H3 receptor antagonist for use in the treatment of alzheimer's disease

• US 9,789,102 B2
• Filed: 10/01/2015
• Issued: 10/17/2017
• Est. Priority Date: 04/06/2012
• Status: Expired due to Fees

• Current Assignee: Sanofi
• Original Assignee: Sanofi
• Inventors: Barneoud, Pascal, Blanchard-Bregeon, Veronique, Mary, Veronique, Menager, Jean, Delay-Goyet, Philippe, Lopez-Grancha, Mathilde, Rooney, Thomas, Schussler, Nathalie
• Primary Examiner(s): NORTHINGTON DAVIS, ZINNA
• Application Number:
  US14/872,812
• Publication Number:
  US 20160101099A1
• Time in Patent Office: 747 Days
• Field of Search: None
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 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 Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

This disclosure relates to methods of using 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide in a disease modifying therapy of Alzheimer'"'"'s disease, other tauopathies and related neurodegenerative diseases.

Claims

1. A method of delaying the disease progression of a tauopathy or related neurodegenerative disease, comprising administering to a patient in need thereof 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or a pharmaceutically acceptable salt thereof;

and wherein abnormal tau hyperphosphorylation or abnormal tau aggregation in said patient is thereby inhibited.

2. The method according to claim 1 in which the level of phosphorylated tau protein in said patient having a tauopathy or related neurodegenerative disease is reduced.

3. The method according to according to claim 1 in which formation of neurofibrillary tangles in said patient is inhibited.

4. The method according to according to claim 1 in which the level of neurofibrillary tangles in a neuronal cell in said patient is inhibited.

5. The method according to according to claim 1 in which cytoskeleton dysfunction or perturbation of other tau-dependent functions is slowed or stopped.

6. The method according to according to claim 1 in which the level of phosphorylated tau and tau in the patient'"'"'s cerebrospinal fluid is reduced.

7. The method according to according to claim 1 in which tau aggregates in said patient are disrupted or dissolved.

8. The method according to according to claim 1 in which phosphorylation of tau protein in a neuron, glial cell or Lewy body in said patient is inhibited or reduced.

9. The method according to according to claim 8 in which the tau protein is microtubule-associated tau protein.

10. The method according to according to claim 9 in which the tau protein is in a neurofibrillary tangle.

11. The method according to according to claim 1 in which hyperphosphorylation of tau protein is inhibited or prevented.

12. The method according to according to claim 1 in which the tauopathy or related neurodegenerative disease is Alzheimer'"'"'s disease.

13. The method according to according to claim 1 in which the tauopathy or related neurodegenerative disease is mild-to-moderate Alzheimer'"'"'s disease.

14. The method according to according to claim 1 in which the tauopathy or related neurodegenerative disease is moderate-to-severe Alzheimer'"'"'s disease.

15. The method according to according to claim 1 in which the tauopathy or related neurodegenerative disease is preclinical Alzheimer'"'"'s disease.

16. The method according to according to claim 1 in which the tauopathy or related neurodegenerative disease is mild cognitive impairment.

17. The method according to according to claim 1 in which 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or pharmaceutically acceptable salt thereof is administered at least one time a day for a prolonged duration.

18. The method according to according to claim 1 in which 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or pharmaceutically acceptable salt thereof is 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide difumarate monohydrate.

19. The method according to according to claim 1 in which 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or pharmaceutically acceptable salt thereof is to be administered at least one time per day over a prolonged period.