Crystalline compounds
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.
1. Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride belonging to the P2 1 2 1 2 1 space group and having the following unit cell parameters:
a=5.7779(2) Å, b=8.6633(2) Å, c=25.7280(8) Å, α=β=γ=90° or Crystalline Form B of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride belonging to the P2 1 2 1 2 1 space group and having the following unit cell parameters:
a=5.9055(2) Å, b=7.4645(3) Å, c=29.1139(13) Å, α=β=γ=90°.
2. The Crystalline Form A of claim 1 having an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å comprising five peaks selected from those shown in FIG. 1 .
3. The Crystalline Form A of claim 1 having an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å substantially as shown in FIG. 1 .
4. The Crystalline Form A of claim 1 having an X-ray powder diffraction (XRPD) pattern measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å as shown in FIG. 1 .
5. 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 2-theta (°) values of 15.4, 16.6, 17.2, 18.5, 19.5, 20.5, 20.7, 22.9, and 25.7, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 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 2-theta (°) values of 12.3, 13.8, 15.4, 16.6, 17.2, 18.2, 18.5, 19.5, 20.5, 20.7, 22.9, and 25.7, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.
7. The Crystalline Form A of claim 5 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising the following 2-theta (°) values:
6.9, 12.3, 13.8, 14.5, 15.4, 16.6, 17.2, 18.2, 18.5, 19.5, 20.1, 20.5, 20.7, 21.0, 21.5, 22.9, 24.7, 25.2, 25.4, 25.7, 26.4, 27.5, and 27.8,
wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.
8. 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 d-spacing (A) values of 5.7, 5.4, 5.2, 4.8, 4.6, 4.3, 3.9, and 3.5.
9. The Crystalline Form A of claim 8 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising the d-spacing (Å) values selected from Table A, B, and C below:
TABLE A
°2θ
d space (Å)
Intensity (%)
15.42 ± 0.20
5.741 ± 0.074
26
16.55 ± 0.20
5.352 ± 0.064
40
17.15 ± 0.20
5.167 ± 0.060
29
18.50 ± 0.20
4.792 ± 0.051
100
19.45 ± 0.20
4.560 ± 0.046
38
20.46 ± 0.20
4.338 ± 0.042
43
20.68 ± 0.20
4.291 ± 0.041
80
22.90 ± 0.20
3.880 ± 0.033
22
25.69 ± 0.20
3.466 ± 0.027
70
TABLE B
°2θ
d space (Å)
Intensity (%)
12.26 ± 0.20
7.211 ± 0.117
22
13.78 ± 0.20
6.421 ± 0.093
36
15.42 ± 0.20
5.741 ± 0.074
26
16.55 ± 0.20
5.352 ± 0.064
40
17.15 ± 0.20
5.167 ± 0.060
29
18.19 ± 0.20
4.873 ± 0.053
100
18.50 ± 0.20
4.792 ± 0.051
100
19.45 ± 0.20
4.560 ± 0.046
38
20.46 ± 0.20
4.338 ± 0.042
43
20.68 ± 0.20
4.291 ± 0.041
80
22.90 ± 0.20
3.880 ± 0.033
22
25.69 ± 0.20
3.466 ± 0.027
70
TABLE C
°2θ
d space (Å)
Intensity (%)
6.87 ± 0.20
12.859 ± 0.374
6
12.26 ± 0.20
7.211 ± 0.117
22
13.78 ± 0.20
6.421 ± 0.093
36
14.49 ± 0.20
6.106 ± 0.084
6
15.42 ± 0.20
5.741 ± 0.074
26
16.55 ± 0.20
5.352 ± 0.064
40
17.15 ± 0.20
5.167 ± 0.060
29
18.19 ± 0.20
4.873 ± 0.053
100
18.50 ± 0.20
4.792 ± 0.051
100
19.45 ± 0.20
4.560 ± 0.046
38
20.06 ± 0.20
4.422 ± 0.044
9
20.46 ± 0.20
4.338 ± 0.042
43
20.68 ± 0.20
4.291 ± 0.041
80
20.96 ± 0.20
4.236 ± 0.040
11
21.54 ± 0.20
4.123 ± 0.038
10
22.90 ± 0.20
3.880 ± 0.033
22
24.69 ± 0.20
3.602 ± 0.029
3
25.17 ± 0.20
3.535 ± 0.028
14
25.44 ± 0.20
3.499 ± 0.027
13
25.69 ± 0.20
3.466 ± 0.027
70
26.36 ± 0.20
3.378 ± 0.025
13
27.52 ± 0.20
3.239 ± 0.023
23
27.76 ± 0.20
3.211 ± 0.023
7
10. The Crystalline Form A of claim 8 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 7.2, 6.4, 5.7, 5.4, 5.2, 4.9, 4.8, 4.6, 4.3, 3.9, and 3.5.
11. The Crystalline Form A of claim 8 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 12.9, 7.2, 6.4, 6.1, 5.7, 5.4, 5.2, 4.9, 4.8, 4.6, 4.4, 4.3, 4.2, 4.1, 3.9, 3.6, 3.5, 3.4, and 3.2.
12. The Crystalline Form A of claim 8 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern measured using radiation of wavelength 1.54059 Å substantially as shown in any figure selected from FIGS. 35, 37, and 47 .
13. The Crystalline Form A of claim 8 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern measured using radiation of wavelength 1.54059 Å as shown in any figure selected from FIGS. 35, 37, and 47 .
14. Crystalline Form B of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 14.6, 5.1, 4.7, 4.6, and 3.6.
15. The Crystalline Form B of claim 14 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values selected from Table D, E, and F below:
TABLE D
°2θ
d space (Å)
Intensity (%)
6.04 ± 0.20
14.620 ± 0.484
13
17.41 ± 0.20
5.089 ± 0.058
14
18.94 ± 0.20
4.681 ± 0.049
79
19.19 ± 0.20
4.622 ± 0.048
100
24.39 ± 0.20
3.646 ± 0.029
23
TABLE E
°2θ
d space (Å)
Intensity (%)
6.04 ± 0.20
14.620 ± 0.484
13
13.21 ± 0.20
6.699 ± 0.101
21
17.41 ± 0.20
5.089 ± 0.058
14
18.94 ± 0.20
4.681 ± 0.049
79
19.19 ± 0.20
4.622 ± 0.048
100
23.59 ± 0.20
3.769 ± 0.032
16
23.79 ± 0.20
3.737 ± 0.031
43
24.39 ± 0.20
3.646 ± 0.029
23
28.15 ± 0.20
3.168 ± 0.022
24
TABLE F
°2θ
d space (Å)
Intensity (%)
6.04 ± 0.20
14.620 ± 0.484
13
12.12 ± 0.20
7.296 ± 0.120
6
13.21 ± 0.20
6.699 ± 0.101
21
14.86 ± 0.20
5.958 ± 0.080
8
15.13 ± 0.20
5.853 ± 0.077
5
16.02 ± 0.20
5.529 ± 0.069
1
16.90 ± 0.20
5.242 ± 0.062
4
17.41 ± 0.20
5.089 ± 0.058
14
18.23 ± 0.20
4.861 ± 0.053
10
18.94 ± 0.20
4.681 ± 0.049
79
19.19 ± 0.20
4.622 ± 0.048
100
19.91 ± 0.20
4.457 ± 0.044
4
21.05 ± 0.20
4.217 ± 0.040
11
21.27 ± 0.20
4.173 ± 0.039
2
21.74 ± 0.20
4.085 ± 0.037
4
22.55 ± 0.20
3.939 ± 0.034
6
23.59 ± 0.20
3.769 ± 0.032
16
23.79 ± 0.20
3.737 ± 0.031
43
24.39 ± 0.20
3.646 ± 0.029
23
25.34 ± 0.20
3.512 ± 0.027
1
26.06 ± 0.20
3.416 ± 0.026
2
26.61 ± 0.20
3.347 ± 0.025
1
27.15 ± 0.20
3.282 ± 0.024
2
28.15 ± 0.20
3.168 ± 0.022
24
28.66 ± 0.20
3.112 ± 0.021
13
29.47 ± 0.20
3.028 ± 0.020
13
16. The Crystalline Form B of claim 14 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 14.6, 6.7, 5.1, 4.7, 4.6, 3.8, 3.7, 3.6, and 3.2.
17. The Crystalline Form B of claim 14 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 14.6, 7.3, 6.7, 6.0, 5.9, 5.5, 5.2, 5.1, 4.9, 4.7, 4.6, 4.5, 4.2, 4.1, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, and 3.0.
18. The Crystalline Form B of claim 14 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern measured using radiation of wavelength 1.54059 Å substantially as shown in any figure selected from FIGS. 40 and 48 .
19. The Crystalline Form B of claim 14 , wherein the Crystalline Form B exhibits an X-ray powder diffraction (XRPD) pattern measured using radiation of wavelength 1.54059 Å as shown in any figure selected from FIGS. 40 and 48 .
20. A pharmaceutical composition comprising Crystalline Form A of claim 1 and a pharmaceutically acceptable diluent or carrier.
21. A method for treatment of attention deficit hyperactivity disorder comprising administering to a patient in need thereof a therapeutically effective amount of Crystalline Form A of claim 1 .
22. A pharmaceutical composition comprising Crystalline Form B of claim 14 , and a pharmaceutically acceptable diluent or carrier.
23. The Crystalline Form A of claim 8 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 5.74, 5.35, 5.17, 4.79, 4.56, 4.34, 4.29, 3.88, and 3.47.
24. The Crystalline Form A of claim 8 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 7.21, 6.42, 5.74, 5.35, 5.17, 4.87, 4.79, 4.56, 4.34, 4.29, 3.88, and 3.47.
25. The Crystalline Form A of claim 8 , wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising d-spacing (Å) values of 12.86, 7.21, 6.42, 6.11, 5.74, 5.35, 5.17, 4.87, 4.79, 4.56, 4.42, 4.34, 4.29, 4.24, 4.12, 3.88, 3.60, 3.54, 3.50, 3.47, 3.38, 3.24, and 3.21.
26. A pharmaceutical composition comprising Crystalline Form A of claim 5 and a pharmaceutically acceptable diluent or carrier.
27. A pharmaceutical composition comprising Crystalline Form A of claim 6 and a pharmaceutically acceptable diluent or carrier.
28. A pharmaceutical composition comprising Crystalline Form A of claim 9 and a pharmaceutically acceptable diluent or carrier.
29. A pharmaceutical composition comprising Crystalline Form A of claim 23 and a pharmaceutically acceptable diluent or carrier.
30. A pharmaceutical composition comprising Crystalline Form A of claim 24 and a pharmaceutically acceptable diluent or carrier.
31. A pharmaceutical composition comprising Crystalline Form A of claim 8 and a pharmaceutically acceptable diluent or carrier.
32. A method for treatment of attention deficit hyperactivity disorder comprising administering to a patient in need thereof a therapeutically effective amount of Crystalline Form A of claim 8 .