Granted Patent B2

US 12,344,578 · App. 17/620,885 · Granted Jul 1, 2025

Inventors: Richard Copp (Pinckney, MI); Mohamed Abdelnasser (New City, NY); Christopher M. Cimarusti (Clementon, NJ); Chengxiang Liu (Cambridge, MA)

Assignee: Esperion Therapeutics, Inc.

C07C51/04C07C59/285C07B2200/13

Abstract

Claims (33)

1. A crystalline form of the compound of formula (V):

wherein the crystalline form of the compound of formula (V) is selected from the group consisting of a crystalline betaine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.2±0.2°, 13.5±0.2°, and 25.6±0.2°;

a crystalline calcium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.9±0.2°, 9.1±0.2°, and 19.7±0.2°;

a crystalline calcium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.0±0.2°, 6.8±0.2°, 8.5±0.2°, and 9.8±0.2°;

a crystalline diethylamine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 9.6±0.2°, 14.1±0.2°, and 19.8±0.2°;

a crystalline ethylenediamine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 10.8±0.2°, 16.2±0.2°, and 18.3±0.2°;

a crystalline isonicotinamide salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.4±0.2°, 18.8±0.2°, 20.1±0.2°, and 24.5±0.2°;

a crystalline potassium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 5.7±0.2°, 7.3±0.2°, 9.6±0.2°, and 22.1±0.2°;

a crystalline L-lysine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.2±0.2°, 19.1±0.2°, and 21.9±0.2°;

a crystalline sodium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.1±0.2°, 14.2±0.2°, 18.3±0.2°, and 24.5±0.2°;

a crystalline ammonium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 7.1±0.2°, 14.3±0.2°, and 16.0±0.2°;

a crystalline piperazine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.7±0.2°, 15.7±0.2°, and 16.0±0.2°; and

a crystalline tromethamine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.6±0.2°, 18.2±0.2°, 18.6±0.2°, and 19.8±0.2°.

2. The crystalline form of claim 1 , wherein the crystalline form is the crystalline calcium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.9±0.2°, 9.1±0.2°, and 19.7±0.2°.

3. The crystalline form of claim 1 , wherein the crystalline form is the crystalline calcium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.0±0.2°, 6.8±0.2°, 8.5±0.2°, and 9.8±0.2°.

4. The crystalline form of claim 1 , wherein the crystalline form is the crystalline diethylamine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 9.6±0.2°, 14.1±0.2°, and 19.8±0.2°.

5. The crystalline form of claim 1 , wherein the crystalline form is the crystalline ethylenediamine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 10.8±0.2°, 16.2±0.2°, and 18.3±0.2°.

6. The crystalline form of claim 1 , wherein the crystalline form is the crystalline isonicotinamide salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.4±0.2°, 18.8±0.2°, 20.1±0.2°, and 24.5±0.2°.

7. The crystalline form of claim 1 , wherein the crystalline form is the crystalline potassium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 5.7±0.2°, 7.3±0.2°, 9.6±0.2°, and 22.1±0.2°.

8. The crystalline form of claim 1 , wherein the crystalline form is the crystalline L-lysine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.2±0.2°, 19.1±0.2°, and 21.9±0.2°.

9. The crystalline form of claim 1 , wherein the crystalline form is the crystalline sodium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.1±0.2°, 14.2±0.2°, 18.3±0.2°, and 24.5±0.2°.

10. The crystalline form of claim 1 , wherein the crystalline form is the crystalline ammonium salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 7.1±0.2°, 14.3±0.2°, and 16.0±0.2°.

11. The crystalline form of claim 1 , wherein the crystalline form is the crystalline piperazine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.7±0.2°, 15.7±0.2°, and 16.0±0.2°.

12. The crystalline form of claim 1 , wherein the crystalline form is the crystalline tromethamine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.6±0.2°, 18.2±0.2°, 18.6±0.2°, and 19.8±0.2°.

13. The crystalline form of claim 1 , wherein the crystalline form is the crystalline betaine salt characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 6.2±0.2°, 13.5±0.2°, and 25.6±0.2°.

14. A co-crystal comprising the compound of formula (V):

wherein the co-crystal of the compound of formula (V) is selected from the group consisting of a cocrystal of aspartame and the compound of formula (V), characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 7.6±0.2°, 17.3±0.2°, and 18.4±0.2°;

a cocrystal of aspartame and the compound of formula (V), characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.4±0.2°, 10.6±0.2°, and 18.4±0.2°; and

a cocrystal of palmitic acid and the compound of formula (V), characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.3±0.2°, 6.3±0.2°, 8.5±0.2°, and 17.0±0.2°.

15. The co-crystal of claim 14 , wherein the cocrystal of aspartame and the compound of formula (V) is characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 7.6±0.2°, 17.3±0.2°, and 18.4±0.2°.

16. The co-crystal of claim 14 , wherein the cocrystal of aspartame and the compound of formula (V) is characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.4±0.2°, 10.6±0.2°, and 18.4±0.2°.

17. The co-crystal of claim 14 , wherein the cocrystal of palmitic acid and the compound of formula (V) is characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 4.3±0.2°, 6.3±0.2°, 8.5±0.2°, and 17.0±0.2°.

18. A method of lowering LDL-C or treating cardiovascular disease, the method comprising administering to a patient a therapeutically-effective amount of the crystalline form of the compound of formula (V) of claim 1 .

Assignments (4)

Continuity (2)

References Cited (301)