Solid forms of (S)-ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-pyrimidin-4-yl)phenyl)propanoate and methods of their use
View Patent ↗Solid forms of (S)-ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate and salts thereof are disclosed.
1. A method of treating or managing a disease or disorder mediated by peripheral serotonin, which comprises administering to a patient in need of such treatment, or management a therapeutically effective amount of a compound, which is crystalline (S)-ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the disease or disorder is carcinoid syndrome.
3. The method of claim 1 , wherein the disease or disorder is a gastrointestinal disease or disorder.
4. The method of claim 3 , wherein the disease or disorder is irritable bowel syndrome.
5. The method of claim 1 , wherein the disease or disorder is Crohn's disease.
6. The method of claim 1 , wherein the compound is crystalline (S)-ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate.
7. The method of claim 6 , wherein the compound has a melting point of about 104° C.
8. The method of claim 6 , wherein the compound has an X-ray powder diffraction pattern with peaks at one or more of about 10.7, 12.2, 12.8, 17.7 and/or 22.0 degrees 2θ.
9. The method of claim 6 , wherein the compound has an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 1 .
10. The method of claim 1 , wherein the compound is a crystalline salt of (S)-ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate.
11. The method of claim 10 , wherein the compound is a hippurate salt.
12. The method of claim 11 , wherein the compound has a melting point of about 145° C.
13. The method of claim 11 , wherein the compound has an X-ray powder diffraction pattern comprising peaks at one or more of about 8.2, 9.5, 12.6, 16.9, 21.8, 22.0, 22.7, 24.3 and/or 29.1 degrees 2θ.
14. The method of claim 11 , wherein the compound has an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 2 .
15. The method of claim 11 , wherein the compound has a Raman spectrum that is substantially the same as that shown in FIG. 3 .
16. The method of claim 10 , wherein the compound is a succinate salt.
17. The method of claim 16 , wherein the compound has an X-ray powder diffraction pattern comprising peaks at one or more of about 7.7, 11.5, 11.7, 15.7, 17.9, 21.1 and/or 23.2 degrees 2θ.
18. The method of claim 16 , wherein the compound has an X-ray powder diffraction pattern that is substantially the same as that shown in FIG. 4 .