IP Library › Granted Patent US 9,365,547

Granted Patent B2

US 9,365,547 · App. 14/149,741 · Granted Jun 14, 2016

Substituted pyridinone-pyridinyl compounds

Inventors: Shaun R. Selness (Chesterfield, MO); Joseph B. Monahan (St. Louis, MO); John F. Schindler (Chesterfield, MO); Balekudru Devadas (Chesterfield, MO)

Assignee: CONFLUENCE LIFE SCIENCES INC.

C07D401/14 A61K31/444 A61K31/506 A61K45/06 C07D401/04 C07D409/14 C07D413/14 C07D417/14

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Patent No.: US 9,365,547
App. No.: 14/149,741
Granted: Jun 14, 2016
Kind: B2

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Abstract

The present disclosure provides pyridinone-pyridinyl compounds useful in the treatment of p38 kinase mediated diseases, such as lymphoma and auto-inflammatory disease, having the structure of Formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , X and Y are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating p38 kinase mediated diseases using the compound.

Claims (371)

1. A compound having the structure of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

X and Y are independently selected from the group consisting of CH and N, with the proviso that when X is CH, Y is N, and when X is N, Y is CH;

R 1 is selected from the group consisting of C 1 -C 6 -alkyl, halo and —H;

R 2 is selected from the group consisting of alkyl and alkoxy; wherein the alkyl or alkoxy is optionally substituted with one or more heterocyclyl which is optionally substituted with one or more substituents independently selected from the group consisting of alkyl, alkoxy and cyano;

R 3 and R 4 are independently selected from the group consisting of alkyl, halo and —H; and

R 5 is selected from the group consisting of cycloalkyl, aryl, and heterocyclyl; wherein the cycloalkyl or aryl is optionally substituted with one or more substituents independently selected from the group consisting of halo, cyano, alkyl, hydroxyalkyl, alkoxyalkyl and aminoalkyl; and wherein the heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, alkyl, hydroxyalkyl, alkoxyalkyl and aminoalkyl.

2. The compound according to claim 1 , wherein X is CH and Y is N.

3. The compound according to claim 2 , wherein:

R 1 is selected from the group consisting of C 1 -C 3 -alkyl, bromo, chloro and fluoro;

R 2 is alkoxy optionally substituted with one or more heterocyclyl substituents optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 3 -alkyl and cyano;

R 3 is C 1 -C 3 -alkyl;

R 4 is selected from the group consisting of —H, C 1 -C 3 -alkyl, bromo, chloro and fluoro; and

R 5 is heterocyclyl optionally substituted with one or more substituents independently selected from the group consisting of alkyl, hydroxyalkyl and aminoalkyl.

4. The compound according to claim 3 , wherein:

R 1 is methyl, bromo or chloro;

R 2 is alkoxy optionally substituted with five- or six-membered heteroaryl optionally substituted with one or more substituents independently selected from C 1 -C 3 -alkyl;

R 3 is methyl;

R 4 is —H, methyl or chloro; and

R 5 is five- or six-membered heteroaryl optionally substituted with one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl.

5. The compound according to claim 4 , wherein:

R 2 is alkoxy substituted with five-membered heteroaryl optionally substituted with one or more methyl substituents; and

R 5 is pyridinyl or pyrimidinyl, wherein the pyridinyl or pyrimidinyl is optionally substituted with one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl.

6. The compound according to claim 5 , wherein the compound has the structure of Formula (II):

wherein:

R 1 is methyl, bromo or chloro;

R 4 is —H, methyl or chloro;

R 20 is five-membered heteroaryl optionally substituted with one or more methyl substituents;

R 50 is —H or methyl; and

R 51 is —H, methyl or hydroxy.

7. The compound according to claim 6 , selected from the group consisting of:

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.

8. The compound according to claim 6 , selected from the group consisting of:

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-di methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl) pyrimidin-4-yl) -6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.

9. The compound according to claim 6 , selected from the group consisting of:

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1 H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1 H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((1-methyl-1 H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.

10. A compound according to claim 6 , selected from the group consisting of:

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.

11. The compound according to claim 6 , selected from the group consisting of:

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((5-methylthiophen-3-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.

12. The compound according to claim 1 , wherein X is N and Y is CH.

13. The compound according to claim 12 , wherein:

R 1 is selected from the group consisting of C 1 -C 3 -alkyl, bromo, chloro and fluoro;

R 2 is alkoxy, optionally substituted with one or more heterocyclyl optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 3 -alkyl and cyano;

R 3 and R 4 are independently selected from the group consisting of —H and C 1 -C 3 -alkyl; and

R 5 is heterocyclyl optionally substituted with one or more substituents independently selected from the group consisting of alkyl, hydroxyalkyl and aminoalkyl.

14. The compound according to claim 13 , wherein:

R 1 is methyl or chloro;

R 2 is alkoxy optionally substituted with five- or six-membered heteroaryl optionally substituted with one or more substituents independently selected from C 1 -C 3 -alkyl;

R 3 is methyl;

R 4 is —H or methyl; and

R 5 is five- or six-membered heteroaryl optionally substituted with one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl.

15. The compound according to claim 14 , wherein:

R 2 is alkoxy substituted with five-membered heteroaryl optionally substituted with one or more methyl substituents; and

16. The compound according to claim 15 , wherein the compound has the structure of Formula (III):

wherein:

R 1 is methyl or chloro;

R 4 is —H or methyl;

R 20 is five-membered heteroaryl optionally substituted with one or more methyl substituents; and

R 51 is methyl or hydroxy.

17. The compound according to claim 16 , selected from the group consisting of:

5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,3,6-trimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl) -2′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-2′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

3-chloro-5′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-2′,6-dimethyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methyloxazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one;

5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((2-methylthiazol-4-yl)methoxy)-2H-[1,3′-bipyridin]-2-one; and

5′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-2H-[1,3′-bipyridin]-2-one.

18. The compound according to claim 1 , wherein:

X and Y are independently selected from the group consisting of CH and N, with the proviso that when X is CH, Y is N, and when X is N, Y is CH;

R 1 is selected from the group consisting of C 1 -C 3 -alkyl, bromo, chloro and fluoro;

R 2 is alkoxy, optionally substituted with one or more heterocyclyl substituents optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy and cyano;

R 3 is C 1 -C 3 -alkyl;

R 4 is selected from the group consisting of —H, C 1 -C 3 -alkyl, bromo, chloro and fluoro; and

R 5 is heterocyclyl optionally substituted with one or more substituents independently selected from the group consisting of alkyl, hydroxyalkyl and aminoalkyl.

19. The compound according to claim 18 , wherein:

R 1 is methyl, bromo or chloro;

R 2 is alkoxy optionally substituted with five- or six-membered heteroaryl optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 3 -alkyl and C 1 -C 3 -alkoxy;

R 3 is methyl;

R 4 is —H, methyl or chloro; and

R 5 is five- or six-membered heteroaryl optionally substituted with one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl.

20. The compound according to claim 19 , wherein:

R 2 is alkoxy substituted with six-membered heteroaryl optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 3 -alkyl and C 1 -C 3 -alkoxy; and

21. The compound according to claim 20 , wherein the compound has the structure of Formula (VIII):

wherein:

X and Y are independently selected from the group consisting of CH and N, with the proviso that when X is CH, Y is N, and when X is N, Y is CH;

R 1 is methyl, bromo or chloro;

R 4 is —H, methyl or chloro;

R 21 is methyl or methoxy;

R 50 is —H or methyl; and

R 51 is —H, methyl or hydroxy.

22. The compound according to claim 21 , selected from the group consisting of:

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,5′-dichloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-5′-chloro-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3-chloro-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(tert-butyl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-isopropyl-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-isopropyl-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)pyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-5′,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,5′,6-trimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3,5′-dichloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

5′-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-bromo-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one;

3-chloro-2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-6-methyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one; and

2′-(2-(2-hydroxypropan-2-yl)-5-methylpyrimidin-4-yl)-3,6-dimethyl-4-((6-methylpyridin-2-yl)methoxy)-2H-[1,4′-bipyridin]-2-one.

23. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

24. A method for treating lymphoma comprising:

administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or pharmaceutically acceptable salt thereof.

25. The method of claim 24 , wherein the subject is a mammal selected from a canine and a humane.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2018

From: ACLARIS LIFE SCIENCES, INC.

To: ACLARIS THERAPEUTICS, INC.

Reel/Frame 046153/0695 →

MERGER Recorded Nov 16, 2017

From: CONFLUENCE LIFE SCIENCES, INC.

To: ACLARIS LIFE SCIENCES, INC.

Reel/Frame 044477/0208 →

Continuity (3)

Continuation 13312924 · Dec 6, 2011

Provisional Application 61420074 · Dec 6, 2010

Related Publication 20140171450A1 · Jun 19, 2014