2-aminoaryl-5-aryloxazole analogs for the treatment of neurodegenerative diseases

Patent metadata

Field	Value
Publication number	US-11905258-B2
Application number	US-202217893091-A
Country	US
Kind code	B2
Filing date	Aug 22, 2022
Priority date	Feb 21, 2018
Publication date	Feb 20, 2024
Grant date	Feb 20, 2024

Abstract

The present disclosure is concerned with 2-aminoaryl-5-aryloxazole compounds that are capable of activating NF-κB signaling. The present disclosure is also concerned with methods of using these compounds for the treatment of neurological disorders such as, for example, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, spinal muscular atrophy, traumatic brain injury, vascular dementia, Huntington's disease, mental retardation, and attention deficit and hyperactivity disorder (ADHD), and neuromuscular disorders such as, for example, Duchenne muscular dystrophy (DMD). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

What is claimed is:

1. A compound having a structure represented by a formula:

wherein R 1 is selected from hydrogen and C1-C4 alkyl;
wherein Ar 1 is selected from monocyclic aryl and pyridinyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino;
wherein Ar 3 is pyridinyl substituted with 0, 1, 2, or 3 R 4 groups; and
wherein each occurrence of R 4 is independently selected from halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino,

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein Ar 1 is monocyclic aryl substituted with 1, 2, or 3 —F groups.

3. The compound of claim 1 , wherein the compound has a structure represented by a formula:

wherein each of R 41a , R 41b , R 41c , R 41d , and R 41e when present, is independently selected from hydrogen, halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

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

5. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 and a pharmaceutically acceptable carrier.

6. A method for the treatment of a disorder in a subject, the method comprising the step of administering to the subject an effective amount of the compound of claim 1
or a pharmaceutically acceptable salt thereof,
wherein the disorder is a neurological disorder or a neuromuscular disorder.

7. The method of claim 6 , wherein the subject has been diagnosed with a need for treatment of a neurological disorder prior to the administering step.

8. The method of claim 6 , further comprising the step of identifying a subject in need of treatment of a neurological disorder.

9. The method of claim 6 , wherein the effective amount is a therapeutically effective amount.

10. The method of claim 6 , wherein the disorder is a neurological disorder.

11. The method of claim 10 , wherein the neurological disorder is ALS.

12. The method of claim 6 , wherein the disorder is a neuromuscular disorder.

13. The method of claim 12 , wherein the neuromuscular disorder is Duchenne muscular dystrophy (DMD) or amyotrophic lateral sclerosis (ALS).

Assignees

• Southern Res Inst

Inventors

• Suto Mark J
• Mathew Bini
• Cowell Rita
• Augelli-Szafran Corinne E

Classifications

• C07D263/48 Primary

  Nitrogen atoms not forming part of a nitro radical · CPC title

• C07D413/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D413/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D263/32

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title