Inhibitors of Akt activity
View Patent ↗Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
1. A compound:
N-{(1S)-2-amino-1-[(3,4-difluorophenyl)methyl]ethyl]-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide;
or a pharmaceutically acceptable salt thereof.
2. A compound of claim 1 which is:
N-{(1S)-2-amino-1-[(3,4-difluorophenyl)methyl]ethyl]-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide.
3. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
4. A pharmaceutical composition comprising a compound according to claim 2 and a pharmaceutically acceptable carrier.
5. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier and a compound of claim 1 which process comprises bringing the compound of claim 43 into association with a pharmaceutically acceptable carrier.
6. a method of inhibiting Akt activity in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of claim 1 .
7. The method of claim 6 wherein the mammal is a human.
8. A pharmaceutical composition according to claim 3 , wherein the composition is in tablet form.
9. A pharmaceutical composition according to claim 4 , wherein the composition is in tablet form.
10. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
brain cancer (gliomas), glioblastomas, medulloblastoma, prostate cancer, breast cancer, inflammatory breast cancer, colon cancer, head and neck cancer, kidney cancer, Wilm's tumor, renal cancer, lung cancer, endometrial cancer, gastric cancer, liver cancer and ovarian cancer,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
11. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
Lymphoblastic T cell leukemia, Chronic myelogenous leukemia, Chronic lymphocytic leukemia, Hairy-cell leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, Chronic neutrophilic leukemia, Acute lymphoblastic T cell leukemia, Plasmacytoma, Immunoblastic large cell leukemia, Mantle cell leukemia, Megakaryoblastic leukemia, multiple myeloma, acute megakaryocytic leukemia, promyelocytic leukemia and Erythroleukemia,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
12. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
malignant lymphoma, hodgkins lymphoma, non-hodgkins lymphoma, lymphoblastic T cell lymphoma, Burkitt's lymphoma and follicular lymphoma,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
13. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
pancreatic cancer, Bannayan-Zonana syndrome, Cowden disease, and Lhermitte-Duclos disease,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
14. A pharmaceutically acceptable salt of the compound:
15. A pharmaceutical composition comprising a compound according to claim 14 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition according to claim 15 , wherein the composition is in tablet form.
17. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
brain cancer (gliomas), glioblastomas, medulloblastoma, prostate cancer, breast cancer, inflammatory breast cancer, colon cancer, head and neck cancer, kidney cancer, Wilm's tumor, renal cancer, lung cancer, endometrial cancer, gastric cancer, liver cancer and ovarian cancer, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
18. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
Lymphoblastic T cell leukemia, Chronic myelogenous leukemia, Chronic lymphocytic leukemia, Hairy-cell leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, Chronic neutrophilic leukemia, Acute lymphoblastic T cell leukemia, Plasmacytoma, Immunoblastic large cell leukemia, Mantle cell leukemia, Megakaryoblastic leukemia, multiple myeloma, acute megakaryocytic leukemia, promyelocytic leukemia and Erythroleukemia,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
19. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
malignant lymphoma, hodgkins lymphoma, non-hodgkins lymphoma, lymphoblastic T cell lymphoma, Burkitt's lymphoma and follicular lymphoma,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
20. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
pancreatic cancer, Bannayan-Zonana syndrome, Cowden disease, and Lhermitte-Duclos disease,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
21. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier and a compound of claim 14 which process comprises bringing the compound of claim 14 into association with a pharmaceutically acceptable carrier.
22. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
Multiple myeloma, melanoma, mesothelioma, sarcoma, Ewing's sarcoma, Rhabdomyosarcoma, osteosarcoma, and thyroid cancer,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
23. A method of treating or lessening the severity of cancer, wherein said cancer is selected from:
Multiple myeloma, melanoma, mesothelioma, sarcoma, Ewing's sarcoma, Rhabdomyosarcoma, osteosarcoma, and thyroid cancer,
in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
24. A method of treating or lessening the severity of Lymphoblastic T cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
25. A method of treating or lessening the severity of Chronic myelogenous leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
26. A method of treating or lessening the severity of Chronic lymphocytic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
27. A method of treating or lessening the severity of Hairy-cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
28. A method of treating or lessening the severity of acute lymphoblastic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
29. A method of treating or lessening the severity of acute myelogenous leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
30. A method of treating or lessening the severity of Chronic neutrophilic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
31. A method of treating or lessening the severity of Acute lymphoblastic T cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
32. A method of treating or lessening the severity of Plasmacytoma, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
33. A method of treating or lessening the severity of Immunoblastic large cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
34. A method of treating or lessening the severity of Mantle cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
35. A method of treating or lessening the severity of Megakaryoblastic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
36. A method of treating or lessening the severity of multiple myeloma, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
37. A method of treating or lessening the severity of acute megakaryocytic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
38. A method of treating or lessening the severity of promyelocytic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
39. A method of treating or lessening the severity of Erythroleukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 2 .
40. A method of treating or lessening the severity of Lymphoblastic T cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
41. A method of treating or lessening the severity of Chronic myelogenous leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
42. A method of treating or lessening the severity of Chronic lymphocytic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
43. A method of treating or lessening the severity of Hairy-cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
44. A method of treating or lessening the severity of acute lymphoblastic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
45. A method of treating or lessening the severity of acute myelogenous leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
46. A method of treating or lessening the severity of Chronic neutrophilic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
47. A method of treating or lessening the severity of Acute lymphoblastic T cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
48. A method of treating or lessening the severity of Plasmacytoma, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
49. A method of treating or lessening the severity of Immunoblastic large cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
50. A method of treating or lessening the severity of Mantle cell leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
51. A method of treating or lessening the severity of Megakaryoblastic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
52. A method of treating or lessening the severity of multiple myeloma, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
53. A method of treating or lessening the severity of acute megakaryocytic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
54. A method of treating or lessening the severity of promyelocytic leukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
55. A method of treating or lessening the severity of Erythroleukemia, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
56. A method of treating or lessening the severity of melanoma, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 14 .
57. A method of treating or lessening the severity of mesothelioma, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
58. A method of treating or lessening the severity of sarcoma, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
59. A method of treating or lessening the severity of thyroid cancer, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
60. A method of treating or lessening the severity of brain cancer, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
61. A method of treating or lessening the severity of breast cancer, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
62. A method of treating or lessening the severity of prostate cancer, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
63. A method of treating or lessening the severity of lung cancer, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .
64. A method of treating or lessening the severity of colon cancer, in a human in need thereof, which comprises administering to such human a therapeutically effective amount of a compound of claim 1 .