# US 10,864,191 B2 · 5-HT6 receptor antagonists for use in the treatment of Alzheimer's disease with apathy as comorbidity

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- Number: US 10,864,191 B2
- Document ID: US10864191B2
- Status: Granted
- Kind: B2
- Application number: 15/587,935
- Filed: 2017-05-05
- Published: 2017-11-16
- Granted: 2020-12-15
- Earliest claimed: 2016-05-11
- Assignees: H. Lundbeck A/S
- Applicants: H. Lundbeck A/S
- Inventors: Karl Tomas Odergren
- Web page: https://patentgrep.com/patent/US10864191B2

## CPC

- A61K 31/4045: Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
- A61K 31/27: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
- A61K 31/325: Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof (thiurams A61K31/145)
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to 5-HT6 receptor antagonists for the treatment of Alzheimer's disease with comorbid apathy comprising administering an effective dose of a 5-HT6 receptor antagonist to improve or augment the effect of an acetylcholinesterase inhibitor.

## Claims

### Claim 1

A method for improving activities of daily living in a subject with Alzheimer's Disease and comorbid apathy, comprising administration of (i) a therapeutically effective amount of a 5HT6 receptor antagonist or pharmaceutically acceptable salt thereof, and (ii) an acetylcholinesterase inhibitor or a pharmaceutically acceptable salt thereof to said subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein said 5-HT6 receptor antagonist is selected from the group consisting of:
N-(2-(6-fluoro-1H-indol-3-yl)-ethyl)-3-(2,2,3,3-tetrafluoropropoxy)-benzylamine, 3-Benzenesulfonyl-5,7-dimethyl-2-methylsulfanyl-pyrazolo[1,5-a]pyrimidine, and 3-phenylsulfonyl-8-piperazin-1-yl-quinoline.

### Claim 3 (depends on 1)

The method of claim 1, wherein said 5-HT6 receptor antagonist is a pharmaceutically acceptable salt of N-(2-(6-fluoro-1H-indol-3-yl)-ethyl)-3-(2,2,3,3-tetrafluoropropoxy)-benzyl amine.

### Claim 4 (depends on 3)

The method of claim 3, wherein said 5-HT6 receptor antagonist is the hydrochloride salt of N-(2-(6-fluoro-1H-indol-3-yl)-ethyl)-3-(2,2,3,3-tetrafluoropropoxy)-benzylamine.

### Claim 5 (depends on 2)

The method of claim 2, wherein the acetylcholinesterase inhibitor is selected from the group consisting of the compounds: donepezil, rivastigmine and galantamine, or is a pharmaceutically acceptable salt of such compounds.

### Claim 6 (depends on 2)

The method of claim 2, wherein the acetylcholinesterase inhibitor is the hydrochloride salt of donepezil.

### Claim 7 (depends on 1)

The method of claim 1, wherein the 5-HT6 receptor antagonist is the hydrochloride salt of N-(2-(6-fluoro-1H-indol-3-yl)-ethyl)-3-(2,2,3,3-tetrafluoropropoxy)-benzylamine, and the acetylcholinesterase inhibitor is the hydrochloride salt of donepezil.

### Claim 8 (depends on 3)

The method of claim 3, wherein the dosing range of said 5-HT6 receptor antagonist is from 30 mg/day to 60 mg/day.

### Claim 9 (depends on 4)

The method of claim 4, wherein the dosing range of said 5-HT6 receptor antagonist is from 30 mg/day to 60 mg/day.

### Claim 10 (depends on 5)

The method of claim 5, wherein said 5-HT6 receptor antagonist is N-(2-(6-fluoro-1H-indol-3-yl)-ethyl)-3-(2,2,3,3-tetrafluoropropoxy)-benzyl amine and wherein the dosing range of said 5-HT6 receptor antagonist is from 30 mg/day to 60 mg/day.

### Claim 11 (depends on 6)

The method of claim 6, wherein said 5-HT6 receptor antagonist is N-(2-(6-fluoro-1H-indol-3-yl)-ethyl)-3-(2,2,3,3-tetrafluoropropoxy)-benzyl amine and wherein the dosing range of said 5-HT6 receptor antagonist is from 30 mg/day to 60 mg/day.

### Claim 12 (depends on 7)

The method of claim 7, wherein the dosing range of said 5-HT6 receptor antagonist is from 30 mg/day to 60 mg/day.

### Claim 13 (depends on 1)

The method of claim 1, further comprising treating cognitive impairment in the subject with Alzheimer's Disease and comorbid apathy.

### Claim 14 (depends on 1)

The method of claim 1, further comprising identifying the subject with Alzheimer's Disease and comorbid apathy prior to administration.

### Claim 15 (depends on 13)

The method of claim 13, further comprising identifying the subject with Alzheimer's Disease and comorbid apathy prior to administration.