Compounds and pharmaceutical compositions thereof for the treatment of inflammatory disorders

1. A compound according to Formula I:

wherein

R 1a is H, halo or C 1-4 alkyl;

R 1b is:

halo,

C 1-4 alkyl (which alkyl is optionally substituted with one or more independently selected halo), or

C 1-4 alkoxy (which alkoxy is optionally substituted with one or more independently selected halo);

X is —S—, —O—, —N═CH—, —CH═N— or —CH═CH—;

W is N, or CR 3

when W is N, R 2 is:

H,

—CN,

halo,

C 1-4 alkyl (which alkyl is optionally substituted with one or more independently selected OH, or CN),

—C(═O)CH 3 ,

—C(═O)CF 3 ,

—C(═O)OCH 3 ,

—C(═O)NH 2 ,

—NHC(═O)CH 3 , or

when W is CR 3 , one of R 2 or R 3 is:

H,

—CN,

halo,

C 1-4 alkyl (which alkyl is optionally substituted with one or more independently selected OH, or CN),

—C(═O)CH 3 ,

—C(═O)CF 3 ,

—C(═O)OCH 3 ,

—C(═O)NH 2 ,

—NHC(═O)CH 3 ,

and the other is H, or C 1-4 alkyl;

R 4 is C 1-4 alkyl;

R 5 is C 1-4 alkyl optionally substituted with one or more independently selected CN, OH, halo, or —C(═O)NH 2 ;

one of Y and Z is CH and the other is N;

R 6 is selected from H, —CH 3 and halo;

Cy is:

C 4-10 cycloalkyl,

4-10 membered mono or bicyclic heterocycloalkyl containing one or more heteratoms independently selected from O, N, and S, or

4-7 membered heterocycloalkenyl containing 1 double bond, containing one or more heteroatoms independently selected from O, N, and S;

each R 7 is independently selected from:

OH,

oxo,

halo, and

C 1-4 alkyl (which alkyl is optionally substituted with one or more independently selected OH, or C 1-4 alkoxy);

the subscript a is 0, 1 or 2;

R 8 is -(L 1 -W 1 ) m -L 2 -G 1 ,

wherein

L I is absent, or is —O—, —C(═O)—, —NR i , —NR h C(═O)—, or —SO 2 ;

W 1 is C 1-4 alkylene;

the subscript m is 0, or 1;

L 2 is absent, or is —O—, —C(═O)—, —C(═O)O—, —OC(═O)—, —C(═O)—C(═O)—, —C(═O)—C(═O)NR a —, —NR b —, —C(═O)NR c —, —NR d C(═O)—, —NR d C(═O)O—, —SO 2 —, —SO 2 NR e — or —NR f SO 2 —;

G 1 is

H,

—CN,

C 1-4 alkyl (which alkyl is optionally substituted with one or more independently selected —CN, OH, halo or phenyl),

C 3-7 cycloalkyl (which cycloalkyl is optionally substituted with —NH 2 ),

5-6 membered heterocycloalkenyl containing 1 double bond containing one or more heteroatoms independently selected from O, N, and S, (which heterocycloalkenyl is optionally substituted with one or more independently selected R 9 groups),

4-10 membered mono, bi or spirocyclic heterocycloalkyl containing one or more heteroatoms independently selected from O, N, and S, (which heterocycloalkyl is optionally substituted with one or more independently selected R 9 groups), or

5-6 membered heteroaryl containing one or more heteroatoms independently selected from O, N, and S, (which heteroaryl is optionally substituted with one or more independently selected R 10 groups), or

each R 9 is oxo, or R 10 ;

each R 10 is:

—OH,

halo,

—CN,

C 1-4 alkyl (which alkyl is optionally substituted with one or more independently selected OH, halo, or phenyl),

C 1-4 alkoxy,

C 3-7 cycloalkyl,

phenyl,

—SO 2 CH 3 ,

—C(═O)C 1-4 alkoxy,

—C(═O)C 1-4 alkyl, or

—NR g C(═O)C 1-4 alkyl; and

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

or a pharmaceutically acceptable salt, or a solvate, or a pharmaceutically acceptable salt of a solvate thereof, or a biologically active metabolite thereof.

2. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 1a is F, Cl, —CH 3 or —C 2 H 5 .

3. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 1b is F, Cl, —CH 3 , —C 2 H 5 , —CF 3 , —OCH 3 , or —OCF 3 .

4. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein Cy is oxetanyl, azetidinyl, tetrahydrofuranyl, pyrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, or thiomorpholinyl.

5. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the subscript a is 1 or 2, and R 7 is OH, oxo, F, Cl, or —CH 3 .

6. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is according to Formula IVa, IVb, IVc or IVd:

wherein Y, Z, R 6 , L 1 , W 1 , L 2 , G 1 and the subscript m are according to claim 1 .

7. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is according to Formula Va, Vb, Vc, or Vd:

wherein Y, Z, R 6 , W 1 , and G 1 are according to claim 1 .

8. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein W I is —CH 2 —, —CH 2 —CH 2 —, —C(CH 3 )H—, —CH 2 —CH 2 —CH 2 — or —CH 2 —C(CH 3 )H—.

9. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein G 1 is oxetanyl, azetidinyl, tetrahydrofuranyl, pyrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, or thiomorpholinyl, each of which is substituted with one or two independently selected R 9 groups.

10. A compound or pharmaceutically acceptable salt thereof, according to claim 9 , wherein R 9 is R 10 and R 10 is selected from OH, F, Cl, and —CN.

11. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 6 is H, —CH 3 or F.

12. A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein Y is N and Z is CH.

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

2-((2-ethyl-6-(piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((6-(4-(2-(3,3-difluoroazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)-2-ethylimidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((6-(4-(2-(azetidin-1-yl)-2-oxoethyl)piperazin-1-yl)-2-ethylimidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-(4-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-a]pyrazin-6-yl)piperazin-1-yl)-N,N-dimethylacetamide,

(R)-2-((2-ethyl-6-(4-(2-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

(S)-2-((2-ethyl-6-(4-(2-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(4-(2-oxo-2-(pyrrolidin-1-yl)ethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-(4-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-a]pyrazin-6-yl)piperazin-1-yl)-N-methylacetamide,

2-((2-ethyl-6-(4-(2-morpholino-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(4-(2-(3-fluoroazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)acetoyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

1-(azetidin-1-yl)-2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-a]pyrazin-6-yl)piperazin-1-yl)ethanone,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-a]pyrazin-6-yl)piperazin-1-yl)-1-(3-hydroxyazetidin-1-yl)ethanone,

2-(2-((2-ethyl-6-(piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)thiazol-4-yl)-5-fluorobenzonitrile,

2-(2-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)thiazol-4-yl)-5-fluorobenzonitrile,

2-(6-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)pyridin-2-yl)-5-fluorobenzonitrile,

2-(2-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)pyrimidin-4-yl)-5-fluorobenzonitrile,

2-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)pyrimidine-5-carbonitrile,

2-((2-ethyl-6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)-1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(piperidin-4-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

(R)-2-((2-ethyl-6-(1-(2-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

(S)-2-((2-ethyl-6-(1-(2-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-a]pyrazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-1-(3-hydroxyazetidin-1-yl)ethanone,

2-((2-ethyl-6-(4-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-1-(2-methylpyrrolidin-1-yl)ethanone,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-1-(2-(hydroxymethyl)pyrrolidin-1-yl)ethanone,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N-methylacetamide,

1-(3,3-difluoropyrrolidin-1-yl)-2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)ethanone,

1-(2,5-dimethylpyrrolidin-1-yl)-2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)ethanone,

(R)-2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-1-(3-hydroxypyrrolidin-1-yl)ethanone,

(S)-2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-1-(3-hydroxypyrrolidin-1-yl)ethanone,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N-(2-hydroxyethyl)acetamide,

1-(azetidin-1-yl)-2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)ethanone,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N-isopropyl-N-methylacetamide,

N-(2-ethyl-6-(4-(oxetan-3-yl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(2-ethyl-6-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

5-((4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)methyl)oxazolidin-2-one,

5-((4-(2-ethyl-3-((4-(4-fluorophenyl)-5-(hydroxymethyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)methyl)oxazolidin-2-one,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N,N-dimethylacetamide,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)-5-(hydroxymethyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N,N-dimethylacetamide,

2-(4-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N,N-dimethylacetamide,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)-5-(2,2,2-trifluoroacetoyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N,N-dimethylacetamide,

1-(2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)ethyl)pyrrolidin-2-one,

(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)(tetrahydrofuran-2-yl)methanone,

N-(2-ethyl-6-(4-((tetrahydrofuran-2-yl)methyl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

3-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)propan-1-ol,

3-(4-(2-ethyl-3-((4-(4-fluorophenyl)-5-(hydroxymethyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)propan-1-ol,

3-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)propanenitrile,

3-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)propanamide,

N-(2-ethyl-6-(4-(2-methoxyethyl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N-isopropylacetamide,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-1-(pyrrolidin-1-yl)ethanone,

tert-butyl 2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)ethylcarbamate,

N-(2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)ethyl)acetamide,

ethyl 2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)ethylcarbamate,

(S)-tert-butyl 4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-2-(hydroxymethyl)piperazine-1-carboxylate,

(S)-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-2-yl)methanol,

(S)-7-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)tetrahydro-1H-oxazolo[3,4-a]pyrazin-3 (5H)-one,

(S)—N-(2-ethyl-6-(3-(methoxymethyl)-4-(methylsulfonyl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

(S)-(1-(3-(dimethylamino)propylsulfonyl)-4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-2-yl)methanol,

(S)-2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-2-(hydroxymethyl)piperazin-1-yl)-1-(pyrrolidin-1-yl)ethanone,

(S)-2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-2-(hydroxymethyl)piperazin-1-yl)-1-morpholinoethanone,

(S)-8-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)hexahydropyrazino[2,1-c][1,4]oxazin-4(1H)-one,

(S)-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-1-(methylsulfonyl)piperazin-2-yl)methanol,

(S)-(4-(2-ethyl-3-((4-(4-fluorophenyl)-5-(hydroxymethyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-1-(methylsulfonyl)piperazin-2-yl)methanol,

(R)-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-1-(methylsulfonyl)piperazin-2-yl)methanol,

3-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-1-(4-methoxybenzyl)pyrrolidin-2-one,

N-(2-ethyl-6-(4-(ethylsulfonyl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-1-(methylsulfonyl)piperazin-2-yl)ethanol,

2-(4-(2-ethyl-3-((4-(4-fluoro-2-methylphenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperazin-1-yl)-N,N-dimethylacetamide,

tert-butyl-(1R,4S)-5-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate,

1-((1R,4S)-5-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethanone,

N-(2-ethyl-6-((1 S,4R)-5-(methylsulfonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(2-ethyl-6-(3-azaspiro[5.5]undecan-3-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(2-ethyl-6-morpholinoimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

6-(1,1-Dioxo-thiomorpholin-4-yl)-2-ethyl-imidazo[1,2-b]pyridazin-3-yl]-[4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amine,

N-(6-(4-(dimethylamino)piperidin-1-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

tert-butyl 1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-ylcarbamate,

N-(6-(4-aminopiperidin-1-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)methane sulfonamide,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)tetrahydro-2H-pyran-4-carboxamide,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)-2-hydroxyacetamide,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)-3-methyloxetane-3-carboxamide,

tert-butyl 4-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-ylcarbamoyl)piperidine-1-carboxylate,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)piperidine-4-carboxamide,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)pyrrolidine-1-carboxamide,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-ol,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-ol,

N-ethyl-2-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-yloxy)acetamide,

(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)methanol,

(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-yl)methanol,

1-(2-Ethyl-3-{[4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amino}-imidazo[1,2-b]pyridazin-6-yl)-piperidine-4-carboxylic acid ethyl ester,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidine-4-carboxylic acid,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-hydroxyethyl)piperidine-4-carboxamide,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidine-4-carboxamide,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidine-3-carboxamide,

[1-(2-Ethyl-3-{[4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amino}-imidazo[1,2-b]pyridazin-6-yl)-piperidin-3-ylmethyl]-carbamic acid tert-butyl ester,

N-(6-(3-(aminomethyl)piperidin-1-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-((1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-yl)methyl)methanesulfonamide,

[1-(2-Ethyl-3-{[4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amino}-imidazo[1,2-b]pyridazin-6-yl)-piperidin-4-ylmethyl]-carbamic acid tert-butyl ester,

N-(6-(4-(aminomethyl)piperidin-1-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-((1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)methyl)methanesulfonamide,

3-((1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)methyl)-1,1-dimethylurea,

N-((1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)methyl)tetrahydro-2H-pyran-4-carboxamide,

2-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-4-yl)-N,N-dimethylacetamide,

N-(2-ethyl-6-(4-morpholinopiperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(2-ethyl-6-(3-morpholinopiperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(6-(1,4′-bipiperidin-1′-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

1′-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-1,3′-bipiperidin-4-ol,

N-(2-ethyl-6-(4-phenylpiperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-cyclopropyl-1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidine-4-sulfonamide,

1-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-1,4-diazepan-1-yl)ethanone,

N-(2-ethyl-6-(4-(methylsulfonyl)-1,4-diazepan-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(2-ethyl-6-(8-oxa-2-azaspiro[4.5]decan-2-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

7-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-1-oxa-3,7-diazaspiro[4.4]nonan-2-one,

7-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-3-methyl-1-oxa-3,7-diazaspiro[4.4]nonan-2-one,

7-(2-ethyl-3-((4-(4-fluorophenyl)-5-(hydroxymethyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-3-methyl-1-oxa-3, 7-diazaspiro[4.4]nonan-2-one,

7-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-2,7-diazaspiro[4.4]nonane-1,3-dione,

tert-butyl 5-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate,

N-(2-ethyl-6-(5-(methylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

1-(5-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)ethanone,

N-(6-(5-(3-chloropropylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(6-(5-(3-(dimethylamino)propylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

N-(2-ethyl-6-(5-(3-morpholinopropylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

(S)-1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidine-3-carbonitrile,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ol,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl formate,

N-(2-ethyl-6-(3-thiomorpholinopyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

1-(3-((5-chloro-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-one,

tert-butyl 1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylcarbamate,

N-(6-(3-aminopyrrolidin-1-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

methyl 2-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylamino)acetate,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)-2-hydroxyacetamide,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)methane sulfonamide,

(S)-1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidine-2-carboxylic acid,

1-(2-Ethyl-3-{[4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amino}-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidine-3-carboxylic acid methyl ester,

1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-hydroxyethyl)pyrrolidine-3-carboxamide,

(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)(morpholino)methanone,

(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-2-yl)methanol,

(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)methanol,

(1-(2-ethyl-3-((4-(4-fluorophenyl)-5-(hydroxymethyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)methanol,

3-(4-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)piperazin-1-yl)propan-1-ol,

4-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)piperazin-2-one,

N-(2-ethyl-6-(3-morpholinopyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

(2-((2-ethyl-6-(3-morpholinopyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazol-5-yl)methanol,

2-((2-ethyl-6-(3-morpholinopyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

{6-[3-(1,1-Dioxo-thiomorpholin-4-yl)-pyrrolidin-1-yl]-2-ethyl-imidazo[1,2-b]pyridazin-3-yl}-[4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amine,

N-(2-ethyl-6-(3-(piperidin-1-yl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

1-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)piperidin-4-ol,

(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)azetidin-3-yl)methanol,

[1-(2-Ethyl-3-{[4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amino}-imidazo[1,2-b]pyridazin-6-yl)-azetidin-3-yl]-carbamic acid tert-butyl ester,

2-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)azetidin-3-ylamino)-1-(3-hydroxyazetidin-1-yl)ethanone,

2-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)azetidin-3-ylamino)-N,N-dimethylacetamide,

2-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)azetidin-3-ylamino)-N-methylacetamide,

N-(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)azetidin-3-yl)methane sulfonamide,

(1-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)azetidin-3-yl)(3-hydroxypyrrolidin-1-yl)methanone,

2-((2-ethyl-6-(4-((2-oxooxazolidin-5-yl)methyl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

(S)-2-((2-ethyl-6-(3-(hydroxymethyl)-4-(methylsulfonyl)piperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(2-oxo-1-oxa-3,7-diazaspiro[4.5]decan-7-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(3-methyl-2-oxo-1-oxa-3,7-diazaspiro[4.5]decan-7-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(3-methyl-2-oxo-1-oxa-3,7-diazaspiro[4.4]nonan-7-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

tert-butyl 7-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)-2,7-diazaspiro[4.4]nonane-2-carboxylate,

2-((2-ethyl-6-(2,7-diazaspiro[4.4]nonan-2-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((6-(7-acetoyl-2,7-diazaspiro[4.4]nonan-2-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

methyl (1-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)-3-hydroxypyrrolidin-3-yl),

N-((1-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)-3-hydroxypyrrolidin-3-yl)methyl)acetamide,

N-((1-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)-3-hydroxypyrrolidin-3-yl)methyl)isobutyramide,

2-((2-ethyl-6-(3-hydroxypyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(3-oxopyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(3-(hydroxymethyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

(S)-2-((2-ethyl-6-(3-(2-(3-hydroxyazetidin-1-yl)-2-oxoethylamino)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

(S)-2-(1-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylamino)-N,N-dimethylacetamide,

(R)-2-((2-ethyl-6-(3-(2-(3-hydroxyazetidin-1-yl)-2-oxoethylamino)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

(R)-2-(1-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylamino)-N,N-dimethylacetamide,

2-((6-(3-((2S,6R)-2,6-dimethylmorpholino)pyrrolidin-1-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(3-(4-(hydroxymethyl)piperidin-1-yl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((6-(3-(4-acetoylpiperazin-1-yl)pyrrolidin-1-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

N-(1-(1-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)piperidin-4-yl)-N-methylacetamide,

2-((2-ethyl-6-(3-(4-hydroxypiperidin-1-yl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(3-(4-methoxypiperidin-1-yl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-((3S,4S)-3-hydroxy-4-morpholinopyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

1-(2-ethyl-3-((4-(4-fluorophenyl)-5-(hydroxymethyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ol,

(2-((2-ethyl-6-(8-oxa-2-azaspiro[4.5]decan-2-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazol-5-yl)methanol,

[1-(3-{[5-Cyano-4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amino}-2-ethyl-imidazo[1,2-b]pyridazin-6-yl)-azetidin-3-yl]-carbamic acid tert-butyl ester,

2-((6-(3-aminoazetidin-1-yl)-2-ethylimidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(3-(2-(3-hydroxyazetidin-1-yl)-2-oxoethylamino)azetidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

N-(1-(3-((5-cyano-4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)azetidin-3-yl)methanesulfonamide,

2-((2-ethyl-6-(3-(morpholine-4-carbonyl)azetidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-((2-ethyl-6-(3-(3-hydroxypyrrolidine-1-carbonyl)azetidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

4-(2-Ethyl-3-{[4-(4-fluoro-phenyl)-thiazol-2-yl]-methyl-amino}-imidazo[1,2-b]pyridazin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester,

N-(2-ethyl-6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(4-fluorophenyl)-N-methylthiazol-2-amine,

(3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)methanol,

2-(3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetonitrile,

3-(3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-6-(1-(methylsulfonyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-2-yl)propanamide,

3-(3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-6-(1-(methylsulfonyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-2-yl)propanenitrile,

3-(3-((4-(4-fluorophenyl)-5-(2,2,2-trifluoroacetoyl)thiazol-2-yl)(methyl)amino)-6-(1-(methylsulfonyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-2-yl)propanenitrile,

3-(3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)-6-(1-(methylsulfonyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-2-yl)propan-1-ol,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-1-(3-hydroxyazetidin-1-yl)ethanone,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-N,N-dimethylacetamide,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)-5-(hydroxymethyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-N,N-dimethylacetamide,

2-(2-((2-ethyl-6-(1-(methylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)thiazol-4-yl)-5-fluorobenzonitrile,

2-(2-((2-ethyl-6-(1-(methylsulfonyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)thiazol-4-yl)-5-fluorobenzonitrile,

2-(2-((2-ethyl-6-(1-(methylsulfonyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-5-(hydroxymethyl)thiazol-4-yl)-5-fluorobenzonitrile,

2-(2-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)thiazol-4-yl)-5-fluorobenzonitrile,

2-(4-(3-((4-(2-cyano-4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-N,N-dimethylacetamide,

2-(4-(3-((4-(2-cyano-4-fluorophenyl)thiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-N-methylacetamide,

2-(2-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-5-methylthiazol-4-yl)-5-fluorobenzonitrile,

2-(4-(3-((4-(2-cyano-4-fluorophenyl)-5-methylthiazol-2-yl)(methyl)amino)-2-ethylimidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-N-methylacetamide,

2-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-4-(4-fluorophenyl)thiazole-5-carbonitrile,

2-(6-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)pyridin-2-yl)-5-fluorobenzonitrile,

2-(4-(2-ethyl-3-((6-(4-fluorophenyl)pyridin-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-1-(3-hydroxyazetidin-1-yl)ethanone,

2-(4-(2-ethyl-3-((4-(4-fluorophenyl)pyrimidin-2-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-1-(3-hydroxyazetidin-1-yl)ethanone,

2-(4-(2-ethyl-3-((2-(4-fluorophenyl)pyrimidin-4-yl)(methyl)amino)imidazo[1,2-b]pyridazin-6-yl)piperidin-1-yl)-1-(3-hydroxyazetidin-1-yl)ethanone,

2-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-6-(4-fluorophenyl)nicotinonitrile,

6-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-2-(4-fluorophenyl)nicotinonitrile,

2-(5-((2-ethyl-6-(piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-1,2,4-thiadiazol-3-yl)-5-fluorobenzonitrile, and 2-(5-((2-ethyl-6-(1-(2-(3-hydroxyazetidin-1-yl)-2-oxoethyl)piperidin-4-yl)imidazo[1,2-b]pyridazin-3-yl)(methyl)amino)-1,2,4-thiadiazol-3-yl)-5-fluorobenzonitrile.

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

15. A method of inhibiting ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), which method comprises contacting the ENPP2 with a compound or pharmaceutically acceptable salt thereof according to claim 1 .