Substituted benzene compounds

• US 10,098,888 B2
• Filed: 11/22/2016
• Issued: 10/16/2018
• Est. Priority Date: 10/15/2012
• Status: Active Grant

• Current Assignee: Epizyme, Inc. (Ipsen Sa)
• Original Assignee: Epizyme, Inc. (Ipsen Sa)
• Inventors: Kuntz, Kevin Wayne, Campbell, John Emmerson, Seki, Masashi
• Primary Examiner(s): Gembeh, Shirley V
• Application Number:
  US15/359,538
• Publication Number:
  US 20170290837A1
• Time in Patent Office: 693 Days
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• 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: C07D 213/64 attached in position 2 or 6
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• 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

Abstract

The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

Claims

1. A method of treating a cancer being lymphoma, leukemia, or melanoma, comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of

2. The method of claim 1, wherein the cancer is diffuse large B-cell lymphoma (DLBCL), non-Hodgkin'"'"'s lymphoma (NHL), follicular lymphoma, chronic myelogenous leukemia (CML), acute myeloid leukemia, acute lymphocytic leukemia, or mixed lineage leukemia.

3. A method of treating an INI1-deficient tumor, comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of

4. The method of claim 3, wherein the INI1-deficient tumor is malignant rhabdoid tumor.

5. A method of treating myelodysplastic syndrome (MDS), comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of

6. A method of modulating an activity of EZH2 or a mutant thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of

7. The method of claim 6, being of inhibiting the histone methyltransferase activity of EZH2 or the mutant thereof.

8. The method of claim 6, wherein the mutant of EZH2 is EZH2 Y641 mutant, EZH2 A677 mutant, or EZH2 A687 mutant.

9. The method of claim 8, wherein the EZH2 Y641 mutant is EZH2 Y641F mutant, EZH2 Y641N mutant, EZH2 Y641H mutant, EZH2 Y641S mutant, or EZH2 Y641C mutant.

10. The method of claim 6, wherein the subject has cancer.

11. The method of claim 10, wherein the cancer is lymphoma, leukemia, or melanoma.

12. The method of claim 10, wherein the cancer is diffuse large B-cell lymphoma (DLBCL), non-Hodgkin'"'"'s lymphoma (NHL), follicular lymphoma, chronic myelogenous leukemia (CML), acute myeloid leukemia, acute lymphocytic leukemia, or mixed lineage leukemia.

13. The method of claim 10, wherein the cancer is an INI1-deficient tumor.

14. The method of claim 13, wherein the INI-deficient tumor is malignant rhabdoid tumor.

15. The method of claim 6, wherein the subject has a precancerous condition.

16. The method of claim 15, wherein the precancerous condition is myelodysplastic syndrome (MDS).