Salts of IJAK inhibitors and methods of using the same

Patent metadata

Field	Value
Publication number	US-11149029-B2
Application number	US-201916513781-A
Country	US
Kind code	B2
Filing date	Jul 17, 2019
Priority date	Jul 18, 2018
Publication date	Oct 19, 2021
Grant date	Oct 19, 2021

Abstract

The present disclosure relates to salts of compounds of Formula (I) prepared as a xinafoate (1-hydroxy-2-naphthoate) salt (Formula (Ia)), pharmaceutically acceptable compositions comprising same and methods of using the same.

First claim

The invention claimed is:

1. A xinafoate salt of Formula (Ia):

2. The salt according to claim 1 , which is in crystalline form.

3. A pharmaceutically acceptable composition comprising a xinafoate salt of claim 1 , in association with a pharmaceutically-acceptable excipient, diluent or carrier.

4. A pharmaceutically acceptable composition comprising a xinafoate salt of claim 2 , in association with a pharmaceutically-acceptable excipient, diluent or carrier.

5. The salt according to claim 1 , which is in crystalline Form A wherein crystalline Form A has an X-ray powder diffraction pattern with specific peaks at about 2θ measured using CuKα radiation 15.0° and 21.0° and 22.6° (±0.1°).

6. The salt according to claim 5 , wherein crystalline Form A has an X-ray powder diffraction pattern with specific peaks at about 2θ measured using CuKα radiation 8.2, 8.9, 11.2, 14.2, 15.0, 15.3, 16.2, 17.5, 21.0, 22.6, 23.0, 23.7, 24.6 and 26.2° (±0.1°).

7. A process for the preparation of a xinafoate salt of claim 1 comprising:
(i) Dissolving (R)—N-(3-(5-fluoro-2-(2-fluoro-3-(methylsulfonyl)phenylamino)pyrimidin-4-yl)-1H-indol-7-yl)-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide free base in a suitable solvent;
(ii) Dissolving xinafoate acid in a suitable solvent;
(iii) Mixing the two solutions;
(iv) Crystallising the xinafoate salt of (R)—N-(3-(5-fluoro-2-(2-fluoro-3-(methylsulfonyl)phenylamino)pyrimidin-4-yl)-1H-indol-7-yl)-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide; and
(v) Isolating the xinafoate salt of (R)—N-(3-(5-fluoro-2-(2-fluoro-3-(methylsulfonyl)phenylamino)pyrimidin-4-yl)-1H-indol-7-yl)-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide.

8. A method of treating a JAK kinase mediated disease selected from asthma or COPD in a subject in need thereof, comprising administering to the subject an effective amount of a xinafoate salt of Formula (Ia) according to claim 1 .

9. The method of claim 8 , wherein the JAK kinase mediated disease is asthma.

10. A method of treating JAK kinase mediated disease selected from asthma or COPD in a subject in need thereof, comprising administering to the subject an effective amount of crystalline Form A of Formula (Ia) according to claim 5 .

11. The method of claim 10 , wherein the JAK kinase mediated disease is asthma.

12. The process of claim 7 , further comprising:
adding seed crystals of the xinafoate salt of (R)—N-(3-(5-fluoro-2-(2-fluoro-3-(methylsulfonyl)phenylamino)pyrimidin-4-yl)-1H-indol-7-yl)-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide,
after mixing the two solutions and before crystallising the xinafoate salt of (R)—N-(3-(5-fluoro-2-(2-fluoro-3-(methylsulfonyl)phenylamino)pyrimidin-4-yl)-1H-indol-7-yl)-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide.

Assignees

• Astrazeneca Ab

Inventors

• Pettersen Anna Matilda Angelica
• Mccabe James
• Aurell Carl-Johan

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C59/255

  Tartaric acid · CPC title

• C07C51/412

  by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part · CPC title

• C07D295/15

  to an acyclic saturated chain · CPC title

• A61P11/06 Primary

  Antiasthmatics · CPC title