US2021017163A1PendingUtilityA1

Hydrochloride salt form for ezh2 inhibition

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Assignee: EPIZYME INCPriority: Oct 16, 2013Filed: Jun 3, 2020Published: Jan 21, 2021
Est. expiryOct 16, 2033(~7.2 yrs left)· nominal 20-yr term from priority
Inventors:Kevin Wayne KuntzHyeong Wook ChoiSteven MathieuKristen SandersArani Chanda
C07D 413/14C07B 2200/13A61P 35/00A61K 31/5377C07D 413/12C07D 405/12A61P 43/00A61P 35/02
65
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Claims

Abstract

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.

Claims

exact text as granted — not AI-modified
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.

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