Hydrochloride salt form for EZH2 inhibition

Patent metadata

Field	Value
Publication number	US-10040782-B2
Application number	US-201415029848-A
Country	US
Kind code	B2
Filing date	Oct 15, 2014
Priority date	Oct 16, 2013
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

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.

First claim

The invention claimed is:

1. 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.

2. The solid crystalline form of claim 1 , 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.

3. The solid crystalline form of claim 1 , 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.

4. The solid crystalline form of claim 1 , 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.

5. The solid crystalline form of claim 1 , 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.

6. A pharmaceutical composition comprising a polymorph of claim 1 , and a pharmaceutically acceptable carrier or diluent.

7. The solid crystalline form of claim 1 , 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 11.22, 12.0, 13.116, 18.032, 19.399, 22.499, 24.363, 24.7, 24.958, 30.557, and 30.879.

8. The solid crystalline form of claim 1 , 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 11.22, 12.0, 13.116, 18.032, 19.399, 22.499, 24.363, 24.7, 24.958, 30.557, and 30.879.

9. The solid crystalline form of claim 1 , 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 8.438, 13.318, 17.78, 23.725, 24.159, 25.498 and 26.863.

10. The solid crystalline form of claim 1 , 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 8.438, 13.318, 17.78, 23.725, 24.159, 25.498 and 26.863.

11. The solid crystalline form of claim 1 , 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 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.

12. The solid crystalline form of claim 1 , 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 10.940, 13.418, 13.899, 16.583, 17.124, 18.340, and 20.199.

13. The solid crystalline form of claim 1 , wherein the solid crystalline form exhibits an X-ray powder diffraction pattern having peaks expressed in degrees 2-theta (+/−0.2) at 17.124, 18.340, and 21.917.

14. 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 monohydrochloride, 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 17.124, 18.340 and 21.917.

Assignees

• Epizyme Inc
• Eisai R&D Man Co Ltd

Inventors

• Kuntz Kevin W
• Choi Hyeong-Wook
• Mathieu Steven
• Sanders Kristen
• Chanda Arani

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/5377 Primary

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title