Use of benzimidazole-proline derivatives

Patent metadata

Field	Value
Publication number	US-9914721-B2
Application number	US-201415101871-A
Country	US
Kind code	B2
Filing date	Dec 3, 2014
Priority date	Dec 4, 2013
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

The present invention relates to compounds of the formula (I)

wherein Ar 1 and Ar 2 are as described in the description and to their use as pharmaceuticals for the treatment of sundown syndrome. The invention also relates to the preparation of such compounds and of pharmaceutically acceptable salts thereof.

First claim

The invention claimed is:

1. A method of treatment of sundown syndrome, comprising administering to a patient in need thereof a compound of the formula (I):

in free or pharmaceutically acceptable salt form,
wherein the compound of formula (I) is in absolute configuration (S);
Ar 1 represents

and Ar 2 represents

2. The method according to claim 1 , wherein the compound is:
[(S)-2-(5-Chloro-4-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)-methanone;
[(S)-2-(5-Bromo-7-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(5-Bromo-7-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)-methanone;
[(S)-2-(5-Chloro-4-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methoxy-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(6-Bromo-5-fluoro-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(5,6-Dimethoxy-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(5,6-Dimethoxy-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-pyrazol-1-yl-phenyl)-methanone;
[(S)-2-(5,6-Dimethoxy-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methoxy-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
[(S)-2-(6-Chloro-5-trifluoromethyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-yl-phenyl)-methanone;
(5-Methyl-2-[1,2,3]triazol-2-yl-phenyl)-[(S)-2-methyl-2-(5-trifluoromethyl-1H-benzoimidazol-2-yl)-pyrrolidin-1-yl]-methanone; or
(5-Methyl-2-[1,2,3]triazol-2-yl-phenyl)-[(S)-2-methyl-2-(5-trifluoromethoxy-1H-benzoimidazol-2-yl)-pyrrolidin-1-yl]-methanone,
in free or pharmaceutically acceptable salt form.

3. The method according to claim 1 , wherein the compound is:
[(S)-2-(5-Bromo-7-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methyl-2-pyrimidin-2-yl-phenyl)-methanone,
in free or pharmaceutically acceptable salt form.

4. The method according to claim 1 , wherein the compound is:
[(S)-2-(5-Chloro-4-methyl-1H-benzoimidazol-2-yl)-2-methyl-pyrrolidin-1-yl]-(5-methoxy-2-[1,2,3]triazol-2-yl-phenyl)-methanone,
in free or pharmaceutically acceptable salt form.

5. The method according to claim 1 , wherein said patient has a dementia of Alzheimer's type.

6. The method of claim 5 , wherein the patient has middle stage Alzheimer dementia.

7. The method of claim 5 , wherein the sundown syndrome is afternoon sundown syndrome.

8. The method according to claim 4 , wherein said patient has a dementia of Alzheimer's type.

9. The method of claim 8 , wherein the patient has middle stage Alzheimer dementia.

10. The method of claim 8 , wherein the sundown syndrome is afternoon sundown syndrome.

11. The method of claim 4 , wherein what is treated is increased agitation.

12. The method of claim 8 , wherein what is treated is increased agitation.

13. The method of claim 9 , wherein what is treated is increased agitation.

14. The method of claim 10 , wherein what is treated is increased agitation.

Assignees

• Idorsia Pharmaceuticals Ltd

Inventors

• Boss Christoph
• Roch Catherine
• Brotschi Christine
• Gude Markus
• Heidmann Bibia
• Jenck Francois
• Sifferlen Thierry
• Steiner Michel
• Williams Jodi T

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · 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

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K31/4178

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• A61K31/4192

  1,2,3-Triazoles · CPC title