IP Library Granted Patent US 11,339,166
Granted Patent B2
US 11,339,166 · App. 16/768,825 · Granted May 24, 2022

Compounds and pharmaceutical compositions thereof for the treatment of diseases

Inventors: Luke Jonathan Alvey (Romainville, FR); Denis Maurice Annoot (Romainville, FR); Florence Marie-Emilie Bonnaterre (Romainville, FR); Denis Bucher (Rheinfelden, CH); Béranger Duthion (Romainville, FR); Hélène Marie Jary (Romainville, FR); Christophe Peixoto (Romainville, FR); Taoues Temal-Laib (Romainville, FR); Amynata Tirera (Romainville, FR); Nicolas Desroy (Romainville, FR)
Assignee: GALAPAGOS NV
C07D487/04C07D401/04C07D403/04C07D403/14C07D413/04C07D471/04C07D491/10C07D495/10
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Quick Facts
Patent No.
US 11,339,166
App. No.
16/768,825
Granted
May 24, 2022
Kind
B2
Abstract

The present invention discloses compounds according to Formula I: wherein R 1 , R 2 , R 3a , R 3b , X, Y 1 , Y 2 , Y 3 , and Z are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of inflammatory diseases, autoinflammatory diseases, autoimmune diseases, proliferative diseases, fibrotic diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformation, diseases involving impairment of bone turnover, diseases associated with hypersecretion of TNFα, interferons, IL-6, IL-12 and/or IL-23, respiratory diseases, endocrine and/or metabolic diseases, cardiovascular diseases, dermatological diseases, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.

Claims (419)

1. A compound according to Formula I:

wherein,

X is N or CR 4 ;

Y 1 is C;

one of Y 2 and Y 3 is N and the other is C;

Z is

—NR 5a R 5b ,

—NR 5c —, wherein the N atom and R 3b together with the atoms onto which they are attached form a fused 5-6 membered heterocycloalkenyl comprising one double bond and further comprising zero, one, or two additional heteroatoms independently selected from N, O, and S, or

N-linked 4-7 membered heterocycloalkyl further comprising zero, one, or two additional heteroatoms independently selected from N, O, and S, optionally substituted with one, two or three independently selected R 6 groups;

R 1 is H, halo, C 1-4 alkyl, or C 1-4 alkoxy optionally substituted with C 1-4 alkoxy, phenyl, —CN, —C(═O)OH, or —C(═O)—C 1-4 alkoxy;

R 2 is 5-6 membered monocyclic heteroaryl comprising one, two or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected R 7 groups;

R 3a and R 3b are independently selected from

halo,

C 1-4 alkyl,

C 1-4 alkoxy optionally substituted with one or more independently selected halo, —OH or C 1-4 alkoxy,

—NR 8a R 8b , and

—OH;

R 4 is H or C 1-4 alkyl;

R 5a is H or C 1-4 alkyl;

R 5b is selected from

C 1-6 alkyl optionally substituted with one or more independently selected R 9 ,

C 3-7 cycloalkyl optionally substituted with one or more independently selected R 10 ,

4-7 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more oxo, and

5-6 membered monocyclic heteroaryl comprising one, two or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C 1-4 alkyl;

R 5c is selected from C 3-7 cycloalkyl, and C 1-6 alkyl optionally substituted with one or more independently selected halo;

each R 6 is independently selected from

oxo,

halo,

—CN,

—OH,

—NR 11a R 11b

phenyl,

C 3-7 cycloalkyl,

C 2-4 alkynyl,

—C(═O)—C 1-4 alkoxy,

—C 1-4 alkoxy optionally substituted with one or more halo or phenyl,

C 1-4 alkyl optionally substituted with one or more halo, —OH, or C 1-4 alkoxy, and

4-7 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S;

each R 7 is selected from

halo,

—CN,

C 1-6 alkyl optionally substituted with one or more independently selected

halo,

—CN,

—OH,

C 1-4 alkoxy optionally substituted with one or more independently selected halo,

NR 11c R 11d ,

—C(═O)R 12 , or

4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S,

C 1-4 alkoxy,

C 3-7 cycloalkyl,

4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with —C(═O)C 1-4 alkoxy or C 1-4 alkyl optionally substituted with —CN,

—NR 13a R 13b , and

—C(═O)NR 13c R 13d ;

each R 8a and R 8b is independently selected from H and C 1-4 alkyl optionally substituted with one —OH or C 1-4 alkoxy;

each R 9 is independently selected from

halo,

—CN,

—NR 11e R 11f

—OH,

C 1-4 alkoxy,

—S(═O) 2 -C 1-4 alkyl,

4-7 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, and

5-6 membered monocyclic heteroaryl comprising one, two or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C 1-4 alkyl;

each R 10 is independently selected from

halo,

C 1-4 alkyl optionally substituted with one or more independently selected halo, —OH, or C 1-4 alkoxy,

—OH,

C 1-4 alkoxy, and

—NR 11g R 11h ;

each R 11a , R 11b , R 11c , R 11d , R 11e , R 11f , R 11g , and R 11h is independently selected from H and C 1-4 alkyl; each R 12 is

—NR 14a R 14b wherein each R 14a and R 14b is independently selected from H and C 1-4 alkyl,

—OH,

C 1-4 alkoxy optionally substituted with one or more independently selected C 3-7 cycloalkyl, halo, —NR 15a R 15b or 4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S,

—O-(4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S), or

—O-(C 3-7 monocyclic cycloalkyl);

each R 13a , R 13b , R 13c , and R 13d , is independently selected from H and C 1-4 alkyl; and

each R 15a and R 15b is independently selected from H and C 1-4 alkyl;

or a pharmaceutically acceptable salt thereof.

2. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 1 is H, halo, C 1-4 alkyl, or C 1-4 alkoxy optionally substituted with C 1-4 alkoxy;

each R 7 is selected from

halo,

—CN,

C 1-4 alkyl optionally substituted with one or more independently selected

halo,

—CN,

—OH,

C 1-4 alkoxy optionally substituted with one or more independently selected halo,

NR 11c R 11d ,

—C(═O)R 12 , or

4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S,

C 1-4 alkoxy,

C 3-7 cycloalkyl,

4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with —C(═O)C 1-4 alkoxy or C 1-4 alkyl optionally substituted with —CN,

—NR 13a R 13b ), and

C(═O)NR 13c R 13d , and

each R 12 is

—NR 14a R 14b ) wherein each R 14a and R 14b ) is independently selected from H and C 1-4 alkyl,

—OH,

C 1-4 alkoxy optionally substituted with one or more independently selected C 3-7 cycloalkyl, or halo,

—O-(4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S), or

—O—(C 3-7 monocyclic cycloalkyl).

3. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 2 is imidazolyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, each of which is optionally substituted with one or more independently selected R 7 groups.

4. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is according to any one of Formulae Vb, Vc, Ve, and Vf:

5. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 7 is C 1-4 alkyl.

6. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 3b is —O—CH 3 , —O—CH 2 CH 3 , or —O—CH(CH 3 ) 2 , each of which is optionally substituted with one or more independently selected halo, —OH or C 1-4 alkoxy.

7. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 3a is halo, —OH, C 1-4 alkoxy, or C 1-4 alkoxy substituted with one or more independently selected halo, —OH or C 1-4 alkoxy.

8. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is according to any one of Formulae VIIIa-VIIId:

9. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein Z is —NR 5a R 5b .

10. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 5a is H, —CH 3 , —CH 2 CH 3 , or —CH(CH 3 ) 2 .

11. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 5b is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

12. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 5b is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —C(CH 3 ) 3 , —CH(CH 3 )CH 2 CH 3 , or —CH(CH 3 )CH(CH 3 ) 2 , each of which is substituted with one or more independently selected R 9 .

13. A compound or pharmaceutically acceptable salt thereof, according to claim 12 , wherein R 9 is F,

Cl, —CN, —OH, —O—CH 3 , —O—CH 2 CH 3 , —O—CH(CH 3 ) 2 , —S(═O) 2 —CH 3 , —S(═O) 2 —CH 2 CH 3 , or —S(═O) 2 —CH(CH 3 ) 2 .

14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 .

15. A method for inhibiting salt-inducible kinase (SIK) or tumor necrosis factor-alpha (TNF-α) activity or treating diseases associated with SIK or TNF-α activity, comprising administering an effective amount of the compound or pharmaceutically acceptable salt thereof, according to claim 1 , to a subject in need thereof.

16. A method for inhibiting salt-inducible kinase (SIK) or tumor necrosis factor-alpha (TNF-α) activity or treating diseases associated with SIK or TNF-α activity, comprising administering the pharmaceutical composition according to claim 14 , to a subject in need thereof.

17. The compound of claim 1 , wherein the compound is

N-ethyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-benzamide,

N-ethyl-2,6-dimethoxy-4-[5-(3-pyridyl)benzimidazol-1-yl]benzamide,

N-ethyl-2,6-dimethoxy-4-[5-(6-morpholino-3-pyridyl)benzimidazol-1-yl]benzamide,

N-ethyl-2,6-dimethoxy-4-[5-[1-(2-morpholinoethyl)pyrazol-4-yl]benzimidazol-1-yl]benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-N-(2-hydroxyethyl)-2,6-dimethoxy-benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-methyl-benzamide,

N-ethyl-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

4-[5-(1,3-dimethylpyrazol-4-yl)benzimidazol-1-yl]-N-ethyl-2,6-dimethoxy-benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-N-(2-fluoroethyl)-2,6-dimethoxy-benzamide,

N-(2,2-difluoroethyl)-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

N-ethyl-2,6-dimethoxy-4-[5-[1-(2-methoxyethyl)pyrazol-4-yl]benzimidazol-1-yl]benzamide,

N-ethyl-2,6-dimethoxy-4-[5-(1-tetrahydropyran-4-ylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

4-[5-[1-(cyanomethyl)pyrazol-4-yl]benzimidazol-1-yl]-N-ethyl-2,6-dimethoxy-benzamide,

N-ethyl-4-[5-[1-(2-hydroxyethyl)pyrazol-4-yl]benzimidazol-1-yl]-2,6-dimethoxy-benzamide,

2-(difluoromethoxy)-N-ethyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-6-methoxy-benzamide,

4-[5-[1-(2-amino-2-oxo-ethyl)pyrazol-4-yl]benzimidazol-1-yl]-N-ethyl-2,6-dimethoxy-benzamide,

N-cyclopropyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-propyl-benzamide,

N-ethyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2-hydroxy-6-methoxy-benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclobutyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2-methoxyethyl)-N-methyl-benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-N-isobutyl-2,6-dimethoxy-N-methyl-benzamide,

4-[6-(1-ethylpyrazol-4-yl)imidazo[4,5-b]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclopropyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-methyl-benzamide,

N-(cyanomethyl)-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-methyl-benzamide,

2,6-dimethoxy-4-[5-(6-morpholino-3-pyridyl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-[1-(2-hydroxyethyl)pyrazol-4-yl]benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(6-pyrrolidin-1-yl-3-pyridyl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(5-methoxy-3-pyridyl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-(6-cyano-3-pyridyl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-[6-(dimethylamino)-3-pyridyl]benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-(6-amino-3-pyridyl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(3-pyridyl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-[1-(cyanomethyl)pyrazol-4-yl]benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-[1-(2-morpholinoethyl)pyrazol-4-yl]benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-[1-(4-piperidyl)pyrazol-4-yl]benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-tert-butyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(3,3,3-trifluoropropyl)benzamide,

N-cyclopentyl-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-benzamide,

2,6-dimethoxy-4-[5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(1H-pyrazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-[(2R)-2-methylcyclopropyl]benzamide,

N-(cyanomethyl)-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-benzamide,

4-(5-isoxazol-4-ylbenzimidazol-1-yl)-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-cyclopropyl-2-(difluoromethoxy)-4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-6-methoxy-benzamide,

4-[5-[1-(cyanomethyl)pyrazol-4-yl]benzimidazol-1-yl]-N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[5-[1-(2-morpholinoethyl)pyrazol-4-yl]benzimidazol-1-yl]benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[5-[1-(2-morpholinoethyl)pyrazol-4-yl]benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-[(1R)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

N-(2-cyanoethyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-N-(3-methoxypropyl)-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-[(1-methylpyrazol-3-yl)methyl]benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-(2-pyridylmethyl)benzamide,

N-(3-hydroxypropyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-(1,1-dioxothietan-3-yl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-(2-methyl sulfonyl ethyl)benzamide,

N-(1,1-dioxothiolan-3-yl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-[[(2R)-1,4-dioxan-2-yl]methyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoro-1,1-dimethyl-ethyl)benzamide,

N-[[(2 S)-1,4-dioxan-2-yl]methyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-N-(5-methylpyrazin-2-yl)-4-[ 5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-N-[(1-methylimidazol-2-yl)methyl]-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-isoxazol-3-yl-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-N-(2-methylpyrazol-3-yl)-4-[ 5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-(cyanomethyl)-2,6-dimethoxy-N-methyl-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-(cyanomethyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-tert-butyl-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-cyclobutyl-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-(2,2-difluoroethyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-(2-fluoroethyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-[(1 S)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

2,6-dimethoxy-N-(1-methylpyrazol-3-yl)-4-[ 5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-N-(1-methylimidazol-4-yl)-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-N-(1-methylpyrazol-4-yl)-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-[1-(2-methoxyethyl)pyrazol-4-yl]benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-[1-(oxetan-3-yl)pyrazol-4-yl]benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclopropyl-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-(1-cyanoethyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-3-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-(2,2-difluorocyclopentyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-(2,2-difluoro-1-methyl-ethyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-(oxetan-3-yl)benzamide,

2,6-dimethoxy-4-(5-pyridazin-4-ylbenzimidazol-1-yl)-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-[1-(azetidin-3-yl)pyrazol-4-yl]benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-(1-isopropylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-(1-cyclopropylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-[1-(difluoromethyl)pyrazol-4-yl]benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-[1-(1-methylazetidin-3-yl)pyrazol-4-yl]benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-[1-[1-(cyanomethyl)azetidin-3-yl]pyrazol-4-yl]benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(3-methyl-1H-pyrazol-5-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclopropyl-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

2,6-dimethoxy-4-[5-(1-propylpyrazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-(5-pyrimidin-5-ylbenzimidazol-1-yl)-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(2-methoxypyrimidin-5-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(2-methoxy-4-pyridyl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(3-methylisoxazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(3-methylisoxazol-5-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-(1-isobutylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-[1-(tetrahydrofuran-2-ylmethyl)pyrazol-4-yl]benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclopropyl-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]benzamide,

N-isobutyl-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]-N-sec-butyl-benzamide,

N-isopropyl-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]benzamide,

N-cyclopropyl-2-isopropoxy-6-methoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-[2-(4-methylpiperazin-1-yl)-4-pyridyl]benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(6-methylpyridazin-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-(cyanomethyl)-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[7-(3-methylisoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-(3,3-difluorocyclobutyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(5-methyl-1,2,4-oxadiazol-3-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(5-methyl-4H-1,2,4-triazol-3-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-(5-pyrazin-2-ylbenzimidazol-1-yl)-N-(2,2,2-trifluoroethyl)benzamide,

N-isobutyl-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-(1,1-dioxothietan-3-yl)-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

2,6-dimethoxy-N-(2-methoxyethyl)-N-methyl-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-[(1S)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

N-(2,2-difluoroethyl)-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylimidazol-2-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(3-methylimidazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[5-(5-methyl-1,2,4-oxadiazol-3-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methylimidazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-(2,3-dimethylimidazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

N-[(1R,2R)-2-aminocyclohexyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-[(1R,2R)-2-hydroxycyclopentyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-[(1R,2S)-2-hydroxycyclopentyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

(3,3-difluoroazetidin-1-yl)-[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]methanone,

N-[(1R,2R)-2-hydroxycyclopentyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-[(1R,2S)-2-fluorocyclopropyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-(7-pyridazin-4-ylimidazo[1,2-a]pyridin-3-yl)benzamide,

4-[7-(6-cyano-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-2-(difluoromethoxy)-N-ethyl-6-methoxy-benzamide,

tert-butyl 4-[4-[3-[3-(difluoromethoxy)-4-(ethylcarbamoyl)-5-methoxy-phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]piperidine-1-carboxylate,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[7-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[7-[1-(4-piperidyl)pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[5-(5-methyl-4H-1,2,4-triazol-3-yl)benzimidazol-1-yl]benzamide,

2-(difluoromethoxy)-4-[7-[1-(difluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-N-ethyl-6-methoxy-benzamide,

2,6-dimethoxy-4-[5-(2-methyl-1H-imidazol-5-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-(1H-imidazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(3-methylpyrazol-1-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(4-methylimidazol-1-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-[(1R,2R)-2-(hydroxymethyl)cyclopropyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-[(1R,2R)-2-(difluoromethyl)cyclopropyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-[(1R,2 S)-2-(difluoromethyl)cyclopropyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-[(1R,2R)-2-hydroxycyclobutyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[5-(1-methyltriazol-4-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-N-(2-methoxycyclohexyl)-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

azetidin-1-yl-[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]m ethanone,

N-(2-aminoethyl)-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

N-[(1S,2S)-2-hydroxycyclohexyl]-2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

4-[5-(3,5-dimethylpyrazol-1-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(3-methyl-1,2,4-triazol-1-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(5-methyl-1,3,4-oxadiazol-2-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[5-(4,5-dimethyl-1,2,4-triazol-3-yl)benzimidazol-1-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[5-(3-methyl-1,2,4-oxadiazol-5-yl)benzimidazol-1-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-[(1S,2S)-2-hydroxycyclobutyl]-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-isopropyl-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-[(1S,2S)-2-(difluoromethyl)cyclopropyl]-2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

(3,3-difluoroazetidin-1-yl)-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]methanone,

2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-[(1R)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

2-ethyl-7-fluoro-5-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]isoindolin-1-one,

2-ethyl-7-methoxy-5-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]isoindolin-1-one,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-3-yl]benzamide,

2-(difluoromethoxy)-N-ethyl-6-methoxy-4-[7-(1-methylimidazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3,3-dimethylazetidin-1-yl)methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-phenylazetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(2,4-dimethylazetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(2-methylazetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-[3-(hydroxymethyl)azetidin-1-yl]methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-hydroxyazetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-[3-(dimethylamino)azetidin-1-yl]methanone,

(3-benzyloxyazetidin-1-yl)-[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(2-phenylazetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-morpholinoazetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(2,2,4-trimethylazetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-methoxyazetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-tetrahydropyran-4-ylazetidin-1-yl)methanone,

1-[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzoyl]azetidine-3-carbonitrile,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-[2-(hydroxymethyl)azetidin-1-yl]methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(2-oxa-6-azaspiro[3.3]heptan-6-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(2,2-dioxo-2λ 6 -thia-6-azaspiro[3.3]heptan-6-yl)methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-phenylpyrrolidin-1-yl)methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(4-fluoro-1-piperidyl)methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-[4-(trifluoromethoxy)-1-piperidyl]methanone,

N-tert-butyl-2-(difluoromethoxy)-6-methoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]benzamide,

2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-[2-methyl-1-(trifluoromethyl)propyl]benzamide,

2-ethyl-7-(2-hydroxyethylamino)-5-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]isoindolin-1-one,

2-ethyl-7-(2-hydroxyethylamino)-5-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]isoindolin-1-one,

2-fluoro-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2-methoxy-6-(methylamino)-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2-(2-hydroxyethylamino)-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2-methoxy-6-methyl-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2-chloro-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-(3,3-dimethylazetidin-1-yl)methanone,

1-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzoyl]azetidine-3-carbonitrile,

1-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzoyl]pyrrolidine-3-carbonitrile,

(3,3-difluoropyrrolidin-1-yl)-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]methanone,

(4,4-difluoro-1-piperidyl)-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]methanone,

[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]phenyl]-[3-(trifluoromethyl)azetidin-1-yl]methanone,

8-methoxy-6-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-3,4-dihydro-2H-isoquinolin-1-one,

2,6-dimethoxy-4-[7-(1-methylimidazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-[(1R)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

2,6-dimethoxy-4-[7-(1-methylimidazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-[(1S)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-hydroxy-3-methyl-azetidin-1-yl)methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-ethyl-3-hydroxy-azetidin-1-yl) methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]methanone,

(3-cyclopropyl-3-hydroxy-azetidin-1-yl)-[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]methanone,

[2,6-dimethoxy-4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-(3-ethynyl-3-hydroxy-azetidin-1-yl)methanone,

2,6-dimethoxy-4-[7-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-[(1R)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

2,6-dimethoxy-4-[7-(3-methylisoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl]-N-[(1R)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

2,6-dimethoxy-4-[7-(3-methylisoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl]-N-[(1S)-2,2,2-trifluoro-1-methyl-ethyl]benzamide,

8-methoxy-6-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one,

methyl 1-[2,6-dimethoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridine-3-yl]benzoyl]azetidine-3-carboxylate,

2,6-dimethoxy-4-[7-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetic acid,

tert-butyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

ethyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

isopropyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

2,6-dimethoxy-4-[7-(3-methylisoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2-hydroxy-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

cyclopropyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

2-fluoroethyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

methyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

tetrahydrofuran-3-yl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

cyclobutylmethyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

2,6-dimethoxy-4-[7-(6-methoxy-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[7-(6-cyano-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[7-(2-methoxypyrimidin-5-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-(7-pyrimidin-5-ylimidazo[1,2-a]pyridin-3-yl)-N-(2,2,2-trifluoroethyl)benzamide,

tert-butyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]propanoate,

methyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]propanoate,

2,6-dimethoxy-4-[7-(5-methoxy-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[7-(2-aminopyrimidin-5-yl)imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-(7-pyridazin-4-ylimidazo[1,2-a]pyridin-3-yl)-N-(2,2,2-trifluoroethyl)benzamide,

4-[7-(5-ethoxy-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[7-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[7-(2-methoxy-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[7-(6-morpholino-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[7-(6-methylpyridazin-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

4-[7-(4-isopropylpyrimidin-5-yl)imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]propanoic acid,

4-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]butanoic acid,

methyl 4-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]butanoate,

ethyl 4-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]butanoate,

4-[7-(4-cyano-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

3-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyridine-4-carboxamide,

tert-butyl 3-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]azetidine-1-carboxylate,

7-methoxy-5-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)isoindolin-1-one,

2-cyclopropyl-8-methoxy-6-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-3,4-dihydroisoquinolin-1-one,

ethyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]propanoate,

4-[7-[1-[1-(2-cyanoethyl)azetidin-3-yl]pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

4-[7-[14-[1-(cyanomethyl)azetidin-3-yl]pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-2,6-bis(trideuteriomethoxy)-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(6-methoxy-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]benzamide,

4-[7-(2-cyano-3-pyridyl)imidazo[1,2-a]pyridin-3-yl]-2,6-dimethoxy-N-(2,2,2-trifluoroethyl)benzamide,

2,6-dimethoxy-4-[7-(6-methylpyridazin-3-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(3-methylisoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

2,6-difluoro-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-(2,2,2-trifluoroethyl)benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(6-methylpyridazin-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(6-methylpyridazin-3-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(3-methylimidazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

8-methoxy-6-[7-(6-methylpyridazin-3-yl)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one,

N-cyclopropyl-2-fluoro-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-cyclopropyl-2-(isopropylamino)-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-cyclopropyl-2-methoxy-6-(2-methoxyethoxy)-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-cyclopropyl-2-(2-hydroxyethoxy)-6-methoxy-4-[7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(6-methoxypyridazin-3-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-[6-(trifluoromethyl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]benzamide,

4-[7-(6-cyanopyridazin-3-yl)imidazo[1,2-a]pyridin-3-yl]-N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-benzamide,

N-cyclopropyl-2-(difluoromethoxy)-4-[7-[6-(dimethylamino)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-6-methoxy-benzamide,

ethyl 2-[4-[3-[4-(cyclopropylcarbamoyl)-3-(difluoromethoxy)-5-methoxy-phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

N-cyclopropyl-4-[7-(6-cyclopropylpyridazin-3-yl)imidazo[1,2-a]pyridin-3-yl]-2-(difluoromethoxy)-6-methoxy-benzamide,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(6-morpholinopyridazin-3-yl)imidazo[1,2-a]pyridin-3-yl]benzamide,

7-[5-(5-fluoro-3-pyridyl)benzimidazol-1-yl]-5-methoxy-2,3-dihydro-1,3-benzoxazin-4-one,

5-methoxy-7-[5-(5-methoxy-3-pyridyl)benzimidazol-1-yl]-2,3-dihydro-1,3-benzoxazin-4-one,

7-[5-(3-fluoro-2-pyridyl)benzimidazol-1-yl]-5-methoxy-2,3-dihydro-1,3-benzoxazin-4-one,

7-[5-(2-isopropylthiazol-4-yl)benzimidazol-1-yl]-5-methoxy-2,3-dihydro-1,3-benzoxazin-4-one,

ethyl 3-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]-2-methyl-propanoate,

ethyl 2-[[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]methyl]-3-methyl-butanoate,

ethyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]-2-methyl-propanoate,

ethyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]-3-methyl-butanoate,

tetrahydrofuran-2-ylmethyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]acetate,

ethyl 2-[3-[4-(cyclopropylcarbamoyl)-3-(difluoromethoxy)-5-methoxy-phenyl]-7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-6-yl]oxyacetate,

2-[3-[4-(cyclopropylcarbamoyl)-3-(difluoromethoxy)-5-methoxy-phenyl]-7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-6-yl]oxyacetic acid,

4-[6-benzyloxy-7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-benzamide,

4-[6-(1-cyanoethoxy)-7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-benzamide,

ethyl 2-[3-[4-(cyclopropylcarbamoyl)-3-(difluoromethoxy)-5-methoxy-phenyl]-7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-6-yl]oxypropanoate,

2-[3-[4-(cyclopropylcarbamoyl)-3-(difluoromethoxy)-5-methoxy-phenyl]-7-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-6-yl]oxypropanoic acid,

2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]-2-methyl-propanoic acid,

2-(diethylamino)ethyl 2-[4-[3-[3,5-dimethoxy-4-(2,2,2-trifluoroethylcarbamoyl)phenyl]imidazo[1,2-a]pyridin-7-yl]pyrazol-1-yl]-2-methyl-propanoate,

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[5-(1H-pyrazol-4-yl)benzimidazol-1-yl]benzamide, or

N-cyclopropyl-2-(difluoromethoxy)-6-methoxy-4-[7-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]benzamide.

18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 17 or pharmaceutically acceptable salt thereof.

19. A method of treating inflammatory bowel disease, collagen-induced arthritis, psoriatic-like epidermal hyperplasia, systemic lupus erythematosus, and psoriatic arthritis, comprising administering an effective amount of the compound or pharmaceutically acceptable salt thereof, according to claim 1 , to a subject in need thereof.

20. A method of treating inflammatory bowel disease, collagen-induced arthritis, psoriatic-like epidermal hyperplasia, systemic lupus erythematosus, and psoriatic arthritis, comprising administering the pharmaceutical composition according to claim 14 , to a subject in need thereof.

Assignments (9)
RELEASE OF PLEDGE Recorded Jun 24, 2026
From: COULTREON BIOPHARMA BV
To: LAKEFRONT BIOTHERAPEUTICS NV
Reel/Frame 075984/0816 →
RELEASE OF SECURITY INTEREST Recorded May 8, 2026
From: GILEAD SCIENCES, INC.
To: GALAPAGOS NV
Reel/Frame 074602/0603 →
CERTIFICATE OF PLEDGE Recorded May 27, 2025
From: GALAPAGOS NV
To: ONCO3R THERAPEUTICS BV
Reel/Frame 071406/0864 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 27, 2025
From: GALAPAGOS NV
To: ONCO3R THERAPEUTICS BV
Reel/Frame 071222/0843 →
SECURITY INTEREST Recorded Nov 23, 2020
From: GALAPAGOS NV
To: GILEAD SCIENCES, INC.
Reel/Frame 054503/0967 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 1, 2020
From: ALVEY, LUKE JONATHAN; ANNOOT, DENIS MAURICE; BONNATERRE, FLORENCE MARIE-EMILIE; BUCHER, DENIS; DUTHION, BÉRANGER; JARY, HÉLÈNE MARIE; PEIXOTO, CHRISTOPHE; TEMAL-LAIB, TAOUES; TIRERA, AMYNATA
To: GALAPAGOS SASU
Reel/Frame 052803/0784 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 1, 2020
From: GALAPAGOS SASU
To: GALAPAGOS NV
Reel/Frame 052803/0877 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 1, 2020
From: DESROY, NICOLAS
To: GALAPAGOS SASU
Reel/Frame 052803/0852 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 1, 2020
From: GALAPAGOS SASU
To: GALAPAGOS NV
Reel/Frame 052803/0843 →
Priority Claims (2)
GB 1720101 · Dec 2, 2017 · national
GB 1817343 · Oct 25, 2018 · national
Continuity (1)
Related Publication 20210101903A1 · Apr 8, 2021