Benzimidazole-proline derivatives

Patent metadata

Field	Value
Publication number	US-9732075-B2
Application number	US-201314405649-A
Country	US
Kind code	B2
Filing date	Jun 3, 2013
Priority date	Jun 4, 2012
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

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

wherein Ar 1 , R 1 , R 2 , R 3 , R 4a , R 4b and (R 5 ) n are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.

First claim

The invention claimed is:

1. A compound of the formula (V); wherein the absolute configuration is as depicted in formula (V):

wherein
Ar 1 represents a group independently selected from a member of the following groups A and L:
A.

and
L.

and the fragment:

represents a group independently selected from one of the following groups:

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising, as active principle, one or more compounds according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

3. A method to treat a disease or disorder selected from
a) a sleep disorder selected from an insomnia; a primary insomnia; an idiopathic insomnia; an insomnia associated with depression, emotional/mood disorders, aging, Alzheimer's disease or cognitive impairment; REM sleep interruptions; a breathing-related sleep disorder; a sleep apnea; a periodic limb movement disorder, a restless leg syndrome; a circadian rhythm sleep disorder; a shift work sleep disorder; and a jet-lag syndrome; and
b) an anxiety disorder;
comprising administering to a patient in need thereof, the compound of claim 1 in free or pharmaceutically acceptable salt form.

4. The compound [(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; or a pharmaceutically acceptable salt thereof.

5. The compound [(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 pharmaceutically acceptable salt form.

6. The compound [(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 form.

7. A pharmaceutical composition comprising, as active principle, the compound according to claim 4 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

8. A pharmaceutical composition comprising, as active principle, the compound according to claim 5 , and at least one therapeutically inert excipient.

9. A pharmaceutical composition comprising, as active principle, the compound according to claim 6 , and at least one therapeutically inert excipient.

10. A method to treat a disease or disorder selected from
a) a sleep disorder selected from an insomnia; a primary insomnia; an idiopathic insomnia; an insomnia associated with depression, emotional/mood disorders, aging, Alzheimer's disease or cognitive impairment; REM sleep interruptions; a breathing-related sleep disorder; a sleep apnea; a periodic limb movement disorder, a restless leg syndrome; a circadian rhythm sleep disorder; a shift work sleep disorder; and a jet-lag syndrome; and
b) an anxiety disorder selected from a post-traumatic stress disorder, an obsessive compulsive disorder, a panic attack, a phobic anxiety, and an avoidance;
comprising administering to a patient in need thereof, the compound of claim 4 in free or pharmaceutically acceptable salt form.

11. A method to treat a disease or disorder selected from
a) a sleep disorder selected from an insomnia; a primary insomnia; an idiopathic insomnia; an insomnia associated with depression, emotional/mood disorders, aging, Alzheimer's disease or cognitive impairment; REM sleep interruptions; a breathing-related sleep disorder; a sleep apnea; a periodic limb movement disorder, a restless leg syndrome; a circadian rhythm sleep disorder; a shift work sleep disorder; and a jet-lag syndrome; and
b) an anxiety disorder selected from a post-traumatic stress disorder, an obsessive compulsive disorder, a panic attack, a phobic anxiety, and an avoidance;

comprising administering to a patient in need thereof, the compound of claim 5 .

12. A method to treat a disease or disorder selected from
a) a sleep disorder selected from an insomnia; a primary insomnia; an idiopathic insomnia; an insomnia associated with depression, emotional/mood disorders, aging, Alzheimer's disease or cognitive impairment; REM sleep interruptions; a breathing-Related sleep disorder; a sleep apnea; a periodic limb movement disorder, a restless leg syndrome; a circadian rhythm sleep disorder; a shift work sleep disorder; and a jet-lag syndrome; and
b) an anxiety disorder selected from a post-traumatic stress disorder, an obsessive compulsive disorder, a panic attack, a phobic anxiety, and an avoidance;

comprising administering to a patient in need thereof, the compound of claim 6 .

Assignees

• Idorsia Pharmaceuticals Ltd

Inventors

• Boss Christoph
• Brotschi Christine
• Gude Markus
• Heidmann Bibia
• Sifferlen Thierry
• Williams Jodi

Classifications

• A61P43/00

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

• A61P25/30

  for treating abuse or dependence · 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

• A61P25/22

  Anxiolytics · CPC title

• A61P25/20

  Hypnotics; Sedatives · CPC title