# US 10,478,426 B2 · Enhancer of Zeste Homolog 2 inhibitors

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- Number: US 10,478,426 B2
- Document ID: US10478426B2
- Status: Granted
- Kind: B2
- Application number: 15/926,015
- Filed: 2018-03-20
- Published: 2018-07-26
- Granted: 2019-11-19
- Earliest claimed: 2012-05-16
- Assignees: GlaxoSmithKline LLC
- Applicants: GlaxoSmithKline LLC
- Inventors: Joelle Lorraine Burgess; Steven David Knight
- Web page: https://patentgrep.com/patent/US10478426B2

## CPC

- A61K 31/4412: having oxo groups directly attached to the heterocyclic ring
- A61K 31/443: containing a five-membered ring with oxygen as a ring hetero atom
- A61K 31/4433: containing a six-membered ring with oxygen as a ring hetero atom
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- C07D 211/86: Oxygen atoms
- C07D 213/64: attached in position 2 or 6
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

This invention relates to novel substituted benzamide according to Formula (I) which are inhibitors of Enhancer of Zeste Homolog 2 (EZH2), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the treatment of cancers.

## Claims

### Claim 1

A method of treating a hematologic cancer comprising administering to a patient with cancer a therapeutically effective amount of a compound of formula (I):
wherein:
R1 is methyl;
R2 is methyl;
R3 is hydrogen;
R4 is methyl;
R5 is —NRaRb;
R6 is phenyl, wherein said phenyl is optionally substituted by —(C1-C6)alkyl(Rc);
Rc is —NRaRb; and
Ra and Rb are each independently hydrogen, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C10)cycloalkyl, (C5-C8)cycloalkenyl, heterocycloalkyl, or aryl, wherein said (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or aryl group is optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of halo, hydroxyl, (C1-C4)alkoxy, amino, (C1-C4)alkylamino, —N((C1-C4)alkyl)2, —CO2H, —CO2(C1-C4)alkyl, —CONH2, —CONH(C1-C4)alkyl, —CON((C1-C4)alkyl)2, —SO2(C1-C4)alkyl, —SO2NH2, —SO2NH(C1-C4)alkyl, and —SO2N((C1-C4)alkyl)2; and wherein said heterocycloalkyl is selected from the group consisting of pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, and tetrahydropyranyl;
or Ra and Rb taken together with the nitrogen to which they are attached represent a 5 or 6 membered saturated ring, optionally containing an additional heteroatom selected from oxygen, nitrogen, and sulfur, wherein said ring is optionally substituted by 1, 2 or 3 groups independently selected from the group consisting of (C1-C4)alkyl, (C1-C4)haloalkyl, amino, (C1-C4)alkylamino, ((C1-C4)alkyl)((C1-C4)alkyl)amino, hydroxyl, oxo, (C1-C4)alkoxy, and (C1-C4)alkoxy(C1-C4)alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein said hematologic cancer is selected from the group consisting of: acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative diseases, multiple myeloma, myelodysplastic syndrome, and Hodgkin's disease.