CRYSTALLINE FORMS OF AN ANDROGEN RECEPTOR MODULATOR

摘要

Described herein are amorphous and crystalline forms of the androgen receptor modulator 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide. Also described are pharmaceutical compositions suitable for administration to a mammal that include the androgen receptor modulator, and methods of using the androgen receptor modulator, alone and in combination with other compounds, for treating diseases or conditions that are associated with androgen receptor activity.

主权项

1. A crystalline Form A of 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide that is characterized as having:
(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1; (b) an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 4.8±0.1° 2-Theta, 7.1±0.1° 2-Theta, 14.2±0.1° 2-Theta, 16.3±0.1° 2-Theta, 20.1±0.1° 2-Theta; (c) unit cell parameters substantially equal to the following at −173° C.:Crystal systemOrthorhombicSpace groupP2(1)2(1)2a16.3429(3) Åα90°b37.7298(7) Åβ90°c7.23410(10) Å γ90°V446O.65(13) Å3Z8Dc1.446 g · cm−1 (d) substantially the same X-ray powder diffraction (XRPD) pattern post storage at 40° C. and 75% RH for at least a week; (e) a DSC thermogram with an endotherm having an onset temperature at about 108-120° C. and a peak at about 133-135° C.; (f) a DSC thermogram substantially similar to the one set forth in FIG. 19; (g) an observed aqueous solubility of about 0.01 mg/mL; or (h) combinations thereof.