IP Library › Patent Application 17620275

Patent Application

App. No. 17/620,275

COMPOUNDS FOR TREATING CNS DISORDERS

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App. No.: 17/620,275

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Abstract

Provided herein in part is a compound of Formula (I): or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of Formula I, and methods of using the compounds, e.g, in the treatment of CNS- related disorders.

Claims (234)

1 - 30 . (canceled)

31 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof; wherein:

represents a single or double bond, provided if a double bond is present, then one of R 6a or R 6b is absent and R 5 is absent;

L is selected from the group consisting of:

wherein A indicates the point of attachment at C17;

X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a );

each of R 55a and R 55b is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A 1)C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2, —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; or R 55a and R 55b may join together with the intervening atoms to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl;

R 3 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each R GA is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocyclyl, substituted or unsubstituted 3- to 6- membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R GA groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclyl or heteroaryl ring;

each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently hydrogen, halogen, cyano, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

each of R 6a and R 6b is independently hydrogen, halogen, cyano, —NO 2 , —OH, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl; or R 6a and R 6b are joined to form an oxo (═O) group;

each of R 15a , R 15b , R 16a , and R 16b is each independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR c3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R C3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C 3, —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

R 18 is substituted or unsubstituted alkyl;

R 19 is hydrogen or substituted or unsubstituted alkyl; and

t is 2 or 3.

32 . The compound or pharmaceutically acceptable salt of claim 31 , wherein L is

33 . The compound or pharmaceutically acceptable salt of claim 32 , wherein each of R 1a , R 1b , R 2a , and R 2b is independently hydrogen, unsubstituted C 1-6 alkyl, C 1-3 haloalkyl, or —OR A1 wherein R A1 is hydrogen or unsubstituted alkyl.

34 . The compound or pharmaceutically acceptable salt of claim 33 , wherein each of R 1a , R 1b , R 2a , and R 2b is hydrogen.

35 . The compound or pharmaceutically acceptable salt of claim 32 , wherein each of R 4a , R 4b , R 7a , and R 7b is independently hydrogen, unsubstituted C 1-6 alkyl, C 1-3 haloalkyl, or —OR A1 wherein R A1 is hydrogen or unsubstituted alkyl.

36 . The compound or pharmaceutically acceptable salt of claim 35 , wherein each of R 4a , R 4b , R 7a , and R 7b is hydrogen.

37 . The compound or pharmaceutically acceptable salt of claim 32 , wherein each of R 11a , R 11b , R 12a , and R 12b is independently hydrogen, unsubstituted C 1-6 alkyl, C 1-3 haloalkyl, or —OR A1 wherein R A1 is hydrogen or unsubstituted alkyl.

38 . The compound or pharmaceutically acceptable salt of claim 37 , wherein each of R 11a , R 11b , R 12a , and R 12b is hydrogen.

39 . The compound or pharmaceutically acceptable salt of claim 32 , wherein R 3 is substituted or unsubstituted C 1-6 alkyl.

40 . The compound or pharmaceutically acceptable salt of claim 39 , wherein R 3 is C 1-3 alkyl optionally substituted with C 1-3 alkoxy.

41 . The compound or pharmaceutically acceptable salt of claim 40 , wherein R 3 is methyl, ethyl, propyl, butyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 .

42 . The compound or pharmaceutically acceptable salt of claim 32 , wherein

is a single bond, and R 5 is hydrogen or methyl in the alpha or beta configuration.

43 . The compound or pharmaceutically acceptable salt of claim 42 , wherein R 5 is hydrogen.

44 . The compound or pharmaceutically acceptable salt of claim 42 , wherein R 5 is methyl.

45 . The compound or pharmaceutically acceptable salt of claim 32 , wherein

is a single bond, and each of R 6a and R 6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

46 . The compound or pharmaceutically acceptable salt of claim 45 , wherein each of R 6a and R 6b is independently hydrogen or substituted or unsubstituted C 1-6 alkyl.

47 . The compound or pharmaceutically acceptable salt of claim 46 , wherein each of R 6a and R 6b is hydrogen.

48 . The compound or pharmaceutically acceptable salt of claim 32 , wherein R 18 is substituted or unsubstituted C 1-6 alkyl.

49 . The compound or pharmaceutically acceptable salt of claim 48 , wherein R 18 is unsubstituted methyl or ethyl.

50 . The compound or pharmaceutically acceptable salt of claim 32 , wherein R 19 is hydrogen or substituted or unsubstituted C 1-6 alkyl.

51 . The compound or pharmaceutically acceptable salt of claim 50 , wherein R 19 is unsubstituted C 1-3 alkyl.

52 . The compound or pharmaceutically acceptable salt of claim 51 , wherein R 19 is unsubstituted methyl or ethyl.

53 . The compound or pharmaceutically acceptable salt of claim 50 , wherein R 19 is hydrogen.

54 . The compound or pharmaceutically acceptable salt of claim 32 , wherein t is 2, and each R 15a and R 15b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heteroaryl.

55 . The compound or pharmaceutically acceptable salt of claim 54 , wherein each R 15a and R 15b is independently hydrogen or substituted or unsubstituted C 1-6 alkyl.

56 . The compound or pharmaceutically acceptable salt of claim 55 , wherein each R 15a and R 15b is hydrogen.

57 . The compound or pharmaceutically acceptable salt of claim 32 , wherein each R 16a and R 16b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heteroaryl.

58 . The compound or pharmaceutically acceptable salt of claim 57 , wherein each R 16a and R 16b is independently hydrogen or substituted or unsubstituted C 1-6 alkyl.

59 . The compound or pharmaceutically acceptable salt of claim 58 , wherein each R 16a and R 16b is hydrogen.

60 . The compound or pharmaceutically acceptable salt of claim 32 , wherein X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a ); R 55a is substituted or unsubstituted carbocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R 55b is hydrogen or substituted or unsubstituted C 1-6 alkyl.

61 . The compound or pharmaceutically acceptable salt of claim 32 , wherein X is selected from the group consisting of:

62 . The compound or pharmaceutically acceptable salt of claim 31 , wherein the compound of Formula (I) is a compound of Formula (IV):

or a pharmaceutically acceptable salt thereof.

63 . The compound or pharmaceutically acceptable salt of claim 62 , wherein the compound of Formula (IV) is a compound of Formula (Iva), (IVb), or (IVc):

or a pharmaceutically acceptable salt thereof.

64 . The compound or pharmaceutically acceptable salt of claim 62 , wherein the compound of Formula (IV) is a compound of Formula (IVd):

or a pharmaceutically acceptable salt thereof.

65 . A compound of Formula (II):

or a pharmaceutically acceptable salt thereof; wherein:

represents a single or double bond, provided if a double bond is present, then one of R 6a or R 6b is absent and R 5 is absent;

L is selected from the group consisting of:

wherein A indicates the point of attachment at C17;

X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a );

each of R 55a and R 55b is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; or R 55a and R 55b may join together with the intervening atoms to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently hydrogen, halogen, cyano, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O)zR A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 0R A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

each of R 15a , R 15b , R 16a , and R 16b is each independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR C3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R C3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C 3, —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

R 18 is substituted or unsubstituted alkyl; and

R 19 is hydrogen or substituted or unsubstituted alkyl, provided that when R 5 is —H, then R 18 is not —CH 3 or —CH 2 CH 3 .

66 . The compound or pharmaceutically acceptable salt of claim 65 , wherein L is

67 . The compound or pharmaceutically acceptable salt of claim 66 , wherein each of R 1a , R 1b , R 2a , R 2b R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently hydrogen, unsubstituted C 1-6 alkyl, C 1-3 haloalkyl, or —OR A1 wherein R A1 is hydrogen or unsubstituted alkyl.

68 . The compound or pharmaceutically acceptable salt of claim 67 , wherein each of R 1a , R 1b , R 2a , and R 2b is hydrogen.

69 . The compound or pharmaceutically acceptable salt of claim 67 , wherein each of R 4a , R 4b , R 7a , and R 7b is hydrogen.

70 . The compound or pharmaceutically acceptable salt of claim 67 , wherein each of R 11a , R 11b , R 12a , and R 12b is hydrogen.

71 . The compound or pharmaceutically acceptable salt of claim 66 , wherein R 3 is substituted or unsubstituted C 1-6 alkyl.

72 . The compound or pharmaceutically acceptable salt of claim 71 , wherein R 3 is C 1-3 alkyl optionally substituted with C 1-3 alkoxy.

73 . The compound or pharmaceutically acceptable salt of claim 72 , wherein R 3 is methyl, ethyl, propyl, butyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 .

74 . The compound or pharmaceutically acceptable salt of claim 66 , wherein

is a single bond, and R 5 is hydrogen or methyl in the alpha or beta configuration.

75 . The compound or pharmaceutically acceptable salt of claim 74 , wherein R 5 is hydrogen.

76 . The compound or pharmaceutically acceptable salt of claim 66 , wherein

is a single bond, and each of R 6a and R 6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

77 . The compound or pharmaceutically acceptable salt of claim 76 , wherein each of R 6a and R 6b is independently hydrogen or substituted or unsubstituted C 1-6 alkyl.

78 . The compound or pharmaceutically acceptable salt of claim 77 , wherein each of R 6a and R 6b is hydrogen.

79 . The compound or pharmaceutically acceptable salt of claim 66 , wherein R 18 is substituted or unsubstituted C 1-6 alkyl.

80 . The compound or pharmaceutically acceptable salt of claim 79 , wherein R 18 is unsubstituted methyl or ethyl.

81 . The compound or pharmaceutically acceptable salt of claim 66 , wherein R 19 is hydrogen or substituted or unsubstituted C 1-6 alkyl.

82 . The compound or pharmaceutically acceptable salt of claim 81 , wherein R 19 is unsubstituted methyl or ethyl.

83 . The compound or pharmaceutically acceptable salt of claim 81 , wherein R 19 is hydrogen.

84 . The compound or pharmaceutically acceptable salt of claim 66 , wherein t is 2, and each R 15a and R 15b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heteroaryl.

85 . The compound or pharmaceutically acceptable salt of claim 84 , wherein each R 15a and R 15b is hydrogen.

86 . The compound or pharmaceutically acceptable salt of claim 66 , wherein each R 16a and R 16b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heteroaryl.

87 . The compound or pharmaceutically acceptable salt of claim 86 , wherein each R 16a and R 16b is hydrogen.

88 . The compound or pharmaceutically acceptable salt of claim 66 , wherein X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a ); R 55a is substituted or unsubstituted carbocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R 55b is hydrogen or substituted or unsubstituted C 1-6 alkyl.

89 . The compound or pharmaceutically acceptable salt of claim 66 , wherein X is selected from the group consisting of:

90 . The compound or pharmaceutically acceptable salt of claim 65 , wherein the compound of Formula (II) is a compound of Formula (IIIa) or (IIIb):

or a pharmaceutically acceptable salt thereof.

91 . A compound of Formula (V):

or a pharmaceutically acceptable salt thereof; wherein:

represents a single or double bond, provided if a double bond is present, then one of R 6a or R 6b is absent and R 5 is absent;

L is selected from the group consisting of:

wherein A indicates the point of attachment at C17;

X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a );

each of R 55a and R 55b is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; or R 55a and R 55b may join together with the intervening atoms to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each of R 15a and R 15b is each independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR C3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R C3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C3 , —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; and

R 19 is hydrogen or substituted or unsubstituted alkyl.

92 . A compound of Formula (VIa) or Formula (VIb):

or a pharmaceutically acceptable salt thereof; wherein:

represents a single or double bond, provided if a double bond is present, then one of R 6a or R 6b is absent and R 5 is absent;

L is selected from the group consisting of:

wherein A indicates the point of attachment at C17;

X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a );

each of R 55a and R 55b is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O)2R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; or R 55a and R 55b may join together with the intervening atoms to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , k 7b , R 11a , R 11b , R 12a , and R 12b is independently hydrogen, halogen, cyano, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R Al groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

each of R 15a , R 15b , R 16a , and R 16b is each independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR C3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R C3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C3 , —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

R 19 is hydrogen or substituted or unsubstituted alkyl; and

each r is independently 2 or 3.

93 . The compound or pharmaceutically acceptable salt of claim 92 , wherein the compound of Formula (VIa) is a compound of Formula (VIc) or the compound of Formula (VIb) is a compound of Formula (VId):

or a pharmaceutically acceptable salt thereof.

94 . A compound of Formula (VII):

or a pharmaceutically acceptable salt thereof; wherein:

represents a single or double bond, provided if a double bond is present, then one of R 6a or R 6b is absent and R 5 is absent;

L is selected from the group consisting of:

wherein A indicates the point of attachment at C17;

X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a );

each of R 55a and R 55b is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O)2R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; or R 55a and R 55b may join together with the intervening atoms to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each of R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently hydrogen, halogen, cyano, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

each of R 15a , R 15b , R 16a , and R 16b is each independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR C3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R C3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C3 , —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; and

R 19 is hydrogen or substituted or unsubstituted alkyl.

95 . A compound of Formula (VIII):

or a pharmaceutically acceptable salt thereof; wherein:

represents a single or double bond, provided if a double bond is present, then one of R 6a or R 6b is absent and R 5 is absent;

L is selected from the group consisting of:

wherein A indicates the point of attachment at C17;

X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a );

each of R 55a and R 55b is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O)2R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; or R 55a and R 55b may join together with the intervening atoms to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each R GA is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocylyl, substituted or unsubstituted 3- to 6- membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R GA groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclyl or heteroaryl ring;

each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , k 7b , R 11a , R 11b , R 12a , and R 12b is independently hydrogen, halogen, cyano, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

each of R 15a , R 15b , R 16a , and R 16b is each independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR C3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R C3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C3 , —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

R 19 is hydrogen or substituted or unsubstituted alkyl; and

s is 2.

96 . A compound of Formula (IX):

or a pharmaceutically acceptable salt thereof; wherein:

L is selected from the group consisting of:

wherein A indicates the point of attachment at C17;

X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a );

each of R 55a and R 55b is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O)2R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; or R 55a and R 55b may join together with the intervening atoms to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , k 7b , R 11a , R 11b , R 12a , and R 12b is independently hydrogen, halogen, cyano, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

each of R 15a , R 15b , R 16a , and R 16b is each independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR C3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R C3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C3 , —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; and

R 19 is hydrogen or substituted or unsubstituted alkyl.

97 . A compound of Formula (X):

or a pharmaceutically acceptable salt thereof; wherein:

represents a single or double bond, provided if a double bond is present, then one of R 6a or R 6b is absent and R 5 is absent;

L is selected from the group consisting of:

wherein A indicates the point of attachment at C17;

X is —N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a );

each of R 55a and R 55b is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; or R 55a and R 55b may join together with the intervening atoms to form a substituted or unsubstituted heterocyclic ring or a substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently hydrogen, halogen, cyano, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A 1, —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

each of R 15a , R 15b , R 16a , and R 16b is each independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR C3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R C3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C3 , —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

R 19 is hydrogen or substituted or unsubstituted alkyl; and

q is 2.

98 . The compound or pharmaceutically acceptable salt of claim 97 , wherein L is

99 . The compound or pharmaceutically acceptable salt of claim 98 , wherein each of R 1a , R 1b , R 2a , and R 2b is independently hydrogen, unsubstituted C 1-6 alkyl, C 1-3 haloalkyl, or —OR A1 wherein R A1 is hydrogen or unsubstituted alkyl.

100 . The compound or pharmaceutically acceptable salt of claim 99 , wherein each of R 1a , R 1b , R 2a , and R 2b is hydrogen.

101 . The compound or pharmaceutically acceptable salt of claim 98 , wherein each of R 4a , R 4b , R 7a , and R 7b is independently hydrogen, unsubstituted C 1-6 alkyl, C 1-3 haloalkyl, or —OR A1 wherein R A1 is hydrogen or unsubstituted alkyl.

102 . The compound or pharmaceutically acceptable salt of claim 101 , wherein each of R 4a , R 4b , R 7a , and R 7b is hydrogen.

103 . The compound or pharmaceutically acceptable salt of claim 98 , wherein each of R 11a , R 11b , R 12a , and R 12b is independently hydrogen, unsubstituted C 1-6 alkyl, C 1-3 haloalkyl, or —OR A1 wherein R A1 is hydrogen or unsubstituted alkyl.

104 . The compound or pharmaceutically acceptable salt of claim 103 , wherein each of R 11a , R 11b , R 12a , and R 12b is hydrogen.

105 . The compound or pharmaceutically acceptable salt of claim 98 , wherein R 3 is substituted or unsubstituted C 1-6 alkyl.

106 . The compound or pharmaceutically acceptable salt of claim 105 , wherein R 3 is C 1-3 alkyl optionally substituted with C 1-3 alkoxy.

107 . The compound or pharmaceutically acceptable salt of claim 106 , wherein R 3 is methyl, ethyl, propyl, butyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 .

108 . The compound or pharmaceutically acceptable salt of claim 98 , wherein is a single bond, and R 5 is hydrogen or methyl in the alpha or beta configuration.

109 . The compound or pharmaceutically acceptable salt of claim 108 , wherein R 5 is hydrogen.

110 . The compound or pharmaceutically acceptable salt of claim 98 , wherein is a single bond, and each of R 6a and R 6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

111 . The compound or pharmaceutically acceptable salt of claim 110 , wherein each of R 6a and R 6b is independently hydrogen or substituted or unsubstituted C 1-6 alkyl.

112 . The compound or pharmaceutically acceptable salt of claim 111 , wherein each of R 6a and R 6b is hydrogen.

113 . The compound or pharmaceutically acceptable salt of claim 98 , wherein R 19 is hydrogen or substituted or unsubstituted C 1-6 alkyl.

114 . The compound or pharmaceutically acceptable salt of claim 113 , wherein R 19 is unsubstituted C 1-3 alkyl.

115 . The compound or pharmaceutically acceptable salt of claim 114 , wherein R 19 is unsubstituted methyl or ethyl.

116 . The compound or pharmaceutically acceptable salt of claim 113 , wherein R 19 is hydrogen.

117 . The compound or pharmaceutically acceptable salt of claim 98 , wherein each R 15a and R 15b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heteroaryl.

118 . The compound or pharmaceutically acceptable salt of claim 117 , wherein each R 15a and R 15b is independently hydrogen or substituted or unsubstituted C 1-6 alkyl.

119 . The compound or pharmaceutically acceptable salt of claim 118 , wherein each R 15a and R 15b is hydrogen.

120 . The compound or pharmaceutically acceptable salt of claim 98 , wherein each R 16a and R 16b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heteroaryl.

121 . The compound or pharmaceutically acceptable salt of claim 120 , wherein each R 16a and R 16b is independently hydrogen or substituted or unsubstituted C 1-6 alkyl.

122 . The compound or pharmaceutically acceptable salt of claim 121 , wherein each R 16a and R 16b is hydrogen.

123 . The compound or pharmaceutically acceptable salt of claim 98 , wherein X is -N(R 55a )(R 55b ) or —N(R 55b )C(O)(R 55a ); R 55a is substituted or unsubstituted carbocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and R 55b is hydrogen or substituted or unsubstituted C 1-6 alkyl.

124 . The compound or pharmaceutically acceptable salt of claim 98 , wherein X is selected from the group consisting of:

125 . A compound selected from:

or a pharmaceutically acceptable salt thereof.

126 . A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt of claim 1 , and a pharmaceutically acceptable excipient.

127 . A method of modulating a GABA A receptor in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound or pharmaceutically acceptable salt of claim 1 .

128 . A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound or pharmaceutically acceptable salt of claim 1 .

129 . The method of claim 128 , wherein the CNS-related disorder is depression.

130 . The method of claim 129 , wherein the depression is post-partum depression.

131 . The method of claim 128 , wherein the CNS-related disorder is tremor.

132 . The method of claim 131 , wherein the tremor is essential tremor.

133 . The method of claim 128 , wherein the CNS-related disorder is seizure.

134 . The method of claim 128 , wherein the CNS-related disorder is epilepsy or status epilepticus.

135 . The method of claim 134 , wherein the status epilepticus is convulsive status epilepticus or non-convulsive status epilepticus.

136 . A method of inducing sedation and/or anesthesia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound or pharmaceutically acceptable salt of claim 1 .

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 5, 2022

From: BLANCO-PILLADO, MARIA JESUS; SALITURO, FRANCESCO G.; MORNINGSTAR, MARSHALL LEE

To: SAGE THERAPEUTICS, INC.

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