of claim 83, wherein RG1 is H; RG2 is
;

O CH RG4 is H; and RG5 is 3.

CH

N 3 86. The compound of claim 83, wherein RG1 is H; RG2 is CH3
; RG4 is Cl or F; and RG5 is H.

87. The compound of claim 83, wherein RG1 is H; RG2 is

RG4 is H; and RG5 is H.

88. The compound of claim 83, wherein RG1 is H; RG2 is
;


89. The compound of claim 78, wherein RG1 and RG2, RG2 and RG3, RG3 and RG4, and/or RG4 and RG5, together with the carbon atoms to which each is attached, combine to form optionally substituted C2-C9 heterocyclyl.

90. The compound of claim 78, wherein RG1 and RG2, RG2 and RG3, RG3 and RG4, and/or RG4 and RG5, together with the carbon atoms to which each is attached, combine to form optionally substituted C2-C9 heteroaryl.

91. The compound of claim 89, wherein Gʹʹ is
, ,


wherein RG6 is H or optionally substituted C1-C6 alkyl.

R

92. The compound of claim 90, wherein Gʹʹ is

G6

wherein RG6 is H or optionally substituted C1-C6 alkyl.

CH3

93. The compound of claim 91 or 92, wherein RG6 is H or .

94. The compound of claim 93, wherein RG6 is H.

95. The compound of claim 75, wherein Gʹʹ is optionally substituted C2-C9 heteroaryl.

96. The compound of claim 95, wherein Gʹʹ is
, , or


,

wherein

each of RG7, RG8, RG9, RG10, and RG11 is, independently, H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally

substituted -O-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl, hydroxyl, thiol, or optionally substituted amino; or RG7 and RG8, RG8 and RG9, RG9 and RG10, and/or RG10 and RG11, together with the carbon atoms to which each is attached, combine to form optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or C2-C9 heterocyclyl.

97. The compound of claim 96, wherein each of RG7, RG8, RG9, RG10, and RG11 is, independently, H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted -O-C3-C6 carbocyclyl, or optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl.

R

98. The compound of claim 96 or 97, wherein Gʹʹ is


99. The compound of claim 98, wherein RG7 is H; RG8 is


100. The compound of claim 89, wherein Gʹʹ is


,

wherein

each of RG12, RG13, and RG14 is, independently, H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted -O-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C3-C6 carbocyclyl, optionally substituted -C1-C3 alkyl-C2-C5 heterocyclyl, hydroxyl, thiol, or optionally substituted amino; or RG12 and RG14, together with the carbon atoms to which each is attached, combine to form optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or optionally substituted C2-C9 heterocyclyl.

101. The compound of any one of claims 74 to 100, wherein R7ʹ is H, optionally substituted C1-C6 alkyl, or optionally substituted C3-C10 carbocycylyl.

102. The compound of claim 101, wherein R7ʹ is H or optionally substituted C1-C6 alkyl.

103. The compound of claim 102, wherein R7ʹ is H,
, , ,

104. The compound of claim 103, wherein R7ʹ is H or


105. The compound of claim 104, wherein R7ʹ is H.

106. The compound of claim 104, wherein R7ʹ is


107. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIa:


Formula IIIa,

or a pharmaceutically acceptable salt thereof.

108. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIc:


Formula IIIc,

or a pharmaceutically acceptable salt thereof.

109. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIe:

Formula IIIe,

or a pharmaceutically acceptable salt thereof.

110. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIf:

Formula IIIf,

or a pharmaceutically acceptable salt thereof.

111. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIg:

Formula IIIg,

or a pharmaceutically acceptable salt thereof.

112. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIh:

Formula IIIh,

or a pharmaceutically acceptable salt thereof.

113. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIj:

Formula IIIj,

or a pharmaceutically acceptable salt thereof.

114. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIn:

Formula IIIn,

or a pharmaceutically acceptable salt thereof.

115. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIo:

Formula IIIo,

or a pharmaceutically acceptable salt thereof.

116. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIs:

Formula IIIs,

or a pharmaceutically acceptable salt thereof.

117. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIu:

Formula IIIu,

or a pharmaceutically acceptable salt thereof.

118. The compound of any one of claims 2 to 106, wherein A has the structure of Formula IIIv:

Formula IIIv,

or a pharmaceutically acceptable salt thereof.

119. The compound of any one of claims 2 to 118, wherein the degradation moiety is a ubiquitin ligase binding moiety.

120. The compound of claim 119, wherein the ubiquitin ligase binding moiety comprises Cereblon ligands, IAP (Inhibitors of Apoptosis) ligands, mouse double minute 2 homolog (MDM2), or von Hippel-Lindau (VHL) ligands, or derivatives or analogs thereof.

121. The compound of claim 119 or 120, wherein the degradation moiety comprises the structure of Formula Y:

where

A2 is a bond between the degradation moiety and the linker;

v1 is 0, 1, 2, 3, 4, or 5;

u1 is 1, 2, or 3;

R5A is H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl; each RJ1 is, independently, halogen, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;

JA is absent, O, optionally substituted amino, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl; and

J is absent, optionally substituted C3-C10 carbocyclylene, optionally substituted C6-C10 arylene, optionally substituted C2-C9 heterocyclylene, or optionally substituted C2-C9 heteroarylene,

or a pharmaceutically acceptable salt thereof.

122. The compound of claim 121, wherein T2 is
.

123. The compound of claim 122, wherein T2 is
.

124. The compound of claim 122, wherein T2 is

125. The compound of any one of claims 121 to 124, wherein the structure of Formula Y has the structure of Formula Y1:

Formula Y1,

or a pharmaceutically acceptable salt thereof.

126. The compound of claim 125, wherein T1 is a bond.

127. The compound of claim 125, wherein

128. The compound of any one of claims 121 to 127, wherein the structure of Formula Y has the structure of Formula Y2:

A2

Formula Y2,

or a pharmaceutically acceptable salt thereof.

129. The compound of any one of claims 121 to 127, wherein the structure of Formula Y has the structure of Formula Z:

Formula Z,

or a pharmaceutically acceptable salt thereof.

130. The compound of any one of claims 121 to 129, wherein u1 is 2.

131. The compound of claim 130, wherein the structure of Formula Z has the structure of Formula AA0:

Formula AA0,

or a pharmaceutically acceptable salt thereof.

132. The compound of any one of claims 121 to 129, wherein u1 is 1.

133. The compound of claim 132, wherein the structure of Formula Z has the structure of Formula AB:

Formula AB,

or a pharmaceutically acceptable salt thereof.

134. The compound of any one of claims 121 to 129, wherein u1 is 3.

135. The compound of claim 134, wherein the structure of Formula Z has the structure of Formula AC:

Formula AC,

or a pharmaceutically acceptable salt thereof.

136. The compound of any one of claims 121 to 135, wherein JA is absent.

137. The compound of any one of claims 121 to 135, wherein JA is optionally substituted C1-C6 alkyl.

138. The compound of claim 137, wherein JA is
.

139. The compound of claim 138, wherein the structure of Formula AA0 has the structure of Formula AA0:

Formula AA,

or a pharmaceutically acceptable salt thereof.

140. The compound of any one of claims 121 to 139, wherein v1 is 0, 1, 2, or 3.

141. The compound of claim 140, wherein v1 is 0.

142. The compound of claim 141, wherein the structure of Formula AA has the structure of Formula AA1:

Formula AA1,

or a pharmaceutically acceptable salt thereof.

143. The compound of any one of claims 121 to 142, wherein RA5 is H or optionally substituted C1-C6 alkyl.

144. The compound of claim 143, wherein RA5 is H.

145. The compound of claim 143, wherein RA5 is methyl.

146. The compound of any one of claims 121 to 142, wherein RA5 is optionally substituted C1-C6 heteroalkyl.

147. The compound of claim 146, wherein

148. The compound of claim 139, wherein the structure of Formula AA has the structure of Formula AA1:

Formula AA1,

or a pharmaceutically acceptable salt thereof.

149. The compound of claim 133, wherein the structure of Formula AB has the structure of Formula AB1:

Formula AB1,

or a pharmaceutically acceptable salt thereof.

150. The compound of claim 135, wherein the structure of Formula AC has the structure of Formula AC1:

or a pharmaceutically acceptable salt thereof.

151. The compound of any one of claims 121 to 150, wherein J is absent.

152. The compound of claim 151, wherein the structure of Formula AA1 has the structure of Formula AA2:

Formula AA2,

or a pharmaceutically acceptable salt thereof.

153. The compound of any one of claims 121 to 150, wherein J is optionally substituted C3-C10 carbocyclylene or optionally substituted C6-C10 arylene.

154. The compound of claim 153, wherein the structure of Formula AA has the structure of Formula AA4:

Formula AA4,

or a pharmaceutically acceptable salt thereof.

155. The compound of any one of claims 121 to 150, wherein J is optionally substituted C2-C9 heterocyclylene or optionally substituted C2-C9 heteroarylene.

156. The compound of claim 155, wherein the structure of Formula AA has the structure of Formula AA3:

Formula AA3,

or a pharmaceutically acceptable salt thereof.

157. The compound of claim 155, wherein the structure of Formula AA has the structure of Formula A:

,


RA5 is H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;

RA6 is H or optionally substituted C1-C6 alkyl; and RA7 is H or optionally substituted C1-C6 alkyl; or RA6 and RA7, together with the carbon atom to which each is bound, combine to form optionally substituted C3-C6 carbocyclyl or optionally substituted C2-C5 heterocyclyl; or RA6 and RA7, together with the carbon atom to which each is bound, combine to form optionally substituted C3-C6 carbocyclyl or optionally substituted C2-C5 heterocyclyl;

RA8 is H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;

each of RA1, RA2, RA3, and RA4 is, independently, H, A2, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted -O-C3-C6 carbocyclyl, hydroxyl, thiol, or optionally substituted amino; or RA1 and RA2, RA2 and RA3, and/or RA3 and

RA4, together with the carbon atoms to which each is attached, combine to form
; and


is optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or C2-C9 heterocyclyl, any of which is optionally substituted with A2,

wherein one of RA1, RA2, RA3, and
is substituted with A2, or a pharmaceutically acceptable salt thereof.

158. The compound of claim 157, each of RA1, RA2, RA3, and RA4 is, independently, H, A2, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6

heteroalkenyl, hydroxyl, thiol, or optionally substituted amino; or RA1 and RA2, RA2 and RA3, and/or RA3 and

RA4, together with the carbon atoms to which each is attached, combine to form
; and


is optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or C2-C9 heterocyclyl, any of which is optionally substituted with A2,

wherein one of RA1, RA2, RA3, and
is substituted with A2, or a pharmaceutically acceptable salt thereof.

159. The compound of claim 158, wherein each of RA1, RA2, RA3, and RA4 is, H, A2, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted -O-C3-C6 carbocyclyl, hydroxyl, optionally substituted amino; or RA1 and RA2, RA2 and RA3, or RA3 and RA4, together

with the carbon atoms to which each is attached, combine to form
and

N

is optionally substituted C2-C9 heterocyclyl, which is optionally substituted with A2,

N

wherein one of RA1, RA2, RA3, and RA4 is A2, or is substituted with A2.

160. The compound of claim 159, wherein each of RA1, RA2, RA3, and RA4 is, independently, H,

together with the carbon atoms to which each is attached, combine to form
and

N

is optionally substituted C2-C9 heterocyclyl, which is optionally substituted with A2,

N

wherein one of RA1, RA2, RA3, and RA4 is A2, or is substituted with A2.

161. The compound of any one of claims 157 to 160, wherein Y1
.

O

162. The compound of claim 161, wherein Y1 is .

RA6 RA7

163. The compound of claim 161, wherein Y1 is .

164. The compound of claim 163, wherein Y1 is ,
, , ,

165. The compound of claim 164, wherein Y1 is .

166. The compound of any one of claims 157 to 165, wherein the structure of Formula A has the structure of Formula A1:

,

Formula A1

or a pharmaceutically acceptable salt thereof.

167. The compound of any one of claims 157 to 165 wherein the structure of Formula A has the structure of Formula A2:

,

Formula A2

or a pharmaceutically acceptable salt thereof.

168. The compound of any one of claims 157 to 165, wherein the structure of Formula A has the structure of Formula A3:

,

Formula A3

or a pharmaceutically acceptable salt thereof.

169. The compound of any one of claims 157 to 167, wherein the structure of Formula A has the structure of Formula A4:

,

Formula A4

or a pharmaceutically acceptable salt thereof.

170. The compound of any one of claims 157 to 167, wherein the structure of Formula A has the structure of Formula A5:

,

Formula A5

or a pharmaceutically acceptable salt thereof.

171. The compound of any one of claims 157 to 167, wherein the structure of Formula A has the structure of Formula A6:

,

Formula A6

or a pharmaceutically acceptable salt thereof.

172. The compound of any one of claims 157 to 167, wherein the structure of Formula A has the structure of Formula A7:

,

Formula A7

or a pharmaceutically acceptable salt thereof.

173. The compound of any one of claims 157 to 167, wherein the structure of Formula A has the structure of Formula A8:

,

Formula A8

or a pharmaceutically acceptable salt thereof.

174. The compound of any one of claims 157 to 167, wherein the structure of Formula A has the structure of Formula A9:


,

Formula A9

or a pharmaceutically acceptable salt thereof.

175. The compound of any one of claims 157 to 167, wherein the structure of Formula A has the structure of Formula A10:


,

Formula A10

or a pharmaceutically acceptable salt thereof.

176. The compound of any one of claims 157 to 175, wherein the structure of Formula A is

A2

or derivative or analog thereof.


177. The compound of claim 176, wherein the structure of Formula A is

O

178. The compound of claim 177, wherein the structure of Formula A is

or derivative or analog thereof.


179. The compound of any one of claims 157 to 175, wherein

,

wherein RA9 is H, A2, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl. 180. The compound of claim 179, wherein the structure of Formula A is


.

181. The compound of claim 180, wherein RA9 is H.

182. The compound of claim 180, wherein RA9 is A2.

183. The compound of claim 182, wherein the structure of Formula A is

184. The compound of claim 155, wherein the structure of Formula AA has the structure of Formula B:

,


wherein

RA5 is H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;

each of RA1, RA2, RA3, and RA4 is, independently, H, A2, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted -O-C3-C6 carbocyclyl, hydroxyl, thiol, or optionally substituted amino; or RA1 and RA2, RA2 and RA3, and/or RA3 and

RA4, together with the carbon atoms to which each is attached, combine to form
; and


is optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or C2-C9 heterocyclyl, any of which is optionally substituted with A2,

wherein one of RA1, RA2, RA3, and
is substituted with A2,

or a pharmaceutically acceptable salt thereof.

185. The compound of claim 184, wherein each of RA1, RA2, RA3, and RA4 is, H, A2, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted -O-C3-C6 carbocyclyl, hydroxyl, optionally substituted amino; or RA1 and RA2, RA2 and RA3, or RA3 and RA4, together

with the carbon atoms to which each is attached, combine to form
and


is optionally substituted C2-C9 heterocyclyl, which is optionally substituted with A2,

wherein one of RA1, RA2, RA3, and
is substituted with A2.

186. The compound of claim 185, wherein each of RA1, RA2, RA3, and RA4 is, independently, H,

together with the carbon atoms to which each is attached, combine to form
; and


is optionally substituted C2-C9 heterocyclyl, which is optionally substituted with A2,

wherein one of RA1, RA2, RA3, and RA4 is A2,
is substituted with A2.

187. The compound of any one of claims 184 to 186, wherein the structure of Formula B has the structure of Formula B1:

,


or a pharmaceutically acceptable salt thereof.

188. The compound of any one of claims 184 to 186, wherein the structure of Formula B has the structure of Formula B2:

,


or a pharmaceutically acceptable salt thereof.

189. The compound of any one of claims 184 to 186, wherein the structure of Formula B has the structure of Formula B3:

,

Formula B3

or a pharmaceutically acceptable salt thereof.

190. The compound of any one of claims 184 to 186, wherein the structure of Formula B has the structure of Formula B4:


or a pharmaceutically acceptable salt thereof.

191. The compound of any one of claims 184 to 186, wherein the structure of Formula B is A2 N N

N O N O N NH A2 N NH

O O or O O .

192. The compound of any one of claims 2 to 118, wherein the degradation moiety comprises the structure of Formula C:

R


wherein

RB1 is H, A2, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;

RB2 is H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;

RB3 is A2, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C6-C10 aryl, optionally substituted C1-C6 alkyl C3-C10 carbocyclyl, or optionally substituted C1-C6 alkyl C6-C10 aryl;

RB4 is H, optionally substituted C1-C6 alkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C6-C10 aryl, optionally substituted C1-C6 alkyl C3-C10 carbocyclyl, or optionally substituted C1-C6 alkyl C6-C10 aryl;

RB5 is H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;

v2 is 0, 1, 2, 3, or 4;

each RB6 is, independently, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino; and each of RB7 and RB8 is, independently, H, halogen, optionally substituted C1-C6 alkyl, or optionally substituted C6-C10 aryl,

wherein one of RB1 and RB3 is A2,

or a pharmaceutically acceptable salt thereof.

193. The compound of claim 192, wherein the structure of Formula C is


194. The compound of any one of claims 2 to 118, wherein the degradation moiety comprises the structure of Formula D:


wherein

A2 is a bond between B and the linker;

each of RC1, RC2, and RC7 is, independently, H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;

RC3 is optionally substituted C1-C6 alkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C6-C10 aryl, optionally substituted C1-C6 alkyl C3-C10 carbocyclyl, or optionally substituted C1-C6 alkyl C6-C10 aryl;

RC5 is optionally substituted C1-C6 alkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C6-C10 aryl, optionally substituted C1-C6 alkyl C3-C10 carbocyclyl, or optionally substituted C1-C6 alkyl C6-C10 aryl;

v3 is 0, 1, 2, 3, or 4;

each RC8 is, independently, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;

v4 is 0, 1, 2, 3, or 4; and

each RC9 is, independently, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino,

or a pharmaceutically acceptable salt thereof.

195. The compound of claim 194, wherein the structure of Formula D is


r derivative or analog thereof.

196. The compound of any one of claims 2 to 118, wherein the degradation moiety comprises the structure of Formula E:

wherein

A2 is a bond between B an
d the linker;

each of RC10 and RC11 is, independently, H, optionally substituted C1-C6 alkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C6-C10 aryl, optionally substituted C1-C6 alkyl C3-C10 carbocyclyl, or optionally substituted C1-C6 alkyl C6-C10 aryl;

v5 is 0, 1, 2, 3, or 4;

each RC12 is, independently, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino;

v6 is 0, 1, 2, 3, or 4; and

each R21 is, independently, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl,

optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxy, thiol, or optionally substituted amino,

or a pharmaceutically acceptable salt thereof.

197. The compound of claim 196, wherein the structure of Formula E is

CH

O

A2

, or derivative or analog thereof.


198. The compound of any one of claims 2 to 118, wherein the degradation moiety comprises the structure of Formula FA:


where

or a bicyclic moiety which is substituted with A2 and substituted

with one or more groups independently selected from H, RFF1, and oxo;

is a single bond or a double bond;

u2 is 0, 1, 2, or 3;

A2 is a bond between the degrader and the linker;

YFa is CRFbRFc, C═O, C═S, C═CH2, SO2, S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl)2, P(O)alkyl, P(O)OH, P(O)NH2;

YFb is NH, NRFF1, CH2, CHRFF1, C(RFF1)2, O, or S;

YFc is CRFdRFe, C═O, C═S, C═CH2, SO2, S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl)2, P(O)alkyl, P(O)OH, P(O)NH2;

each of RFb, RFc, RFd, and RFe is, independently, H, alkyl, aliphatic, heteroaliphatic, aryl, heteroaryl, carbocyclyl, hydroxyl, alkoxy, amino,—NHalkyl, or—Nalkyl2;

or RFb and RFc, together with the carbon atom to which each is attached, combine to form a 3-, 4-, 5-, or 6-membered spirocarbocyclylene, or a 4-, 5-, or 6-membered spiroheterocyclylene comprising 1 or 2 heteroatoms selected from N and O;

or RFd and RFe, together with the carbon atom to which each is attached, combine to form a 3-, 4-, 5-, or 6-membered spirocarbocyclylene, or a 4-, 5-, or 6-membered spiroheterocyclylene comprising 1 or 2 heteroatoms selected from N and O; and

or RFd and RFb, together with the carbon atoms to which each is attached, combine to form a 1, 2, 3, or 4 carbon bridged ring;

each of YFd and YFf is, independently, CH2, CHRFF2, C(RFF2)2, C(O), N, NH, NRFF3, O, S, or S(O); YFe is a bond or a divalent moiety attached to YFd and YFf that contains 1 to 5 contiguous carbon atoms that form a 3 to 8-membered ring,

wherein 1, 2, or 3 carbon atoms can be replaced with a nitrogen, oxygen, or sulfur atom; wherein one of the ring atoms is substituted with A2 and the others are substituted with one or more groups independently selected from H and RFF1; and

wherein the contiguous atoms of YFe can be attached through a single or double bond; each RFF1 is, independently, H, alkyl, alkenyl, alkynyl, aliphatic, heteroaliphatic, carbocyclyl, halogen, hydroxyl, amino, cyano, alkoxy, aryl, heteroaryl, heterocyclyl, alkylamino, alkylhydroxyl, or haloalkyl;

each RFF2 is, independently, alkyl, alkene, alkyne, halogen, hydroxyl, alkoxy, azide, amino, —C(O)H,—C(O)OH,—C(O)(aliphatic, including alkyl),—C(O)O(aliphatic, including alkyl),

—NH(aliphatic, including alkyl),—N(aliphatic including alkyl)(aliphatic including alkyl),—NHSO2alkyl, —N(alkyl)SO2alkyl,—NHSO2aryl,—N(alkyl)SO2aryl,—NHSO2alkenyl,—N(alkyl)SO2alkenyl, —NHSO2alkynyl,—N(alkyl)SO2alkynyl, aliphatic, heteroaliphatic, aryl, heteroaryl, hetercyclic, carbocyclic, cyano, nitro, nitroso,—SH,—Salkyl, or haloalkyl; and

RFF3 is alkyl, alkenyl, alkynyl,—C(O)H,—C(O)OH,—C(O)alkyl, or—C(O)Oalkyl,

wherein if YFd or YFf is substituted with A2, then YFe is a bond, or a pharmaceutically acceptable salt thereof.

199. The compound of any one of claims 2 to 118, wherein the degradation moiety comprises the structure of Formula FB:

where


bicyclic moiety which is substituted with A2 and substituted with one or more groups independently selected from H, RFF1, and oxo;

A2 is a bond between the degrader and the linker;

YFa is CRFbRFc, C═O, C═S, C═CH2, SO2, S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl)2, P(O)alkyl, P(O)OH, P(O)NH2;

each of YFb and YFg is, independently, NH, NRFF1, CH2, CHRFF1, C(RFF1)2, O, or S;

YFc is CRFdRFe, C═O, C═S, C═CH2, SO2, S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl)2, P(O)alkyl, P(O)OH, P(O)NH2;

each of RFb, RFc, RFd, RFe, RFf, and RFg is, independently, H, alkyl, aliphatic, heteroaliphatic, aryl, heteroaryl, carbocyclyl, hydroxyl, alkoxy, amino,—NHalkyl, or—Nalkyl2;

or RFb and RFc, together with the carbon atom to which each is attached, combine to form a 3-, 4-, 5-, or 6-membered spirocarbocyclylene, or a 4-, 5-, or 6-membered spiroheterocyclylene comprising 1 or 2 heteroatoms selected from N and O;

or RFd and RFe, together with the carbon atom to which each is attached, combine to form a 3-, 4-, 5-, or 6-membered spirocarbocyclylene, or a 4-, 5-, or 6-membered spiroheterocyclylene comprising 1 or 2 heteroatoms selected from N and O;

or RFf and RFg, together with the carbon atom to which each is attached, combine to form a 3-, 4-, 5-, or 6-membered spirocarbocyclylene, or a 4-, 5-, or 6-membered spiroheterocyclylene comprising 1 or 2 heteroatoms selected from N and O;

or RFd and RFb, together with the carbon atoms to which each is attached, combine to form a 1, 2, 3, or 4 carbon bridged ring;

or RFd and RFf, together with the carbon atoms to which each is attached, combine to form a 1, 2, 3, or 4 carbon bridged ring;

or RFb and RFg, together with the carbon atoms to which each is attached, combine to form a 1, 2, 3, or 4 carbon bridged ring;

each of YFd and YFf is, independently, CH2, CHRFF2, C(RFF2)2, C(O), N, NH, NRFF3, O, S, or S(O); YFe is a bond or a divalent moiety attached to YFd and YFf that contains 1 to 5 contiguous carbon atoms that form a 3 to 8-membered ring,

wherein 1, 2, or 3 carbon atoms can be replaced with a nitrogen, oxygen, or sulfur atom; wherein one of the ring atoms is substituted with A2 and the others are substituted with one or more groups independently selected from H and RFF1; and

wherein the contiguous atoms of YFe can be attached through a single or double bond; each RFF1 is, independently, H, alkyl, alkenyl, alkynyl, aliphatic, heteroaliphatic, carbocyclyl, halogen, hydroxyl, amino, cyano, alkoxy, aryl, heteroaryl, heterocyclyl, alkylamino, alkylhydroxyl, or haloalkyl;

each RFF2 is, independently, alkyl, alkene, alkyne, halogen, hydroxyl, alkoxy, azide, amino, —C(O)H,—C(O)OH,—C(O)(aliphatic, including alkyl),—C(O)O(aliphatic, including alkyl),

—NH(aliphatic, including alkyl),—N(aliphatic including alkyl)(aliphatic including alkyl),—NHSO2alkyl, —N(alkyl)SO2alkyl,—NHSO2aryl,—N(alkyl)SO2aryl,—NHSO2alkenyl,—N(alkyl)SO2alkenyl, —NHSO2alkynyl,—N(alkyl)SO2alkynyl, aliphatic, heteroaliphatic, aryl, heteroaryl, hetercyclic, carbocyclic, cyano, nitro, nitroso,—SH,—Salkyl, or haloalkyl; and

RFF3 is alkyl, alkenyl, alkynyl,—C(O)H,—C(O)OH,—C(O)alkyl, or—C(O)Oalkyl,

wherein if YFd or YFf is substituted with A2, then YFe is a bond, or a pharmaceutically acceptable salt thereof.

200. The compound of any one of claims 2 to 118, wherein the degradation moiety comprises the structure of Formula F1:

Formula F1,

wherein

A2 is a bond between the degrader and the linker; and

RF1 is absent or O,

or a pharmaceutically acceptable salt thereof.

201. The compound of any one of claims 2 to 118, wherein the degradation moiety comprises the structure of Formula F2:

wherein

A2 is a bond between the degrader and the linker; and

RF1 is absent or O,

or a pharmaceutically acceptable salt thereof.

202. The compound of any one of claims 2 to 118, wherein the degradation moiety comprises the structure of Formula G:

Formula G,

wherein

A2 is a bond between the degrader and the linker; and

RF1 is absent or O,

or a pharmaceutically acceptable salt thereof.

203. The compound of any one of claims 2 to 202, wherein the linker has the structure of Formula IV:

A1-(B1)f-(C1)g-(B2)h-(D)-(B3)i-(C2)j-(B4)k–A2

Formula IV

wherein

A1 is a bond between the linker and A;

A2 is a bond between B and the linker;

each of B1, B2, B3, and B4 is, independently, optionally substituted C1-C2 alkyl, optionally substituted C1-C3 heteroalkyl, O, S, S(O)2, or NRN;

each RN is, independently, H, optionally substituted C1–4 alkyl, optionally substituted C2–4 alkenyl, optionally substituted C2–4 alkynyl, optionally substituted C2–6 heterocyclyl, optionally substituted C6–12 aryl, or optionally substituted C1–7 heteroalkyl;

each of C1 and C2 is, independently, carbonyl, thiocarbonyl, sulphonyl, or phosphoryl;

each of f, g, h, i, j, and k is, independently, 0 or 1; and

D is optionally substituted C1–10 alkyl, optionally substituted C2–10 alkenyl, optionally substituted C2–10 alkynyl, optionally substituted C2–6 heterocyclyl, optionally substituted C6–12 aryl, optionally substituted C2-C10 polyethylene glycol, or optionally substituted C1–10 heteroalkyl, or a chemical bond linking A1-(B1)f-(C1)g-(B2)h- to -(B3)i-(C2)j-(B4)k–A2.

204. The compound of claim 203, wherein each of B1, B2, B3, and B4 is, independently, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 heteroalkyl, or NRN.

205. The compound of claim 202 or 203, wherein each RN is, independently, H or optionally substituted C1-C4 alkyl.

206. The compound of any one of claims 202 to 205, wherein each RN is, independently, H or methyl.

207. The compound of any one of claims 203 to 206, wherein each of B1 and B4 is,

independently,

208. The compound of claim 207 wherein B1 is


.

209. The compound of any one of claims 203 to 208, wherein each of C1 and C2 is,

independently,

210. The compound of claim 209, wherein C1 is


211. The compound of any one of claims 203 to 210, wherein B2 is NRN.

212. The compound of any one of claims 203 to 210, wherein B2 is optionally substituted C1-C4 alkyl.

213. The compound of any one of claims 203 to 212, wherein f is 0.

214. The compound of any one of claims 203 to 212, wherein f is 1.

215. The compound of any one of claims 203 to 214, wherein g is 1.

216. The compound of any one of claims 203 to 215, wherein h is 0.

217. The compound of any one of claims 203 to 215, wherein h is 1.

218. The compound of any one of claims 203 to 217, wherein i is 0.

219. The compound of any one of claims 203 to 218, wherein j is 0.

220. The compound of any one of claims 203 to 219, wherein k is 0.

221. The compound of any one of claims 203 to 220, wherein the linker has the structure of


wherein

x is 1, 2, 3, 4, 5, 6, 7, or 8;

y is 1, 2, 3, or 4;

Rx is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl;

Ry is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl; and

W is O or NRw, wherein Rw is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl.

222. The compound of any one of claims 203 to 221, wherein the linker has the structure of:

223. The compound of any one of claims 203 to 221, wherein the linker has the structure of


.

224. The compound of any one of claims 2 to 202, wherein the linker has the structure of Formula V:

A1–(E1)–(F1)–(C3)m–(E3)n–(F2)o1–(F3)o2–(E2)p–A2,

Formula V

wherein

A1 is a bond between the linker and A;

A2 is a bond between B and the linker;

each of m, n, o1, o2, and p is, independently, 0 or 1;

each of E1 and E2 is, independently, O, S, NRN, optionally substituted C1–10 alkylene, optionally substituted C2–10 alkenylene, optionally substituted C2–10 alkynylene, optionally substituted C2-C10 polyethylene glycol, or optionally substituted C1–10 heteroalkylene;

E3 is optionally substituted C1-C6 alkylene, optionally substituted C1-C6 heteroalkylene, O, S, or NRN;

each RN is, independently, H, optionally substituted C1–4 alkyl, optionally substituted C2–4 alkenyl, optionally substituted C2–4 alkynyl, optionally substituted C2–6 heterocyclyl, optionally substituted C6–12 aryl, or optionally substituted C1–7 heteroalkyl;

C3 is carbonyl, thiocarbonyl, sulphonyl, or phosphoryl; and

each of F1, F2, and F3 is, independently, optionally substituted C3-C10 carbocyclylene, optionally substituted C2–10 heterocyclylene, optionally substituted C6-C10 arylene, or optionally substituted C2-C9 heteroarylene.

225. The compound of claim 224, wherein the linker has the structure of Formula Va:

A1–(E1)–(F1)–(C3)m–(E2)p–A2.

Formula Va

226. The compound of claim 224, wherein the linker has the structure of Formula Vb:

A1–(E1)–(F1)–(E2)p–A2.

Formula Vb

227. The compound of claim 224, wherein the linker has the structure of Formula Vc:

A1–(E1)–(F1)–A2.

Formula Vc

228. The compound of claim 224, wherein the linker has the structure of Formula Vd:

A1–(E1)–(F1)–(C3)m–(F2)o1–A2.

Formula Vd

229. The compound of claim 224, wherein the linker has the structure of Formula Ve:

A1–(E1)–(F1)–(E3)n–(F2)o1–(E2)p–A2.

Formula Ve

230. The compound of claim 224, wherein the linker has the structure of Formula Vf:

A1–(E1)–(F1)–(C3)m–(E3)n–(F2)o1–(E2)p–A2.

Formula Vf

231. The compound of claim 224, wherein the linker has the structure of Formula Vg:

A1–(E1)–(F1)–(E3)n–(F2)o1–A2,

Formula Vg

232. The compound of any one of claims 224 to 231, wherein each of E1 and E2 is, independently, NRN, optionally substituted C1–10 alkylene, optionally substituted C2-C10 polyethylene glycolene, or optionally substituted C1–10 heteroalkylene.

233. The compound of any one of claims 224 to 232, wherein E3 is optionally substituted C1-C6 alkylene, O, S, or NRN.

234. The compound of claim 233, wherein E3 is optionally substituted C1-C6 alkylene.

235. The compound of claim 233, wherein E3 is optionally substituted C1-C3 alkylene.

237. The compound of claim 233, wherein E3 is
, , ,

238. The compound of claim 233, wherein E3 is O.

239. The compound of any one of claims 224 to 238, wherein each RN is, independently, H or optionally substituted C1–4 alkyl.

240. The compound of claim 239, wherein each RN is, independently, H or methyl.

241. The compound of any one of claims 224 to 240, wherein E1 is , ,


, , , , , , , or

, where a is 0, 1, 2, 3, 4, or 5.


242. The compound of claim 241, wherein E1 is
, , , ,

243. The compound of claim 242, wherein E1 is


244. The compound of any one of claims 224 to 243, wherein E1 is
,


wherein

b is 0, 1, 2, 3, 4, 5, or 6;

Ra is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl;

Rb is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl; and

Rc is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl.

245. The compound of claim 244, wherein E1 is
, ,

F CH

246. The compound of claim 245, wherein E1 is

H H

247. The compound of claim 246, wherein


248. The compound of claim 247, wherein

CH3

N

O .

249. The compound of any one of claims 244 to 248, wherein Ra is H or methyl.

250. The compound of claim 249, wherein Ra is H.

251. The compound of claim 249, wherein Ra is methyl.

252. The compound of any one of claims 224 to 251, wherein E2 is O, NRw,
,

F F

wherein

c is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

d is 0, 1, 2, or 3;

e is 0, 1, 2, 3, 4, 5, or 6;

f is 0, 1, 2, 3, or 4;

Rd is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl;

Re is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl;

Rf is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl;

Rg is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl; and

W is O or NRw, wherein Rw is H or optionally substituted C1-C6 alkyl.

253. The compound of claim 252, wherein E2 is O, ,

254. The compound of any one of claims 224 to 253, wherein each of F1, F2, or F3 is, independently, optionally substituted C3-C10 carbocyclylene.

255. The compound of claim 254, wherein the C3-C10 carbocyclylene is monocyclic.

256. The compound of claim 254, wherein the C3-C10 carbocyclylene is polycyclic.

257. The compound of claim 256, wherein the C3-C10 carbocyclylene is fused.

258. The compound of claim 256, wherein the C3-C10 carbocyclylene is spirocyclic.

259. The compound of claim 256, wherein the C3-C10 carbocyclylene is bridged.

260. The compound of claim 259, wherein the C3-C10 carbocyclylene


261. The compound of claim 260, wherein the C3-C10 carbocyclylene is .

262. The compound of any one of claims 224 to 253, wherein each of F1, F2, or F3 is, independently, optionally substituted C2-C6 heterocyclylene.

263. The compound of claim 262, wherein the C2-C6 heterocyclylene is monocyclic.

264. The compound of claim 263, wherein the C2-C6 heterocyclylene is
,

( )q ,

wherein

q1 is 0, 1, 2, 3, or 4;

q2 is 0, 1, 2, 3, 4, 5, or 6;

q3 is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

each Rh is, independently, 2H, halogen, optionally substituted C1-C6 alkyl, ORi2, or NRi3Ri4; or two Rh groups, together with the carbon atom to which each is attached, combine to form optionally substituted C3-C10 carbocyclyl or optionally substituted C2-C9 heterocyclyl; or two Rh groups, together with the carbon atoms to which each is attached, combine to form optionally substituted C3-C10 carbocyclyl or optionally substituted C2-C9 heterocyclyl;

Ri1 is H or optionally substituted C1-C6 alkyl;

Ri2 is H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C6 carbocyclyl;

265. The compound of claim 264, wherein the C2–C9 heterocyclylene

266. The compound of claim 264 or 265, wherein each Rh is, independently, 2H, halogen, cyano, optionally substituted C1-C6 alkyl, ORi2, or NRi3Ri4.

CF3 267. The compound of claim 266, wherein each Rh is, independently, 2H, F, methyl, ,

268. The compound of claim 267, wherein each Rh is, independently, F, methyl, or NRi3Ri4.

269. The compound of any one of claims 264 to 268, wherein q1 is 0, 1, or 2.

270. The compound of any one of claims 264 to 269, wherein q2 is 0, 1, or 2.

271. The compound of any one of claims 264 to 270, wherein q3 is 0, 1, or 2.

272. The compound of any one of claims 264 to 271, wherein the C2–C9 heterocyclylene is


273. The compound of claim 272, wherein the C2–C9 heterocyclylene is
,

274. The compound of claim 273, wherein the C2–C9 heterocyclylene is


275. The compound of any one of claims 264 to 274, wherein F1 is

276. The compound of any one of claims 264 to 275, wherein F2 is
,

277. The compound of any one of claims 264 to 275, wherein F3 is
,

278. The compound of claim 262, wherein the C2-C6 heterocyclylene is polycyclic. 279. The compound of claim 278, wherein the C2-C6 heterocyclylene is bicyclic.

280. The compound of claim 278 or 279, wherein the C2-C6 heterocyclylene is bridged.

281. The compound of claim 280, wherein the C2-C6 heterocyclylene is


282. The compound of claim 278 or 279, wherein the C2-C6 heterocyclylene is fused. 283. The compound of claim 282, wherein the C2–C9 heterocyclylene is
,

284. The compound of claim 283, wherein F1 is

285. The compound of claim 283 or 284, wherein


286. The compound of claim 278 or 279, wherein the C2-C6 heterocyclylene is spirocyclic. 287. The compound of claim 286, wherein the C2-C6 heterocyclylene is
,

288. The compound of claim 287, wherein F1 is

289. The compound of claim 287 or 288, wherein F2 is

290. The compound of any one of claims 287 to 289, wherein F3 is
,

291. The compound of any one of claims 262 to 290 wherein the C2-C9 heterocyclylene comprises a quaternary amine.

292. The compound of any one of claims 224 to 253, wherein each of F1, F2, or F3 is, independently, optionally substituted C6-C10 arylene.

293. The compound of claim 292, wherein the C6-C10 arylene i

294. The compound of any one of claims 224 to 253, wherein each of F1, F2, or F3 is, independently, optionally substituted C2-C9 heteroarylene.

295. The compound of claim 294, wherein the C2-C9 heteroarylene is
,

296. The compound of claim 295, wherein F2 is
or .

297. The compound of claim 296, wherein F2 is
.

O O O

298. The compound of any one of claims 224 to 297, C3 is
.

O

299. The compound of claim 298, wherein C3 is .

300. The compound of any one of claims 224 to 299, wherein m is 1.

301. The compound of any one of claims 224 to 299, wherein m is 0.

302. The compound of any one of claims 224 to 301, wherein p is 1.

303. The compound of any one of claims 224 to 301, wherein p is 0.

304. The compound of any one of claims 224 to 303, wherein o1 is 1.

305. The compound of any one of claims 224 to 303, wherein o1 is 0.

306. The compound of any one of claims 224 to 305, wherein o2 is 1.

307. The compound of any one of claims 224 to 305, wherein o2 is 0.

308. The compound of any one of claims 224 to 307, wherein n is 1.

309. The compound of any one of claims 224 to 307, wherein n is 0.

310. The compound of any one of claims 224 to 309, wherein the linker has the structure of

,


, ,

311. The compound of any one of claims 224 to 309, wherein the linker has the structure of


312. The compound of any one of claims 224 to 309, wherein the linker has the structure of:

313. The compound of any one of claims 2 to 202, wherein the linker is optionally substituted C3-C10 carbocyclylene, optionally substituted C2–10 heterocyclylene, optionally substituted C6-C10 arylene, or optionally substituted C2-C9 heteroarylene.

314. The compound of claim 313, wherein the linker is optionally substituted C2–10 heterocyclylene

315. The compound of claim 312, wherein the linker has the structure of


316. The compound of claim 315, wherein the linker has the structure of


317. The compound of any one of claims 2 to 202, wherein the linker is absent.

318. The compound of claim 1, wherein the compound has the structure of any one of compounds B1-B6 in Table 1, or a pharmaceutically acceptable salt thereof.

319. The compound of any one of claims 2 to 317, wherein the compound has the structure of any one of compounds D1-D31 in Table 2A, or a pharmaceutically acceptable salt thereof.

320. The compound of any one of claims 2 to 317, wherein the compound has the structure of any one of compounds D32-D184 in Table 2B, or a pharmaceutically acceptable salt thereof.

321. The compound of any one of claims 2 to 317, wherein the compound has the structure of any one of compounds D185-D316 in Table 2C, or a pharmaceutically acceptable salt thereof.

322. A pharmaceutical composition comprising the compound of any one of claims 1 to 321 and a pharmaceutically acceptable excipient.

323. A method of inhibiting the level of BRD9 in a cell, the method involving contacting the cell with an effective amount of a compound of any one of claims 1 to 321, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 322.

324. A method of inhibiting the activity of BRD9 in a cell, the method involving contacting the cell with an effective amount of a compound of any one of claims 1 to 321, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 322.

325. The method of claim 323 or 324, wherein the cell is a cancer cell.

326. The method of claim 325, wherein the cancer is a malignant, rhabdoid tumor, a CD8+ T-cell lymphoma, endometrial carcinoma, ovarian carcinoma, bladder cancer, stomach cancer, pancreatic cancer, esophageal cancer, prostate cancer, renal cell carcinoma, melanoma, colorectal cancer, a sarcoma, non-small cell lung cancer, stomach cancer, or breast cancer.

327. The method of claim 326, wherein the cancer is a sarcoma.

328. The method of claim 327, wherein the sarcoma is a soft tissue sarcoma, synovial sarcoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma, adult fibrosarcoma, alveolar soft-part sarcoma, angiosarcoma, clear cell sarcoma, desmoplastic small round cell tumor, epithelioid sarcoma, fibromyxoid sarcoma, gastrointestinal stromal tumor, Kaposi sarcoma, liposarcoma, leiomyosarcoma, malignant mesenchymoma malignant peripheral nerve sheath tumors, myxofibrosarcoma, or low-grade rhabdomyosarcoma.

329. The method of claim 328, wherein the sarcoma is synovial sarcoma.

330. A method of treating a BAF complex-related disorder in a subject in need thereof, the method involving administering to the subject an effective amount of a compound of any one of claims 1 to 321, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 322.

331. A method of treating an SS18-SSX fusion protein-related disorder in a subject in need thereof, the method involving administering to the subject an effective amount of a compound of any one of claims 1 to 321, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 322.

332. A method of treating a BRD9-related disorder in a subject in need thereof, the method involving administering to the subject an effective amount of a compound of any one of claims 1 to 321, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 322.

333. The method of any one of claims 330 to 332, wherein the disorder is cancer.

334. A method of treating a cancer in a subject in need thereof, the method including administering to the subject an effective amount of a compound of any one of claims 1 to 321, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 322.

335. The method of claim 333 or 334, wherein the cancer is a malignant, rhabdoid tumor, a CD8+ T-cell lymphoma, endometrial carcinoma, ovarian carcinoma, bladder cancer, stomach cancer,

pancreatic cancer, esophageal cancer, prostate cancer, renal cell carcinoma, melanoma, colorectal cancer, a sarcoma, non-small cell lung cancer, stomach cancer, or breast cancer.

336. The method of claim 335, wherein the cancer is a sarcoma.

337. The method of claim 336, wherein the sarcoma is a soft tissue sarcoma, synovial sarcoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma, adult fibrosarcoma, alveolar soft-part sarcoma, angiosarcoma, clear cell sarcoma, desmoplastic small round cell tumor, epithelioid sarcoma, fibromyxoid sarcoma, gastrointestinal stromal tumor, Kaposi sarcoma, liposarcoma, leiomyosarcoma, malignant mesenchymoma malignant peripheral nerve sheath tumors, myxofibrosarcoma, or low-grade rhabdomyosarcoma.

338. The method of claim 337, wherein the sarcoma is synovial sarcoma.

339. The method of any one of claims 330 to 332, wherein the disorder is infection.

340. A method of treating infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of any one of claims 1 to 321, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 322.

341. The method of claim 339 or 340, wherein the infection is viral infection.

342. The method of claim 341, wherein the viral infection is an infection with a virus of the Retroviridae family, Hepadnaviridae family, Flaviviridae family, Adenoviridae family, Herpesviridae family, Papillomaviridae family, Parvoviridae family, Polyomaviridae family, Paramyxoviridae family, or

Togaviridae family.

343. The method of claim 341 or 342, wherein the viral infection is Coffin Siris,

Neurofibromatosis, or Multiple Meningioma.