Crystalline compounds

Inventors: Anthony Alexander McKinney (Newton Center, MA); Franklin Bymaster (Brownsburg, IN); Walter Piskorski (Nashua, NH); Fred J. Fleitz (Germantown, WI); Yonglai Yang (Hockessin, DE); David A. Engers (West Lafayette, IN); Valeriya Smolenskaya (West Lafayette, IN); Venkat Kusukuntla (Germantown, WI)

Assignee: OTSUKA AMERICA PHARMACEUTICAL, INC.

C07D209/52 C07C211/17

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Quick Facts

Patent No.: US 10,800,740
App. No.: 16/298,179
Granted: Oct 13, 2020
Kind: B2

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Abstract

The present invention relates to crystalline forms of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and compositions comprising the same and methods of making and using the same.

Claims (26)

1. Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least three 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu radiation.

2. The Crystalline Form A of claim 1 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least five 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation.

3. The Crystalline Form A of claim 2 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least nine 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation.

4. The Crystalline Form A of claim 3 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least ten 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation.

5. The Crystalline Form A of claim 4 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least twelve 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation having a wavelength of 1.54059 Å.

6. The Crystalline Form A of claim 5 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least fifteen 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation having a wavelength of 1.54059 Å.

7. The Crystalline Form A of claim 6 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least twenty 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation having a wavelength of 1.54059 Å.

8. The Crystalline Form A of claim 1 , wherein the Crystalline Form A comprises less than 5 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

9. The Crystalline Form A of claim 3 , wherein the Crystalline Form A comprises less than 5 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

10. The Crystalline Form A of claim 3 , wherein the Crystalline Form A comprises less than 2 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

11. The Crystalline Form A of claim 3 , wherein the Crystalline Form A comprises less than 1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

12. The Crystalline Form A of claim 5 , wherein the Crystalline Form A comprises less than 1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

13. The Crystalline Form A of claim 3 , wherein the Crystalline Form A comprises less than 0.1 wt. % of any other crystalline form of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride.

14. A pharmaceutical composition comprising Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and a pharmaceutically acceptable diluent or carrier, wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least three 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu radiation.

15. The pharmaceutical composition of claim 14 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least nine 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation.

16. The pharmaceutical composition of claim 15 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least twelve 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation having a wavelength of 1.54059 Å.

17. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition is an oral sustained release pharmaceutical composition.

18. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is an oral sustained release pharmaceutical composition.

19. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is an oral sustained release pharmaceutical composition.

20. A method for treatment of attention deficit hyperactivity disorder in a patient in need thereof, wherein the method comprises administering to the patient Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least three 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu radiation.

21. The method of claim 20 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least nine 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation.

22. The method of claim 21 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least twelve 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation having a wavelength of 1.54059 Å.

23. A method of treatment of attention deficit hyperactivity disorder, a fragile X-associated disorder, autism spectrum disorder, or a substance abuse disorder in a patient in need thereof, wherein the method comprises administering to the patient the pharmaceutical composition of claim 14 .

24. A method of treatment of attention deficit hyperactivity disorder in a patient in need thereof, wherein the method comprises administering to the patient the pharmaceutical composition of claim 17 .

25. A method of treatment of attention deficit hyperactivity disorder in a patient in need thereof, wherein the method comprises administering to the patient the pharmaceutical composition of claim 18 .

26. A method of treatment of attention deficit hyperactivity disorder in a patient in need thereof, wherein the method comprises administering to the patient the pharmaceutical composition of claim 19 .

Assignments (6)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 30, 2019

From: KUSUKUNTLA, VENKAT

To: NEUROVANCE, INC.

Reel/Frame 049040/0046 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 30, 2019

From: AMRI SSCI, LLC

To: NEUROVANCE, INC.

Reel/Frame 049040/0176 →

MERGER Recorded Apr 30, 2019

From: NEUROVANCE, INC.

To: OTSUKA AMERICA PHARMACEUTICAL, INC.