IP Library › Granted Patent US 12,187,725
Granted Patent B2
US 12,187,725 · App. 18/237,535 · Granted Jan 7, 2025

Tricyclic urea compounds as JAK2 V617F inhibitors

Inventors: Yanran Ai (West Chester, PA); Yu Bai (Claymont, DE); Joseph Barbosa (Lambertville, NJ); Hao Feng (Glen Mills, PA); Leah C. Konkol (Newark, DE); Xun Liu (Glenn Mills, PA); Jun Pan (Media, PA); Haisheng Wang (Hockessin, DE); Liangxing Wu (Wilmington, DE); Wenqing Yao (Chadds Ford, PA); Eddy W. Yue (Landenberg, PA)
Assignee: Incyte Corporation
C07D471/14C07D519/00C07B2200/05
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Quick Facts
Patent No.
US 12,187,725
App. No.
18/237,535
Granted
Jan 7, 2025
Kind
B2
Abstract

The present application provides tricyclic urea compounds that modulate the activity of the V617F variant of JAK2, which are useful in the treatment of various diseases, including cancer.

Claims (42)

1. A method of treating a myeloproliferative disorder selected from polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post polycythemia vera myelofibrosis in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound, which is 7-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-3-methyl-8-(1-methyl-1H-indazol-5-yl)-1-(tetrahydro-2H-pyran-4-yl)-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one, or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the myeloproliferative disorder is polycythemia vera.

3. The method of claim 1 , wherein the myeloproliferative disorder is essential thrombocythemia.

4. The method of claim 1 , wherein the myeloproliferative disorder is myelofibrosis with myeloid metaplasia.

5. The method of claim 1 , wherein the myeloproliferative disorder is primary myelofibrosis.

6. The method of claim 1 , wherein the myeloproliferative disorder is post-essential thrombocythemia myelofibrosis.

7. The method of claim 1 , wherein the myeloproliferative disorder is post polycythemia vera myelofibrosis.

8. A method of treating a myeloproliferative disorder selected from polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post polycythemia vera myelofibrosis in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound, which is 2-((1S,4S)-4-(7-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-3-methyl-8-(1-methyl-1H-indazol-5-yl)-2-oxo-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(2H)-yl)cyclohexyl) acetonitrile, or a pharmaceutically acceptable salt thereof.

9. The method of claim 8 , wherein the myeloproliferative disorder is polycythemia vera.

10. The method of claim 8 , wherein the myeloproliferative disorder is essential thrombocythemia.

11. The method of claim 8 , wherein the myeloproliferative disorder is myelofibrosis with myeloid metaplasia.

12. The method of claim 8 , wherein the myeloproliferative disorder is primary myelofibrosis.

13. The method of claim 8 , wherein the myeloproliferative disorder is post-essential thrombocythemia myelofibrosis.

14. The method of claim 8 , wherein the myeloproliferative disorder is post polycythemia vera myelofibrosis.

15. A method of treating a myeloproliferative disorder selected from polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post polycythemia vera myelofibrosis in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound, which is 1-(4-(3-methyl-7-(4-((4-(methylsulfonyl) piperidin-1-yl) methyl) phenyl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-8-yl)phenyl)cyclopropane-1-carbonitrile, or a pharmaceutically acceptable salt thereof.

16. The method of claim 15 , wherein the myeloproliferative disorder is polycythemia vera.

17. The method of claim 15 , wherein the myeloproliferative disorder is essential thrombocythemia.

18. The method of claim 15 , wherein the myeloproliferative disorder is myelofibrosis with myeloid metaplasia.

19. The method of claim 15 , wherein the myeloproliferative disorder is primary myelofibrosis.

20. The method of claim 15 , wherein the myeloproliferative disorder is post-essential thrombocythemia myelofibrosis.

21. The method of claim 15 , wherein the myeloproliferative disorder is post polycythemia vera myelofibrosis.

22. The method of claim 1 , wherein the compound is 7-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-3-methyl-8-(1-methyl-1H-indazol-5-yl)-1-(tetrahydro-2H-pyran-4-yl)-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2 (1H)-one.

23. The method of claim 22 , wherein the myeloproliferative disorder is polycythemia vera.

24. The method of claim 22 , wherein the myeloproliferative disorder is essential thrombocythemia.

25. The method of claim 22 , wherein the myeloproliferative disorder is myelofibrosis with myeloid metaplasia.

26. The method of claim 22 , wherein the myeloproliferative disorder is primary myelofibrosis.

27. The method of claim 22 , wherein the myeloproliferative disorder is post-essential thrombocythemia myelofibrosis.

28. The method of claim 22 , wherein the myeloproliferative disorder is post polycythemia vera myelofibrosis.

29. The method of claim 8 , wherein the compound is 2-((15,4S)-4-(7-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-3-methyl-8-(1-methyl-1H-indazol-5-yl)-2-oxo-3,6-dihydroimidazo [4,5-d]pyrrolo [2,3-b]pyridin-1 (2H)-yl)cyclohexyl) acetonitrile.

30. The method of claim 29 , wherein the myeloproliferative disorder is polycythemia vera.

31. The method of claim 29 , wherein the myeloproliferative disorder is essential thrombocythemia.

32. The method of claim 29 , wherein the myeloproliferative disorder is myelofibrosis with myeloid metaplasia.

33. The method of claim 29 , wherein the myeloproliferative disorder is primary myelofibrosis.

34. The method of claim 29 , wherein the myeloproliferative disorder is post-essential thrombocythemia myelofibrosis.

35. The method of claim 29 , wherein the myeloproliferative disorder is post polycythemia vera myelofibrosis.

36. The method of claim 15 , wherein the compound is 1-(4-(3-methyl-7-(4-((4-(methylsulfonyl)piperidin-1-yl)methyl)phenyl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,6-tetrahydroimidazo [4,5-d] pyrrolo [2,3-b]pyridin-8-yl)phenyl) cyclopropane-1-carbonitrile.

37. The method of claim 36 , wherein the myeloproliferative disorder is polycythemia vera.

38. The method of claim 36 , wherein the myeloproliferative disorder is essential thrombocythemia.

39. The method of claim 36 , wherein the myeloproliferative disorder is myelofibrosis with myeloid metaplasia.

40. The method of claim 36 , wherein the myeloproliferative disorder is primary myelofibrosis.

41. The method of claim 36 , wherein the myeloproliferative disorder is post-essential thrombocythemia myelofibrosis.

42. The method of claim 36 , wherein the myeloproliferative disorder is post polycythemia vera myelofibrosis.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 5, 2024
From: AI, YANRAN; ATASOYLU, ONUR; BAI, YU; BARBOSA, JOSEPH; BURNS, DAVID M.; LEVY, DANIEL; DOUTY, BRENT; FENG, HAO; KONKOL, LEAH C.; LAI, CHENG-TSUNG; LIU, XUN; MEI, SONG; PAN, JUN; WANG, HAISHENG; WU, LIANGXING; YAO, WENQING; YUE, EDDY W.
To: INCYTE CORPORATION
Reel/Frame 066033/0223 →
Continuity (4)
Continuation 17365789 · Jul 1, 2021
Provisional Application 63047483 · Jul 2, 2020
Provisional Application 63164302 · Mar 22, 2021
Related Publication 20240150354A1 · May 9, 2024
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