IP Library › Granted Patent US 10,710,992
Granted Patent B2
US 10,710,992 · App. 15/531,526 · Granted Jul 14, 2020

Substituted pyridinones as bromodomain inhibitors

Inventors: May Xiaowu Jiang (Guilderland, NY); Bruce Francis Molino (Slingerlands, NY); Shuang Liu (Schenectady, NY); Ruifang Wang (Schenectady, NY); Bryan Cordell Duffy (Glenmont, NY); John Frederick Quinn (Albany, NY); Gregory Steven Wagner (Foster City, CA)
Assignee: Zenith Epigenetics Ltd.
C07D413/14A61K31/444A61K31/4439A61K31/4709A61K45/06C07D409/14C07D413/04C07D417/14
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Quick Facts
Patent No.
US 10,710,992
App. No.
15/531,526
Granted
Jul 14, 2020
Kind
B2
Abstract

The present disclosure relates to substituted pyridinones, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.

Claims (56)

1. A compound of Formula I:

or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:

A is selected from

each of which is optionally substituted with 1 to 3 groups independently selected from halogen, alkyl (C 1 -C 6 ), alkoxy (C 1 -C 6 ), —CF 3 , and —CN;

L is —CH 2 — or

L may be absent in which case A is connected to X via a covalent bond;

X is —NH—;

R 1 and R 2 are independently selected from hydrogen and alkyl (C 1 -C 6 ); and

R 3 and R 4 are independently selected from alkyl (C 1 -C 6 ) optionally substituted with halogen and hydroxyl.

2. A compound selected from:

5-(3,5-dimethylisoxazol-4-yl)-3-(phenylamino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-(pyridin-3-ylamino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((3-fluorophenyl)amino)pyridin-2(1H)-one;

3-(benzylamino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-phenoxypyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-(m-tolylamino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((3-methoxyphenyl)amino)pyridin-2(1H)-one;

3-((4-chlorobenzyl)amino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

4-(((5-(3,5-dimethylisoxazol-4-yl)-2-oxo-1,2-dihydropyridin-3-yl)amino)methyl)benzonitrile;

5-(3,5-dimethylisoxazol-4-yl)-3-((4-(trifluoromethyl)benzyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((pyridin-4-ylmethyl)amino)pyridin-2(1H)-one;

3-(((5-chlorothiophen-2-yl)methyl)amino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((thiophen-3-ylmethyl)amino)pyridin-2(1H)-one;

3-(benzyloxy)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((2-fluorophenyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((4-fluorophenyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((pyridin-2-ylmethyl)amino)pyridin-2(1H)-one;

34(1-(4-chlorophenyl)ethyl)amino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

3-((4-bromobenzyl)amino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((1-(pyridin-2-yl)ethyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((4-fluorobenzyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-(phenethylamino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((pyridin-3-ylmethyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((4-iodobenzyl)amino)pyridin-2(1H)-one;

4-(((5-(3,5-dimethylisoxazol-4-yl)-2-oxo-1,2-dihydropyridin-3-yl)oxy)methyl)benzonitrile;

5-(3,5-dimethylisoxazol-4-yl)-3-(pyridin-2-ylmethoxy)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((4-fluorobenzyl)oxy)pyridin-2(1H)-one;

4-((5-(3,5-dimethylisoxazol-4-yl)-2-oxo-1,2-dihydropyridin-3-yl)amino)benzonitrile;

3-((4-chlorophenyl)amino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((thiazol-2-ylmethyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((isoxazol-4-ylmethyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((naphthalen-2-ylmethyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((3,5-dimethylisoxazol-4-yl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((quinolin-2-ylmethyl)amino)pyridin-2(1H)-one;

5-(((5-(3,5-dimethylisoxazol-4-yl)-2-oxo-1,2-dihydropyridin-3-yl)amino)methyl)thiophene-2-carbonitrile;

3-(((3-chloropyridin-2-yl)methyl)amino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

3-(((1H-benzo[d]imidazol-2-yl)methyl)amino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((quinolin-5-ylmethyl)amino)pyridin-2(1H)-one;

3-((benzo[d]thiazol-2-ylmethyl)amino)-5-(3,5-dimethylisoxazol-4-yl)pyridin-2(1H)-one;

(S)-5-(3,5-dimethylisoxazol-4-yl)-3-((1-(pyridin-2-yl)ethyl)amino)pyridin-2(1H)-one;

(R)-5-(3,5-dimethylisoxazol-4-yl)-3-((1-(pyridin-2-yl)ethyl)amino)pyridin-2(1H)-one;

5-(3,5-dimethylisoxazol-4-yl)-3-((2-methylpyridin-3-yl)oxy)pyridin-2-ol;

3,5-bis(3,5-dimethyl isoxazol-4-yl) pyridin-2(1H)-one;

and stereoisomers, tautomers, and pharmaceutically acceptable salts thereof.

3. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.

4. A pharmaceutical composition comprising the compound of claim 2 , and a pharmaceutically acceptable carrier.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 13, 2020
From: JIANG, MAY XIAOWU; MOLINO, BRUCE FRANCIS; LIU, SHUANG; WANG, RUIFANG; DUFFY, BRYAN CORDELL; QUINN, JOHN FREDERICK; WAGNER, GREGORY STEVEN
To: ZENITH EPIGENETICS CORP.
Reel/Frame 051810/0797 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 13, 2020
From: ZENITH CAPITAL CORP.
To: ZENITH EPIGENETICS LTD.
Reel/Frame 051810/0821 →
CHANGE OF NAME Recorded Feb 13, 2020
From: ZENITH EPIGENETICS CORP.
To: ZENITH CAPITAL CORP.
Reel/Frame 051928/0678 →
Continuity (2)
Provisional Application 62086117 · Dec 1, 2014
Related Publication 20170320866A1 · Nov 9, 2017