IP Library › Granted Patent US 12,286,420
Granted Patent B2
US 12,286,420 · App. 17/959,654 · Granted Apr 29, 2025

EAAT2 activators and methods of using thereof

Inventors: Kevin Hodgetts (Boston, MA); Chien-Liang Glenn Lin (Columbus, OH)
Assignees: OHIO STATE INNOVATION FOUNDATION; THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
C07D401/14A61P25/22A61P25/24A61P25/28C07D237/14C07D401/04C07D413/14
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Quick Facts
Patent No.
US 12,286,420
App. No.
17/959,654
Granted
Apr 29, 2025
Kind
B2
Abstract

Disclosed are compounds that activate excitatory amino acid transporter 2 (EAAT2), as well as methods of using these compounds to treat or preventing diseases, disorders, and conditions associated with glutamate excitotoxicity.

Claims (20)

1. A compound selected from

or a pharmaceutically acceptable salt, ester, or N-oxide thereof.

2. The compound of claim 1 , wherein the compound is selected from

3. The compound of claim 1 , wherein the compound is

4. The compound of claim 1 , wherein the compound is

5. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

6. A method for treating glutamate excitotoxicity in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1 .

7. A method for increasing EAAT2 protein expression in a cell or a subject in need thereof, the method comprising contacting the cell or administering to the subject an effective amount of a compound of claim 1 .

8. A method for activating the NRF2 pathway in a cell or a subject in need thereof, the method comprising contacting the cell or administering to the subject an effective amount of a compound of claim 1 .

9. A method for treating a disease or disorder selected from the group consisting of ischemic stroke, epilepsy, or a trauma, including blunt trauma, an abrasion, an avulsion, an incision, a laceration, a puncture, a penetration, a surgical trauma, iatrogenic trauma, a spinal cord injury, a traumatic brain injury, or any combination thereof; a chronic neurodegenerative disorder, including mild cognitive impairment, Parkinson's disease, Alzheimer's disease, multiple sclerosis, mesial temporal sclerosis, Huntington's disease, AIDS dementia complex, essential tremor, or amyotrophic lateral sclerosis (ALS); a psychotic disorder including schizophrenia, bipolar disorder, or autism; a pain disorder including migraine, temporomandibular disorders, neuropathic pain, visceral pain, or complex regional pain syndrome; an addiction including alcohol addiction, cocaine addiction, heroin addiction, methamphetamine addiction, or nicotine addiction; or a cancer, including glioblastoma; or a mood disorder, including anxiety disorders, depressive disorders, borderline personality disorder, attention-deficit-hyperactivity disorder, suicidal behavior, eating disorders, posttraumatic stress disorder, gulf war illness, and obsessive-Compulsive Disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1 .

10. A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable excipient.

11. A method for treating glutamate excitotoxicity in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 3 .

12. A method for increasing EAAT2 protein expression in a cell or a subject in need thereof, the method comprising contacting the cell or administering to the subject an effective amount of a compound of claim 3 .

13. A method for activating the NRF2 pathway in a cell or a subject in need thereof, the method comprising contacting the cell or administering to the subject an effective amount of a compound of claim 3 .

14. A method for treating a disease or disorder selected from the group consisting of ischemic stroke, epilepsy, or a trauma, including blunt trauma, an abrasion, an avulsion, an incision, a laceration, a puncture, a penetration, a surgical trauma, iatrogenic trauma, a spinal cord injury, a traumatic brain injury, or any combination thereof; a chronic neurodegenerative disorder, including mild cognitive impairment, Parkinson's disease, Alzheimer's disease, multiple sclerosis, mesial temporal sclerosis, Huntington's disease, AIDS dementia complex, essential tremor, or amyotrophic lateral sclerosis (ALS); a psychotic disorder including schizophrenia, bipolar disorder, or autism; a pain disorder including migraine, temporomandibular disorders, neuropathic pain, visceral pain, or complex regional pain syndrome; an addiction including alcohol addiction, cocaine addiction, heroin addiction, methamphetamine addiction, or nicotine addiction; or a cancer, including glioblastoma; or a mood disorder, including anxiety disorders, depressive disorders, borderline personality disorder, attention-deficit-hyperactivity disorder, suicidal behavior, eating disorders, posttraumatic stress disorder, gulf war illness, and obsessive-Compulsive Disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 3 .

15. A pharmaceutical composition comprising a compound of claim 4 and a pharmaceutically acceptable excipient.

16. A method for treating glutamate excitotoxicity in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 4 .

17. A method for increasing EAAT2 protein expression in a cell or a subject in need thereof, the method comprising contacting the cell or administering to the subject an effective amount of a compound of claim 4 .

18. A method for activating the NRF2 pathway in a cell or a subject in need thereof, the method comprising contacting the cell or administering to the subject an effective amount of a compound of claim 4 .

19. A method for treating a disease or disorder selected from the group consisting of ischemic stroke, epilepsy, or a trauma, including blunt trauma, an abrasion, an avulsion, an incision, a laceration, a puncture, a penetration, a surgical trauma, iatrogenic trauma, a spinal cord injury, a traumatic brain injury, or any combination thereof; a chronic neurodegenerative disorder, including mild cognitive impairment, Parkinson's disease, Alzheimer's disease, multiple sclerosis, mesial temporal sclerosis, Huntington's disease, AIDS dementia complex, essential tremor, or amyotrophic lateral sclerosis (ALS); a psychotic disorder including schizophrenia, bipolar disorder, or autism; a pain disorder including migraine, temporomandibular disorders, neuropathic pain, visceral pain, or complex regional pain syndrome; an addiction including alcohol addiction, cocaine addiction, heroin addiction, methamphetamine addiction, or nicotine addiction; or a cancer, including glioblastoma; or a mood disorder, including anxiety disorders, depressive disorders, borderline personality disorder, attention-deficit-hyperactivity disorder, suicidal behavior, eating disorders, posttraumatic stress disorder, gulf war illness, and obsessive-Compulsive Disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 4 .

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 4, 2023
From: LIN, CHIEN-LIANG GLENN
To: OHIO STATE INNOVATION FOUNDATION
Reel/Frame 062267/0490 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 4, 2023
From: HODGETTS, KEVIN
To: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
Reel/Frame 062267/0504 →
Continuity (4)
Continuation 16972311
Provisional Application 62680418 · Jun 4, 2018
Provisional Application 62680423 · Jun 4, 2018
Related Publication 20230138663A1 · May 4, 2023
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