Elafibranor salts

Patent metadata

Field	Value
Publication number	US-12030840-B2
Application number	US-201917265058-A
Country	US
Kind code	B2
Filing date	Aug 2, 2019
Priority date	Aug 3, 2018
Publication date	Jul 9, 2024
Grant date	Jul 9, 2024

Abstract

The present invention relates to salts of elafibranor.

First claim

The invention claimed is:

1. A crystalline salt of elafibranor, selected from the group consisting of a tromethamine salt (salt I), a potassium salt (salt II), and an L-arginine salt (salt IV), of elafibranor.

2. The crystalline salt according to claim 1 , which is the tromethamine salt of elafibranor having an X-ray powder diffraction pattern comprising peaks (2θ in angular degrees ±0.2°) at 6.5°, 12.2°, 15.0°, 15.3°, 16.9°, 17.3°, 17.6°, 18.4°, 19.4°, and 22.6°.

3. The crystalline salt according to claim 1 , which is the potassium salt of elafibranor having an X-ray powder diffraction pattern comprising peaks (20 in angular degrees ±0.2°) at 4.6°, 8.0°, 11.7°, 13.1°, and 13.6°.

4. The crystalline salt according to claim 1 , which is the L-arginine salt of elafibranor having an X-ray powder diffraction pattern comprising peaks (20 in angular degrees ±0.2°) at 5.9°, 8.8°, 11.7°, 13.2°, 19.8°, and 19.9°.

5. A method for preparing a crystalline salt of elafibranor comprising the steps of:
(i) away from the light, dissolving the free acid of Formula (I) and a base providing the counter-ion for salt formation at an acid/base molar ratio which is selected from 1:1 to 2:1 depending on the base in a suitable solvent

(ii) stirring the free acid of Formula (I) and the base at a temperature from 40° C. to 100° ° C.,
(iii) adding a suitable solvent to mixture obtained in (ii) and slowly cooling down to room temperature or (iii) removing the solvent of mixture obtained in (ii), adding a suitable crystallization solvent to the residue, and
(iv) isolating the precipitated crystals by filtration.

6. A pharmaceutical composition comprising the crystalline salt of elafibranor according to claim 1 , and a pharmaceutically acceptable carrier.

7. The pharmaceutical composition according to claim 6 , which is formulated in the form of injectable suspensions, gels, oils, pills, suppositories, powders, gel caps, capsules, aerosols or means of galenic forms or devices assuring a prolonged and/or slow release.

8. A method of treating a disease selected in the group consisting of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver fibrosis and liver cirrhosis, comprising administering to a subject in need thereof a therapeutically effective amount of the crystalline salt of claim 1 .

Assignees

• Genfit

Inventors

• Bertrand Karine
• Roudot Alice
• Joissains Marie-Jeanne

Classifications

• C07C319/28

  Separation; Purification · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• C07D207/06

  with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms · CPC title

• C07C229/08

  the nitrogen atom of the amino group being further bound to hydrogen atoms · CPC title