Granted Patent B2

US 12,473,327 · App. 18/455,007 · Granted Nov 18, 2025

Inventors: Boyd L. Harrison (Princeton Junction, NJ); Gabriel Martinez Botella (Wayland, MA); Albert Jean Robichaud (Boston, MA); Francesco G. Salituro (Marlborough, MA)

Assignee: Sage Therapeutics, LLP

C07J41/005C07J5/0015C07J7/002C07J7/009C07J17/00C07J1/0011C07J7/007C07J7/0085C07J13/007C07J21/00C07J21/006C07J21/008

Abstract

Claims (39)

1 . A method for treating a CNS-related disorder, wherein the CNS-related disorder is a traumatic brain injury in a human subject in need thereof comprising administering to the human subject a therapeutically effective amount of a) a compound of Formula (I) or a pharmaceutically acceptable salt thereof or b) a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, wherein:

R 1 is 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 ring;

R 3 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 , or —C(O) NR B R C ;

R 4 is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, 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 6 and CR 5a R 5b is a double bond, then one of R 5a or R 5b is absent; and

when one of the is a double bond, R 6 is absent;

each of R 5a and R 5b is independently absent, hydrogen, C 1 -C 6 alkyl, or halo;

R 6 is absent or hydrogen;

Z is —CR 7a R 7b —, wherein each of R 7a and R 7b is independently hydrogen or C 1 -C 6 alkyl, or R 7a and R 7b , together with the carbon atom to which they are attached, form a ring;

R A is hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; and

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 ring.

2 . The method of claim 1 , wherein R 1 is methyl.

3 . The method of claim 1 , wherein both R 2a and R 2b are hydrogen.

4 . The method of claim 1 , wherein R 3 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, heterocyclyl, C(O)R A , —C(O)OR A , or —C(O)NR B R C .

5 . The method of claim 1 , wherein R 4 is hydrogen, C 1 -C 6 alkyl, or —OH.

6 . The method of claim 1 , wherein both R 2a and R 2b are hydrogen, the between —CR 6 and —CR 5a R 5b is a single bond, and both R 5a and R 5b are hydrogen.

7 . The method of claim 1 , wherein Z is —CH 2 —.

8 . The method of claim 1 , wherein R 7a is hydrogen and R 7b is C 1 -C 6 alkyl.

9 . The method of claim 1 , wherein the compound of Formula (I) is a compound of Formula (Ia) or a compound of Formula (Ib):

wherein:

R 1 is 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 ring;

R 3 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 , or —C(O) NR B R C ,

R 4 is hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, or OR A ;

each of R 5a and R 5b is independently hydrogen, C 1 -C 6 alkyl, or halo;

Z is —CR 7a R 7b —, wherein each of R 7a and R 7b is independently hydrogen or C 1 -C 6 alkyl, or R 7a and R 7b , together with the carbon atom to which they are attached, form a ring;

R A is hydrogen, C 1 -C 6 alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl; and

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 ring.

10 . The method of claim 9 , wherein R 1 is methyl.

11 . The method of claim 9 , wherein R 3 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, carbocyclyl, heterocyclyl, —C(O)R A , —C(O)OR A , or —C(O)NR B R C .

12 . The method of claim 9 , wherein R 4 is hydrogen or —OH.

13 . The method of claim 9 , wherein both R 2a and R 2b are hydrogen and both R 5a and R 5b are hydrogen.

14 . The method of claim 9 , wherein the compound of Formula (I) is the compound of Formula (Ia), and the compound of Formula (Ia) is selected from a group consisting of:

15 . The method of claim 9 , wherein the compound of Formula (I) is the compound of Formula (Ib), and the compound of Formula (Ib) is selected from a group consisting of:

16 . The method of claim 1 , wherein the compound is administered orally, subcutaneously, intravenously, or intramuscularly.

Assignments (2)

Continuity (6)

References Cited (400)