Crystalline form of N-[1-(5-cyano-pyridin-2- ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide

Patent metadata

Field	Value
Publication number	US-11059803-B2
Application number	US-201816628618-A
Country	US
Kind code	B2
Filing date	Jul 4, 2018
Priority date	Jul 5, 2017
Publication date	Jul 13, 2021
Grant date	Jul 13, 2021

Abstract

The present invention relates to crystalline forms of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide, pharmaceutical compositions comprising said crystalline forms and their use as T-type calcium channel blockers in the treatment or prevention of diseases or disorders where T-type calcium channels are involved.

First claim

The invention claimed is:

1. A crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide, characterized by:
a. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.7°, 14.1°, and 20.1°, or b. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.8°, 18.0°, and 18.3°.

2. A crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide according to claim 1 , characterized by
a. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.7°, 9.3°, 14.1°, 20.1°, and 24.7°; or
b. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.4°, 12.8°, 15.7°, 18.0°, and 18.3°.

3. A crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide according to claim 1 , characterized by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.7°, 14.1°, and 20.1°.

4. A crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide according to claim 1 , characterized by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.7°, 9.3°, 12.0°, 14.1°, 16.3°, 18.4°, 20.1°, 21.8°, 24.7°, and 28.6°.

5. A crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide according to claim 1 , characterized by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.8°, 18.0°, and 18.3°.

6. A crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide according to claim 1 , characterized by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 10.9°, 12.4°, 12.8°, 13.2°, 15.7°, 16.3°, 18.0°, 18.3°, 21.1°, and 29.3°.

7. A crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide, characterized by:
a. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.7°, 14.1°, and 20.1°, or
b. obtainable by:
a. heating a suspension comprising N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide in about 5 vol. toluene at reflux until dissolution;
b. cooling of the solution to about 25° C. within 1 to 5 hours;
c. cooling to 0° C.; and
d. isolating of the obtained solid residue.

8. A pharmaceutical composition comprising as active ingredient a crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide according to claim 1 , and at least one pharmaceutically acceptable carrier.

9. A method for treating a disease or disorder selected from epilepsy; sleep disorders; sleep disturbances; pain selected from inflammatory pain, neuropathic pain, peripheral pain, and chronic pain associated with peripheral axonal injury; neurological disorders selected from essential tremors, Parkinson's disease, schizophrenia, depression, anxiety, psychosis, neurodegenerative disorders, autism and drug addiction; cardiovascular disorders selected from hypertension, cardiac arrhythmias, atrial fibrillation, congenital heart failure and heart block; cancer; diabetes; and diabetic neuropathy, the method comprising administering a pharmaceutically effective amount of the crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide according to claim 1 to a subject in need thereof.

10. A method for treating epilepsy, the method comprising administering a pharmaceutically effective amount of the crystalline form of N-[1-(5-cyano-pyridin-2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide according to claim 1 to a subject in need thereof.

11. The method according to claim 9 , wherein the crystalline form of N-[1-(5-cyano-pyridin -2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide is characterized by
a. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.7°, 9.3°, 14.1°, 20.1°, and 24.7°; or
b. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.4°, 12.8°, 15.7°, 18.0°, and 18.3°.

12. The method according to claim 10 , wherein the crystalline form of N-[1-(5-cyano-pyridin -2-ylmethyl)-1H-pyrazol-3-yl]-2-[4-(1-trifluoromethyl-cyclopropyl)-phenyl]-acetamide is characterized by
a. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.7°, 9.3°, 14.1°, 20.1°, and 24.7°; or b. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.4°, 12.8°, 15.7°, 18.0°, and 18.3°.

Assignees

• Idorsia Pharmaceuticals Ltd

Inventors

• Heidmann Bibia
• Von Raumer Markus

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• C07D401/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · 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

• A61K31/4439 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title