IP Library › Patent Application 18254209

Patent Application

App. No. 18/254,209

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

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Patent No.: US None
App. No.: 18/254,209

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Abstract

Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein ring D and the substituents are defined herein. Also provided are pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof and methods of using the compound of Formula (I) in the treatment of CNS-related disorders.

Claims (742)

1 . A compound of Formula (I)

or a pharmaceutically acceptable salt thereof, wherein

Ring D is selected from

Each of R 1a , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 13 , R 15 , R 16 , R 17 , R 20a , R 20b , R 20c , and R 21 , is -L A -R 30 ;

Each L A is independently selected from a bond and an optionally substituted branched or straight C 1-6 alkylene chain, wherein up to two carbon atoms of L A are optionally and independently replaced by —NR′—, —S—, —O—, —OC(O)—, —C(O)O—, —C(O)—, —C(O)C(O)—, —C(O)NR′—, —NR′C(O)—, —NR′C(O)O—, —S(O) 2 NR′—, —NR′S(O) 2 —, —C(O)NR′NR′—, —NR′C(O)NR′—, —OC(O)NR′—, —NR′NR′—, —NR′S(O) 2 NR′—, —S(O)—, or —S(O) 2 —;

Each R 30 is independently selected from R′, —OH, halo, —CN, —NO 2 , and —CF 3 ;

Each R′ is independently selected from —H, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 1-6 alkyl-O—C 1-6 alkyl, and an optionally substituted 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, or

R 1a and R 1b taken together form oxo, or

R 2a and R 2b taken together form oxo, or

R 4a and R 4b taken together form oxo, or

R 6a and R 6b taken together form oxo, or

R 7a and R 7b taken together form oxo, or

R 1a and R 11b taken together form oxo, or

R 12a and R 12b taken together form oxo, or

R 20a and R 20b taken together form oxo;

Each of R 5 and R 20c is independently selected from —H and optionally substituted C 1-6 alkyl;

R 10 is —H, optionally substituted C 1-6 alkyl, or optionally substituted C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 31a and R 31b is independently selected from —H, halo, C 1-6 alkyl, and —OR 32 , wherein R 32 is —H, C 1-6 alkyl, or a 3-6-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S;

m is 1 or 2; and

n is 0, 1, or 2,

provided that when one of R 31a and R 31b is —OR 32 , the other of R 31a and R 31b is —H.

2 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (I) is a compound of Formula (II)

or a pharmaceutically acceptable salt thereof, wherein

Ring D is a fused bicyclic ring selected from

Each of R 1a , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 6a , R 6b , R 7a , R 71 , R 11a , R 11b , R 12a , R 12b , R 20a , R 20b , and R 21 is -L A -R 30 ;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ;

Each R′ is independently selected from —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein each alkyl, alkenyl, alkynyl, or 3-8 membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 , or

R 1a and R 1b taken together form oxo, or

R 2a and R 2b taken together form oxo, or

R 4a and R 4b taken together form oxo, or

R 6a and R 6b taken together form oxo, or

R 7a and R 7b taken together form oxo, or

R 11a and R 11b taken together form oxo, or

R 12a and R 12b taken together form oxo, or

R 20a and R 20b taken together form oxo;

R 5 is —H or C 1-6 alkyl;

R 10 is —H or optionally substituted C 1-6 alkyl;

R 13 is —H or optionally substituted C 1-6 alkyl;

n is 0, 1, or 2,

provided that when one of R 31a and R 31b is —OR 32 , the other of R 31a and R 31b is —H.

3 . The compound or pharmaceutically acceptable salt of claim 2 , wherein R 3 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

4 . The compound or pharmaceutically acceptable salt of claim 2 or claim 3 , wherein R 3 is —H or C 1-6 alkyl optionally substituted with R′.

5 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 4 , wherein R 3 is —H, —CH 3 , —CH 2 —CH 2 —CH 3 , or —CH 2 —O—CH 3 .

6 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 5 , wherein R 13 is —H, C 1-6 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl.

7 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 6 , wherein R 13 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl.

8 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 7 , wherein R 13 is —H, methyl, ethyl, propyl, iso-propyl, methoxymethyl, ethoxymethyl, methoxyethyl, or ethoxyethyl.

9 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 8 , wherein R 13 is methyl.

10 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 9 , wherein each of R 20a and R 20b are independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′, or R 20a and R 20b taken together form oxo.

11 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 10 , wherein each of R 20a and R 20b are independently selected from —H, C 1-6 alkyl, —N(R′) 2 , and —O—R′, or R 20a and R 20b taken together form oxo.

12 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 11 , wherein R 20a and R 20b taken together form oxo.

13 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 12 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —, or —NH—; and R 30 is a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein the 3-8 membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

14 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 13 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, or —NH—; and R 30 is a 5-6-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

15 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 14 , wherein R 21 is -L A -R 30 ; L A is a bond or —CH 2 —; and R 30 is a 5-6-membered partially unsaturated or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-2 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

16 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 15 , wherein R 21 is -L A -R 30 L A is a bond or —CH 2 —; and R 30 is

wherein

each of X 1 , X 2 , X 3 , and X 4 is independently N or CR″, wherein each R″ is independently selected from —H, halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 , provided that

(i) at least one of X 1 , X 2 , X 3 , and X 4 is N, and

(ii) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

17 . The compound or pharmaceutically acceptable salt of claim 2 , wherein the compound of Formula (II) is a compound of Formula (II-A) or (II-B)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1 , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 20a , R 20b , and R 21 is -L A -R 30 ;

Each R 30 is independently selected from R′, halo, —CN, —NO 2 , and —CF 3 ;

R 20a and R 20b taken together form oxo;

R 5 is —H or C 1-6 alkyl;

R 10 is —H or optionally substituted C 1-3 alkyl; and

R 13 is —H or optionally substituted C 1-3 alkyl.

18 . The compound or pharmaceutically acceptable salt of claim 17 , wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H and C 1-6 alkyl;

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-3 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —CH 2 OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain, wherein up to two carbon atoms of L A are optionally and independently replaced by —NR′—, —S—, —O—, —OC(O)—, —C(O)O—, —C(O)—, —C(O)C(O)—, —C(O)NR′—, —NR′C(O)—, —NR′C(O)O—, —S(O) 2 NR′—, —NR′S(O) 2 —, —C(O)NR′NR′—, —NR′C(O)NR′—, —OC(O)NR′—, —NR′NR′—, —NR′S(O) 2 NR′—, —S(O)—, or —S(O) 2 —;

R 30 is independently selected from R′, halo, —CN, —NO 2 , and —CF 3 ;

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8 membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

19 . The compound or pharmaceutically acceptable salt of claim 2 , wherein the compound of Formula (II) is a compound of Formula (II-C)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 6a , R 6b , R 7a , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 20a , R 20b , and R 21 is -L A -R 30 ;

Each R 30 is independently selected from R′, halo, —CN, —NO 2 , and —CF 3 ;

R 20a and R 20b taken together form oxo;

R 5 is —H or C 1-6 alkyl;

R 10 is —H or optionally substituted C 1-3 alkyl; and

R 13 is —H or optionally substituted C 1-3 alkyl.

20 . The compound or pharmaceutically acceptable salt of claim 19 , wherein

each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H or C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-3 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

21 . The compound or pharmaceutically acceptable salt of claim 17 or claim 18 , wherein the compound of Formula (II-A) is a compound of Formula (II-A1) or (II-A2)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H and C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A-R 303 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , or —CH 3 .

22 . The compound or pharmaceutically acceptable salt of claim 17 or claim 18 , wherein the compound of Formula (II-B) is a compound of Formula (II-B1) or (II-B2)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 1 b, R 12a , and R 12b is independently selected from —H and C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

23 . The compound or pharmaceutically acceptable salt of claim 19 or claim 20 , wherein the compound of Formula (II-C) is a compound of Formula (II-C1) or (II-C2)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H or C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

24 . The compound or pharmaceutically acceptable salt of claim 21 , wherein the compound of Formula (II-A1) is a compound of Formula (II-A1a), (II-A1b), (II-A1c), or (II-A1d)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H and C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

25 . The compound or pharmaceutically acceptable salt of claim 21 , wherein the compound of Formula (II-A2) is a compound of Formula (II-A2a), (II-A2b), (II-A2c) or (II-A2d)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H and C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , or —CH 3 .

26 . The compound or pharmaceutically acceptable salt of claim 22 , wherein the compound of Formula (II-B1) is a compound of Formula (II-B1a), (II-B1b), (II-B1c), or (II-B1d)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H or C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , or —CH 3 .

27 . The compound or pharmaceutically acceptable salt of claim 22 , wherein the compound of Formula (II-B2) is a compound of Formula (II-B2a), (II-B2b), (II-B2c) or (II-B2d)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H and C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

28 . The compound or pharmaceutically acceptable salt of claim 23 , wherein the compound of Formula (II-C1) is a compound of Formula (II-C1a), (II-C1b), (II-C1c) or (II-C1d)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 11b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H and C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

29 . The compound or pharmaceutically acceptable salt of claim 23 , wherein the compound of Formula (II-C2) is a compound of Formula (II-C2a), (II-C2b), (II-C2c) or (II-C2d)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from —H or C 1-6 alkyl,

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 13 is —H or optionally substituted C 1-3 alkyl;

Each of R 20a and R 20b is independently —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, or —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is selected from R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

30 . The compound or pharmaceutically acceptable salt of claim 2 , wherein the compound of Formula (II) is a compound of Formula (III)

or a pharmaceutically acceptable salt thereof, wherein

Ring D is a fused bicyclic ring selected from

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 13 is —H or C 1-6 alkyl;

Each of R 20a and R 20b is independently —H, —OH, C 1-6 alkyl, or

R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

R 30 is —H, halo, —OH, —CN, —NO 2 , —CF 3 , or a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein the 3-8 membered ring of R 30 is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

31 . The compound or pharmaceutically acceptable salt of claim 30 , wherein R 13 is C 1-6 alkyl.

32 . The compound or pharmaceutically acceptable salt of claim 30 or claim 31 , wherein R 13 is methyl, ethyl, or propyl.

33 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 32 , wherein R 13 is methyl.

34 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 33 , wherein R 20a and R 20b taken together form oxo.

35 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 33 , wherein one of R 20a and R 20b is —H, and the other of R 20a and R 20b is C 1-6 alkyl.

36 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 33 , wherein one of R 20a and R 20b is C 1-6 alkyl, and the other of R 20a and R 20b is —OH.

37 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 33 or 36 wherein one of R 20a and R 20b is methyl, ethyl, or propyl, and the other of R 20a and R 20b is —OH.

38 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 33 , wherein R 20a , R 20b , and the carbon to which they are attached form

39 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 38 , wherein R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-3 alkylene chain, or —N(H)—; and

R 30 is —H, —OH, —CN, —NO 2 , —CF 3 , or a 5-6-membered partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein the 5-6 membered ring of R 30 is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

40 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 39 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —, or —N(H)—; and R 30 is —H or a 5-6-membered partially unsaturated, or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

41 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 40 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —, or —N(H)—; and R 30 is a 5-6-membered partially unsaturated, or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

42 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 41 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, or —N(H)—; and R 30 is,

wherein each of X 1 , X 2 , X 3 , and X 4 is independently N or CR″, wherein each R″ is independently selected from —H, halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 , provided that

(i) at least one of X 1 , X 2 , X 3 , and X 4 is N, and

(ii) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

43 . The compound or pharmaceutically acceptable salt of claim 41 , wherein R 30 is

X 1 is N; and each of X 2 , X 3 , and X 4 is independently selected from N or CR″, wherein each R″ is independently selected from —H, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH, provided that

(i) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

44 . The compound or pharmaceutically acceptable salt of claim 30 , wherein the compound of Formula (III) is a compound of Formula (III-A) or (III-B)

or a pharmaceutically acceptable salt thereof.

45 . The compound or pharmaceutically acceptable salt of claim 44 , wherein

R 3 is methyl;

R 5 is —H;

R 10 is —H;

R 13 is —H or methyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and methyl, or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond, —NH—, or —CH 2 —;

R 30 is independently selected from pyrazolyl, tetrazolyl, and pyridyl, each of which is optionally substituted with halo, C 1-6 alkyl, or cyano.

46 . The compound or pharmaceutically acceptable salt of claim 30 , wherein the compound of Formula (III) is a compound of Formula (III-C)

or a pharmaceutically acceptable salt thereof.

47 . The compound or pharmaceutically acceptable salt of claim 46 , wherein

R 3 is methyl, ethyl, propyl, or methoxymethyl;

R 5 is —H;

R 10 is —H;

R 13 is —H or methyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and methyl, or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond, —NH—, or —CH 2 —;

R 30 is independently selected from methyl, pyrazolyl, tetrazolyl, and pyridyl, each of which is optionally substituted with halo, C 1-6 alkyl, or cyano.

48 . The compound or pharmaceutically acceptable salt of claim 44 or claim 45 , wherein the compound of Formula (III-A) is a compound of Formula (III-A1) or (III-A2)

or a pharmaceutically acceptable salt thereof.

49 . The compound or pharmaceutically acceptable salt of claim 44 or claim 45 , wherein the compound of Formula (III-B) is a compound of Formula (III-B1) or (III-B2)

or a pharmaceutically acceptable salt thereof.

50 . The compound or pharmaceutically acceptable salt of claim 46 or claim 47 , wherein the compound of Formula (III-C) is a compound of Formula (III-C1) or (III-C2)

or a pharmaceutically acceptable salt thereof.

51 . The compound or pharmaceutically acceptable salt of claim 48 , wherein the compound of Formula (III-A1) is a compound of Formula (III-A1a), (III-A1b), (III-A1c), or (III-A1d)

or a pharmaceutically acceptable salt thereof.

52 . The compound or pharmaceutically acceptable salt of claim 48 , wherein the compound of Formula (III-A2) is a compound of Formula (III-A2a), (III-A2b), (III-A2c) or (III-A2d)

or a pharmaceutically acceptable salt thereof.

53 . The compound or pharmaceutically acceptable salt of claim 49 , wherein the compound of Formula (III-B1) is a compound of Formula (III-B1a), (III-B1b), (III-B1c), or (III-B1d)

or a pharmaceutically acceptable salt thereof.

54 . The compound or pharmaceutically acceptable salt of claim 49 , wherein the compound of Formula (III-B2) is a compound of Formula (III-B2a), (III-B2b), (III-B2c) or (III-B2d)

or a pharmaceutically acceptable salt thereof.

55 . The compound or pharmaceutically acceptable salt of claim 50 , wherein the compound of Formula (III-C1) is a compound of Formula (III-C1a), (III-C1b), (III-C1c) or (III-C1d)

or a pharmaceutically acceptable salt thereof.

56 . The compound or pharmaceutically acceptable salt of claim 50 , wherein the compound of Formula (III-C2) is a compound of Formula (III-C2a), (III-C2b), (III-C2c) or (III-C2d)

or a pharmaceutically acceptable salt thereof.

57 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (I) is a compound of Formula (IV)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15 , R 16 , R 20a , R 20b , and R 21 is -L A -R 30 ;

Each R 30 is independently selected from R′, halo, —CN, —NO 2 , and —CF 3 ;

Each R′ is independently selected from —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein each alkyl, alkenyl, alkynyl, or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, or —C(CH 3 ) 3 , or

R 1a and R 1b taken together form oxo, or

R 2a and R 2b taken together form oxo, or

R 4a and R 4b taken together form oxo, or

R 6a and R 6b taken together form oxo, or

R 7a and R 7b taken together form oxo, or

R 11a and R 11b taken together form oxo, or

R 12a and R 12b taken together form oxo, or

R 20a and R 20b taken together form oxo;

R 5 is —H or C 1-3 alkyl;

R 10 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

m is 1 or 2; and

n is 0, 1, or 2.

58 . The compound or pharmaceutically acceptable salt of claim 57 , wherein R 3 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

59 . The compound or pharmaceutically acceptable salt of claim 57 or claim 58 , wherein R 3 is —H or C 1-6 alkyl optionally substituted with R′.

60 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 59 , wherein R 3 is —H, —CH 3 , —CH 2 —CH 2 —CH 3 , or —CH 2 —O—CH 3 .

61 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 60 , wherein m is 1 and R 15 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

62 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 61 , wherein m is 1 and R 15 is —H or C 1-6 alkyl optionally substituted with R′.

63 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 62 , wherein m is 1 and R 15 is —H or C 1-3 alkyl.

64 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 63 , wherein R 16 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

65 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 64 , wherein R 16 is —H or C 1-6 alkyl optionally substituted with R′.

66 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 65 , wherein R 16 is —H or C 1-3 alkyl.

67 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 66 , wherein each of R 20a and R 20b are independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′, or R 20a and R 20b taken together form oxo.

68 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 67 , wherein each of R 20a and R 20b are independently selected from —H, C 1-6 alkyl, —N(R′) 2 , and —O—R′, or R 20a and R 20b taken together form oxo.

69 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 68 , wherein R 20a and R 20b taken together form oxo.

70 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 69 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —, or —NH—; and R 30 is a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein the 3-8-membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

71 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 70 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, or —NH—; and R 30 is a 5-6-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

72 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 71 , wherein R 21 is -L A -R 30 ; L A is a bond or —CH 2 —; and R 30 is a 5-6-membered partially unsaturated or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-2 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

73 . The compound or pharmaceutically acceptable salt of any one of claims 57 - 72 , wherein R 21 is -L A -R 30 L A is a bond or —CH 2 —; and R 30 is

wherein

(i) at least one of X 1 , X 2 , X 3 , and X 4 is N, and

(ii) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

74 . The compound or pharmaceutically acceptable salt of claim 57 , wherein the compound of Formula (IV) is a compound of Formula (IV-A)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1 , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15 , R 16 , R 20a , R 20b , and R 21 is -L A -R 30 ;

Each R 30 is independently selected from R′, halo, —CN, —NO 2 , and —CF 3 ;

Each R′ is independently selected from —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein each alkyl, alkenyl, alkynyl, or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 , or

R 20a and R 20b taken together form oxo;

R 5 is —H or C 1-3 alkyl; and

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl.

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

each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15 , and R 16 is independently selected from —H or C 1-6 alkyl;

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-5 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-3 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

Each of R 15 and R 16 is independently —H or C 1-6 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —C 1-5 alkyl-OH, C 1-6 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

R 30 is R′, halo, —CN, —NO 2 , and —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

76 . The compound or pharmaceutically acceptable salt of claim 74 or claim 75 , wherein the compound of Formula (IV-A) is a compound of Formula (IV-A1)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1 , R 1b , R 2a , and R 2b is independently selected from —H and C 1-3 alkyl;

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-3 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —CH 2 OH, C 1-3 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or a straight or branched C 1-3 alkylene chain;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

R′ is —H, C 1-6 alkyl, or a 3-8-membered partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein the 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

77 . The compound or pharmaceutically acceptable salt of claim 76 , wherein the compound of Formula (IV-A1) is a compound of Formula (IV-A1a) or (IV-A1b)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , and R 2b is selected from —H and C 1-3 alkyl;

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or C 1-3 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —CH 2 OH, C 1-3 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or a straight or branched C 1-3 alkylene chain;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

78 . The compound or pharmaceutically acceptable salt of claim 77 , wherein the compound of Formula IV-A1a) is a compound of Formula (IV-A1a1) or (IV-A1a2)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , and R 2b is independently selected from —H and C 1-3 alkyl;

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or C 1-3 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —CH 2 OH, C 1-3 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or a straight C 1-3 alkylene chain;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

79 . The compound or pharmaceutically acceptable salt of claim 77 , wherein the compound of Formula (TV-A11h) is a compound of Formula (TV-A1b1) or (TV-A1b2)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , and R 2b is independently selected from —H and C 1-3 alkyl;

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or C 1-3 alkyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, —CH 2 OH, C 1-3 alkyl, and —NH 2 , or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or a straight C 1-3 alkylene chain;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

80 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (I) is a compound of Formula (V)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-6 alkyl, or

R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

81 . The compound or pharmaceutically acceptable salt of claim 80 , wherein R 20a and R 20b taken together form oxo.

82 . The compound or pharmaceutically acceptable salt of claim 80 , wherein one of R 20a and R 20b is —H, and the other of R 20a and R 20b is C 1-6 alkyl.

83 . The compound or pharmaceutically acceptable salt of claim 80 , wherein one of R 20a and R 20b is C 1-6 alkyl, and the other of R 20a and R 20b is —OH.

84 . The compound or pharmaceutically acceptable salt of claim 80 or claim 83 , wherein one of R 20a and R 20b is methyl, ethyl, or propyl, and the other is —OH.

85 . The compound or pharmaceutically acceptable salt of any one of claim 80 , wherein R 20a , R 20b , and the carbon to which they are attached form

86 . The compound or pharmaceutically acceptable salt of any one of claims 80 - 85 , wherein R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-3 alkylene chain, or —N(H)—; and

87 . The compound or pharmaceutically acceptable salt of any one of claims 80 - 86 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —, or —N(H)—; and R 30 is —H or a 5-6-membered partially unsaturated, or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

88 . The compound or pharmaceutically acceptable salt of any one of claims 80 - 87 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —, or —N(H)—; and R 30 is a 5-6-membered partially unsaturated, or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

89 . The compound or pharmaceutically acceptable salt of any one of claims 80 - 88 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, or —N(H)—; and R 30 is

(i) at least one of X 1 , X 2 , X 3 , and X 4 is N, and

(ii) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

90 . The compound or pharmaceutically acceptable salt of claim 88 , wherein R 30 is

(i) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

91 . The compound or pharmaceutically acceptable salt of claim 80 , wherein the compound of Formula (V) is a compound of Formula (V-A)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-6 alkyl, or

R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

92 . The compound or pharmaceutically acceptable salt of claim 91 , wherein

R 3 is —H, C 1-3 alkyl, C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-3 alkyl, or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

R 30 is —H, halo, —OH, —CN, —NO 2 , —CF 3 , or a 5-6-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring of R 30 is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

93 . The compound or pharmaceutically acceptable salt of claim 91 , wherein the compound of Formula (V-A) is a compound of Formula (V-A1) or (V-A2)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-6 alkyl, or

R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

94 . The compound or pharmaceutically acceptable salt of claim 93 , wherein

R 3 is —H, C 1-3 alkyl, C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-3 alkyl, or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

95 . The compound or pharmaceutically acceptable salt of claim 93 , wherein the compound of Formula (V-A1) is a compound of Formula (V-A1a) or (V-A1b)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-6 alkyl, or

R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

96 . The compound or pharmaceutically acceptable salt of claim 94 , wherein

R 3 is —H, C 1-3 alkyl, C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-3 alkyl, or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

97 . The compound or pharmaceutically acceptable salt of claim 93 , wherein the compound of Formula (V-A2) is a compound of Formula (V-A2a) or (V-A2b)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

R 10 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-6 alkyl, or

R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

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

R 3 is —H, C 1-3 alkyl, C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

Each of R 20a and R 20b is independently selected from —H, —OH, and C 1-3 alkyl, or R 20a and R 20b taken together form oxo;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

99 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (I) is a compound of Formula (VI)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 3 , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 13 , R 15 , R 16 , R 17 , and R 21 is -L A -R 30 ;

Each R 30 is independently selected from R′, halo, —CN, —NO 2 , and —CF 3 ;

R 1a and R 1b taken together form oxo, or

R 2a and R 2b taken together form oxo, or

R 4a and R 4b taken together form oxo, or

R 6a and R 6b taken together form oxo, or

R 7a and R 7b taken together form oxo, or

R 11a and R 11b taken together form oxo, or

R 12a and R 12b taken together form oxo;

Each of R 5 and R 20c is independently selected from —H and methyl;

R 10 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

Each of R 31a and R 31b is

(i) independently selected from —H, halo, and C 1-6 alkyl, or

(ii) when one of R 31a and R 31b is —H, the other of R 31a and R 31b is —H, halo, C 1-6 alkyl, or —OR 32 , wherein R 32 is —H, C 1-6 alkyl, or a 3-6-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S;

n is 0, 1, or 2; and

m is 1 or 2.

100 . The compound or pharmaceutically acceptable salt of claim 99 , wherein R 3 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

101 . The compound or pharmaceutically acceptable salt of claim 99 or claim 100 , wherein R 3 is —H or C 1-6 alkyl optionally substituted with R′.

102 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 101 , wherein R 3 is —H or methyl.

103 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 102 , wherein R 13 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

104 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 103 , wherein R 13 is —H or C 1-6 alkyl optionally substituted with R′.

105 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 104 , wherein R 13 is —H or C 1-3 alkyl.

106 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 105 , wherein R 13 is methyl.

107 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 106 , wherein m is 1 and R 15 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

108 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 107 , wherein m is 1 and R 15 is —H or C 1-6 alkyl optionally substituted with R′.

109 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 108 , wherein m is 1 and R 15 is —H or C 1-3 alkyl.

110 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 109 , wherein R 16 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

111 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 110 , wherein R 16 is —H or C 1-6 alkyl optionally substituted with R′.

112 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 111 , wherein R 16 is —H or C 1-3 alkyl.

113 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 112 , wherein R 17 is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

114 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 113 , wherein R 17 is —H or C 1-6 alkyl optionally substituted with R′.

115 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 114 , wherein R 17 is —H or C 1-3 alkyl.

116 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 115 , wherein R 20 is —H.

117 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 116 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —CH 2 —, or —CH 2 —CH 2 —; and R 30 is a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein the 3-8-membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

118 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 117 , wherein R 21 is -L A -R 30 ; L A is a bond or —CH 2 —; and R 30 is a 5-6-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 heteroatoms independently selected from N, O, and S, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

119 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 118 , wherein R 21 is -L A -R 30 ; L A is a bond or —CH 2 —; and R 30 is a 5-6-membered partially unsaturated or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-2 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

120 . The compound or pharmaceutically acceptable salt of any one of claims 99 - 119 , wherein R 21 is -L A -R 30 L A is a bond or —CH 2 —; and R 30 is

(i) at least one of X 1 , X 2 , X 3 , and X 4 is N, and

(ii) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

121 . The compound of pharmaceutically acceptable salt of claim 99 , wherein the compound of Formula (VI) is a compound of Formula (VI-A) or (VI-B)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 13 , R 15 , R 16 , and R 17 is independently selected from —H and C 1-6 alkyl;

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 5 and R 20c is independently selected from —H and methyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 21 is -L A -R 30 ;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

122 . The compound or pharmaceutically acceptable salt of claim 121 , wherein the compound of Formula (VI-A) is a compound of Formula (VI-A1) or (VI-A2)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 13 , R 15 , R 16 , and R 17 is independently selected from —H or C 1-6 alkyl;

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 5 and R 20c is independently selected from —H and methyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 21 is -L A -R 30 ;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

123 . The compound or pharmaceutically acceptable salt of claim 121 , wherein the compound of Formula (VI-B) is a compound of Formula (VI-B1) or (VI-B2)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 13 , R 15 , R 16 , and R 17 is independently selected from —H or C 1-6 alkyl;

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 5 and R 20c is independently selected from —H and methyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 21 is -L A -R 30 ;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

124 . The compound or pharmaceutically acceptable salt of claim 121 wherein the compound of Formula (VI-A) is a compound of Formula (VI-A1a), (VI-A1b), (VI-A1c), or (VI-A1d)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 13 , R 15 , R 16 , and R 17 is independently selected from —H and C 1-6 alkyl;

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 5 and R 20c is independently selected from —H and methyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 21 is -L A -R 30 ;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

125 . The compound or pharmaceutically acceptable salt of claim 121 , wherein the compound of Formula (VI-B) is a compound of Formula (VI-B1a), (VI-B1b), (VI-B1c), or (VI-B1d)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 13 , R 15 , R 16 , and R 17 is independently selected from —H and C 1-6 alkyl;

R 3 is —H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 1-6 alkyl-O—C 1-6 alkyl;

Each of R 5 and R 20c is independently selected from —H and methyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 21 is -L A -R 30 ;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

Each R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein each alkyl or 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

126 . The compound or pharmaceutically acceptable salt of claim 99 , wherein the compound of Formula (VI) is a compound of Formula (VI-A3a), (VI-A3b), (VI-B3a), or (VI-B3b)

or a pharmaceutically acceptable salt thereof, wherein

Each of R 1a , R 1b , R 2a , and R 2b is independently selected from —H and C 1-3 alkyl;

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

Each of R 5 , R 13 , R 17 , and R 20c is independently selected from —H and methyl;

R 10 is —H, C 1-3 alkyl, or C 1-6 alkyl-O—C 1-3 alkyl;

R 21 is -L A -R 30 ;

L A is a bond or a straight C 1-3 alkylene chain;

R 30 is R′, halo, —CN, —NO 2 , or —CF 3 ; and

R′ is independently selected from —H, C 1-6 alkyl, and a 3-8-membered partially unsaturated, or fully unsaturated monocyclic ring having 0-4 nitrogen atoms, wherein the 3-8-membered ring of R′ is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , and —CH 3 .

127 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (I) is a compound of Formula (VII)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

Each of R 10 and R 13 is independently selected from —H, C 1-6 alkyl, and C 1-6 alkyl-O—C 1-6 alkyl;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

128 . The compound or pharmaceutically acceptable salt of claim 127 , wherein R 13 is —H, C 1-6 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl.

129 . The compound or pharmaceutically acceptable salt claim 127 or claim 128 , wherein R 13 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl.

130 . The compound or pharmaceutically acceptable salt of any one of claims 127 - 129 , wherein R 13 is —H, methyl, ethyl, propyl, iso-propyl, methyoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, or propoxyethyl.

131 . The compound or pharmaceutically acceptable salt of any one of claims 127 - 130 , wherein R 13 is methyl.

132 . The compound or pharmaceutically acceptable salt of any one of claims 127 - 131 , wherein R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-3 alkylene chain, or —N(H)—; and

133 . The compound or pharmaceutically acceptable salt of any one of claims 127 - 132 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —, or —N(H)—; and R 30 is —H or a 5-6-membered partially unsaturated, or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

134 . The compound or pharmaceutically acceptable salt of any one of claims 127 - 133 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, —CH 2 —CH 2 —, or —N(H)—; and R 30 is a 5-6-membered partially unsaturated, or fully unsaturated monocyclic ring having 1-4 nitrogen atoms, wherein the 5-6-membered ring is optionally substituted with 1-3 groups independently selected from —CN, —NO 2 , —CF 3 , —CH 3 , —CH 2 OH, and —C(CH 3 ) 3 .

135 . The compound or pharmaceutically acceptable salt of any one of claims 127 - 134 , wherein R 21 is -L A -R 30 ; L A is a bond, —CH 2 —, or —N(H)—; and R 30 is

(i) at least one of X 1 , X 2 , X 3 , and X 4 is N, and

(ii) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

136 . The compound or pharmaceutically acceptable salt of claim 134 , wherein R 30 is

(i) no greater than 2 instances of R″ are independently selected from halo, —OH, —CN, —NO 2 , —CF 3 , —CH 3 , and —CH 2 OH.

137 . The compound or pharmaceutically acceptable salt of claim 127 , wherein the compound of Formula (VII) is a compound of Formula (VII-A) or (VII-B)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

Each of R 10 and R 13 is independently selected from —H, C 1-6 alkyl, and C 1-6 alkyl-O—C 1-6 alkyl;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

138 . The compound or pharmaceutically acceptable salt of claim 137 , wherein

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 13 is —H, or C 1-3 alkyl;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

139 . The compound or pharmaceutically acceptable salt of claim 137 , wherein the compound of Formula (VII-A) is a compound of Formula (VII-A1) or (VII-A2)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

Each of R 10 and R 13 is independently selected from —H, C 1-6 alkyl, and C 1-6 alkyl-O—C 1-6 alkyl;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

140 . The compound or pharmaceutically acceptable salt of claim 139 , wherein

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 13 is —H, or C 1-3 alkyl;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

141 . The compound or pharmaceutically acceptable salt of claim 137 , wherein the compound of Formula (VII-B) is a compound of Formula (VII-B1) or (VII-B2)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

Each of R 10 and R 13 is independently selected from —H, C 1-6 alkyl, and C 1-6 alkyl-O—C 1-6 alkyl;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

142 . The compound or pharmaceutically acceptable salt of claim 141 , wherein

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 13 is —H, or C 1-3 alkyl;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

143 . The compound or pharmaceutically acceptable salt of claim 137 , wherein the compound of Formula (VII-A) is a compound of Formula (VII-A1a), (VII-A1b), (VII-A1c), or (VII-A1d)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

Each of R 10 and R 13 is independently selected from —H, C 1-6 alkyl, and C 1-6 alkyl-O—C 1-6 alkyl;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

144 . The compound or pharmaceutically acceptable salt of claim 143 , wherein

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 13 is —H, or C 1-3 alkyl;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

145 . The compound or pharmaceutically acceptable salt of claim 137 , wherein the compound of Formula (VII-B) is a compound of Formula (VII-B1a), (VII-B1b), (VII-B1c), or (VII-B1d)

or a pharmaceutically acceptable salt thereof, wherein

R 3 is —H, C 1-6 alkyl, or C 1-6 alkyl-O—C 1-6 alkyl;

R 5 is —H or C 1-6 alkyl;

Each of R 10 and R 13 is independently selected from —H, C 1-6 alkyl, and C 1-6 alkyl-O—C 1-6 alkyl;

R 21 is -L A -R 30 ;

L A is a bond, a branched or straight C 1-6 alkylene chain, or —N(H)—; and

146 . The compound or pharmaceutically acceptable salt of claim 145 , wherein

R 3 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 5 is —H or methyl;

R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl;

R 13 is —H, or C 1-3 alkyl;

R 21 is -L A -R 30 ;

L A is a bond or an optionally substituted branched or straight C 1-3 alkylene chain; and

147 . The compound of pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , or 99 - 120 , wherein each of R 1 and R 1b is independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′, or R 1a and R 1b taken together form oxo.

148 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 , wherein each of R 1 and R 1b is independently selected from —H and C 1-6 alkyl optionally substituted with R′, or R 1a and R 1b taken together form oxo.

149 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 , wherein one of R 1a and R 1b is —H, and the other is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

150 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 149 , wherein one of R 1a and R 1b is —H, and the other is —H or C 1-6 alkyl optionally substituted with R′.

151 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 150 , wherein each of R 1a and R 1b is —H.

152 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 151 , wherein each of R 2a and R 2b is independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′, or R 2a and R 2b taken together form oxo.

153 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 152 , wherein each of R 2a and R 2b is independently selected from —H and C 1-6 alkyl optionally substituted with R′, or R 2a and R 2b taken together form oxo.

154 . The compound or pharmaceutically acceptable salt of any one of 2-16, 57-73, 99-120, or 147-152, wherein one of R 2a and R 2b is —H, and the other is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

155 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , 147 - 152 , or 154 , wherein one of R 2a and R 2b is —H, and the other is —H or C 1-6 alkyl optionally substituted with R′.

156 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 155 , wherein each of R 2a and R 2b is —H.

157 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 156 , wherein n is 1 and each of R 4a and R 4b is independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′, or R 4a and R 4b taken together form oxo.

158 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 157 , wherein n is 1 and each of R 4a and R 4b is independently selected from —H or C 1-6 alkyl optionally substituted with R′, or R 4a and R 4b taken together form oxo.

159 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 156 , wherein n is 1, one of R 4a and R 4b is —H, and the other is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

160 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , 147 - 156 , or 159 , wherein n is 1, one of R 4a and R 4b is —H, and the other is —H or C 1-6 alkyl optionally substituted with R′.

161 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 160 , wherein n is 1 and each of R 4a and R 4b is —H.

162 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 161 , wherein R 5 is —H.

163 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 162 , wherein each of R 6a , R 6b , R 7a , and R 7b is independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′, or R 6a and R 6b taken together form oxo, or R 7a and R 7b taken together form oxo.

164 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 163 , wherein each of R 6a , R 6b , R 7a , and R 7b is independently selected from —H and C 1-6 alkyl optionally substituted with R′.

165 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 163 , wherein two of R 6a , R 6b , R 7a , and R 7b are —H, and the other two of R 6a , R 6b , R 7a , and R 7b are independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′.

166 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , 147 - 163 , or 165 , wherein three of R 6a , R 6b , R 7a , and R 7b are —H, and the other of R 6a , R 6b , R 7a , and R 7b is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

167 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 166 , wherein each of R 6a , R 6b , R 7a , and R 7b is —H.

168 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 167 , wherein R 10 is —H, C 1-6 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl.

169 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 168 , wherein R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl.

170 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 169 , wherein R 10 is —H, methyl, ethyl, propyl, iso-propyl, methoxymethyl, ethoxymethyl, methoxyethyl, or ethoxyethyl.

171 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 170 , wherein each of R 11a , R 11b , R 12a , and R 12b is independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′, or R 11a and R 11b taken together form oxo, or R 12a and R 12b taken together form oxo.

172 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 171 , wherein each of R 11a , R 11b , R 12a , and R 12b is independently selected from —H and C 1-6 alkyl optionally substituted with R′.

173 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 171 , wherein two of R 11a , R 11b , R 12a , and R 12b are —H, and the other two of R 11a , R 11b , R 12a , and R 12b are independently selected from —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , and —O—R′.

174 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , 147 - 171 , or 173 , wherein three of R 11a , R 11b , R 12a , and R 12b are —H, and the other of R 11a , R 11b , R 12a , and R 12b is —H, C 1-6 alkyl optionally substituted with R′, —N(R′) 2 , or —O—R′.

175 . The compound or pharmaceutically acceptable salt of any one of claims 2 - 16 , 57 - 73 , 99 - 120 , or 147 - 174 , wherein each of R 11a , R 1b , R 12a , and R 12b is —H.

176 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , or 127 - 136 , wherein R 3 is C 1-6 alkyl or C 1-6 alkyl-O—C 1-6 alkyl.

177 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , 127 - 136 , or 176 , wherein R 3 is methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, neopentyl, methyoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, or propoxyethyl.

178 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , 127 - 136 , 176 , or 177 , wherein R 3 is —CH 3 , —CH 2 —CH 3 , —CH 2 —CH 2 —CH 3 , or —CH 2 —O—CH 3 .

179 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , 127 - 136 , or 176 - 178 , wherein R 5 is —H or C 1-3 alkyl.

180 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , 127 - 136 , or 176 - 179 , wherein R 5 is —H or methyl.

181 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , 127 - 136 , or 176 - 180 , wherein R 10 is —H, C 1-6 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl.

182 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , 127 - 136 , or 176 - 181 , wherein R 10 is —H, C 1-3 alkyl, or C 1-3 alkyl-O—C 1-3 alkyl.

183 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , 127 - 136 , or 176 - 182 , wherein R 10 is —H, methyl, ethyl, propyl, iso-propyl, methyoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, or propoxyethyl.

184 . The compound or pharmaceutically acceptable salt of any one of claims 30 - 43 , 80 - 90 , 127 - 136 , or 176 - 183 , wherein R 10 is —H or methyl.

185 . A compound selected from

or a pharmaceutically acceptable salt thereof.

186 . A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of any one of claims 1 - 185 , and a pharmaceutically acceptable carrier, vehicle, or excipient.

187 . A method of modulating a GABA A receptor in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of claims 1 - 185 or a pharmaceutical composition of claim 186 .

188 . A method of modulating a GABA A receptor mediated CNS-related disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of claims 1 - 185 or a pharmaceutical composition of claim 186 .

189 . A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of any one of claims 1 - 185 or a pharmaceutical composition of claim 186 .

190 . The method of claim 188 or claim 189 , wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, an autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, tinnitus, or status epilepticus.

191 . The method of claim 190 , wherein the CNS-related disorder is a mood disorder.

192 . The method of claim 191 , wherein the mood disorder is depression.

193 . The method of claim 192 , wherein the depression is postpartum depression.

194 . The method of claim 192 , wherein the depression is a major depressive disorder.

195 . The method of claim 194 , wherein the major depressive disorder is a moderate major depressive disorder.

196 . The method of claim 195 , wherein the major depressive disorder is a severe major depressive disorder.

Assignments (7)

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 Oct 19, 2023