Compounds, compositions, and methods for modulating ferroptosis and treating excitotoxic disorders

Patent metadata

Field	Value
Publication number	US-10597381-B2
Application number	US-201916247354-A
Country	US
Kind code	B2
Filing date	Jan 14, 2019
Priority date	Apr 2, 2012
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

Abstract

The present invention provides, inter alia, a compound having the structure:

Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for treating or ameliorating the effects of an excitotoxic disorder in a subject, methods of modulating ferroptosis in a subject, methods of reducing reactive oxygen species (ROS) in a cell, and methods for treating or ameliorating the effects of a neurodegenerative disease.

First claim

What is claimed is:

1. A method for treating or ameliorating the effects of a neurodegenerative disease in a subject in need thereof comprising administering to the subject an effective amount of a compound having the structure:

or pharmaceutically acceptable salts thereof.

2. The method according to claim 1 , wherein the neurodegenerative disease is selected from the group consisting of Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, Friedreich's ataxia, Multiple sclerosis, Huntington's Disease, Transmissible spongiform encephalopathy, Charcot-Marie-Tooth disease, Dementia with Lewy bodies, Corticobasal degeneration, Progressive supranuclear palsy, and Hereditary spastic paraparesis.

3. The method according to claim 1 further comprising co-administering to the subject an effective amount of one or more compositions selected from the group consisting of Donepezil, Rivastigmine, Galantamine, Tacrine, Memantine, Vitamin E, CERE-110, LY450139, Exenatide, Varenicline, PF-04360365, Resveratrol, Carbidopa/levodopa immediate-release, Carbidopa/levodopa oral disintegrating, Carbidopa/levodopa/Entacapone, Ropinirole, Pramipexole, Rotigotine, Apomorphine, Selegiline, Rasagiline, Zydis selegiline HCL Oral disintegrating, Entacapone, Tolcapone, Amantadine, Trihexyphenidyl, Benztropine, IPX066, ioflupane 123I, safinamide, Pioglitazone, riluzole, Lithium carbonate, Arimoclomol, Creatine, Tamoxifen, Mecobalam in, tauroursodeoxycholic acid, Idebenone, Coenzyme Q, 5-hydroxytryptophan, Propranolol, Enalapril, Lisinopril, Digoxin, Erythropoietin, Lu AA24493, Deferiprone, IVIG, EGb 761, Avonex, Betaseron, Extavia, Rebif, Glatiramer, Fingolimod, Natalizumab, Mitoxantrone, baclofen, tizanidine, methylprednisolone, CinnoVex, ReciGen, Masitinib, Prednisone, Interferon beta 1a, Interferon beta 1b, ELND002, Tetrabenazine, haloperidol, clozapine, clonazepam, diazepam, escitalopram, fluoxetine, sertraline, valproic acid, divalproex, lamotrigine, Dimebon, AFQ056, Ethyl-EPA, SEN0014196, sodium phenylbutyrate, citalopram, ursodiol, minocycline, remacemide, mirtazapine, Quinacrine, Ascorbic acid, PXT3003, Armodafinil, Ramelteon, Davunetide, Tideglusib, alpha-lipoic acid/L-acetyl carnitine, Niacinamide, Oxybutinin chloride, Tolterodine, Botulinum toxin, and combinations thereof.

4. The method according to claim 1 , wherein the subject is a mammal.

5. The method according to claim 4 , wherein the mammal is selected from the group consisting of humans, veterinary animals, and agricultural animals.

6. The method according to claim 5 , wherein the subject is a human.

Assignees

• Univ Columbia

Inventors

• Stockwell Brent R
• Dixon Scott J
• Skouta Rachid

Classifications

• A61K31/5375

  1,4-Oxazines, e.g. morpholine · CPC title

• C07D211/58

  attached in position 4 · CPC title

• A61K31/27

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title

• C07C271/24

  with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring · CPC title

• C07C237/30

  having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms · CPC title