Granted Patent B2

US 12,404,227 · App. 18/450,591 · Granted Sep 2, 2025

Inventors: Richard Copp (Pinckney, MI); Mohamed Abdelnasser (New City, NY); Christopher M. Cimarusti (Clementon, NJ); Jonathan Lane (Longmont, CO); Michael Barkman (Louisville, CO); Rasidul Amin (Cary, NC); Arthur John Cooper (Mentor, OH); Damodaragounder Gopal (Highland Heights, OH); Philipp Selig (Linz, AT)

Assignee: Esperion Therapeutics, Inc.

C07C51/04C07C59/285C07B2200/13

Abstract

Claims (30)

1. A pharmaceutical material comprising a crystalline form of the compound of formula (V):

or a pharmaceutically acceptable salt thereof;

wherein the pharmaceutical material comprises the compound of formula (V), or a pharmaceutically acceptable salt thereof, in an amount greater than 99.0% by weight based on the total weight of the pharmaceutical material; and the pharmaceutical material comprises 0.0001% to 0.15%

or a pharmaceutically acceptable salt thereof, based on the total weight of the pharmaceutical material.

2. The pharmaceutical material of claim 1 , wherein the crystalline form of the compound of formula (V) exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ):10.4±0.2, 17.91±0.2, 18.8±0.2, 19.5±0.2, and 20.7±0.2.

3. The pharmaceutical material of claim 1 , wherein the crystalline form of the compound of formula (V) is characterized by an X-ray powder diffraction pattern substantially the same as shown in FIG. 4 .

4. The pharmaceutical material claim 1 , wherein the crystalline form of the compound of formula (V) has a melting point onset as determined by differential scanning calorimetry in the range of from about 90° C. to about 94° C.

5. The pharmaceutical material of claim 1 , wherein the pharmaceutical material comprises the compound of formula (V) in an amount greater than 99.5% by weight based on the total weight of the pharmaceutical material.

6. A pharmaceutical material comprising a crystalline form of the compound of formula (V):

wherein the pharmaceutical material comprises the compound of formula (V) in an amount of from about 98% to about 102% by weight based on the total weight of the pharmaceutical material, as determined by a high performance liquid chromatography (HPLC) assay; and the pharmaceutical material comprises 0.0001% to 0.15% of a compound of formula (VIII):

or a pharmaceutically acceptable salt thereof, based on the total weight of the pharmaceutical material.

7. The pharmaceutical material of claim 6 , wherein the HPLC assay uses a C18 column (4.6 mm i.d.×150 mm, 2.5 μm) at a temperature of about 40° C., with isocratic elution of a mobile phase comprising about 0.05% phosphoric acid in water/acetonitrile (about 50:50) at a flow rate of about 1.2 mL/minute, and detection at 215 nm, wherein the retention time of the compound of formula (V) is about 4.6 minutes.

8. A method of treating primary hyperlipidemia in a patient in need thereof, the method comprising administering to a patient a therapeutically-effective amount of the pharmaceutical material of claim 1 .

9. A pharmaceutical material comprising a crystalline form of the compound of formula (V):

or a pharmaceutically acceptable salt thereof;

wherein the pharmaceutical material comprises the compound of formula (V), or a pharmaceutically acceptable salt thereof, in an amount greater than 85% by weight based on the total weight of the pharmaceutical material, and the pharmaceutical material comprises 0.0001% to 0.15% of a compound of formula (VIII):

or a pharmaceutically acceptable salt thereof, based on the total weight of the pharmaceutical material.

10. The pharmaceutical material of claim 9 wherein the crystalline form of the compound of formula (V) exhibits an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ):10.4±0.2, 17.9±0.2, 18.8±0.2, 19.5±0.2, and 20.7±0.2.

11. The pharmaceutical material of claim 9 , wherein the pharmaceutical material has a melting point onset as determined by differential scanning calorimetry in a range from 90° C. to 94° C.

12. The pharmaceutical material of claim 9 wherein the pharmaceutical material comprises the compound of formula (V), or a pharmaceutically acceptable salt thereof, in an amount greater than 90% by weight based on the total weight of the pharmaceutical material.

13. The pharmaceutical material of claim 9 , wherein the pharmaceutical material comprises the compound of formula (V) or a pharmaceutically acceptable salt thereof, in an amount greater than 95% by weight based on the total weight of the pharmaceutical material.

14. The pharmaceutical material of claim 9 , wherein the pharmaceutical material comprises the compound of formula (V) or a pharmaceutically acceptable salt thereof, in an amount greater than 96% by weight based on the total weight of the pharmaceutical material.

15. The pharmaceutical material of claim 9 , wherein the pharmaceutical material comprises the compound of formula (V) or a pharmaceutically acceptable salt thereof, in an amount greater than 97% by weight based on the total weight of the pharmaceutical material.

16. The pharmaceutical material of claim 9 , wherein the pharmaceutical material comprises the compound of formula (V) or a pharmaceutically acceptable salt thereof, in an amount greater than 98% by weight based on the total weight of the pharmaceutical material.

17. The pharmaceutical material of claim 9 , further comprising a compound of formula (VI):

or a pharmaceutically acceptable salt thereof.

18. The pharmaceutical material of claim 17 , wherein the pharmaceutical material comprises 0.0001% to 0.15% of a compound of formula (VI), based on the total weight of the pharmaceutical material.

19. The pharmaceutical material of claim 1 , further comprising a compound of formula (VI):

or a pharmaceutically acceptable salt thereof.

20. The pharmaceutical material of claim 19 , wherein the pharmaceutical material comprises 0.0001% to 0.15% of a compound of formula (VI), based on the total weight of the pharmaceutical material.

Assignments (11)

Continuity (5)

References Cited (371)