Crystalline salt form of (S)-(2-(6 chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone as orexin receptor antagonist

Patent metadata

Field	Value
Publication number	US-10023560-B2
Application number	US-201715702281-A
Country	US
Kind code	B2
Filing date	Sep 12, 2017
Priority date	Dec 3, 2013
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

The invention relates to a crystalline form of (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone hydrochloride, processes for the preparation thereof, pharmaceutical compositions containing said crystalline form, and its use as medicament, especially as orexin receptor antagonist.

First claim

The invention claimed is:

1. A method of treatment of a sleep disorder, an anxiety disorder, or an addiction disorder, a cognitive dysfunction, a mood disorder, or an appetite disorder; comprising administering to a patient an effective amount of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone hydrochloride in crystalline form; wherein said crystalline form comprises peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 11.0°, 24.1° and 24.5°, wherein said X-ray powder diffraction diagram is obtained by using combined Cu Kα1 and Kα2 radiation, without Kα2 stripping; and the accuracy of the 2θ values is in the range of 2θ+/−0.2°.

2. The method of claim 1 , wherein said crystalline form comprises peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 9.2°, 11.0°, 13.8°, 15.1°, 16.3°, 16.8°, 19.8°, 24.1°, 24.5°, and 27.3°, wherein said X-ray powder diffraction diagram is obtained by using combined Cu Kα1 and Kα2 radiation, without Kα2 stripping; and the accuracy of the 2θ values is in the range of 2θ+/−0.2°.

3. The method of claim 1 , wherein said crystalline form essentially shows the X-ray powder diffraction pattern as depicted in FIG. 2 .

4. The method of claim 2 , wherein the sleep disorder is a dyssomnia, a parasomnia, a sleep disorders associated with a general medical condition, or a substance-induced sleep disorder.

5. The method of claim 4 , wherein the anxiety disorder is a post-traumatic stress disorder, an obsessive compulsive disorder, a panic attack, a phobic anxiety, or an avoidance.

6. A method of treatment of a sleep disorder; comprising administering to a patient an effective amount of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone hydrochloride in crystalline form; wherein said crystalline form comprises peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 11.0°, 24.1° and 24.5°, wherein said X-ray powder diffraction diagram is obtained by using combined Cu Kα1 and Kα2 radiation, without Kα2 stripping; and the accuracy of the 2θ values is in the range of 2θ+/−0.2°.

7. The method of claim 6 , wherein said crystalline form comprises peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 9.2°, 11.0°, 13.8°, 15.1°, 16.3°, 16.8°, 19.8°, 24.1°, 24.5°, and 27.3°, wherein said X-ray powder diffraction diagram is obtained by using combined Cu Kα1 and Kα2 radiation, without Kα2 stripping; and the accuracy of the 2θ values is in the range of 2θ+/−0.2°.

8. The method of claim 7 , wherein the sleep disorder is a dyssomnia, a parasomnia, a sleep disorder associated with a general medical condition, or a substance-induced sleep disorder.

9. The method of claim 7 , wherein the sleep disorder is an insomnia, a sleep-related dystonia; a restless leg syndrome; a sleep apnea; a jet-lag syndrome; a shift work sleep disorder, a delayed or advanced sleep phase syndrome, or an insomnia related to psychiatric disorders.

10. The method of claim 7 , wherein the sleep disorder is an insomnia.

11. A method of treatment of an anxiety disorder; comprising administering to a patient an effective amount of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone hydrochloride in crystalline form; wherein said crystalline form comprises peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 11.0°, 24.1° and 24.5°, wherein said X-ray powder diffraction diagram is obtained by using combined Cu Kα1 and Kα2 radiation, without Kα2 stripping; and the accuracy of the 2θ values is in the range of 2θ+/−0.2°.

12. The method of claim 11 , wherein said crystalline form comprises peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 9.2°, 11.0°, 13.8°, 15.1°, 16.3°, 16.8°, 19.8°, 24.1°, 24.5°, and 27.3°, wherein said X-ray powder diffraction diagram is obtained by using combined Cu Kα1 and Kα2 radiation, without Kα2 stripping; and the accuracy of the 2θ values is in the range of 2θ+/−0.2°.

13. The method of claim 12 , wherein the anxiety disorder is a post-traumatic stress disorder, an obsessive compulsive disorder, a panic attack, a phobic anxiety, or an avoidance.

Assignees

• Idorsia Pharmaceuticals Ltd

Inventors

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

Classifications

• 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

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title