Salts of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
View Patent ↗The present invention provides salt forms of (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile that are useful in the modulation of Janus kinase activity and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.
1. A method of inhibiting JAK1 and/or JAK2 in a patient suffering from an autoimmune skin disease, comprising administering to said patient a therapeutically effective amount of a compound that is (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphoric acid salt.
2. The method of claim 1 , wherein said autoimmune skin disease is bullous skin disorder.
3. The method of claim 2 , wherein said bullous skin disorder is pemphigus vulgaris (PV) or bullous pemphigoid (BP).
4. The method of claim 3 , wherein said bullous skin disorder is pemphigus vulgaris (PV).
5. The method of claim 1 , wherein the autoimmune skin disease is atopic dermatitis, psoriasis, skin sensitization, skin irritation, skin rash, contact dermatitis, or allergic contact sensitization.
6. The method of claim 5 , wherein the autoimmune skin disease is psoriasis.
7. The method of claim 5 , wherein the autoimmune skin disease is atopic dermatitis.
8. The method of claim 1 , wherein (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphoric acid salt is a crystalline salt.
9. The method of claim 8 , wherein said crystalline salt is a 1:1 (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile:phosphoric acid salt.
10. A method of treating an autoimmune skin disease selected from pemphigus vulgaris (PV), bullous pemphigoid (BP), atopic dermatitis, and psoriasis in a patient, comprising administering to said patient a therapeutically effective amount of a compound that is (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphoric acid salt, wherein said treating refers to ameliorating or inhibiting the disease in a patient.
11. The method of claim 10 , wherein the autoimmune skin disorder is pemphigus vulgaris (PV) or bullous pemphigoid (BP).
12. The method of claim 10 , wherein the autoimmune skin disorder is pemphigus vulgaris (PV).
13. The method of claim 10 , wherein the autoimmune skin disease is psoriasis.
14. The method of claim 10 , wherein the autoimmune skin disease is atopic dermatitis.
15. The method of claim 10 , wherein (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphoric acid salt is a crystalline salt.
16. The method of claim 15 , wherein said crystalline salt is a 1:1 (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile:phosphoric acid salt.
17. A method of treating an autoimmune skin disease selected from pemphigus vulgaris (PV), bullous pemphigoid (BP), atopic dermatitis, and psoriasis in a patient, comprising administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphoric acid salt and a pharmaceutically acceptable carrier, wherein said treating refers to ameliorating or inhibiting the disease in a patient.
18. The method of claim 17 , wherein the autoimmune skin disorder is pemphigus vulgaris (PV).
19. The method of claim 17 , wherein the autoimmune skin disease is psoriasis.
20. The method of claim 17 , wherein the autoimmune skin disease is atopic dermatitis.
21. The method of claim 17 , wherein the pharmaceutical composition is suitable for oral administration.
22. The method of claim 17 , wherein the pharmaceutical composition is suitable for topical administration.
23. The method of claim 17 , wherein (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphoric acid salt is a crystalline salt.
24. The method of claim 23 , wherein said crystalline salt is a 1:1 (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile:phosphoric acid salt.
25. A method of treating atopic dermatitis in a patient, comprising topically administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphoric acid salt and a pharmaceutically acceptable carrier, wherein said treating refers to ameliorating or inhibiting the disease in a patient.
26. The method of claim 1 , wherein said salt is administered topically.
27. The method of claim 10 , wherein said salt is administered topically.
28. The method of claim 17 , wherein said pharmaceutical composition is administered topically.