IP Library › Granted Patent US 12,552,829

Granted Patent B2

US 12,552,829 · App. 17/620,226 · Granted Feb 17, 2026

Compositions and methods for treating CNS disorders

Inventors: Francesco G. Salituro (Marlborough, MA); Maria Jesus Blanco-Pillado (Arlington, MA); Marshall Lee Morningstar (Framingham, MA)

Assignee: Sage Therapeutics, Inc.

C07J43/003 C07J61/00 C07J63/002

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Quick Facts

Patent No.: US 12,552,829
App. No.: 17/620,226
Granted: Feb 17, 2026
Kind: B2

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Abstract

Provided herein is a compound of Formula I, II, IIIa, IIIb, V, VIa, VIb, VII, VIII, IX, or XI: or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of Formula I, II, IIIa, IIIb, V, VIa, VIb, VII, VIII, IX, or X, and methods of using the compounds, e.g., in the treatment of CNS-related disorders.

Claims (212)

1 . 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;

R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;

R Y is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

R 3 is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

R 5 is hydrogen or methyl;

each instance of R 22 is independently selected from the group consisting of halogen, —NO 2 , —CN, —OR GA , —N(R GA ) 2 , —C(═O)R GA , —C(═O)OR GA , —OC(═O)R GA , —OC(═O)OR GA , —C(═O)N(R GA ) 2 , —N(R GA )C(═O)R GA , —OC(═O)N(R GA ) 2 , —N(R GA )C(═O)OR GA , —N(R GA )C(═O)N(R GA ) 2 , —SR GA , —S(═O)R GA , —S(O) 2 R GA , —S(O) 2 OR GA , —OS(═O) 2 R GA , —S(═O) 2 N(R GA ) 2 , —N(R GA )S(═O) 2 R GA , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocylyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein each instance of R GA is independently selected from the group consisting of 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, and a 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 selected from the group consisting of 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 )S(═O) 2 R A1 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)OR A1 , —SC(═O)R 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 the group consisting of 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, or substituted or unsubstituted 3- to 6-membered 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, and 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 selected from the group consisting of hydrogen, halogen, cyano, —NO 2 , —OH, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, and 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 independently selected from the group consisting of 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 3 ) 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 the group consisting of 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 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, and 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;

n is 0, 1, 2, or 3; and

t is 2 or 3.

2 . The compound or pharmaceutically acceptable salt of claim 1 , wherein t is 2.

3 . The compound or pharmaceutically acceptable salt of claim 2 , wherein R 3 is substituted or unsubstituted C 1-6 alkyl.

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

5 . The compound or pharmaceutically acceptable salt of claim 4 , wherein R 3 is methyl, ethyl, propyl, n-propyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 .

6 . The compound or pharmaceutically acceptable salt of claim 2 , wherein R 19 is hydrogen or unsubstituted C 1-3 alkyl.

7 . The compound or pharmaceutically acceptable salt of claim 2 , wherein each of R 15a and R 15b is independently hydrogen or substituted or unsubstituted alkyl.

8 . The compound or pharmaceutically acceptable salt of claim 7 , wherein each of R 15a and R 15b is independently hydrogen or methyl.

9 . The compound or pharmaceutically acceptable salt of claim 2 , wherein each of R 16a and R 16b is hydrogen.

10 . The compound or pharmaceutically acceptable salt of claim 2 , wherein is a single bond, and R 5 is hydrogen or methyl.

11 . The compound or pharmaceutically acceptable salt of claim 2 , wherein is a double bond, and R 5 and one of R 6a and R 6b is absent.

12 . The compound or pharmaceutically acceptable salt of claim 2 , wherein R X is —OH, and R Y is unsubstituted C 1-3 alkyl.

13 . The compound or pharmaceutically acceptable salt of claim 2 , wherein n is 1 and R 22 is halogen, —CN, —OR GA , —N(R GA ) 2 , substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 3-6 carbocylyl, wherein each instance of R GA is independently hydrogen or substituted or unsubstituted C 1-3 alkyl.

14 . The compound or pharmaceutically acceptable salt of claim 2 , 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 hydrogen.

15 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-a) or (I-b):

or a pharmaceutically acceptable salt thereof.

16 . The compound or pharmaceutically acceptable salt of claim 15 , wherein the compound of Formula (I-a) is a compound of Formula (I-c):

or a pharmaceutically acceptable salt thereof.

17 . The compound or pharmaceutically acceptable salt of claim 15 , wherein the compound of Formula (I-b) is a compound of Formula (I-d):

or a pharmaceutically acceptable salt thereof.

18 . 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;

R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;

R Y is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

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 instance of R 22 is independently selected from the group consisting of halogen, —NO 2 , —CN, —OR GA , —N(R GA ) 2 , —C(═O)R GA , —C(═O)OR GA , —OC(═O)R GA , —OC(═O)OR GA , —C(═O)N(R GA ) 2 , —N(R GA )C(═O)R GA , —OC(═O)N(R GA ) 2 , —N(R GA )C(═O)OR GA , —N(R GA )C(═O)N(R GA ) 2 , —SR GA , —S(═O)R GA , —S(O) 2 R GA , —S(O) 2 OR GA , —OS(O) 2 R GA , —S(═O) 2 N(R GA ) 2 , —N(R GA )S(═O) 2 R GA , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocylyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein each instance of R GA is independently selected from the group consisting of 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, and a 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 1i a, R 1l b R 12a , and R 12b is independently selected from the group consisting of 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 )S(═O) 2 R A1 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)OR A1 , —SC(═O)R 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 the group consisting of 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, or substituted or unsubstituted 3- to 6-membered 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, and 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 independently selected from the group consisting of 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 the group consisting of 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 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, and 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;

R 18 is substituted or unsubstituted alkyl; and

n is 0, 1, 2, or 3;

provided that when R 5 is hydrogen, R 18 is not —CH 3 .

19 . The compound or pharmaceutically acceptable salt of claim 18 , 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 hydrogen.

20 . The compound or pharmaceutically acceptable salt of claim 18 , wherein R X is —OH, and R Y is unsubstituted C 1-3 alkyl.

21 . The compound or pharmaceutically acceptable salt of claim 19 , wherein n is 1 and R 22 is halogen, —CN, —OR GA , —N(R GA ) 2 , substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 3-6 carbocylyl, wherein each instance of R GA is independently hydrogen or substituted or unsubstituted C 1-3 alkyl.

22 . The compound or pharmaceutically acceptable salt of claim 18 , wherein the compound of Formula (II) is a compound of Formula (IIIa) or (IIIb)

or a pharmaceutically acceptable salt thereof.

23 . 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;

R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;

R Y is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

R 5 is hydrogen or methyl;

each instance of R 22 is independently selected from the group consisting of halogen, —NO 2 , —CN, —OR GA , —N(R GA ) 2 , —C(═O)R GA , —C(═O)OR GA , —OC(═O)R GA , —OC(═O)OR GA , —C(═O)N(R GA ) 2 , —N(R GA )C(═O)R GA , —OC(═O)N(R GA ) 2 , —N(R GA )C(═O)OR GA , —N(R GA )C(═O)N(R GA ) 2 , —SR GA , —S(═O)R GA , —S(O) 2 R GA , —S(O) 2 OR GA , —OS(═O) 2 R GA , —S(═O) 2 N(R GA ) 2 , —N(R GA )S(═O) 2 R GA substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocylyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein each instance of R GA is independently selected from the group consisting of 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, and a 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 15a , R 15b , R 16a , and R 16b is independently selected from the group consisting of 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 the group consisting of 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 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, and 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

n is 0, 1, 2, or 3.

24 . A compound of Formula (VIa)

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;

R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;

R Y is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

R 5 is hydrogen or methyl;

each of R 5a , R 15b , R 16a , and R 16b is independently selected from the group consisting of 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 the group consisting of 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 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, and 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;

r is 2 or 3; and

n is 0, 1, 2, or 3.

25 . The compound or pharmaceutically acceptable salt of claim 24 , wherein R 3 is substituted or unsubstituted C 1-6 alkyl.

26 . The compound or pharmaceutically acceptable salt of claim 25 , wherein R 3 is C 1-3 alkyl optionally substituted with C 1-3 alkoxy.

27 . The compound or pharmaceutically acceptable salt of claim 25 , wherein R 3 is methyl, ethyl, n-propyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 .

28 . The compound or pharmaceutically acceptable salt of claim 24 , wherein R 19 is hydrogen or unsubstituted C 1-3 alkyl.

29 . The compound or pharmaceutically acceptable salt of claim 24 , wherein each of R 15 and R 15b is independently hydrogen or substituted or unsubstituted alkyl.

30 . The compound or pharmaceutically acceptable salt of claim 29 , wherein each of R 1a and R 15b is independently hydrogen or methyl.

31 . The compound or pharmaceutically acceptable salt of claim 24 , wherein each of R 16a and R 16b is hydrogen.

32 . The compound or pharmaceutically acceptable salt of claim 24 , wherein is a single bond, and R 5 is hydrogen or methyl.

33 . The compound or pharmaceutically acceptable salt of claim 24 , wherein is a double bond, and R 5 and one of R 6a and R 6b is absent.

34 . The compound or pharmaceutically acceptable salt of claim 24 , wherein R X is —OH, and R Y is unsubstituted C 1-3 alkyl.

35 . The compound or pharmaceutically acceptable salt of claim 24 , wherein n is 1 and R 22 is halogen, —CN, —OR GA , —N(R GA ) 2 , substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 3-6 carbocylyl, wherein each instance of R GA is independently hydrogen or substituted or unsubstituted C 1-3 alkyl.

36 . The compound or pharmaceutically acceptable salt of claim 24 , wherein the compound of Formula (VIa) is a compound of Formula (VIa-a):

or a pharmaceutically acceptable salt thereof.

37 . The compound or pharmaceutically acceptable salt of claim 36 , wherein the compound of Formula (VIa-a) is a compound of Formula (VIa-b):

or a pharmaceutically acceptable salt thereof.

38 . The compound or pharmaceutically acceptable salt of claim 36 , wherein the compound of Formula (VIa-b) is a compound of Formula (VIa-c) or (VIa-d):

or a pharmaceutically acceptable salt thereof.

39 . The compound or pharmaceutically acceptable salt of claim 24 , wherein the compound of Formula (VIa) is a compound of Formula (VIa-e):

or a pharmaceutically acceptable salt thereof.

40 . A compound of 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;

R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;

R Y is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

R 5 is hydrogen or methyl;

each instance of R 22 is independently selected from the group consisting of halogen, —NO 2 , —CN, —OR GA , —N(R GA ) 2 , —C(═O)R GA , —C(═O)OR GA , —OC(═O)R GA , —OC(═O)OR GA , —C(═O)N(R GA ) 2 , —N(R GA )C(═O)R GA , —OC(═O)N(R GA ) 2 , —N(R GA )C(═O)OR GA , —N(R GA )C(═O)N(R GA ) 2 , —SR GA , —S(═O)R GA , —S(O) 2 R GA , —S(O) 2 OR GA , —OS(═O) 2 R GA , —S(═O) 2 N(R GA ) 2 , —N(R GA )S(═O) 2 R GA substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocylyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein each instance of R GA is independently selected from the group consisting of 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, and a 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 15a , R 15b , R 16a , and R 16b is independently selected from the group consisting of 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 the group consisting of 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 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, and 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;

p is 2 or 3; and

n is 0, 1, 2, or 3.

41 . The compound or pharmaceutically acceptable salt of claim 40 , wherein R 3 is substituted or unsubstituted C 1-6 alkyl.

42 . The compound or pharmaceutically acceptable salt of claim 41 , wherein R 3 is C 1-3 alkyl optionally substituted with C 1-3 alkoxy.

43 . The compound or pharmaceutically acceptable salt of claim 42 , wherein R 3 is methyl, ethyl, n-propyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 .

44 . The compound or pharmaceutically acceptable salt of claim 40 , wherein R 19 is hydrogen or unsubstituted C 1-3 alkyl.

45 . The compound or pharmaceutically acceptable salt of claim 40 , wherein each of R 15a and R 15b is independently hydrogen or substituted or unsubstituted alkyl.

46 . The compound or pharmaceutically acceptable salt of claim 45 , wherein each of R 15a and R 15b is independently hydrogen or methyl.

47 . The compound or pharmaceutically acceptable salt of claim 40 , wherein each of R 16a and R 16b is hydrogen.

48 . The compound or pharmaceutically acceptable salt of claim 40 , wherein is a single bond, and R 5 is hydrogen or methyl.

49 . The compound or pharmaceutically acceptable salt of claim 40 , wherein is a double bond, and R 5 and one of R 6a and R 6b is absent.

50 . The compound or pharmaceutically acceptable salt of claim 40 , wherein R X is —OH, and R Y is unsubstituted C 1-3 alkyl.

51 . The compound or pharmaceutically acceptable salt of claim 40 , wherein n is 1 and R 22 is halogen, —CN, —OR GA , —N(R GA ) 2 , substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 3-6 carbocylyl, wherein each instance of R GA is independently hydrogen or substituted or unsubstituted C 1-3 alkyl.

52 . The compound or pharmaceutically acceptable salt of claim 40 , wherein the compound of Formula (VIb) is a compound of Formula (VIb-b):

or a pharmaceutically acceptable salt thereof.

53 . The compound or pharmaceutically acceptable salt of claim 52 , wherein the compound of Formula (VIb-b) is a compound of Formula (VIb-c) or (VIb-d):

or a pharmaceutically acceptable salt thereof.

54 . The compound or pharmaceutically acceptable salt of claim 40 , wherein the compound of Formula (VIb) is a compound of Formula (VIb-e):

or a pharmaceutically acceptable salt thereof.

55 . 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;

R X is selected from the group consisting of halo, —OH, —OR G1 , and substituted or unsubstituted alkyl, wherein R G1 is substituted or unsubstituted alkyl;

R is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

R 5 is hydrogen or methyl;

each instance of R 22 is independently selected from the group consisting of halogen, —NO 2 , —CN, —OR GA , —N(R GA ) 2 , —C(═O)R GA , —C(═O)OR GA , —OC(═O)R GA , —OC(═O)OR GA , —C(═O)N(R GA ) 2 , —N(R GA )C(═O)R GA , —OC(═O)N(R GA ) 2 , —N(R GA )C(═O)OR GA , —N(R GA )C(═O)N(R GA ) 2 , —SR GA , —S(═O)R GA , —S(O) 2 R GA , —S(O) 2 OR GA , —OS(O) 2 R GA , —S(═O) 2 N(R GA ) 2 , —N(R GA )S(═O) 2 R GA , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocylyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein each instance of R GA is independently selected from the group consisting of 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, and a 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 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 1a , R 11b , R 12a , and R 12b is independently selected from the group consisting of 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 A 1, —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 )S(═O) 2 R A1 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)OR A1 , —SC(═O)R 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 the group consisting of 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, or substituted or unsubstituted 3- to 6-membered 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, and 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 Ra R 15b , R 16a , and R 16b is independently selected from the group consisting of 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 the group consisting of 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 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, and 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

n is 0, 1, 2, or 3.

56 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 3 is substituted or unsubstituted C 1-6 alkyl.

57 . The compound or pharmaceutically acceptable salt of claim 56 , wherein R 3 is C 1-3 alkyl optionally substituted with C 1-3 alkoxy.

58 . The compound or pharmaceutically acceptable salt of claim 57 , wherein R 3 is methyl, ethyl, n-propyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 .

59 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R 19 is hydrogen or unsubstituted C 1-3 alkyl.

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

61 . The compound or pharmaceutically acceptable salt of claim 60 , wherein each of R 15a and R 15b is independently hydrogen or methyl.

62 . The compound or pharmaceutically acceptable salt of claim 55 , wherein each of R 16a and R 16b is hydrogen.

63 . The compound or pharmaceutically acceptable salt of claim 55 , wherein is a single bond, and R 5 is hydrogen or methyl.

64 . The compound or pharmaceutically acceptable salt of claim 55 , wherein is a double bond, and R 5 and one of R 6a and R 6b is absent.

65 . The compound or pharmaceutically acceptable salt of claim 55 , wherein R X is —OH, and R Y is unsubstituted C 1-3 alkyl.

66 . The compound or pharmaceutically acceptable salt of claim 55 , wherein n is 1 and R 22 is halogen, —CN, —OR GA , —N(R GA ) 2 , substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 3-6 carbocylyl, wherein each instance of R GA is independently hydrogen or substituted or unsubstituted C 1-3 alkyl.

67 . The compound or pharmaceutically acceptable salt of claim 55 , wherein the compound of Formula (VII) is a compound of Formula (VII-b)

or a pharmaceutically acceptable salt thereof.

68 . The compound or pharmaceutically acceptable salt of claim 67 , wherein the compound of Formula (VII-b) is a compound of Formula (VII-c):

or a pharmaceutically acceptable salt thereof.

69 . 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;

R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;

R Y is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

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 selected from the group consisting of 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 A 1, —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 )S(═O) 2 R A1 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)OR A1 , —SC(═O)R 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 the group consisting of 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, or substituted or unsubstituted 3- to 6-membered 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, and 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 independently selected from the group consisting of 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 the group consisting of 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 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, and 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;

s is 2; and

n is 0, 1, 2, or 3.

70 . A compound of Formula (IX):

or a pharmaceutically acceptable salt thereof, wherein

R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;

R Y is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

R 5 is hydrogen or methyl;

each instance of R 22 is independently selected from the group consisting of halogen, —NO 2 , —CN, —OR GA , —N(R GA ) 2 , —C(═O)R GA , —C(═O)OR GA , —OC(═O)R GA , —OC(═O)OR GA , —C(═O)N(R GA ) 2 , —N(R GA )C(═O)R GA , —OC(═O)N(R GA ) 2 , —N(R GA )C(═O)OR GA , —N(R GA )C(═O)N(R GA ) 2 , —SR GA , —S(═O)R GA , —S(O) 2 R GA , —S(O) 2 OR GA , —OS(═O) 2 R GA , —S(═O) 2 N(R GA ) 2 , —N(R GA )S(═O) 2 R GA substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocylyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein each instance of R GA is independently selected from the group consisting of 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, and a 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 selected from the group consisting of 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 A 1, —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 )S(═O) 2 R A1 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)OR A1 , —SC(═O)R 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 the group consisting of 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, or substituted or unsubstituted 3- to 6-membered 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, and 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 independently selected from the group consisting of 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 the group consisting of 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 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, and 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

n is 0, 1, 2, or 3.

71 . 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;

R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;

R Y is halo or substituted or unsubstituted alkyl; or

R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;

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 selected from the group consisting of 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 A 1, —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 )S(═O) 2 R A1 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)OR A1 , —SC(═O)R 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 the group consisting of 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, or substituted or unsubstituted 3- to 6-membered 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, and 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 independently selected from the group consisting of 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 the group consisting of 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 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, and 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;

q is 2; and

n is 0, 1, 2, or 3.

72 . A compound selected from

or a pharmaceutically acceptable salt thereof.

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

74 . A compound selected from

75 . A pharmaceutical composition comprising a compound of claim 74 , and a pharmaceutically acceptable excipient.

Assignments (2)

CHANGE OF NAME Recorded Apr 23, 2026

From: SAGE THERAPEUTICS, INC.

To: SAGE THERAPEUTICS, LLC

Reel/Frame 075472/0569 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 26, 2022

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

To: SAGE THERAPEUTICS, INC.

Reel/Frame 060022/0001 →

Continuity (3)

Provisional Application 62867618 · Jun 27, 2019

Related Publication 20220380405A1 · Dec 1, 2022

Related Publication 20230303616A9 · Sep 28, 2023

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