(N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide

Patent metadata

Field	Value
Publication number	US-9809559-B2
Application number	US-201615231411-A
Country	US
Kind code	B2
Filing date	Aug 8, 2016
Priority date	Jun 12, 2014
Publication date	Nov 7, 2017
Grant date	Nov 7, 2017

Abstract

The present invention relates to stable novel salt forms of N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide that are suitable for the preparation of pharmaceutical formulations thereof, and their therapeutic use.

First claim

What is claimed:

1. A method of treating myelofibrosis or polycythemia vera comprising administering to a subject in need thereof a compound selected from the group consisting of:
N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II;
N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form I; and
N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form III.

2. The method of claim 1 , wherein the compound is in a crystalline form.

3. The method of claim 2 , wherein the crystalline form is N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide dihydrochloride monohydrate Form II.

4. The method of claim 3 , wherein the crystals have unit cell parameters at T=100° K of: a=10.2837(6) Å, b=10.4981(6) Å, c=11.5143(7) Å, α=83.297(2)°, β=87.649(2)°, γ=67.445(2)°, and a triclinic P-1 space group.

5. The method of claim 3 , wherein the crystalline form is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 5 .

6. The method of claim 3 , wherein the crystalline form is characterized by an x-ray powder diffraction (XRPD) pattern having peaks at about 7.7°, 19.3°, 24.0°, 25.7°, and 29.6° 2-θ±0.2° 2-θ.

7. The method of claim 3 , wherein the crystalline form is characterized by differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 8 .

8. The method of claim 3 , wherein the crystalline form is characterized by a dynamic vapor sorption (DVS) pattern substantially as set forth in FIG. 14 .

9. The method of claim 2 , wherein the crystalline form is crystalline N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form I.

10. The method of claim 9 , wherein the crystalline form is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 6 .

11. The method of claim 9 , wherein the crystalline form is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 13.5°, 20.9°, 26.1°, 26.6°, and 28.3° 2-θ±0.2° 2-θ.

12. The method of claim 9 , wherein the crystalline form is characterized by a differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 9 .

13. The method of claim 2 , wherein the crystalline form is crystalline N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide monohydrochloride anhydrous Form III.

14. The method of claim 13 , wherein the crystalline form is characterized by an x-ray powder diffraction (XRPD) pattern substantially as set forth in FIG. 7 .

15. The method of claim 13 , wherein the crystalline form is characterized by an X-ray powder diffraction (XRPD) pattern having peaks at about 12.7°, 14.6°, 17.8°, 19.7°, and 23.3° 2-θ±0.2° 2-θ.

16. The method of claim 13 , wherein the crystalline form is characterized by a differential scanning calorimetry (DSC) pattern substantially as set forth in FIG. 10 .

Assignees

• Gilead Sciences Inc

Inventors

• Brown Brandon H
• Carra Ernest A
• Hemenway Jeffrey N
• Morrison Henry
• Reynolds Troy
• Shi Bing
• Stefanidis Dimitrios
• Wang Fang
• Warr Matthew Robert
• Whitney James Andrew
• Xin Yan

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P43/00

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

• A61K31/5377

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