HYDROCHLORIDE SALT FORM FOR EZH2 INHIBITION
Provided herein are novel solid forms of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrochloride, and related compositions and methods.
1 .- 6 . (canceled)
7 . A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a solid crystalline form of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide, or a salt thereof, wherein the solid crystalline form exhibits an X-ray powder diffraction pattern having two or more peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 8.438, 10.083, 10.18, 10.74, 10.940, 11.22, 12.0, 13.116, 13.318, 13.418, 13.541, 13.762, 13.899, 16.443, 16.583, 17.026, 17.124, 17.219, 17.53, 17.78, 18.032, 18.32, 18.340, 18.419, 18.66, 19.399, 20.182, 20.199, 20.421, 20.500, 20.839, 21.14, 21.84, 21.917, 21.958, 22.22, 22.499, 23.238, 23.46, 23.725, 24.159, 24.363, 24.7, 24.958, 25.498, 26.222, 26.596, 26.863, 27.72, 30.30, 30.557, and 30.879.
8 . The method of claim 7 , wherein the cancer is EZH2 mediated.
9 . The method of claim 7 , wherein the solid crystalline form exhibits an X-ray powder diffraction pattern having two or more characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 17.53, 18.66, 21.14, 22.22, 23.46, 27.72 and 30.30.
10 . The method of claim 7 , wherein the solid crystalline form exhibits an X-ray powder diffraction pattern having three or more characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 17.53, 18.66, 21.14, 22.22, 23.46, 27.72 and 30.30.
11 . The method of claim 7 , wherein the solid crystalline form exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta (+/−0.2) at 17.53, 21.14, 23.46, and 27.72.
12 . The method of claim 7 , wherein the solid crystalline form exhibits a differential scanning calorimetry thermogram showing a primary endotherm expressed in units of ° C. at a temperature of 190+/−5° C., 105+/−5° C., or 228+/−5° C.
13 .- 19 . (canceled)
20 . The method of claim 7 , wherein the solid crystalline form is a hydrochloride salt.
21 . A polymorph of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide monohydrochloride salt.
22 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having two or more peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 8.438, 10.083, 10.18, 10.74, 10.940, 11.22, 12.0, 13.116, 13.318, 13.418, 13.541, 13.762, 13.899, 16.443, 16.583, 17.026, 17.124, 17.219, 17.53, 17.78, 18.032, 18.32, 18.340, 18.419, 18.66, 19.399, 20.182, 20.199, 20.421, 20.500, 20.839, 21.14, 21.84, 21.917, 21.958, 22.22, 22.499, 23.238, 23.46, 23.725, 24.159, 24.363, 24.7, 24.958, 25.498, 26.222, 26.596, 26.863, 27.72, 30.30, 30.557, and 30.879.
23 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having two or more characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 17.53, 18.66, 21.14, 22.22, 23.46, 27.72 and 30.30.
24 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having three or more characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 17.53, 18.66, 21.14, 22.22, 23.46, 27.72 and 30.30.
25 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta (+/−0.2) at 17.53, 21.14, 23.46, and 27.72.
26 . The polymorph of claim 21 , wherein the polymorph exhibits a differential scanning calorimetry thermogram showing a primary endotherm expressed in units of ° C. at a temperature of 190+/−5° C., 105+/−5° C., or 228+/−5° C.
27 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having two or more characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 11.22, 12.0, 13.116, 18.032, 19.399, 22.499, 24.363, 24.7, 24.958, 30.557, and 30.879.
28 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having three or more characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 11.22, 12.0, 13.116, 18.032, 19.399, 22.499, 24.363, 24.7, 24.958, 30.557, and 30.879.
29 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having two or more characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 8.438, 13.318, 17.78, 23.725, 24. 159, 25.498 and 26.863.
30 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having three or more characteristic peaks expressed in degrees 2-theta (+/−0.2), selected from the group consisting of 8.438, 13.318, 17.78, 23.725, 24. 159, 25.498 and 26.863.
31 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having two or more peaks expressed in degrees 2-theta (+/−0.2) selected from the group consisting of about 10.083, 10.940, 13.418, 13.899, 16.583, 17.124, 17.53, 18.340, 18.66, 20.199, 20.500, 20.839, 21.917, and 23.46.
32 . The polymorph of claim 21 , wherein the polymorph exhibits an X-ray powder diffraction pattern having two or more peaks expressed in degrees 2-theta (+/−0.2) selected from the group consisting of 10.940, 13.418, 13.899, 16.583, 17.124, 18.340, and 20.199.
33 . A pharmaceutical composition comprising a polymorph of claim 21 , and a pharmaceutically acceptable carrier or diluent.