CRYSTALLINE FORMS OF N-(4-(1-(2,6-DIFLUOROBENZYL)-5-((DIMETHYLAMINO)METHYL)-3-(6-METHOXY-3-PYRIDAZINYL)-2,4-DIOXO-1,2,3,4-TETRAHYDROTHIENO[2,3-D]PYRIMIDIN-6-YL)PHENYL)-N'-METHOXYUREA
This disclosure relates to novel crystalline forms of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino) methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea. It also relates to methods of making the disclosed crystalline forms, pharmaceutical compositions and kits comprising them, and methods of treatment and uses comprising their administration.
1 - 17 : (canceled)
18 . A crystalline form of a toluene solvate of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea.
19 . The crystalline form of claim 18 , characterized by an X-ray powder diffraction pattern comprising at least three 2-theta (2θ±0.2° 20) peaks selected from 7.1°, 10.6°, 11.2°, 15.3° and 16.7°.
20 . The crystalline form of claim 18 , characterized by an X-ray powder diffraction pattern comprising 2-theta (2θ±0.2° 20) peaks at 7.1°, 10.6°, 11.2°, 15.3° and 16.7°.
21 . The crystalline form of claim 18 , characterized by an X-ray powder diffraction pattern substantially the same as the pattern shown in FIG. 7 , a thermogravimetric (TG) thermogram substantially the same as the pattern shown in FIG. 8 , or a differential scanning calorimetry (DSC) thermogram substantially the same as the pattern shown in FIG. 9 .
22 . A crystalline form of an anisole solvate of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea.
23 . The crystalline form of claim 22 , characterized by an X-ray powder diffraction pattern comprising at least three 2-theta (2θ±0.2° 20) peaks selected from 7.2°, 10.5°, 11.1°, 15.2° and 16.6°.
24 . The crystalline form of claim 22 , characterized by an X-ray powder diffraction pattern comprising 2-theta (2θ±0.2° 20) peaks at 7.2°, 10.5°, 11.1°, 15.2° and 16.6°.
25 . The crystalline form of claim 22 , characterized by an X-ray powder diffraction pattern substantially the same as the pattern shown in FIG. 10 , a TG thermogram substantially the same as the pattern shown in FIG. 11 , or a DSC thermogram substantially the same as the pattern shown in FIG. 12 .
26 . A crystalline form of a dioxane solvate of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea.
27 . The crystalline form of claim 26 , characterized by an X-ray powder diffraction pattern comprising at least three 2-theta (2θ±0.2° 20) peaks selected from 7.4°, 10.6°, 13.7°, 15.2°, and 18.7°.
28 . The crystalline form of claim 26 , characterized by an X-ray powder diffraction pattern comprising 2-theta (2θ±0.2° 20) peaks at 7.4°, 10.6°, 13.7°, 15.2°, and 18.7°.
29 . The crystalline form of claim 26 , characterized by an X-ray powder diffraction pattern substantially the same as the pattern shown in FIG. 16 , a TG thermogram substantially the same as the pattern shown in FIG. 17 , or a DSC thermogram substantially the same as the pattern shown in FIG. 18 .
30 . A crystalline form of a α,α,α-trifluorotoluene solvate of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea.
31 . The crystalline form of claim 30 , characterized by an X-ray powder diffraction pattern comprising 2-theta (2θ±0.2° 20) peaks at 7.8°, 18.3°, 18.6°, and 23.3°.
32 . The crystalline form of claim 30 , characterized by an X-ray powder diffraction pattern substantially the same as the pattern shown in FIG. 19 , a TG thermogram substantially the same as the pattern shown in FIG. 20 , or a DSC thermogram substantially the same as the pattern shown in FIG. 21 .
33 . A crystalline form of a trifluoroethanol solvate of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea.
34 . The crystalline form of claim 33 , characterized by an X-ray powder diffraction pattern comprising at least three 2-theta (2θ±0.2° 20) peaks selected 4.6°, 9.1°, 9.6°, 17.4°, and 18.8°.
35 . The crystalline form of claim 33 , characterized by an X-ray powder diffraction pattern comprising 2-theta (2θ±0.2° 20) peaks at 4.6°, 9.1°, 9.6°, 17.4°, and 18.8°.
36 . The crystalline form of claim 33 , characterized by an X-ray powder diffraction pattern substantially the same as the pattern shown in FIG. 22 , a TG thermogram substantially the same as the pattern shown in FIG. 23 , or a DSC thermogram substantially the same as the pattern shown in FIG. 24 .