PYRROLOTRIAZINE COMPOUNDS AS TAM INHIBITORS

• US 20200131185A1
• Filed: 09/04/2019
• Published: 04/30/2020
• Est. Priority Date: 03/28/2016
• Status: Active Grant

• Current Assignee: Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Li, Yun-Long, Wang, Xiaozhao, He, Chunhong
• Granted Patent: US 10,844,069 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

This application relates to compounds of Formula I:

or pharmaceutically acceptable salts thereof, which are inhibitors of TAM kinases which are useful for the treatment of disorders such as cancer.

Claims

1-50. -50. (canceled)

51. A method for treating a cancer in a patient, said method comprising:

administering to the patient a therapeutically effective amount of a compound which is N-(4-(4-Amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[1,2-f][1,2,4]triazin-5-yl)phenyl)-1-isopropyl-2,4-dioxo-3-(pyridin-2-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide, or a pharmaceutically acceptable salt thereof.

52. The method of claim 51, wherein the cancer is selected from hepatocellular cancer, bladder cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, esophageal cancer, gall bladder cancer, pancreatic cancer, thyroid cancer, skin cancer, leukemia, multiple myeloma, chronic lymphocytic lymphoma, adult T cell leukemia, B-cell lymphoma, acute myelogenous leukemia, Hodgkin'"'"'s or non-Hodgkin'"'"'s lymphoma, Waldenstrom'"'"'s Macroglubulinemia, hairy cell lymphoma, Burkett'"'"'s lymphoma, glioblastoma, melanoma, rhabdosarcoma, Kaposi sarcoma, and osteosarcoma.

53. The method of claim 51, wherein the cancer is lung cancer, prostate cancer, colon cancer, breast cancer, melanoma, renal cell carcinoma, multiple myeloma, gastric cancer, or rhabdomyosarcoma.

54. The method of claim 51, wherein the cancer is a hematological cancer.

55. The method of claim 54, wherein the hematological cancer is acute lymphoblastic leukemia, acute myelogenous leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma, chronic myelogenous leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, Non-Hodgkin lymphoma, follicular lymphoma, Hodgkin lymphoma, lymphoblastic lymphoma, primary myelofibrosis, polycythemia vera, essential thrombocytosis, myelodysplasia syndrome, T-cell acute lymphoblastic lymphoma, multiple myeloma, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, Waldenstrom'"'"'s Macroglubulinemia, hairy cell lymphoma, chronic myelogenic lymphoma and Burkitt'"'"'s lymphoma.

56. The method of claim 51, wherein the compound is N-(4-(4-Amino-7-(1-isobutyrylpiperidin-4-yl)pyrrolo[1,2-f][1,2,4]triazin-5-yl)phenyl)-1-isopropyl-2,4-dioxo-3-(pyridin-2-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide.