Crystalline form of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol

Patent metadata

Field	Value
Publication number	US-10836754-B2
Application number	US-201916503245-A
Country	US
Kind code	B2
Filing date	Jul 3, 2019
Priority date	May 20, 2015
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

The present invention relates to a crystalline form of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

First claim

The invention claimed is:

1. A method of decreasing the number of circulating lymphocytes in a subject in need thereof; wherein the method comprises administering a pharmaceutical composition to the subject; wherein the pharmaceutical composition comprises a crystalline form of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)- [1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol, characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 5.4° , 8.5° , and 10.8° ; and wherein the pharmaceutical composition comprises about 2 mg or about 4 mg of the compound.

2. A method according to claim 1 , wherein the pharmaceutical composition comprises about 2 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

3. A method according to claim 1 , wherein the pharmaceutical composition comprises about 4 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

4. A method according to claim 2 , wherein the crystalline form of the compound is characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.2° , 5.4° , 8.0° , 8.5° , and 10.8° .

5. A method according to claim 3 , wherein the crystalline form of the compound is characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.2° , 5.4° , 8.0° , 8.5° , and 10.8° .

6. A method according to claim 2 , wherein the crystalline form of the compound is characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.2° , 5.4° , 8.0° , 8.5° , 10.8° , 12.7° , 14.4° , 17.7° , 20.4° , and 21.3° .

7. A method according to claim 3 , wherein the crystalline form of the compound is characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.2° , 5.4° , 8.0° , 8.5° , 10.8° , 12.7° , 14.4° , 17.7° , 20.4° , and 21.3° .

8. A method according to claim 6 , wherein the crystalline form of the compound has a melting point of about 79° C. as determined by differential scanning calorimetry.

9. A method according to claim 7 , wherein the crystalline form of the compound has a melting point of about 79° C. as determined by differential scanning calorimetry.

10. A method according to claim 6 , wherein the pharmaceutical composition comprises 2 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

11. A method according to claim 7 , wherein the pharmaceutical composition comprises 4 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

12. A method of treating a disease or disorder comprising administering a pharmaceutical composition to a subject in need thereof; wherein the pharmaceutical composition comprises a crystalline form of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol, characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 5.4° , 8.5° , and 10.8° ; wherein the pharmaceutical composition comprises about 2 mg or about 4 mg of the compound; and wherein the disease or disorder is selected from the group consisting of rejection of transplanted organs selected from kidney, liver, heart, lung, pancreas, cornea, and skin; graft-versus-host disease; autoimmune syndromes selected from Sjogren's syndrome, spondylarthropathy/ankylosing spondylitis, juvenile arthritis, lupus nephritis, systemic sclerosis, diffuse cutaneous systemic sclerosis, vasculitis, giant cell arteritis, Behcet disease, non-infectious uveitis, Goodpasture syndrome, primary biliary cirrhosis, autoimmune hepatitis, vitiligo, alopecia areata, Rasmussen's encephalitis, rheumatoid arthritis, multiple sclerosis, Crohn's disease, ulcerative colitis, and psoriasis; atopic dermatitis; and type I diabetes.

13. A method according to claim 12 , wherein the pharmaceutical composition comprises about 2 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

14. A method according to claim 12 , wherein the pharmaceutical composition comprises about 4 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

15. A method according to claim 13 , wherein the crystalline form of the compound is characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.2° , 5.4° , 8.0° , 8.5° , and 10.8° .

16. A method according to claim 14 , wherein the crystalline form of the compound is characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.2° , 5.4° , 8.0° , 8.5° , and 10.8° .

17. A method according to claim 13 , wherein the crystalline form of the compound is characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.2° , 5.4° , 8.0° , 8.5° , 10.8° , 12.7° , 14.4° , 17.7° , 20.4° , and 21.3° .

18. A method according to claim 14 , wherein the crystalline form of the compound is characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 4.2° , 5.4° , 8.0° , 8.5° , 10.8° , 12.7° , 14.4° , 17.7° , 20.4° , and 21.3° .

19. A method according to claim 17 , wherein the crystalline form of the compound has a melting point of about 79° C. as determined by differential scanning calorimetry.

20. A method according to claim 18 , wherein the crystalline form of the compound has a melting point of about 79° C. as determined by differential scanning calorimetry.

21. A method according to claim 17 , wherein the pharmaceutical composition comprises 2 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

22. A method according to claim 18 , wherein the pharmaceutical composition comprises 4 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

23. A method of treating systemic lupus erythematosus comprising administering a pharmaceutical composition to a subject in need thereof; wherein the pharmaceutical composition comprises a crystalline form of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol, characterised by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 5.4° , 8.5° , and 10.8° ; and wherein the pharmaceutical composition comprises about 2 mg or about 4 mg of the compound.

24. A method according to claim 23 , wherein the pharmaceutical composition comprises about 2 mg of the compound (S)-3-{4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol.

25. A method according to claim 23 , wherein the pharmaceutical composition comprises about 4 mg of t

Assignees

• Idorsia Pharmaceuticals Ltd

Inventors

• Lescop Cyrille
• Dingemanse Jasper
• Krause Andreas

Classifications

• A61K31/047 Primary

  having two or more hydroxy groups, e.g. sorbitol · CPC title

• C07D413/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title