Compounds for treating myelin related disorders

Patent metadata

Field	Value
Publication number	US-12048678-B2
Application number	US-201917282351-A
Country	US
Kind code	B2
Filing date	Oct 1, 2019
Priority date	Oct 2, 2018
Publication date	Jul 30, 2024
Grant date	Jul 30, 2024

Abstract

Disclosed is a pharmaceutical composition comprising a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a myelin related disorder in a subject, the method comprising administering to the subject an effective amount of a compound of Structural Formula (I) or a pharmaceutical composition comprising the compound of Structural Formula (I). The variables of Structural Formula (I) are described herein.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein the compound is represented by the following formula:

wherein:
R 1 is H, alkyl optionally substituted with hydroxyl, alkoxy, thiol, alkylthiol, halo, cyano, or phenyl, wherein the phenyl is optionally substituted with halo, alkoxyl, haloalkoxy, alkyl, haloalkyl, or cyano, or phenyl optionally substituted with halo, alkoxyl, haloalkoxy, alkyl, haloalkyl, or cyano,
each R 2 , R 3 and R 4 is independently halo, alkoxyl, haloalkoxy, alkyl, haloalkyl or cyano;
R 5 is H or alkyl; and
m, n or p are independently 0, 1 or 2.

2. The pharmaceutical composition of claim 1 , where the compound is represented by the following structural formula:

3. The pharmaceutical composition of claim 1 , wherein R 5 is C 1 -C 2 alkyl.

4. A method of promoting myelination in a subject in need thereof, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 1 or the compound recited in claim 1 or a pharmaceutically acceptable salt thereof.

5. A method of treating a myelin related disorder in a subject, the method comprising administering to the subject of the pharmaceutical composition of claim 1 or the compound recited in claim 1 or a pharmaceutically acceptable salt thereof.

6. The method of claim 5 , wherein the myelin related disorder is multiple sclerosis (MS), neuromyelisits optica (NMO), progressive multifocal leukoencephalopathy (PML), encephalomyelitis (EPL), central pontine myelolysis (CPM), adrenoleukodystrophy, Alexander's disease, Pelizaeus Merzbacher disease (PMD), Vanishing White Matter Disease, Wallerian Degeneration, optic neuritis, transverse myelitis, amylotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, Parkinson's disease, spinal cord injury, traumatic brain injury, post radiation injury, neurologic complications of chemotherapy, stroke, acute ischemic optic neuropathy, vitamin E deficiency, isolated vitamin E deficiency syndrome, Bassen-Kornzweig syndrome, Marchiafava-Bignami syndrome, metachromatic leukodystrophy, trigeminal neuralgia, acute dissmeminated encephalitis, Guillian-Barre syndrome, Charcot-Marie-Tooth disease Bell's palsy, a mental health disorder, or schizophrenia.

7. The method of claim 6 , wherein the multiple sclerosis is relapsing remitting multiple sclerosis, primary progressive multiple sclerosis or secondary progressive multiple sclerosis.

Assignees

• Univ Case Western Reserve

Inventors

• Adams Drew
• Tesar Paul J
• Allimuthu Dharmaraja
• Hubler Zita
• Najm Fadi J

Classifications

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K31/4453

  only substituted in position 1, e.g. propipocaine, diperodon · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K31/165 Primary

  having aromatic rings, e.g. colchicine, atenolol, progabide · CPC title