# US 10,370,356 B2 · Pyridinone dicarboxamide for use as bromodomain inhibitors

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,370,356 B2
- Document ID: US10370356B2
- Status: Granted
- Kind: B2
- Application number: 15/762,229
- Filed: 2016-09-20
- Published: 2018-10-04
- Granted: 2019-08-06
- Earliest claimed: 2015-09-22
- Assignees: GlaxoSmithKline Intellectual Property (No. 2) Limited
- Applicants: GlaxoSmithKline Intellectual Property (No. 2) Limited
- Inventors: Stephen John Atkinson; Emmanuel Hubert Demont; Lee Andrew Harrison; Thomas George Christopher Hayhow; David House; Matthew J. Lindon; Alexander G. Preston; Jonathan Thomas Seal; Ian David Wall; Robert J. Watson; James Michael Woolven
- Web page: https://patentgrep.com/patent/US10370356B2

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61K 31/4427: containing further heterocyclic ring systems
- 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 31/4436: containing a heterocyclic ring having sulfur as a ring hetero atom
- 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
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/541: Non-condensed thiazines containing further heterocyclic rings
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/14: containing three or more hetero rings
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and to their use in therapy

## Claims

### Claim 1

A compound of formula (I)
or a pharmaceutically acceptable salt thereof:
wherein
R1 is C1-3 alkyl or cyclopropyl;
R2 is —(CH2)n—C4-10heterocyclyl or —(CH2)pO—C4-10heterocyclyl,
wherein each C4-10heterocyclyl is optionally substituted by one or two substituents independently selected from halo, C1-4alkyl, C3-4cycloalkyl, —CH2CF3, —CH2CHF2, —CH2CH2F, —OR5, —OCH2CH2OR5, —CH2OR5, —CH2CH2OR5, —NR6R7, —CH2NR6R7, —CH2CH2NR6R7, —NHCH2CH2OR5, —NHCO2C(CH3)3, oxo, —CO2H, —SO2C1-3 alkyl, —CO2C(CH3)3, and —C(O)R5;
R3 is phenyl, C5-6heteroaryl, C9-11heteroaryl, or —(CH2)m-phenyl;
wherein said phenyl is optionally substituted by one, two, or three R8 groups which may be the same or different; said C5-6 heteroaryl is optionally substituted by C1-3 alkyl, C1-3alkoxy, or halo; or said C9-11heteroaryl is optionally substituted by one, two, or three groups independently selected from —C1-3 alkylR9, —OCH3, —OC2-3 alkylR9, halo, oxo, and cyano;
R4 is —H, C1-4 alkyl, cyclopropyl, —CH2OR10, or —CH2CH2OR10;
R5 is —H or C1-3 alkyl;
R6 and R7 are each independently selected from —H, C1-3alkyl, COC1-3alkyl, and CO2C1-4 alkyl; or R6 and R7 taken together with the nitrogen to which they are attached form a C4-7 heterocyclyl optionally containing a further heteroatom selected from nitrogen, oxygen, and sulphur and optionally substituted by one or two substituents independently selected from C1-3alkyl, —OH, and fluoro;
R8 is —NR11R12, halo, —CN, —CH2CN, —CO2R10, —C(O)C1-3 alkyl, —OH, —OCHF2, —OCF3, —O—C2-6 alkylR9, —OCH3, —CH2CH2NR11R12, —C1-6alkylR9, —OC6heterocyclyl, —OCH2C6heterocyclyl, —CH2C6heterocyclyl, —CH2CH2C6heterocyclyl, —CO2CH3, —NHC(O)R10, —SO2R10, or —SOR10;
R9 is —H, —OR10, or —NR11R12;
R10 is —H or C1-3alkyl;
R11 and R12 are each independently selected from —H and C1-3alkyl; or R11 and R12 taken together with the nitrogen to which they are attached form a C4-7heterocyclyl optionally containing a further heteroatom selected from nitrogen, oxygen, and sulphur and optionally substituted by one or two substituents independently selected from C1-3alkyl, —OH, and fluoro;
n is an integer selected from 0, 1, 2, 3, and 4;
m is an integer selected from 1 and 2; and
p is an integer selected from 2 and 3.

### Claim 2 (depends on 1)

The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R1 is methyl.

### Claim 3 (depends on 1)

The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R2 is —(CH2)n—C4-10 heterocyclyl,
wherein C4-10 heterocyclyl is selected from tetrahydro-2H-pyranyl, piperidinyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperazinyl, morpholinyl, tetrahydro-2H-thiopyranyl, tetrahydrothiophenyl, thiomorpholinyl, and 2-oxabicyclo[4.2.0]octanyl;
wherein tetrahydro-2H-pyranyl, piperidinyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperazinyl, morpholinyl, tetrahydro-2H-thiopyranyl, tetrahydrothiophenyl, thiomorpholinyl, or 2-oxabicyclo[4.2.0]octanyl is optionally substituted by one or two substituents independently selected from halo, C1-4 alkyl, phenyl, —CH2CF3, —CH2CHF2, —CH2CH2F, —OR5, —OCH2CH2OR5, —CH2CH2OR5, —NR6R7, —NHCH2CH2OR5, —NHCO2C(CH3)3, oxo, —CO2H, —CO2C(CH3)3, and —C(O)R5.

### Claim 4 (depends on 3)

The compound or pharmaceutically acceptable salt thereof according to claim 3, wherein R2 is —(CH2)n—C4-10 heterocyclyl,
wherein C4-10 heterocyclyl is piperidinyl or morpholinyl,
wherein piperidinyl or morpholinyl is optionally substituted by one or two substituents independently selected from halo, C1-4 alkyl, —CH2CF3, —CH2CHF2, —CH2CH2F, —OR5, —OCH2CH2OR5, —CH2CH2OR5, —NR6R7, —NHCH2CH2OR5, —NHCO2C(CH3)3, oxo, —CO2H, —CO2C(CH3)3, and —C(O)R5.

### Claim 5 (depends on 4)

The compound or pharmaceutically acceptable salt thereof according to claim 4, wherein piperidinyl or morpholinyl is optionally substituted by one or two substituents independently selected from fluoro, methyl, —CH2CF3, —CH2CHF2, —CH2CH2F, —OH, —CH2CH2OH, —CO2C(CH3)3 —C(O)CH3, and —C(O)CH3.

### Claim 6 (depends on 3)

The compound or pharmaceutically acceptable salt thereof according to claim 3, wherein the C4-10 heterocyclyl is selected from:

### Claim 7 (depends on 1)

The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein n is 3.

### Claim 8 (depends on 1)

The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R3 is phenyl optionally substituted by one or two R8 groups independently selected from halo, O—C1-6 alkylR9, and —C1-6 alkylR9.

### Claim 9 (depends on 8)

The compound or pharmaceutically acceptable salt thereof according to claim 8, wherein R3 is phenyl optionally substituted by one or two R8 groups independently selected from fluoro, —OCH3, —OCH2CH2OH, and methyl.

### Claim 10 (depends on 1)

The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R3 is unsubstituted indolyl.

### Claim 11 (depends on 1)

The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R4 is —H or methyl.

### Claim 12 (depends on 1)

The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein p is 2.

### Claim 13 (depends on 1)

The compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R5 and R10 are each independently selected from —H and methyl.

### Claim 14 (depends on 1)

The compound according to claim 1 which is:
1-benzyl-N3-methyl-2-oxo-N5-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(2-(piperidin-4-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(2-(1-methylpiperidin-4-yl)ethyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
tert-butyl 3-(1-benzyl-5-(methylcarbamoyl)-6-oxo-1,6-dihydropyridine-3-carboxamido)azetidine-1-carboxylate;
tert-butyl 4-(3-(1-benzyl-5-(methylcarbamoyl)-6-oxo-1,6-dihydropyridine-3-carboxamido)propyl)piperidine-1-carboxylate;
1-benzyl-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(3-(1-methylpiperidin-4-yl)propyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
N5-(3-(1-acetylpiperidin-4-yl)propyl)-1-benzyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(2-(tetrahydrofuran-3-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(3-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(3-(1-ethylpiperidin-4-yl)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(3-(piperazin-1-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(2-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)ethyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-(2-fluorobenzyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
N3-methyl-1-(3-methylbenzyl)-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
N3-methyl-1-(3-methylbenzyl)-2-oxo-N5-(2-(piperidin-4-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
(R)—N3-methyl-2-oxo-1-(1-phenylethyl)-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
(R)—N3-methyl-2-oxo-1-(1-phenylethyl)-N5-(2-(piperidin-4-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-(3-methoxybenzyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-(3-methoxybenzyl)-N3-methyl-2-oxo-N5-(2-(piperidin-4-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-(4-fluoro-3-methylbenzyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-(4-fluorobenzyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-(3-(2-hydroxyethoxy)benzyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-(3-(2-hydroxyethoxy)benzyl)-N3-methyl-2-oxo-N5-(2-(piperidin-4-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(3-(1-(2-hydroxyethyl)piperidin-4-yl)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-(2-fluoro-3-methylbenzyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-(2-fluoro-3-methylbenzyl)-N3-methyl-2-oxo-N5-(2-(piperidin-4-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(3-(1-(2,2-difluoroethyl)piperidin-4-yl)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(3-(1-(2-fluoroethyl)piperidin-4-yl)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-((1H-indol-4-yl)methyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(2-(tetrahydro-2H-pyran-3-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
tert-butyl 4-(2-(1-benzyl-5-(methylcarbamoyl)-6-oxo-1,6-dihydropyridine-3-carboxamido)ethyl)piperidine-1-carboxylate;
N5-(azetidin-3-yl)-1-benzyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(1-methylazetidin-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(2-oxabicyclo[4.2.0]octan-7-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(2-(1-methylpyrrolidin-3-yl)ethyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(3-morpholinopropyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
tert-butyl 3-(2-(1-benzyl-5-(methylcarbamoyl)-6-oxo-1,6-dihydropyridine-3-carboxamido)ethyl)piperidine-1-carboxylate;
1-benzyl-N3-methyl-2-oxo-N5-(2-(piperidin-3-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(2-(piperidin-2-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(tetrahydro-2H-pyran-4-yl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(1,1-dioxidotetrahydro-2H-thiopyran-3-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(1,1-dioxidotetrahydrothiophen-3-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(3-(piperidin-1-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
(R)-1-benzyl-N3-methyl-2-oxo-N5-((tetrahydro-2H-pyran-3-yl)methyl)-1,2-dihydropyridine-3,5-dicarboxamide;
(S)-1-benzyl-N3-methyl-2-oxo-N5-((tetrahydro-2H-pyran-3-yl)methyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-((1,1-dioxidotetrahydrothiophen-3-yl)methyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-((tetrahydro-2H-pyran-4-yl)methyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(tetrahydro-2H-pyran-3-yl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(3-(4-methylpiperazin-1-yl)propyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(3-(1,1-dioxidothiomorpholino)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
N3-methyl-1-(3-methylbenzyl)-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
(R)—N3-methyl-2-oxo-1-(1-phenylethyl)-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-((1H-indol-4-yl)methyl)-N3-methyl-2-oxo-N5-(2-(piperidin-4-yl)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(3-(4-hydroxypiperidin-4-yl)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-(3-fluorobenzyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
tert-butyl 3-(3-(1-benzyl-5-(methylcarbamoyl)-6-oxo-1,6-dihydropyridine-3-carboxamido)propyl)piperidine-1-carboxylate;
1-benzyl-N3-methyl-2-oxo-N5-(3-(piperidin-3-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(3-(4-fluoropiperidin-4-yl)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-((1H-indol-4-yl)methyl)-N3-methyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-(3-(4-fluoropiperidin-4-yl)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(2-(4-methylmorpholin-2-yl)ethyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
N5-(2-(4-acetylmorpholin-2-yl)ethyl)-1-benzyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(2-(morpholin-2-yl)ethyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(2-(pyrrolidin-3-yloxy)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(2-(piperidin-3-yloxy)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N5-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(3-(1-methylpiperidin-3-yl)propyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(3-(1-methylpiperidin-3-yl)propyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
N5-((1R,5S,6r)-3-oxabicyclo[3.1.0]hexan-6-yl)-1-(3-methoxybenzyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(3-(morpholin-2-yl)propyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-((1H-indol-4-yl)methyl)-N5-(3-(1-acetylpiperidin-4-yl)propyl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
(1R,5S,6s)-tert-butyl 6-(1-benzyl-5-(methylcarbamoyl)-6-oxo-1,6-dihydropyridine-3-carboxamido)-3-azabicyclo[3.1.0]hexane-3-carboxylate;
1-benzyl-N5-((1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(3-(morpholin-2-yl)propyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-ethyl-2-oxo-N5-(3-(piperidin-4-yl)propyl)-1,2-dihydropyridine-3,5-dicarboxamide;
(1R,5S,6s)-tert-butyl 6-(1-((1H-indol-4-yl)methyl)-5-(methylcarbamoyl)-6-oxo-1,6-dihydropyridine-3-carboxamido)-3-azabicyclo[3.1.0]hexane-3-carboxylate;
1-((1H-indol-4-yl)methyl)-N5-((1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-((1H-indol-4-yl)methyl)-N5-((1R,5S,6s)-3-acetyl-3-azabicyclo[3.1.0]hexan-6-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
(R)-1-benzyl-N3-ethyl-N5-(3-(3-fluoropiperidin-3-yl)propyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
(R)-1-benzyl-N3-ethyl-N5-(2-(morpholin-2-yl)ethyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
(R)-1-benzyl-N3-ethyl-N5-(3-(morpholin-2-yl)propyl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
tert-butyl (2-((1R,5S,6s)-6-(1-((1H-indol-4-yl)methyl)-5-(methylcarbamoyl)-6-oxo-1,6-dihydropyridine-3-carboxamido)-3-azabicyclo[3.1.0]hexan-3-yl)ethyl)carbamate;
1-((1H-indol-4-yl)methyl)-N5-((1R,5S,6s)-3-(2-aminoethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-((1H-indol-4-yl)methyl)-N5-((1R,5S,6s)-3-(2-acetamidoethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
N5-(3-((2r,5r)-5-amino-1,3-dioxan-2-yl)propyl)-1-benzyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-2-oxo-N5-(2-(piperidin-4-yloxy)ethyl)-1,2-dihydropyridine-3,5-dicarboxamide;
1-benzyl-N3-methyl-N5-(1-(methylsulfonyl)azetidin-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide; and
1-benzyl-N3-methyl-N5-(oxetan-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide;
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable excipient.

### Claim 16 (depends on 1)

A combination comprising the compound or pharmaceutically acceptable salt thereof as defined in claim 1 together with one or more other therapeutically active agents.

### Claim 17 (depends on 1)

A method of treating a bromodomain-mediated disease or condition in a human in need thereof comprising administering a therapeutically effective amount of the compound, or a pharmaceutically acceptable salt thereof, according to claim 1.

### Claim 18 (depends on 17)

The method according to claim 17, wherein the bromodomain-mediated disease or condition is an acute or chronic autoimmune or inflammatory condition.

### Claim 19 (depends on 18)

The method according to claim 18, wherein the acute or chronic autoimmune or inflammatory condition is rheumatoid arthritis.

### Claim 20 (depends on 1)

A method of treating a bromodomain-mediated disease or condition in a human in need thereof comprising administering a therapeutically effective amount to the human a combination comprising the compound according to claim 1, or a pharmaceutically acceptable salt thereof, and one or more therapeutically active agents.