Heteroaryl substituted pyrrolo[2,3-B] pyridines and pyrrolo[2,3-B] pyrimidines as Janus kinase
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), hypereosinophilic syndrome (HES), systemic mast cell disease (SMCD), acute myelogenous leukemia, multiple myeloma, pancreatic cancer, leukemia, lymphoma, breast cancer, acute lymphoblastic leukemia, and Castleman's disease, comprising administering to said patient a pharmaceutical composition comprising a compound, which 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 pharmaceutically acceptable carrier;
wherein said composition is suitable for oral administration and for providing sustained release of said compound or said salt; and wherein said treating refers to ameliorating or inhibiting the disease in the patient.
2. The method of claim 1 , wherein the 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 the disease is polycythemia vera (PV).
4. The method according to claim 2 , wherein the disease is essential thrombocythemia (ET).
5. The method according to claim 2 , wherein the disease is myeloid metaplasia with myelofibrosis (MMM).
6. The method according to claim 2 , wherein the disease is chronic myelogenous leukemia (CML).
7. The method according to claim 2 , wherein the disease is chronic myelomonocytic leukemia (CMML).
8. The method according to claim 2 , wherein the disease is acute myelogenous leukemia.
9. The method according to claim 2 , wherein said disease is multiple myeloma.
10. The method according to claim 2 , wherein said disease is pancreatic cancer.
11. The method according to claim 2 , wherein said disease is leukemia.
12. The method according to claim 2 , wherein said disease is lymphoma.
13. The method according to claim 2 , wherein said disease is breast cancer.
14. The method according to claim 2 , wherein said disease is acute lymphoblastic leukemia.
15. The method according to claim 2 , wherein said disease is cachexia.
16. The method according to claim 15 , wherein said cachexia results from or is associated with cancer.
17. The method according to claim 2 , wherein said disease is Castleman's disease.
18. The method of claim 2 , wherein said composition is a unit dosage form.
19. The method of claim 18 , wherein said unit dosage form is a tablet.
20. The method of claim 18 , wherein said unit dosage form is a capsule.
21. The method of claim 18 , wherein said unit dosage form further comprises an enteric coating.
22. The method according to claim 18 , wherein the unit dosage form comprises from about 5 to about 1000 mg of said compound or said salt.
23. The method according to claim 2 , wherein the composition further comprises one or more excipients selected from lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, and methyl cellulose.
24. The method according to claim 2 , wherein the composition further comprises microcrystalline cellulose.
25. The method according to claim 2 , wherein the composition further comprises lactose.
26. The method according to claim 2 , wherein the composition further comprises microcrystalline cellulose and lactose.