Crystalline (r)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12410133-B2
Application number	US-202318143765-A
Country	US
Kind code	B2
Filing date	May 5, 2023
Priority date	Sep 13, 2018
Publication date	Sep 9, 2025
Grant date	Sep 9, 2025

Abstract

Provided herein are crystalline forms of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate. Pharmaceutical compositions comprising crystalline forms of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate are also disclosed.

First claim

The invention claimed is:

1. A single unit dosage form comprising a crystalline form of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, wherein:
the crystalline form is Form A of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 18.1, 20.1, and 22.3 degrees 2θ±0.2 degrees 2θ;
the crystalline form is Form B of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 16.2, 18.2, and 19.2 degrees 2θ±0.2 degrees 2θ;
the crystalline form is Form C of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 18.0, 20.0, and 21.0 degrees 2θ±0.2 degrees 2θ;
the crystalline form is Form D of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 13.4, 21.0, and 23.8 degrees 2θ±0.2 degrees 2θ; or
the crystalline form is Form E of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 17.8, 21.3, and 22.8 degrees 2θ±0.2 degrees 2θ.

2. The single unit dosage form of claim 1 , wherein the crystalline form is Form A of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 18.1, 20.1, and 22.3 degrees 2θ±0.2 degrees 2θ.

3. The single unit dosage form of claim 2 , wherein the X-ray powder diffraction pattern further comprises peaks at 9.9, 19.9, and 24.7 degrees 2θ±0.2 degrees 2θ.

4. The single unit dosage form of claim 1 , wherein the crystalline form is Form B of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 16.2, 18.2, and 19.2 degrees 2θ±0.2 degrees 2θ.

5. The single unit dosage form of claim 4 , wherein the X-ray powder diffraction pattern further comprises peaks at 15.1, 18.7, and 20.1 degrees 2θ±0.2 degrees 2θ.

6. The single unit dosage form of claim 1 , wherein the crystalline form is Form C of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 18.0, 20.0, and 21.0 degrees 2θ±0.2 degrees 2θ.

7. The single unit dosage form of claim 6 , wherein the X-ray powder diffraction pattern further comprises peaks at 12.3, 16.8, and 25.5 degrees 2θ±0.2 degrees 2θ.

8. The single unit dosage form of claim 1 , wherein the crystalline form is Form D of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 13.4, 21.0, and 23.8 degrees 2θ±0.2 degrees 2θ.

9. The single unit dosage form of claim 8 , wherein the X-ray powder diffraction pattern further comprises peaks at 18.3, 26.7, and 29.5 degrees 2θ±0.2 degrees 2θ.

10. The single unit dosage form of claim 1 , wherein the crystalline form is Form E of (R)-5-carbamoylpyridin-3-yl-2-methyl-4-(3-(trifluoromethoxy)benzyl)piperazine-1-carboxylate, having an X-ray powder diffraction pattern comprising peaks at 17.8, 21.3, and 22.8 degrees 2θ±0.2 degrees 2θ.

11. The single unit dosage form of claim 10 , wherein the X-ray powder diffraction pattern further comprises peaks at 15.8, 18.4, and 21.9 degrees 2θ±0.2 degrees 2θ.

12. The single unit dosage form of claim 1 , wherein the single unit dosage form is suitable for oral, mucosal, rectal, nasal, vaginal, parenteral, subcutaneous, intramuscular, bolus injection, intraarterial, intravenous, sublingual, transdermal, buccal, or topical administration.

13. The single unit dosage form of claim 12 , wherein the single unit dosage form is a tablet, caplet, capsule, powder, or sterile solid that can be reconstituted to provide a liquid dosage form.

14. The single unit dosage form of claim 12 , wherein the single unit dosage form is a tablet, caplet, capsule, or liquid suitable for oral administration.

15. The single unit dosage form of claim 12 , wherein the single unit dosage form is a solution ready for injection, dry product ready to be dissolved or suspended in a pharmaceutically acceptable vehicle for injection, suspension ready for injection, or an emulsion ready for injection.

16. The single unit dosage form of claim 1 comprising about 0.1 mg to about 1,000 mg of the crystalline form.

Assignees

• Celgene Corp
• Lundbeck La Jolla Research Center Inc

Inventors

• Huang Lianfeng
• Tsou Nancy
• White Nicole Suzanne
• Xu Jun
• Zhang Qun

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61P25/22

  Anxiolytics · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title