CYCLOPROPYLAMINES AS LSD1 INHIBITORS

• US 20190062301A1
• Filed: 05/04/2018
• Published: 02/28/2019
• Est. Priority Date: 02/13/2014
• Status: Active Grant

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation
• Inventors: Wu, Liangxing, Courter, Joel R., He, Chunhong, Konkol, Leah C., Qian, Ding-Quan, Shen, Bo, Yao, Wenqing, Zhang, Fenglei
• Granted Patent: US 10,676,457 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07D 205/04 having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 211/26 with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 211/34 with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 211/98 Nitrogen atom
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

Claims

1-41. -41. (canceled)

42. A method of treating cancer comprising administering to a patient a therapeutically effective amount of 3-(cyanomethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide, or a pharmaceutically acceptable salt thereof.

43. The method of claim 42 wherein the cancer is a hematological cancer.

44. The method of claim 43 wherein the hematological cancer is selected from acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, Non-Hodgkin lymphoma, Hodgkin lymphoma, primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocytosis (ET)), myelodysplasia syndrome (MDS), and multiple myeloma.

45. The method of claim 42 wherein the cancer is a sarcoma, lung cancer, gastrointestinal cancer, genitourinary tract cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, or skin cancer.

47. The method of claim 42, wherein the cancer is relapsed or refractory non-Hodgkin lymphoma, or recurrent follicular non-Hodgkin lymphoma.

48. The method of claim 42, wherein the cancer is acute myelogenous leukemia (AML).

49. The method of claim 42, wherein the cancer is lung cancer.

50. The method of claim 42, wherein the cancer is non-small cell lung cancer, bronchogenic carcinoma, alveolar carcinoma, bronchial adenoma, chondromatous hamartoma, or mesothelioma.

51. The method of claim 42, wherein the cancer is non-small cell lung cancer.

52. The method of claim 42, wherein the cancer is leiomyosarcoma.

53. The method of claim 42, wherein the cancer is hepatocellular carcinoma.

54. The method of claim 42, wherein the cancer is Ewing'"'"'s carcinoma.

55. The method of claim 42, wherein the cancer is neuroblastoma.

56. The method of claim 42, wherein the cancer is glioblastoma.

57. The method of claim 42, wherein the cancer is breast cancer.

58. The method of claim 42, wherein the cancer is prostate cancer.

59. The method of claim 42, wherein the cancer is ovarian cancer.

60. The method of claim 42, wherein the cancer is myelofibrosis.

46. (canceled)