Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines 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 cachexia, polycythemia vera (PV), essential thrombocythemia (ET), myeloid metaplasia with myelofibrosis (MMM), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), multiple myeloma, leukemia, lymphoma, breast cancer, acute myelogenous leukemia, acute lymphoblastic leukemia, and Castleman's disease in a patient, comprising administering to said patient a therapeutically effective amount of a compound that is 3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, and a further therapeutic agent wherein said treating refers to ameliorating or inhibiting the disease in the patient.
2. The method according to claim 1 , wherein said compound is (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof.
3. The method according to claim 2 , wherein said further therapeutic agent is a chemotherapeutic agent.
4. The method according to claim 3 , wherein said method comprises administering said compound, or said salt, and said chemotherapeutic agent simultaneously to the patient.
5. The method according to claim 3 , wherein said method comprises administering said compound, or said salt, and said chemotherapeutic agent sequentially to said patient.
6. The method according to claim 3 , wherein about 5 to about 1000 mg of said compound or said salt is administered to said patient.
7. The method according to claim 2 , wherein said disease is polycythemia vera (PV).
8. The method according to claim 2 , wherein said disease is essential thrombocythemia (ET).
9. The method according to claim 2 , wherein said disease is myeloid metaplasia with myelofibrosis (MMM).
10. The method according to claim 2 , wherein said disease is chronic myelogenous leukemia (CML).
11. The method according to claim 2 , wherein said disease is chronic myelomonocytic leukemia (CMML).
12. The method according to claim 2 , wherein said disease is multiple myeloma.
13. The method according to claim 2 , wherein said disease is leukemia.
14. The method according to claim 2 , wherein said disease is lymphoma.
15. The method according to claim 2 , wherein said disease is breast cancer.
16. The method according to claim 2 , wherein said disease is acute myelogenous leukemia.
17. The method according to claim 3 , wherein said chemotherapeutic agent is lenalidomide.
18. The method according to claim 17 , wherein said method further comprises administering a corticosteroid to said patient.
19. The method according to claim 18 , wherein said corticosteroid is prednisone.
20. The method according to claim 3 , wherein said chemotherapeutic agent is a DNA-damaging agent.
21. The method according to claim 20 , wherein said DNA-damaging agent is selected from melphalan, doxorubicin, cyclophosphamide, vincristine, etoposide, and carmustine.
22. The method according to claim 2 , wherein said further therapeutic agent is selected from melphalan plus prednisone, doxorubicin, dexamethasone, and bortezomib.
23. The method according to claim 2 , wherein said disease is cachexia.
24. The method according to claim 2 , wherein said cachexia results from or is associated with cancer.
25. The method according to claim 2 , wherein the disease is Castleman's disease.
26. The method according to claim 2 , wherein the disease is acute lymphoblastic leukemia.