IP Library › Granted Patent US 12,686,700

Granted Patent B2

US 12,686,700 · App. 18/171,798 · Granted Jul 21, 2026

Neuroactive steroids substituted in position 10 with a cyclic group for use in the treatment of CNS disorders

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

Assignee: Sage Therapeutics, LLC

C07J43/003 A61P23/00 A61P25/08 A61P25/22 A61P25/24 C07J7/002

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Quick Facts

Patent No.: US 12,686,700
App. No.: 18/171,798
Granted: Jul 21, 2026
Kind: B2

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Abstract

Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein n, R 19 , R 5 , R 3a , R 6a , R 6b , R 1 , R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 17b , R 15a , R 15b , R 16a and R 16b are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.

Claims (106)

1 . A method of therapeutically treating a CNS-related disorder related to GABA function in a subject suffering from the CNS-related disorder related to GABA function, comprising administering to the subject a therapeutically effective amount of 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;

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

each of R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , and R 17b is independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 ) R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )C(═NR A1 ) N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)R A1 , —SC(═O)OR A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each R A1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, a sulfur protecting group when attached to sulfur, or two RAI groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;

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

R 5 is hydrogen or methyl; when is a double bond, R 5 is absent;

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

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

R 19 is substituted or unsubstituted C 3 -C 6 carbocyclyl or substituted or unsubstituted aryl; and

n is 0, 1 or 2;

wherein the CNS-related disorder related to GABA function is depression, seizure, tremor, epilepsy, or anxiety.

2 . The method of claim 1 , wherein R 1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.

3 . The method of claim 2 , wherein R 1 is hydrogen, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.

4 . The method of claim 3 , wherein R 1 is selected from the group consisting of:

wherein:

each instance of R a is independently hydrogen, halogen, —NO 2 , —CN, —OR D4 , —N(R D4 ) 2 , —C(═O)R D4 , —C(═O)OR D4 , —C(═O)N(R D4 ) 2 , —OC(═O)R D4 , —OC(═O)OR D4 , —N(R D4 ) C(═O)R D4 , —OC(═O)N(R D4 ) 2 , —N(R D4 ) C(═O)OR D4 , —S(═O) 2 R D4 , —S(═O) 2 OR D4 , —OS(═O) 2 R D4 , —S(═O) 2 N(R D4 ) 2 , or —N(R D4 ) S(═O) 2 R D4 , substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl;

each instance of R D4 is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R D4 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; and

p is an integer selected from 0 to 11.

5 . The method of claim 1 , wherein each of R 2a and R 2b is independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —OR E5 , —OC(═O)R E5 , —OS(═O) 2 OR E5 , —N(R E5 ) 2 , —N(R E5 ) C(═O)R E5 , —N(R E5 ) S(═O) 2 R E5 , or —N(R E5 ) S(═O) 2 OR E5 ;

wherein each instance of R E5 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or two R E5 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring.

6 . The method of claim 5 , wherein each of R 2a and R 2b is independently hydrogen, —OH, substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 1-6 alkoxy.

7 . The method of claim 6 , wherein each of R 2a and R 2b is independently hydrogen, —CH 3 , —CH 2 CH 3 , —OH, —OCH 3 , or —CH(CH 3 ) 2 .

8 . The method of claim 7 , wherein R 2a and R 2b are both hydrogen.

9 . The method of claim 1 , wherein R 3a is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

10 . The method of claim 9 , wherein R 3a is substituted or unsubstituted C 1-6 alkyl.

11 . The method of claim 1 , wherein R 3a is hydrogen, methyl, methoxymethyl, or ethoxymethyl.

12 . The method of claim 1 , wherein each of R 4a and R 4b is independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —OR E5 , —OC(═O)R E5 , —OS(═O) 2 OR E5 , —N(R E5 ) 2 , or —N(R E5 ) C(═O)R E5 , —N(R E5 ) S(═O) 2 R E5 , —N(R E5 ) S(═O) 2 OR E5 ; wherein each instance of R E5 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or two R E5 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring.

13 . The method of claim 12 , wherein each of R 4a and R 4b is independently hydrogen, —CH 3 , —CH 2 CH 3 , —OH, —OCH 3 , or —CH(CH 3 ) 2 .

14 . The method of claim 13 , wherein R 4a and R 4b are both hydrogen.

15 . The method of claim 1 , wherein R 5 is hydrogen or methyl in the cis position, relative to R 19 .

16 . The method of claim 1 , wherein R 5 is hydrogen or methyl in the trans position, relative to R 19 .

17 . The method of claim 1 , wherein each of R 6a and R 6b is independently hydrogen or unsubstituted alkyl.

18 . The method of claim 17 , wherein both of R 6a and R 6b are hydrogen.

19 . The method of claim 1 , wherein each of R 7a and R 7b is independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —OR E5 , —OC(—O)R E5 , —OS(═O) 2 OR E5 , —N(R E5 ) 2 , or —N(R E5 ) C(═O)R E5 , —N(R E5 ) S(═O) 2 R E5 , —N(R E5 ) S(═O) 2 OR E5 ; wherein each instance of R E5 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or two R E5 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring.

20 . The method of claim 19 , wherein each of R 7a and R 7b is independently hydrogen, —OH, substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 1-6 alkoxy.

21 . The method of claim 20 , wherein each of R 7a and R 7b is independently hydrogen, —CH 3 , —CH 2 CH 3 , —OH, —OCH 3 , or —CH(CH 3 ) 2 .

22 . The method of claim 21 , wherein R 7a and R 7b are both hydrogen.

23 . The method of claim 1 , wherein each of R 11a and R 11b is independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —OR E5 , —OC(—O)R E5 , —OS(═O) 2 OR E5 , —N(R E5 ) 2 , —N(R E5 ) C(═O)R E5 , —N(R E5 ) S(═O) 2 R E5 , or —N(R E5 ) S(═O) 2 OR E5 ; wherein each instance of R E5 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or two R E5 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring.

24 . The method of claim 23 , wherein each of R 11a and R 11b is independently hydrogen, —OH, substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 1-6 alkoxy.

25 . The method of claim 24 , wherein each of R 11a and R 11b is independently hydrogen, —CH 3 , —CH 2 CH 3 , —OH, —OCH 3 , or —CH(CH 3 ) 2 .

26 . The method of claim 25 , wherein R 11a and R 11b are both hydrogen.

27 . The method of claim 1 , wherein each of R 12a and R 12b is independently hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —OR E5 , —OC(═O)R E5 , —OS(═O) 2 OR E5 , —N(R E5 ) 2 , —N(R E5 ) C(═O)R E5 , —N(R E5 ) S(═O) 2 R E5 , or —N(R E5 ) S(═O) 2 OR E5 ; wherein each instance of R E5 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or two R E5 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring.

28 . The method of claim 27 , wherein each of R 12a and R 12b is independently hydrogen, —OH, substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 1-6 alkoxy.

29 . The method of claim 28 , wherein each of R 12a and R 12b is independently hydrogen, —CH 3 , —CH 2 CH 3 , —OH, —OCH 3 , or —CH(CH 3 ) 2 .

30 . The method of claim 29 , wherein R 12a and R 12b are both hydrogen.

31 . The method of claim 1 , wherein R 17b is fluorine, hydroxyl, methyl, or hydrogen; wherein the hydrogen could be optionally be replaced with deuterium.

32 . The method of claim 1 , wherein R 19 is substituted or unsubstituted C 3-6 carbocyclyl, or substituted or unsubstituted C 6-10 aryl.

33 . The method of claim 32 , wherein R 19 is selected from the group consisting of:

wherein:

each R b is independently hydrogen, halogen, —NO 2 , —CN, —OR G7 , —N(R G7 ) 2 , —C(═O)R G7 , —C(═O)OR G7 , —C(═O)N(R G7 ) 2 , —OC(═O)R G7 , —OC(═O)OR G7 , —N(R G7 ) C(═O)R G7 , —OC(═O)N(R G7 ) 2 , —N(R G7 ) C(═O)OR G7 , —S(═O) 2 R G7 , —S(═O) 2 OR G7 , —OS(═O) 2 R G7 , —S(═O) 2 N(R G7 ) 2 , or —N(R G7 )S(═O) 2 R G7 , substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted C 6-10 aryl, or substituted or unsubstituted 5- to 10-membered heteroaryl;

each instance of R G7 is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R G7 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring; and

q is an integer selected from 0 to 11.

34 . The method of claim 1 , wherein n is 0.

35 . The method of claim 1 , wherein n is 1.

36 . The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-a), (I-b), or (I-c):

or a pharmaceutically acceptable salt of any of these compounds.

37 . The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-d):

or a pharmaceutically acceptable salt thereof;

wherein:

each instance of R a is independently halogen, cyano, hydroxyl, or substituted or unsubstituted alkyl; and

p is 0, 1, 2 or 3.

38 . The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-e):

or a pharmaceutically acceptable salt thereof;

wherein:

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

39 . The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-f):

or a pharmaceutically acceptable salt thereof;

wherein:

each X is independently-C(R N )—, —C(R N ) 2 —, —O—, —S—, —N—, or —N(R N )—, wherein each R N is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, —C(═O)R GA , —C(═O)OR GA , —C(═O)N(R GA ) 2 , —S(═O) 2 R GA , or —S(═O) 2 N(R GA ) 2 ; each instance of R GA is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, nitrogen protecting group when attached to nitrogen, or two R GA groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclyl or heteroaryl ring.

40 . The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-g):

or a pharmaceutically acceptable salt thereof;

wherein:

each instance of R a is independently halogen, alkyl, hydroxyl, or cyano; and

p is an integer selected from 0 to 11.

41 . The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (I-h):

or a pharmaceutically acceptable salt thereof;

wherein:

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

42 . The method of claim 1 , wherein the compound of Formula (I) is selected from

or a pharmaceutically acceptable salt thereof.

43 . The method of claim 1 , wherein the CNS-related disorder is depression.

44 . The method of claim 43 , wherein the depression is postpartum depression or a major depressive disorder.

45 . The method of claim 44 , wherein the major depressive disorder is moderate major depressive disorder or a severe major depressive disorder.

46 . The method of claim 1 , wherein the CNS-related disorder is seizure.

47 . The method of claim 1 , wherein the CNS-related disorder is tremor.

48 . The method of claim 47 , wherein the tremor is essential tremor or Parkinsonian tremor.

49 . The method of claim 1 , wherein the CNS-related disorder is epilepsy.

50 . The method of claim 1 , wherein the CNS-related disorder is an anxiety disorder.

51 . The method of claim 1 , wherein the compound of Formula (I) or pharmaceutically acceptable salt thereof is administered orally, intravenously, or intramuscularly.

52 . The method of claim 51 , wherein the compound of Formula (I) or pharmaceutically acceptable salt thereof is administered chronically.

53 . The method of claim 1 , wherein the compound of Formula (I) or pharmaceutically acceptable salt thereof is administered in combination with another therapeutic agent.

54 . A method of inducing sedation and/or anesthesia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of 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;

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

R 5 is hydrogen or methyl; when is a double bond, R 5 is absent;

R 19 is substituted or unsubstituted C 3 -C 6 carbocyclyl or substituted or unsubstituted aryl; and

n is 0, 1 or 2.

55 . The method of claim 1 , wherein the compound of Formula (I) is selected from

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 Mar 16, 2023

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

To: SAGE THERAPEUTICS, INC.

Reel/Frame 062998/0548 →

Continuity (4)

Continuation 17284206 · Oct 11, 2019

Provisional Application 62745109 · Oct 12, 2018

Related Publication 20240051987A1 · Feb 15, 2024

Related Publication 20240376144A9 · Nov 14, 2024

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