Sulphate salts of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine, preparation thereof and use of the same

Patent metadata

Field	Value
Publication number	US-10772884-B2
Application number	US-201916552436-A
Country	US
Kind code	B2
Filing date	Aug 27, 2019
Priority date	Dec 27, 2012
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

The present invention relates to sulphate salts of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine and pharmaceutically acceptable solvates thereof, preparation thereof, pharmaceutical compositions containing them and use of the same in the treatment and/or prevention of neurodegenerative diseases.

First claim

The invention claimed is:

1. A method for treating a disease selected from tauopathies comprising administering to a patient in need thereof a pharmaceutically effective amount of a sulphate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine or a pharmaceutically acceptable solvate thereof.

2. The method according to claim 1 , wherein the disease is selected from amyotrophic lateral sclerosis (ALS) with frontotemporal dementia, inclusion body myopathy with Paget's disease of bone and/or frontotemporal dementia (IBMPFD), frontotemporal lobar degeneration, and frontotemporal dementia with Parkinsonism linked to chromosome 17.

3. A method for delaying in a patient the onset of a disease selected from tauopathies comprising administering to the patient in need thereof a pharmaceutically effective amount of a sulphate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine or a pharmaceutically acceptable solvate thereof.

4. The method according to claim 3 , wherein the disease is selected from amyotrophic lateral sclerosis (ALS) with frontotemporal dementia, inclusion body myopathy with Paget's disease of bone and/or frontotemporal dementia (IBMPFD), frontotemporal lobar degeneration, and frontotemporal dementia with Parkinsonism linked to chromosome 17.

5. A method for inhibiting pathological Tau protein phosphorylation while alleviating oxidative stress processes in a human patient in need of treatment for tauopathies, which comprises administering to said human patient an effective amount of a sulphate salt of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine or a pharmaceutically acceptable solvate thereof.

6. The method according to claim 1 wherein the sulphate salt has Formula II

wherein x designates the number of equivalents of sulphuric acid and x is 0.5 to 4, or a pharmaceutically acceptable solvate thereof.

7. The method according to claim 3 wherein the sulphate salt has Formula II

wherein x designates the number of equivalents of sulphuric acid and x is 0.5 to 4, or a pharmaceutically acceptable solvate thereof.

8. The method according to claim 5 wherein the sulphate salt has Formula II

wherein x designates the number of equivalents of sulphuric acid and x is 0.5 to 4, or a pharmaceutically acceptable solvate thereof.

Assignees

• Alzprotect
• Univ Lille Ii Droit & Sante
• Inst Nat Sante Rech Med
• Inserm Institut National De La Sante Et De La Rech

Inventors

• Burlet Stéphane
• Estrella Cécilia
• Barrier Mathieu
• Melnyk Patricia
• Sergeant Nicolas
• Buee Luc
• Verwaerde Philippe

Classifications

• A61K31/4184

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title

• C07D235/30 Primary

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

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K31/496 Primary

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

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title