Hydrochloride salt form for EZH2 inhibition

• US 10,040,782 B2
• Filed: 10/15/2014
• Issued: 08/07/2018
• Est. Priority Date: 10/16/2013
• Status: Active Grant

• Current Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated), Epizyme, Inc. (Ipsen Sa)
• Original Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated), Epizyme, Inc. (Ipsen Sa)
• Inventors: Kuntz, Kevin W., Choi, Hyeong-wook, Mathieu, Steven, Sanders, Kristen, Chanda, Arani
• Primary Examiner(s): Brown-Pettigrew, Angela C
• Application Number:
  US15/029,848
• Publication Number:
  US 20160237068A1
• Time in Patent Office: 1,392 Days
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

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

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.