Crystalline forms of (R)-1-(1-(methylsulfonyl)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile
View Patent ↗This invention relates to crystalline forms of (R)-1-(1-(methylsulfonyl)propan-2-yl)-4-(trifluoromethyl)indoline-5-carbonitrile, a modulator of the androgen receptor, and methods for the use in treatment.
1. A crystalline form of:
that is characterized by an X-ray powder diffraction (XRPD) pattern that has the representative peaks:
Position [° 2Theta]
d-spacing [A]
9.2 ± 0.1
9.6
11.4 ± 0.1
7.8
11.9 ± 0.1
7.4
13.8 ± 0.1
6.4
15.4 ± 0.1
5.7
17.8 ± 0.1
5.0
18.0 ± 0.1
4.9
18.5 ± 0.1
4.8
18.7 ± 0.1
4.7
23.2 ± 0.1
3.8.
2. The crystalline form of claim 1 that is further characterized by an XRPD pattern substantially in accordance with FIG. 1 .
3. The crystalline form of claim 1 that is further characterized by an 19 F SSNMR spectrum comprising isotropic chemical shifts at −52.7±0.2, 56.0±0.2 and −57.1±0.2 ppm, wherein the 19 F SSNMR spectrum is obtained on a spectrometer operating at a frequency of 470.40 MHz for 19 F observation using a cross-polarization pulse sequence with a Bruker 4-mm triple resonance magic-angle spinning probe at a rotor frequency of 12.5 kHz.
4. The crystalline form of claim 1 that is further characterized by an 19 F SSNMR spectrum substantially in accordance with FIG. 4 .
5. The crystalline form of claim 1 that is further characterized by an 13 C SSNMR (solid state nuclear magnetic resonance) spectrum comprising isotropic chemical shifts at 140.1±0.2, 136.9±0.2, 134.9±0.2, 130.4±0.2, 128.5±0.2, 126.6±0.2, 126.0±0.2, 125.7±0.2, 124.8±0.2, 121.9±0.2, 120.9±0.2, 119.7±0.2, 118.6±0.2, 115.5±0.2, 115.1±0.2, 103.6±0.2, 100.3±0.2, 98.9±0.2, 58.1±0.2, 55.7±0.2, 54.7±0.2, 51.1±0.2, 50.4±0.2, 44.7±0.2, 43.6±0.2, 40.7±0.2, 23.5±0.2 and 20.7±0.2 ppm, wherein the 13 C SSNMR spectrum is obtained on a spectrometer operating at a frequency of 125.73 MHz for 13 C observation using a cross-polarization pulse sequence with a Bruker 4-mm triple resonance magic-angle spinning probe at a rotor frequency of 8 kHz.
6. The crystalline form of claim 1 that is further characterized by an 13 C SSNMR spectrum substantially in accordance with FIG. 3 .
7. The crystalline form of claim 1 when prepared by crystallization from a solvent system that is ethyl acetate and n-heptane.
8. The crystalline form of claim 1 when prepared by crystallization from a solvent system that is other than dichloromethane and hexanes.
9. A method of treating a disorder selected from muscle wasting associated with chronic obstructive pulmonary disease (COPD), muscle wasting associated with chronic kidney disease (CKD), muscle wasting associated with chronic heart failure (CHF), and urinary incontinence, wherein said method comprises administering a compound according to claim 1 to a human subject.
10. A method of accelerating hip fracture repair and healing wherein said method comprises administering a compound according to claim 1 to a human subject.
11. A process for preparing a crystalline form of:
that is characterized by an X-ray powder diffraction (XRPD) pattern that has the representative peaks:
Position [° 2Theta]
d-spacing [A]
9.2 ± 0.1
9.6
11.4 ± 0.1
7.8
11.9 ± 0.1
7.4
13.8 ± 0.1
6.4
15.4 ± 0.1
5.7
17.8 ± 0.1
5.0
18.0 ± 0.1
4.9
18.5 ± 0.1
4.8
18.7 ± 0.1
4.7
23.2 ± 0.1
3.8
which process comprises crystallization from a solvent system that is ethyl acetate and n-heptane.
12. A process for preparing a crystalline form of:
that is characterized by an X-ray powder diffraction (XRPD) pattern that has the representative peaks:
Position [° 2Theta]
d-spacing [A]
9.2 ± 0.1
9.6
11.4 ± 0.1
7.8
11.9 ± 0.1
7.4
13.8 ± 0.1
6.4
15.4 ± 0.1
5.7
17.8 ± 0.1
5.0
18.0 ± 0.1
4.9
18.5 ± 0.1
4.8
18.7 ± 0.1
4.7
23.2 ± 0.1
3.8
which process comprises crystallization from a solvent system that is other than dichloromethane and hexanes.