Oxysterols and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12129276-B2
Application number	US-202318116557-A
Country	US
Kind code	B2
Filing date	Mar 2, 2023
Priority date	Jun 18, 2014
Publication date	Oct 29, 2024
Grant date	Oct 29, 2024

Abstract

Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein X, Y, R1, R2a, R2b, R4a, R4b, R5a, R5b, R6a, R6b, R7, and R8 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

First claim

What is claimed is:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, or heterocyclyl;
each of R 2a and R 2b is independently hydrogen, C 1 -C 6 alkyl, halo, cyano,—OR A , or —NR B R C , or
R 2a and R 2b together with the carbon atom to which they are attached form a 3-7 membered ring;
each of R 4a and R 4b is independently absent, hydrogen, C 1 -C 6 alkyl, or halo;
X is —C(R X ) 2 — or —O—, wherein R X is independently hydrogen, halo, or one R X group and R 5b are joined to form a double bond;
Y is —OR Y , wherein R Y is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, —C(O)R A , —C(O)OR A , —C(O)NR B R C , or —S(O) 2 R D ;
each instance of R 5a and R 5b is independently hydrogen, halo, or C 1 -C 6 alkyl;
each of R 6a and R 6b is independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl, or
R 6a and R 6b , taken together with the carbon atom to which they are attached, form a 3-6 membered ring; or
R 5a and R 6a , together with the carbon atoms to which they are attached, form a 3-6-membered ring; and
R 7 is absent or hydrogen in the alpha configuration;
R 8 is hydrogen, halo, C 1 - 6 alkyl, carbocyclyl, or —OR A ;
represents a single or double bond, wherein when one is a double bond, the other is a single bond;
wherein when the between —CR 7 and —CR 4a R 4b is a double bond, then one of R 4a or R 4b is absent; and
when one of the is a double bond, R 7 is absent;
R A is hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl;
each of R B and R C is independently hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, or taken together with the atom to which they are attached form a 3-7-membered ring; and
R D is hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl.

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

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is substituted C 1 - 3 alkyl.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2a or R 2a is hydrogen.

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

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is —CH 2 —.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8 is substituted or unsubstituted C 1 - 3 alkyl.

8. The compound of claim 1 , wherein the compound of Formula (I) is a compound of Formula (II):

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 8 , wherein the compound of Formula (II) is a compound of Formula (II-A):

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 8 , wherein the compound of Formula (II) is a compound of Formula (II-B):

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5a or R 5b is hydrogen.

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

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6a is a substituted or unsubstituted C 2 - 4 alkyl, substituted or unsubstituted C 2 - 3 alkenyl, substituted or unsubstituted C 2 - 3 alkynyl, or substituted or unsubstituted carbocyclyl.

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

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6a and R 6b , taken together with the atom to which they are attached, form a 3-6 membered ring.

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Y is substituted or unsubstituted C 1 - 3 alkyl.

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Y is substituted or unsubstituted heterocyclyl.

18. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

19. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

20. The compound of claim 18 , wherein the compound is:

Assignees

• Sage Therapeutics Inc

Inventors

• Harrison Boyd L
• Martinez Botella Gabriel
• Robichaud Albert Jean
• Salituro Francesco G

Classifications

• A61K9/4866

  Organic macromolecular compounds · CPC title

• A61K9/2063

  Proteins, e.g. gelatin · CPC title

• A61K9/0095

  Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006) · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C07J31/006

  not covered by C07J31/003 · CPC title