Compounds and pharmaceutical compositions thereof for the treatment of inflammatory disorders

1. A compound according to Formula I:

wherein

R 1 is H, or Me;

L 1 is —NR 2 —; —O—, or —CH 2 —;

Cy is pyridinyl;

R 2 is H, or C 1-4 alkyl;

R 3 is H, halo, C 1-4 alkyl optionally substituted with one or more halo, or C 1-4 alkoxy optionally substituted with one or more halo;

R 4 is H, or halo;

R 5 is —CN, halo, or is -L 2 -R 6 ;

-L 2 is absent, or is —C(═O)—, —C(═O)NR 7 —, —NR 7 C(═O)—, —SO 2 —, —SO 2 NR 7 —, or —NR 7 SO 2 —;

R 6 is H, or C 1-6 alkyl optionally substituted with one or more independently selected R 8 groups;

R 7 is H, or C 1-4 alkyl;

R 8 is OH, CN, halo, or C 1-4 alkoxy,

L a is absent, or is —C(═O)—, —C(═O)O—, or —C(═O)NH—;

R a is:

H,

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

C 3-7 monocyclic cycloalkyl optionally substituted with one or more independently selected R c ;

R b is

halo,

CN,

OH,

C 1-4 alkoxy,

C 3-7 cycloalkyl,

—SO 2 —C 1-4 alkyl, or

—C(═O)NR b1 R b2

R c is

halo,

CN,

OH,

C 1-4 alkyl,

—C(═O)OH, or

—C(═O)NR c1 R c2 ; and

each R b1 , R b2 , R c1 and R c2 is independently selected from H, and C 1-4 alkyl, or a pharmaceutically acceptable salt thereof.

2. A compound or pharmaceutically acceptable salt according to claim 1 , wherein R 1 is Me.

3. A compound or pharmaceutically acceptable salt according to claim 1 , wherein the compound is according to Formula IIb, or IIc:

wherein L 1 , R 3 , R 4 , L a , R a and R 5 are as described in claim 1 .

4. A compound or pharmaceutically acceptable salt according to claim 1 , wherein the compound is according to Formula IVb, IVc, IVe or IVf:

wherein R 3 , R 4 , R 5 , L a , and R a are as described in claim 1 .

5. A compound or pharmaceutically acceptable salt according to claim 1 , wherein the compound is according to Formula Vb, Vc, Ve or Vf:

wherein R 3 , R 4 , R 5 , L a , and R a are as described in claim 1 .

6. A compound or pharmaceutically acceptable salt according to claim 1 , wherein R 4 is H, F, or Cl.

7. A compound or pharmaceutically acceptable salt according to claim 1 , wherein R 3 is H, Me, or Et.

8. A compound or pharmaceutically acceptable salt according to claim 1 , wherein R 5 is CN, F, Cl, —SO 2 Me or —SO 2 Et.

9. A compound or pharmaceutically acceptable salt according to claim 1 , wherein R a is:

10. A compound, or pharmaceutically acceptable salt thereof, according to claim 1 wherein the compound is (1R,2R)—N-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide.

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

12. A compound or pharmaceutically acceptable salt according to claim 1 , wherein La is —C(═O)—, —C(═O)O—, or —C(═O)NH—.

13. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ra is Me, or Et.

14. A compound or pharmaceutically acceptable salt according to claim 1 , wherein the compound is selected from

N-(6-((6-cyano-4-ethylpyridin-3-yl)(methyl)amino)-1-methyl-1H-benzo[d]imidazol-4-yl)cyclopropanecarboxamide;

Methyl 6-((6-cyano-4-ethylpyridin-3-yl)(methyl)amino)-1-methyl-1H-benzo[d]imidazol-4-ylcarbamate;

(1R,2R)—N-[6-[(6-cyano-4-ethyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide;

(1R,2R)—N-(6-((6-cyano-4-ethylpyridin-3-yl)(methyl)amino)-1-methyl-1H-benzo[d]imidazol-4-yl)-2-fluorocyclopropanecarboxamide;

(1R,2R)—N-(6-((6-cyano-4-methylpyridin-3-yl)(methyl)amino)-1-methyl-1H-benzo[d]imidazol-4-yl)-2-fluorocyclopropanecarboxamide;

(1R,2R)-2-fluoro-N-[6-[(6-fluoro-4-methyl-3-pyridyl)-methyl-amino]-1-methyl-benzimidazol-4-yl]cyclopropanecarboxamide;

(1R,2R)—N-[6-[(2,6-difluoro-3-pyridyl)-methyl-amino]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide;

(1R,2R)—N-[6-[(6-cyano-2-fluoro-3-pyridyl)-methyl-amino]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide;

N-[6-[(4-ethyl-6-methyl sulfonyl-3-pyridyl)-methyl-amino]-1-methyl-benzimidazol-4-yl]cyclopropanecarboxamide;

(1R,2R)—N-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide;

(1R,2R)—N-[6-[(6-cyano-2-fluoro-4-methyl-3-pyridyl)-methyl-amino]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide;

(1R,2R)—N-[6-[(2-cyano-3-fluoro-5-methyl-4-pyridyl)-methyl-amino]-1-methyl-benzimidazol-4-yl]-2-fluoro-cyclopropanecarboxamide;

N-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]cyclopropanecarboxamide;

5-((4-(cyclopropanecarboxamido)-1-methyl-1H-benzo[d]imidazol-6-yl)(methyl)amino)-4-ethylpicolinamide;

4-ethyl-5-((4-((1R,2R)-2-fluorocyclopropanecarboxamido)-1-methyl-1H-benzo[d]imidazol-6-yl)(methyl)amino)picolinamide;

5-(7-amino-3-methyl-benzimidazol-5-yl)oxy-4-methyl-pyridine-2-carbonitrile;

N-[6-[(4-ethyl-6-methyl sulfonyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]cyclopropanecarboxamide;

5-[7-[[(1R,2R)-2-fluorocyclopropanecarbonyl]amino]-3-methyl-benzimidazol-5-yl]oxy-4-methyl-pyridine-2-carboxamide;

1-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]-3-isopropyl-urea;

4-methyl-5-[3-methyl-7-(methylamino)benzimidazol-5-yl]oxy-pyridine-2-carbonitrile;

5-[7-(dimethylamino)-3-methyl-benzimidazol-5-yl]oxy-4-methyl-pyridine-2-carbonitrile; and

1-[6-[(6-cyano-4-methyl-3-pyridyl)oxy]-1-methyl-benzimidazol-4-yl]-3-isopropyl-urea.