Pro-drugs of riluzole and their method of use for the treatment of amyotrophic lateral sclerosis

Patent metadata

Field	Value
Publication number	US-12343347-B2
Application number	US-202117527428-A
Country	US
Kind code	B2
Filing date	Nov 16, 2021
Priority date	Jun 23, 2012
Publication date	Jul 1, 2025
Grant date	Jul 1, 2025

Abstract

Pharmaceutical compositions of the invention include substituted riluzole pro drugs useful for the treatment of amyotrophic lateral sclerosis (ALS) and related disorders through the release of riluzole, especially to avoid patient to patient variability in first pass, hepatic metabolism promoted by Cyp 1Λ2. Pro-drugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release rihizole in the plasma via either an enzymatic or general biophysical release process. The invention further includes pro-drugs of riluzole useful for the treatment of disease states that can be treated with riluzole through the release of rihizole from a pro-drug agent.

First claim

What is claimed is:

1. A method for treating a non-proliferative disease in which riluzole is clinically relevant, said method comprising administering to a subject an effective amount of at least one compound of the formula (II):

including hydrates, solvates, pharmaceutically acceptable salts, and complexes thereof, wherein:
R 12a , R 12b , R 12c , R 12d , and R 12e are each independently selected from the group consisting of hydrogen, deuterium, halogen, trifluoromethyl, trifluoromethoxy, optionally substituted C1-C6 alkyl, and optionally substituted C1-C6 alkoxy.

2. The method of claim 1 , wherein the at least one compound of the formula (II) is administered in a composition further comprising at least one excipient.

3. The method of claim 1 , wherein the disease in which riluzole is clinically relevant is amyotrophic lateral sclerosis, bipolar disorder, treatment resistant and major depression, obsessive-compulsive disorder, spinal muscular atrophy, radiation therapy, multiple sclerosis, chronic cerebellar ataxia, cervical spondylotic myelopathy, spinal cord injury, hereditary cerebellar ataxia, Tourette syndrome, autism spectrum disorder, schizophrenia, fragile X syndrome, Parkinson's Disease, or Huntington's disease.

Assignees

• Biohaven Pharm Holding Co Ltd
• Biohaven Therapeutics Ltd

Inventors

• Reitz Allen B
• Smith Garry Robert

Classifications

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/4725

  containing further heterocyclic rings · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title