Granted Patent B2

US 12,269,813 · App. 17/431,447 · Granted Apr 8, 2025

Inventors: Carina Leys (Stabroek, BE); Kristof Leonard Kimpe (Beerse, BE); Robert Michael Geertman (Maarheeze, NL); Haojuan Wei (Changzhou, CN); Peng Zhou (Changzhou, CN)

Assignee: Janssen Pharmaceutica NV

C07D401/14C07B2200/13

Abstract

Claims (23)

1. A crystalline form of 1-(1-oxo-1,2-dihydroisoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]-1H-pyrazole-4-carboxamide (Compound A) monohydrate:

wherein the crystalline form is Form III, producing an X-ray powder diffraction pattern comprising peaks at 16.4, 23.7 and 25.7 degrees two theta±0.2 degrees two theta.

2. The crystalline form of claim 1 , wherein the X-ray powder diffraction pattern further comprises peaks at 13.6, 17.9, 22.6, 24.5, 25.2 and 27.1 degrees two theta±0.2 degrees two theta.

3. The crystalline form of claim 2 , wherein the X-ray powder diffraction pattern further comprises at least one peak selected from 8.3, 8.6, 11.5, 14.0, 15.4, 17.5, 19.7, 22.0, 22.2, 24.0 and 29.9 degrees two theta±0.2 degrees two theta.

4. The crystalline form of claim 2 , wherein the X-ray powder diffraction pattern further comprises peaks at 8.3, 8.6, 11.5, 14.0, 15.4, 17.5, 19.7, 22.0, 22.2, 24.0 and 29.9 degrees two theta±0.2 degrees two theta.

5. The crystalline form of claim 1 , further characterized by a differential scanning calorimetry thermogram comprising an endotherm with an onset temperature of about 142° C. and/or a peak temperature at about 158° C.

6. A pharmaceutical composition comprising the crystalline form of claim 1 and at least one of a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and a pharmaceutically acceptable diluent.

7. The pharmaceutical composition of claim 6 , wherein the composition is a solid oral dosage form.

8. The pharmaceutical composition of claim 6 , wherein the composition is a syrup, elixir, or suspension.

9. A method of treating a cancer or an immunological disease comprises administering to a subject in need thereof a therapeutically effective amount of the crystalline form of claim 1 .

10. The method of claim 9 , wherein the cancer or the immunological disease is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and mucosa-associated lymphoid tissue (MALT) lymphoma, rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (Pso), ulcerative colitis (UC), Crohn's disease, systemic lupus erythematosus (SLE), asthma, and chronic obstructive pulmonary disease (COPD).

11. A process for preparing the crystalline form of claim 1 , comprising the step of recrystallising Compound A, wherein the recrystallisation comprises the steps of:

a) adding Compound A, or a hydrate or solvate thereof, to a mixture of ethyl acetate and ethanol, and heating to a temperature in the range of from about 30° C. to solvent reflux temperature;

b) adding water to the mixture and filtering off any precipitate, maintaining said temperature;

c) adding n-heptane to the mixture, seeding with crystalline Form III, and maintaining said temperature; and

d) cooling to room temperature, to yield a precipitate of the crystalline form of claim 1 ;

wherein the quantity of water is from about 0.1 w/w % to about 3.0 w/w %, relative to the total weight of solvent.

12. The process of claim 11 , wherein the temperature is from about 40° C. to about 55° C.

13. A process for preparing the crystalline form of claim 1 , comprising the step of recrystallising Compound A, wherein the recrystallisation comprises the steps of:

a) adding Compound A, or a hydrate or solvate thereof, to a mixture of water and isopropyl alcohol, and heating to a temperature in the range of from about 30° C. to solvent reflux temperature;

b) adding n-heptane to the mixture, seeding with crystalline Form III, and maintaining said temperature; and

c) cooling to room temperature, to yield a precipitate of the crystalline form of claim 1 ;

wherein the quantity of water is from about 1.0 w/w % to about 6.0 w/w %, relative to the total weight of solvent.

Priority Claims (1)

Continuity (1)

References Cited (23)