IP Library › Granted Patent US 12673970
Granted Patent B2
US 12673970 · App. 17/912,301 · Granted Jul 7, 2026

Neuroactive steroids and their methods of use

Inventors: Francesco G. Salituro (Marlborough, MA); Marshall Lee Morningstar (Framingham, MA); Maria Jesus Blanco-Pillado (Arlington, MA)
Assignee: Sage Therapeutics, LLC
C07J43/003A61P25/24C07J41/0094
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Quick Facts
Patent No.
US 12673970
App. No.
17/912,301
Granted
Jul 7, 2026
Kind
B2
Abstract

Provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R 2a , R 2b , R 3 , R 4a , R 4b , R 5 , R 6a , R 6b , R 11a , R 11b , R 15a , R 15b , R 16a , R 16b , R 18 , R 19 , R 20a , R 20b , X, A, Z, q, u, r, s, t, m, and n 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 (77)

1 . A compound of Formula (VI-H):

or a pharmaceutically acceptable salt thereof;

wherein:

m is 1, 2, 3, or 4;

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

X is

R 3 is hydrogen or substituted or unsubstituted alkyl;

R 5 is hydrogen or methyl;

R 18 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

R 19 is hydrogen or substituted or unsubstituted alkyl; and

each of R 20a , R 20b , R 23a , and R 23b is independently selected from the group consisting of hydrogen, an unsubstituted alkyl group, a halogenated alkyl group, an unsubstituted alkoxy group, and a halogenated alkoxy group.

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

3 . The compound or pharmaceutically acceptable salt of claim 2 , wherein R 3 is methyl.

4 . The compound or pharmaceutically acceptable salt of claim 1 , wherein R 5 is hydrogen.

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

6 . The compound or pharmaceutically acceptable salt of claim 5 , wherein R 18 is unsubstituted C 1-6 alkyl.

7 . The compound or pharmaceutically acceptable salt of claim 6 , wherein R 18 is methyl or ethyl.

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

9 . The compound or pharmaceutically acceptable salt of claim 8 , wherein R 19 is unsubstituted C 1-3 alkyl.

10 . The compound or pharmaceutically acceptable salt of claim 9 , wherein R 19 is methyl.

11 . The compound or pharmaceutically acceptable salt of claim 1 , wherein R 19 is hydrogen.

12 . The compound or pharmaceutically acceptable salt of claim 1 , wherein each of R 20a and R 20b is independently hydrogen or an unsubstituted C 1-6 alkyl group.

13 . The compound or pharmaceutically acceptable salt of claim 12 , wherein one of R 20a and R 20b is methyl and the other is hydrogen.

14 . The compound or pharmaceutically acceptable salt of claim 12 , wherein R 20a and R 20b are both hydrogen.

15 . The compound or pharmaceutically acceptable salt of claim 1 , wherein each of R 23a and R 23b is independently hydrogen or unsubstituted C 1-3 alkyl.

16 . The compound or pharmaceutically acceptable salt of claim 15 , wherein one of R 23a and R 23b is hydrogen and the other is unsubstituted C 1-3 alkyl.

17 . The compound or pharmaceutically acceptable salt of claim 16 , wherein one of R 23a and R 23b is hydrogen and the other is methyl or ethyl.

18 . The compound or pharmaceutically acceptable salt of claim 15 , wherein both of R 23a and R 23b are hydrogen.

19 . The compound or pharmaceutically acceptable salt of claim 15 , wherein both of R 23a and R 23b are unsubstituted C 1-3 alkyl.

20 . The compound or pharmaceutically acceptable salt of claim 19 , wherein each of R 23a and R 23b is independently selected from methyl or ethyl.

21 . The compound or pharmaceutically acceptable salt of claim 20 , wherein both of R 23a and R 23b are methyl.

22 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (VI-H) is a compound of Formula (VI-IA):

or a pharmaceutically acceptable salt thereof.

23 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (VI-H) is a compound of Formula (VI-IB):

or a pharmaceutically acceptable salt thereof.

24 . The compound or pharmaceutically acceptable salt of claim 23 , wherein R 3 is substituted or unsubstituted alkyl.

25 . The compound or pharmaceutically acceptable salt of claim 24 , wherein R 3 is methyl.

26 . The compound or pharmaceutically acceptable salt of claim 23 , wherein R 5 is hydrogen.

27 . The compound or pharmaceutically acceptable salt of claim 23 , wherein R 18 is substituted or unsubstituted C 1-6 alkyl.

28 . The compound or pharmaceutically acceptable salt of claim 27 , wherein R 18 is unsubstituted C 1-6 alkyl.

29 . The compound or pharmaceutically acceptable salt of claim 28 , wherein R 18 is methyl or ethyl.

30 . The compound or pharmaceutically acceptable salt of claim 23 , wherein R 19 is unsubstituted C 1-6 alkyl.

31 . The compound or pharmaceutically acceptable salt of claim 30 , wherein R 19 is unsubstituted C 1-3 alkyl.

32 . The compound or pharmaceutically acceptable salt of claim 31 , wherein R 19 is methyl.

33 . The compound or pharmaceutically acceptable salt of claim 23 , wherein R 19 is hydrogen.

34 . The compound or pharmaceutically acceptable salt of claim 23 , wherein each of R 20a and R 20b is independently hydrogen or an unsubstituted C 1-6 alkyl group.

35 . The compound or pharmaceutically acceptable salt of claim 34 , wherein one of R 20a and R 20b is methyl and the other is hydrogen.

36 . The compound or pharmaceutically acceptable salt of claim 34 , wherein R 20a and R 20b are both hydrogen.

37 . The compound or pharmaceutically acceptable salt of claim 23 , wherein each of R 23a and R 23b is independently hydrogen or unsubstituted C 1-3 alkyl.

38 . The compound or pharmaceutically acceptable salt of claim 37 , wherein one of R 23a and R 23b is hydrogen and the other is unsubstituted C 1-3 alkyl.

39 . The compound or pharmaceutically acceptable salt of claim 38 , wherein one of R 23a and R 23b is hydrogen and the other is methyl or ethyl.

40 . The compound or pharmaceutically acceptable salt of claim 37 , wherein both of R 23a and R 23b are hydrogen.

41 . The compound or pharmaceutically acceptable salt of claim 37 , wherein both of R 23a and R 23b are unsubstituted C 1-3 alkyl.

42 . The compound or pharmaceutically acceptable salt of claim 37 , wherein each of R 23a and R 23b is independently selected from methyl or ethyl.

43 . The compound or pharmaceutically acceptable salt of claim 41 , wherein both of R 23a and R 23b are methyl.

44 . The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound of Formula (VI-H) is selected from

or a pharmaceutically acceptable salt thereof.

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

46 . A method of treating a CNS-related disorder related to GABA function in a subject in need thereof, comprising administering to the subject an effective amount of a compound or pharmaceutically acceptable salt of claim 1 , wherein the CNS-related disorder is depression.

47 . The method of claim 46 , wherein the depression is postpartum depression or a major depressive disorder.

48 . The method of claim 47 , wherein the major depressive disorder is a moderate major depressive disorder or a severe major depressive disorder.

49 . The compound or pharmaceutically acceptable salt of claim 44 , wherein the compound of Formula (VI-H) is

or a pharmaceutically acceptable salt thereof.

50 . The compound or pharmaceutically acceptable salt of claim 44 , wherein the compound of Formula (VI-H) is

or a pharmaceutically acceptable salt thereof.

51 . The compound or pharmaceutically acceptable salt of claim 44 , wherein the compound of Formula (VI-H) is

or a pharmaceutically acceptable salt thereof.

52 . The compound or pharmaceutically acceptable salt of claim 44 , wherein the compound of Formula (VI-H) is

or a pharmaceutically acceptable salt thereof.

53 . The compound or pharmaceutically acceptable salt of claim 44 , wherein the compound of Formula (VI-H) is

or a pharmaceutically acceptable salt thereof.

54 . The compound or pharmaceutically acceptable salt of claim 44 , wherein the compound of Formula (VI-H) is

or a pharmaceutically acceptable salt thereof.

55 . A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt of claim 44 , and a pharmaceutically acceptable excipient.

56 . A method of treating a CNS-related disorder related to GABA function in a subject in need thereof, comprising administering to the subject an effective amount of a compound or pharmaceutically acceptable salt of claim 44 , wherein the CNS-related disorder is depression.

57 . The method of claim 56 , wherein the depression is postpartum depression or a major depressive disorder.

58 . The method of claim 57 , wherein the major depressive disorder is a moderate major depressive disorder or a severe major depressive disorder.