Crystalline forms
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 method of treating a disease state selected from muscle wasting associated with cancer and cachexia associated with cancer in a human subject, wherein said method comprises administering a crystalline form of:
that is characterized by an X-ray powder diffraction (XRPD) pattern that has the representative peaks:
Position [°2Theta]
d-spacing [Å]
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
to said human subject.
2. The method of claim 1 wherein the crystalline form is further characterized by an XRPD pattern substantially in accordance with FIG. 1 .
3. The method of claim 1 wherein the crystalline form 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 method of claim 1 wherein the crystalline form is further characterized by an 19 F SSNMR spectrum substantially in accordance with FIG. 4 .
5. The method of claim 1 wherein the crystalline form 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 method of claim 1 wherein the crystalline form is further characterized by an 13 C SSNMR spectrum substantially in accordance with FIG. 3 .
7. A method of treating congestive heart failure in a human subject, wherein said method comprises administering a crystalline form of:
that is characterized by an X-ray powder diffraction (XRPD) pattern that has the representative peaks:
Position [°2Theta]
d-spacing [Å]
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
to said human subject.
8. The method of claim 7 wherein the crystalline form is further characterized by an XRPD pattern substantially in accordance with FIG. 1 .
9. The method of claim 7 wherein the crystalline form 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.
10. The method of claim 7 wherein the crystalline form is further characterized by an 19 F SSNMR spectrum substantially in accordance with FIG. 4 .
11. The method of claim 7 wherein the crystalline form 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.
12. The method of claim 7 wherein the crystalline form is further characterized by an 13 C SSNMR spectrum substantially in accordance with FIG. 3 .