Metabolites of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
The present invention provides active metabolites of 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile that modulate the activity of Janus kinases 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 treating a disease selected from allograft rejection and graft versus host disease in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a compound selected from:
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl)propanenitrile;
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl)propanenitrile; and
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-oxycyclopentyl)propanenitrile,
or a pharmaceutically acceptable salt thereof,
and a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein the disease is graft versus host disease.
3. The method of claim 2 , wherein about 5 to about 1000 mg of the compound, or pharmaceutically acceptable salt thereof, is administered to the patient.
4. The method of claim 2 , further comprising administering to the patient at least one additional therapeutic agent.
5. The method of claim 4 , wherein the therapeutic agent is administered to a patient simultaneously or sequentially.
6. The method of claim 4 , wherein said therapeutic agent is an immunosuppressant.
7. The method of claim 4 , wherein said therapeutic agent is a steroid.
8. The method of claim 4 , wherein said therapeutic agent is a corticosteroid.
9. The method of claim 8 , wherein said corticosteroid is dexamethasone or prednisone.
10. The method of claim 8 , wherein said corticosteroid is dexamethasone.
11. The method of claim 8 , wherein said corticosteroid is prednisone.
12. The method of claim 1 , wherein the disease is allograft rejection.
13. The method of claim 12 , wherein about 5 to about 1000 mg of the compound, or pharmaceutically acceptable salt thereof, is administered to the patient.
14. The method of claim 12 , further comprising administering to the patient at least one additional therapeutic agent.
15. The method of claim 14 , wherein the therapeutic agent is administered to a patient simultaneously or sequentially.
16. The method of claim 14 , wherein said therapeutic agent is an immunosuppressant.
17. The method of claim 14 , wherein said therapeutic agent is a steroid.
18. The method of claim 14 , wherein said therapeutic agent is a corticosteroid.
19. The method of claim 18 , wherein said corticosteroid is dexamethasone or prednisone.
20. The method of claim 18 , wherein said corticosteroid is dexamethasone.
21. The method of claim 18 , wherein said corticosteroid is prednisone.
22. The method of claim 1 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl)propanenitrile.
23. The method of claim 1 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl)propanenitrile.
24. The method of claim 1 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-oxycyclopentyl)propanenitrile.
25. The method of claim 1 , wherein the pharmaceutical composition is suitable for oral administration.
26. The method of claim 1 , wherein the pharmaceutical composition is in tablet form.