Compositions and methods for treating CNS disorders

Patent metadata

Field	Value
Publication number	US-12552829-B2
Application number	US-202017620226-A
Country	US
Kind code	B2
Filing date	Jun 29, 2020
Priority date	Jun 27, 2019
Publication date	Feb 17, 2026
Grant date	Feb 17, 2026

Abstract

Provided herein is a compound of Formula I, II, IIIa, IIIb, V, VIa, VIb, VII, VIII, IX, or XI:

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

First claim

What is claimed:

1 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein
represents a single or double bond, provided if a double bond is present, then one of R 6a or R 6b is absent and R 5 is absent;
R X is selected from the group consisting of halo, —OH, —OR Q1 , and substituted or unsubstituted alkyl, wherein R Q1 is substituted or unsubstituted alkyl;
R Y is halo or substituted or unsubstituted alkyl; or
R Y and R X may join together with the intervening atoms to form a substituted or unsubstituted carbocyclyl or a substituted or unsubstituted heterocyclyl;
R 3 is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
R 5 is hydrogen or methyl;
each instance of R 22 is independently selected from the group consisting of halogen, —NO 2 , —CN, —OR GA , —N(R GA ) 2 , —C(═O)R GA , —C(═O)OR GA , —OC(═O)R GA , —OC(═O)OR GA , —C(═O)N(R GA ) 2 , —N(R GA )C(═O)R GA , —OC(═O)N(R GA ) 2 , —N(R GA )C(═O)OR GA , —N(R GA )C(═O)N(R GA ) 2 , —SR GA , —S(═O)R GA , —S(O) 2 R GA , —S(O) 2 OR GA , —OS(═O) 2 R GA , —S(═O) 2 N(R GA ) 2 , —N(R GA )S(═O) 2 R GA , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocylyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein each instance of R GA is independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocylyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, and a nitrogen protecting group when attached to nitrogen, or two R GA groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclyl or heteroaryl ring;
each of R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , and R 12b is independently selected from the group consisting of hydrogen, halogen, cyano, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —C(═O)R A1 , —C(═O)OR A1 , —C(═O)SR A1 , —C(═O)N(R A1 ) 2 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —OC(═O)SR A1 , —OS(═O) 2 R A1 , —OS(═O) 2 OR A1 , —OS(═O) 2 N(R A1 ) 2 , —N(R A1 )C(═O)R A1 , —N(R A1 )C(═NR A1 )R A1 , —N(R A1 )C(═O)OR A1 , —N(R A1 )C(═O)N(R A1 ) 2 , —N(R A1 )S(═O) 2 R A1 , —N(R A1 )C(═NR A1 )N(R A1 ) 2 , —N(R A1 )S(═O) 2 OR A1 , —N(R A1 )S(═O) 2 N(R A1 ) 2 , —SC(═O)OR A1 , —SC(═O)R A1 , —SC(═O)SR A1 , —SC(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , or —S(═O) 2 N(R A1 ) 2 , wherein each instance of R A1 is independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 carbocyclyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, and a sulfur protecting group when attached to sulfur, or two R A1 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;
each of R 6a and R 6b is independently selected from the group consisting of hydrogen, halogen, cyano, —NO 2 , —OH, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; or R 6a and R 6b are joined to form an oxo (═O) group;
each of R 15a , R 15b , R 16a , and R 16b is independently selected from the group consisting of hydrogen, halogen, —CN, —NO 2 , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR C3 , —N(R C3 ) 2 , —SR C3 , —C(═O)R C3 , —C(═O)OR C3 , —C(═O)SR C3 , —C(═O)N(R C3 ) 2 , —OC(═O)R C3 , —OC(═O)OR C3 , —OC(═O)N(R C3 ) 2 , —OC(═O)SR C3 , —OS(═O) 2 R C3 , —OS(═O) 2 OR C3 , —OS(═O) 2 N(R 3 ) 2 , —N(R C3 )C(═O)R C3 , —N(R C3 )C(═NR C3 )R C3 , —N(R C3 )C(═O)OR C3 , —N(R C3 )C(═O)N(R C3 ) 2 , —N(R C3 )C(═NR C3 )N(R C3 ) 2 , —N(R C3 )S(═O) 2 R C3 , —N(R C3 )S(═O) 2 OR C3 , —N(R C3 )S(═O) 2 N(R C3 ) 2 , —SC(═O)R C3 , —SC(═O)OR C3 , —SC(═O)SR C3 , —SC(═O)N(R C3 ) 2 , —S(═O) 2 R C3 , —S(═O) 2 OR C3 , or —S(═O) 2 N(R C3 ) 2 , wherein each instance of R C3 is independently selected from the group consisting of hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted heterocyclyl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, and a sulfur protecting group when attached to sulfur, or two R C3 groups are taken with the intervening atoms to form a substituted or unsubstituted heterocyclic ring;
R 19 is hydrogen or substituted or unsubstituted alkyl;
n is 0, 1, 2, or 3; and
t is 2 or 3.

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

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

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

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

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

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

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

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

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

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

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

13 . The compound or pharmaceutically acceptable salt of claim 2 , wherein n is 1 and R 22 is halogen, —CN, —OR GA , —N(R GA ) 2 , substituted or

Assignees

• Sage Therapeutics Inc

Inventors

• Salituro Francesco G
• Blanco-Pillado Maria Jesus
• Morningstar Marshall Lee

Classifications

• C07J63/002

  Expansion of ring A by one atom, e.g. A homo steroids · CPC title

• C07J61/00

  Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by contraction of only one ring by one or two atoms · CPC title

• A61P25/24 Primary

  Antidepressants · CPC title

• A61K31/57

  substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone · CPC title

• C07J63/008 Primary

  Expansion of ring D by one atom, e.g. D homo steroids · CPC title