Enhancer of zeste homolog 2 inhibitors

Patent metadata

Field	Value
Publication number	US-9562041-B2
Application number	US-201314400896-A
Country	US
Kind code	B2
Filing date	May 15, 2013
Priority date	May 16, 2012
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

This invention relates to novel substituted benzamides 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.

First claim

The invention claimed is:

1. A compound according to Formula (I):

wherein:
R 1 is methyl;
R 2 is methyl;
R 3 is hydrogen;
R 4 is methyl;
R 5 is —NR a R b ;
R 6 is phenyl, wherein said phenyl is optionally substituted by —(C 1 -C 6 )alkyl(R c );
R c is —NR a R b ; and
R a and R b are each independently hydrogen, (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )alkynyl, (C 3 -C 10 )cycloalkyl, (C 5 -C 8 )cycloalkenyl, heterocycloalkyl, or aryl, wherein said (C 1 -C 8 )alkyl, (C 2 -C 8 )alkenyl, (C 2 -C 8 )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, (C 1 -C 4 )alkoxy, amino, (C 1 -C 4 )alkylamino, —N((C 1 -C 4 )alkyl) 2 , —CO 2 H, —CO 2 (C 1 -C 4 )alkyl, —CONH 2 , —CONH(C 1 -C 4 )alkyl, —CON((C 1 -C 4 )alkyl) 2 , —SO 2 (C 1 -C 4 )alkyl, —SO 2 NH 2 , —SO 2 NH(C 1 -C 4 )alkyl, and —SO 2 N((C 1 -C 4 )alkyl) 2 ; and wherein said heterocycloalkyl is selected from the group consisting of pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, and tetrahydropyranyl;
or R a and R b 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 (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, amino, (C 1 -C 4 )alkylamino, ((C 1 -C 4 )alkyl)((C 1 -C 4 )alkyl)amino, hydroxyl, oxo, (C 1 -C 4 )alkoxy, and (C 1 -C 4 )alkoxy(C 1 -C 4 )alkyl;
or a pharmaceutically acceptable salt thereof.

Assignees

• Glaxosmithkline Llc

Inventors

• Burgess Joelle Lorraine
• Knight Steven David

Classifications

• A61K31/4433

  containing a six-membered ring with oxygen as a ring hetero atom · CPC title

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K31/443

  containing a five-membered ring with oxygen as a ring hetero atom · CPC title

• C07D213/64

  attached in position 2 or 6 · CPC title