Compositions comprising an inhibitor of lysine specific demethylase-1
Described herein are amorphous and crystalline forms of pharmaceutically acceptable salts of the lysine specific demethylase-1 inhibitor 4-[2-(4-amino-piperidin-1-yl)-5-(3-fluoro-4-methoxy-phenyl)-1-methyl-6-oxo-1,6-dihydro-pyrimidin-4-yl]-2-fluorobenzonitrile. Also described are pharmaceutical compositions suitable for administration to a mammal that include the lysine specific demethylase-1 inhibitor, and methods of using the lysine specific demethylase-1 inhibitor for treating diseases or conditions that are associated with lysine specific demethylase-1 activity.
1. A pharmaceutically acceptable salt of 4-[2-(4-amino-piperidin-1-yl)-5-(3-fluoro-4-methoxy-phenyl)-1-methyl-6-oxo-1,6-dihydro-pyrimidin-4-yl]-2-fluorobenzonitrile, wherein the pharmaceutically acceptable salt is in crystalline form.
2. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is a p-toluene sulfonic acid salt, sulfuric acid salt, methanesulfonic acid salt, benzenesulfonic acid salt, phosphoric acid salt, or benzoic acid salt.
3. The pharmaceutically acceptable salt of claim 1 , wherein the pharmaceutically acceptable salt is a benzenesulfonic acid salt.
4. A crystalline form of 4-[2-(4-amino-piperidin-1-yl)-5-(3-fluoro-4-methoxy-phenyl)-1-methyl-6-oxo-1,6-dihydro-pyrimidin-4-yl]-2-fluorobenzonitrile besylate salt, designated Form 1, wherein the crystalline form that exhibits the following characteristics:
(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1 ;
(b) an XRPD pattern with characteristic peaks at 4.9° 2-Theta, 9.7° 2-Theta, 13.4° 2-Theta, 18.0° 2-Theta, and 18.5° 2-Theta;
(c) a DSC thermogram with an endotherm having an onset temperature at about 317° C.;
(d) a DSC thermogram substantially similar to the one set forth in FIG. 2 ; or
(e) combinations thereof.
5. The crystalline form of claim 4 , wherein the crystalline form exhibits a characteristic XRPD pattern substantially the same as shown in FIG. 1 .
6. The crystalline form of claim 4 , wherein the crystalline form exhibits a characteristic XRPD pattern with characteristic peaks at 4.9° 2-Theta, 9.7° 2-Theta, 13.4° 2-Theta, 18.0° 2-Theta, and 18.5° 2-Theta.
7. The crystalline form of claim 4 , wherein the crystalline form exhibits substantially the same characteristic XRPD pattern after storage at 40° C. and 75% RH for at least a week.
8. The crystalline form of claim 4 , wherein the crystalline form exhibits substantially the same characteristic XRPD pattern after storage at 25° C. and 96% RH for at least a week.
9. The crystalline form of claim 4 , wherein the crystalline form exhibits a DSC thermogram with an endotherm having an onset temperature at about 317° C.
10. A composition comprising a crystalline form of claim 1 .
11. A pharmaceutical composition comprising the crystalline form of claim 1 , and at least one pharmaceutically acceptable carrier, diluent, or excipient.
12. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition is in an oral dosage form.
13. The pharmaceutical composition of claim 12 , wherein the oral dosage form is a tablet, capsule or pill.
14. 4-[2-(4-amino-piperidin-1-yl)-5-(3-fluoro-4-methoxy-phenyl)-1-methyl-6-oxo-1,6-dihydro-pyrimidin-4-yl]-2-fluorobenzonitrile besylate salt that is in amorphous form.
15. A pharmaceutical composition comprising amorphous 4-[2-(4-amino-piperidin-1-yl)-5-(3-fluoro-4-methoxy-phenyl)-1-methyl-6-oxo-1,6-dihydro-pyrimidin-4-yl]-2-fluorobenzonitrile besylate salt, and at least one pharmaceutically acceptable carrier, diluent, or excipient.
16. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is an oral dosage form.
17. The pharmaceutical composition of claim 16 , wherein the oral dosage form is a tablet, capsule, or pill.
18. A pharmaceutical composition comprising the crystalline form of claim 4 and at least one pharmaceutically acceptable carrier, diluent, or excipient.
19. A method of treating acute myeloid leukemia, breast or prostate cancer in a mammal comprising administering to the mammal the pharmaceutical composition of claim 18 .
20. A method of treating acute myeloid leukemia, breast or prostate cancer in a mammal comprising administering to the mammal the pharmaceutical composition of claim 15 .