Quinazoline compounds and their use in therapy

Patent metadata

Field	Value
Publication number	US-9932317-B2
Application number	US-201314385268-A
Country	US
Kind code	B2
Filing date	Mar 19, 2013
Priority date	Mar 19, 2012
Publication date	Apr 3, 2018
Grant date	Apr 3, 2018

Abstract

This invention relates to quinazoline compounds of Formula (I) which are inhibitors of the histone lysine methyltransferase (HKMTase) EZH2, and to uses of such compounds as medicaments, in particular in the treatment of a disease or disorder in which inhibition of EZH2 provides a therapeutic or prophylactic effect.

First claim

The invention claimed is:

1. A compound having formula (IA)

or a pharmaceutically acceptable salt thereof;
wherein W is

R a is selected from the group consisting of hydrogen, C 1-8 alkyl, and pyridyl;
either V 1 and D 1 are both absent and E 1 is hydrogen; or
V 1 is O;
D 1 is absent or C 1-8 alkylene;
E 1 is selected from the group consisting of hydrogen and 6-membered carbocyclyl;
either V 2 and D 2 are both absent and E 2 is hydrogen; or
V 2 is O;
D 2 is absent or C 1-8 alkylene;
E 2 is selected from the group consisting of hydrogen and 6-membered carbocyclyl;
V 3 is NR e ;
R e is hydrogen;

n is 0;
R g is selected from the group consisting of hydrogen and optionally substituted 5 to 10-membered carbocyclyl-C 1-6 alkyl, said carbocyclyl being optionally substituted with up to 3 C 1-4 alkyl groups optionally substituted with up to 3 halogens; and
R h is absent.

2. A compound as claimed in claim 1 , wherein R a is selected from the group consisting of C 1-6 alkyl, and pyridyl.

3. A compound as claimed in claim 1 , wherein V 1 is O; D 1 is C 1-6 alkylene; and E 1 is hydrogen or 6-membered aryl.

4. A compound as claimed in claim 1 , wherein R g is selected from the group consisting of hydrogen and optionally substituted 6 to 10-membered aryl-C 1-2 alkyl, said aryl being optionally substituted with up to 3 C 1-4 alkyl groups optionally substituted by up to three halogens.

5. A composition comprising a compound as claimed in claim 1 and a pharmaceutically acceptable excipient.

6. A compound which is any one of the following compounds, or a pharmaceutically acceptable salt thereof:

7. A compound which is any one of the following compounds, or a pharmaceutically acceptable salt thereof:

Assignees

• Imperial Innovations Ltd
• Univ Emory

Inventors

• Brown Robert
• Fuchter Matthew John
• Chapman-Rothe Nadine
• Srimongkolpithak Nitipol
• Caron Joachim
• Snyder James
• Ganesh Thota
• Liu Jin
• Sun Aiming

Classifications

• A61P31/18

  for HIV · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title