Heteroaryl compounds and their uses

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

A 1 is CR 6 ;

A 2 is CR 7 ;

A 3 is CR 8 ;

A 4 is NR 9 , or O;

L is selected from a bond, optionally substituted C 1-4 alkyl, C 3-6 cycloalkyl, C 3-6 heterocycloalkyl, or C 2-4 alkenyl;

R 1 is X—R 16 ;

X is a bond, or C 1-4 alkyl and;

R 16 is selected from the group consisting of C 1-6 alkyl, C 3-6 branched alkyl, C 3-8 cycloalkyl, heterocycloalkyl, C 3-8 -partially unsaturated cycloalkyl, aryl, and heteroaryl;

wherein R 16 is substituted with one to three groups independently selected from halogen, hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 branched alkyl, C 3-6 branched haloalkyl, OH, C 1-6 alkoxy, R 22 —OR 12 , S(O) 0-2 R 12 , R 22 —S(O) 0-2 R 12 , S(O) 2 NR 13 R 14 , R 22 —S(O) 2 NR 13 R 14 , C(O)OR 12 , R 22 —C(O)OR 12 , C(O)R 19 , R 22 —C(O)R 19 , O—C 1-3 alkyl, OC 1-3 haloalkyl, OC(O)R 19 , R 22 —OC(O)R 19 , C(O)NR 13 R 14 , R 22 —C(O)NR 13 R 14 , NR 15 S(O) 2 R 12 , R 22 —NR 15 S(O) 2 R 12 , NR 17 R 18 , R 22 —NR 17 R 18 , NR 15 C(O)R 19 , R 22 —NR 15 C(O)R 19 , NR 15 C(O)OCH 2 Ph, R 22 —NR 15 C(O)OCH 2 Ph, NR 15 C(O)OR 12 , R 22 —NR 15 C(O)OR 12 , NR 15 C(O)NR 13 R 14 , and R 22 —NR 15 C(O)NR 13 R 14 ;

R 17 and R 18 are each, independently, selected from the group consisting of hydrogen, hydroxyl, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 branched alkyl, C 3-6 cycloalkyl, R 22 —OR 12 , R 22 —S(O) 0-2 R 12 , R 22 —S(O) 2 NR 13 R 14 , R 22 —C(O)OR 12 , R 22 —C(O)R 19 , R 22 —OC(O)R 19 , R 22 —C(O)NR 13 R 14 , R 22 —NR 15 S(O) 2 R 12 , R 22 —NR 23 R 24 , R 22 —NR 15 C(O)R 19 , R 22 —NR 15 C(O)OCH 2 Ph, R 22 —NR 15 C(O)OR 12 , R 22 —NR 15 C(O)NR 13 R 14 , cycloalkyl, heterocycloalkyl and heteroaryl; alternatively, R 17 and R 18 along with the nitrogen atom to which they are attached to can be taken together to form a four to six membered heterocyclic ring wherein the carbon atoms of said ring are optionally substituted with R 20 , and the nitrogen atoms of said ring are optionally substituted with R 21 ;

R 19 is selected from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;

R 20 is selected from the group consisting of C 1-6 alkyl or C 1-6 haloalkyl;

R 21 is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C(O)R 12 , C(O)OR 12 , S(O) 2 R 12 ;

R 22 is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 branched alkyl, C 3-6 branched haloalkyl;

R 23 and R 24 are each, independently, selected from die group consisting of hydrogen, C 1-6 alkyl, C 1-6 -haloalkyl, C 3-6 branched alkyl, C 3-6 branched haloalkyl;

R 2 is selected from the group consisting of optionally substituted C 1-6 alkyl, optionally substituted, C 3-6 branched alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;

R 4 , R 5 , and R 6 are each, independently, selected from the group consisting of hydrogen, hydroxyl, cyano, halogen, C 1-4 alkyl, C 1-4 haloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, amino, NR 10 R 11 , and alkoxy;

R 3 and R 7 are each, independently, selected from the group consisting of hydrogen, hydroxyl, cyano, halogen, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, NR 10 R 11 , C(O)R 12 , C(O)OR 12 , C(O)NR 13 R 14 , S(O) 0-2 R 12 , S(O) 0-2 NR 13 R 14 , and optionally substituted C 3-4 cycloalkyl;

R 8 is selected from Cl, F, and methyl;

R 9 is selected from the group consisting of hydrogen, C 1-4 alkyl, alkoxy, C(O)R 12 , C(O)OR 15 , C(O)NR 13 R 14 , S(O) 0-2 R 12 , S(O) 0-2 NR 13 R 14 optionally substituted C 3-4 cycloalkyl, and optionally substituted heterocycloalkyl;

R 10 and R 11 are each, independently, selected from the group consisting of hydrogen, hydroxyl, alkyl, alkoxy, C(O)R 12 , C(O)OR 12 , C(O)NR 13 R 14 , S(O) 0-2 R 12 , and S(O) 0-2 NR 13 R 14 ; alternatively, R 10 and R 11 along with the nitrogen atom to which they are attached to can be taken together to form an optionally substituted four to six membered heteroaromatic, or a non-aromatic heterocyclic ring;

R 12 and R 15 are each, individually, selected from the group consisting of hydrogen, alkyl, branched alkyl, haloalkyl, branched haloalkyl, (CH 2 ) 0-3 -cycloalkyl, (CH 2 ) 0-3 -heterocycloalkyl, (CH 2 ) 0-3 -aryl, and heteroaryl;

R 13 and R 14 are each, independently, selected from the group consisting of hydrogen, hydroxyl, alkyl, branched alkyl, haloalkyl, branched haloalkyl, alkoxy, cycloalkyl or heterocycloalkyl; and alternatively, R 13 and R 14 along with the nitrogen atom to which they are attached to can be taken together to form an optionally substituted four to six membered heteroaromatic, or non-aromatic heterocyclic ring.

2. A compound of claim 1 , wherein:

R 8 is Cl.

3. A compound of claim 1 , wherein:

R 1 is X—R 16 ;

X is a bond, or C 1-2 alkyl;

R 16 is selected from the group consisting of C 1-2 -alkyl, C 4-6 cycloalkyl, heterocycloalkyl, phenyl, and heteroaryl;

wherein R 16 is substituted with one to three groups independently selected from halogen, hydrogen, C 1-3 alkyl, C 3-6 branched alkyl, OH, C 1-2 alkoxy, R 22 —OR 12 , S(O) 1-2 R 12 , C(O)OR 12 , R 22 —C(O)OR 12 , C(O)R 19 , R 22 —OC(O)R 19 , C(O)NR 13 R 14 , NR 15 S(O) 2 R 12 , NR 17 R 18 , R 22 —NR 17 R 18 , NR 15 C(O)R 19 , R 22 —NR 15 C(O)R 19 , and NR 15 C(O)OCH 2 Ph.

4. A compound of claim 1 , wherein:

R 16 selected from the group consisting of C 1-2 -alkyl, cyclopentyl, cyclohexyl, piperidine, piperazine, morpholine, pyridine pyrrolidine, cyclohexenyl, and tetrahydro-2H-pyran;

wherein R 16 is substituted with one to three groups selected from amino, hydroxyl, NHCH 2 -phenyl, CH 2 -amino, COO-t-butyl, H, methoxy, NH—SO 2 -ethyl, CH 2 —NHSO 2 -ethyl, SO 2 -ethyl, t-butyl, methyl, CH 2 —COOH, CO—NHCH 3 , CON(CH 3 ) 2 , NHC(CH 3 )—CH 2 —SO 2 —CH 3 , NH—COO—CH 2 -phenyl, hydroxy-methyl, CH 2 —NH—CH 3 , CH 2 —NH-ethyl, NH—CH 2 —CH 2 -methoxy, CH 2 —NH—CO—CH 3 , NH—CH 2 —CH 2 OH, NH—CO—CH 2 —N(CH 3 ) 2 , NH—CO-methylpyrrolidine, NH—CH 2 —C(CH 3 )-dioxolane, NH—CO-pyridyl, NH-ethyl, pyrrolidine, CH 2 —NH—CO-pyridyl, NH-tetrahydropyran, COCH 2 —N(CH 3 ) 2 , NH—CH 2 —C(CH 3 )-dimethyldioxolane, tetrahydropyran, CO-methylpyrrolidine, CH 2 -methylpiperidine, NH—CO—CH 3 , NH—SO 2 —CH 3 , NH—CH(CH 2 —OCH 3 ) 2 , NH—CH 2 -tetrahydrofuran, NH—CH 2 -oxetane, NH-tetrahydropyran, NH—CH 2 -dioxane, N(CH 3 )—CH 2 CH 2 —OCH 3 , CH(OH)—CH 2 -amino, NH—CH 2 CH 2 —OCF 3 , NHCH 2 —OCH 3 , NH—CH 2 —CH(CF 3 )—OCH 3 , NH—CH(CH 3 )—CH 2 —OH, F, NH-oxetane, CH 2 —CH 2 OCH 3 , CH 2 —OCH 3 , CH 2 -tetrahydropyran, CH 2 -methylpiperizine, NH 2 —CH 2 —CH(OH)—CF 3 , piperidine, CH 2 -pyrrolidine, NH—CH(CH 3 )CH 2 OCH 3 , NH-tetrahydrofuran, (CH 2 ) 3 —NH 2 , hydroxyethyl, propyl, CH 2 -pyridyl, CH 2 -piperidine, morpholine, NH-chloropyrimidine, NH—CH 2 CH 2 —SO 2 -methyl, (CH 3 ) 3 —N(CH 3 ) 2 , piperizine,

and CH 2 -morpholine.

5. A compound of claim 1 wherein:

R 3 is selected from H, methyl, cyano, chloro, CONH 2 , amino, cyclopropyl, ethyl, and fluoro;

R 4 is selected from halogen, methyl, hydrogen, and halo-methyl;

R 6 is H;

R 7 is selected from H, COOH, Cl, F, CONH 2 , CN, and CF 3 ;

R 8 is Cl;

R 17 and R 18 are each, independently, selected from the group consisting of hydrogen, C 1-3 alkyl, C 1-4 haloalkyl, C 3-6 branched alkyl, R 22 —OR 12 , R 22 —S(O) 2 R 12 , R 22 —NR 15 S(O) 2 R 12 , heterocycloalkyl or heteroaryl; alternatively, R 17 and R 18 along with the nitrogen atom to which they are attached to can be taken together to form a four to six membered heterocyclic ring wherein said ring carbon atoms are optionally substituted with R 20 , and the ring nitrogen atoms are optionally substituted with R 21 ;

R 19 is selected from C 1-3 -alkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl;

R 20 represents the group C 1-3 alkyl; and

R 22 is selection from the group consisting of C 1-4 alkyl, and C 3-6 branched alkyl.

6. A compound of claim 1 , wherein:

L is selected from C 1-4 -alkyl, and cyclopropyl;

R 2 is selected from the group consisting of C 3-7 cycloalkyl, a five to seven membered heterocycloalkyl, phenyl, and pyridyl, wherein each said R 2 group is substituted with one, two, or three substituents independently selected from hydrogen, cyano, CO—NH 2 , halogen, methoxy, dihalo-methoxy, trihalo-methoxy, trihalo alkyl, C 1-3 -alkyl, and hydroxy; and

R 9 represents methyl, hydrogen, or ethyl.

7. A compound of claim 1 , wherein:

L is C 1-2 alkyl, or C 3 - 4 -cycloalkyl;

R 1 is X—R 16 ;

X is a bond, or C 1-2 alkyl;

R 16 is selected from the group consisting of C 1-2 -alkyl, cyclopentyl, cyclohexyl, piperidine, piperazine, morpholine, pyridine, pyrrolidine, cyclohexenyl, and tetrahydro-2H-pyran;

wherein R 16 is substituted with one to three groups independently selected from amino, hydroxyl, NHCH 2 -phenyl, CH 2 -amino, COO-t-butyl, H, methoxy, NH—SO 2 -ethyl, CH 2 —NHSO 2 -ethyl, SO 2 -ethyl, t-butyl, methyl, CH 2 —COOH, CO—NHCH 3 , CON(CH 3 ) 2 , NHCH 2 —CH 2 —SO 2 —CH 3 , NH—COO—CH 2 -phenyl, hydroxy-methyl, CH 2 —NH—CH 3 , CH 2 —NH-ethyl, NH—CH 2 —CH 2 -methoxy, CH 2 —NH—CO—CH 3 , NH—CH 2 —CH 2 OH, NH—CO—CH 2 —N(CH 3 ) 2 , NH—CO-methylpyrrolidine, NH—CO-pyridyl, NH-ethyl, pyrrolidine, CH 2 —NH—CO-pyridyl, COCH 2 —N(CH 3 ) 2 , tetrahydropyran, CO-methylpyrrolidine, CH 2 -methylpiperidine, NH—CO—CH 3 , NH—SO 2 —CH 3 , NH—CH 2 -tetrahydrofuran, NH—CH 2 -dioxane, N(CH 3 )—CH 2 CH 2 —OCH 3 , CH(OH)—CH 2 -amino, NH—CH 2 CH 2 OCF 3 , NH(CH 3 )—CH 2 —OCH 3 , NH—CH 2 —CH(CF 3 )—OCH 3 , F, NH-oxetane, CH 2 —CH 2 —OCH 3 , CH 2 —OCH 3 , CH 2 -tetrahydropyran, CH 2 -methylpiperizine, NH 2 —CH 2 —CH(OH)—CF 3 , piperidine, CH 2 -pyrrolidine, NH—CH(CH 3 )CH 2 OCH 3 , NH-tetrahydrofuran, (CH 2 ) 3 —NH 2 , hydroxyethyl, propyl, CH 2 -pyridyl, CH 2 -piperidine, morpholine, NH-chloropyrimidine, NH—CH 2 CH 2 —SO 2 -methyl, (CH 3 ) 3 —N(CH 3 ) 2 , piperizine, CH 2 -morpholine, NH—CH 2 —C(CH 3 )-dioxolane, NH-tetrahydropyran, NH—CH 2 —C(CH 3 )-dimethyldioxolane, NH—CH(CH 2 —OCH 3 ) 2 , NH—CH 2 -oxetane, NH-tetrahydropyran, N(CH 3 )—CH 2 CH 2 —OCH 3 , NH—CH(CH 3 )—CH 2 OH,

and NH—CH(CH 3 )—CH 2 —OH;

R 2 is selected from the group consisting of cyclohexyl; 1,3-dioxane, pyridinyl, phenyl, tetrahydropyranyl, cycloheptyl, 1,4-dioxane, morpholinyl, alkyl substituted dioxane, tetrahydrofuranyl, dioxepane, piperidinyl, and

wherein each said R 2 group is substituted with one, two, or three substituents independently selected from Cl, Br, F, methoxy, hydroxy-methyl, hydrogen, carboxamide, cyano, dihalo-methoxy, trihalo-methoxy, trifluoro-methyl, hydroxyl, and methyl; and

R 4 , is chloro, hydrogen, trifluoro-methyl, fluoro, or bromo;

R 5 , and R 6 are each independently hydrogen;

R 3 is selected from hydrogen, fluoro, cyano, CO—NH 2 , chloro, amino, methyl, and cyclopropyl;

R 7 is selected from H, trifluoro-methyl, COOH, CO—NH 2 , and cyano;

R 8 represents Cl; and

R 9 is selected from the group considering of H, ethyl, and methyl.

8. A compound of claim 1 selected from:

N2′-(trans-4-aminocyclohexyl)-5′-chloro-3,5-difluoro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-fluoro-N6-(3-fluorobenzyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)aminocyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-((tetrahydro-2H-pyran-4-yl)dideuteromethyl)-N2′-(trans-4-(((S)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-5-fluoro-N2′-(trans-4-(2-(methylsulfonyl)ethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-5-fluoro-N2′-(trans-4-(oxetan-2-yl-methylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-(((S)-tetrahydro-2H-pyran-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-(((R)-tetrahydro-2H-pyran-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

4-((5′-chloro-2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-5-fluoro-N6-(3-fluorobenzyl)-2,4′-bipyridine-2′,6-diamine;

2′-(trans-4-aminocyclohexylamino)-5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridine-5-carbonitrile;

N2′-(trans-4-aminocyclohexyl)-3-chloro-5′-fluoro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-(3-fluorobenzyl)-N2′-((1R,3S)-3-((methylamino)methyl)cyclopentyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-3-fluoro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-5-fluoro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-5-fluoro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-((1,1-dioxotetrahydro-2H-thiopyran-4-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-5-fluoro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-(3-fluorobenzyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-(3,5-difluorobenzyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-((5-fluoropyridin-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

trans-4-(5′-chloro-6-(3,5-difluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)cyclohexanol;

(R)-5′-chloro-N6-(3-fluorobenzyl)-N2′-(2-(piperidin-3-yl)ethyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

2-(trans-4-(3,5′-dichloro-6-((tetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)ethanol;

3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(((R)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(((S)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-((2-methoxyethyl)(methyl)amino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(((R)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(((S)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-3-fluoro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-3-fluoro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-3-bromo-5′-chloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

3-bromo-5′-chloro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

trans-4-(3,5′-dichloro-6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexanol;

(2S)-3-(trans-4-(3,5′-dichloro-6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)-1,1,1-trifluoropropan-2-ol;

(2R)-3-(trans-4-(3,5′-dichloro-6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)-1,1,1-trifluoropropan-2-ol;

3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(2-(trifluoromethoxy)ethylamino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-(((R)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-3,5,5′-trichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-5-fluoro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-((4-methyltetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-5-fluoro-N6-((4-methyltetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

trans-4-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)cyclohexanol;

5′-chloro-N2′-(trans-4-(dimethylamino)cyclohexyl)-N6-(3-fluorobenzyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-(3-fluorobenzyl)-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

2-(trans-4-(5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)ethanol;

5′-chloro-N6-(3,5-difluorobenzyl)-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-(3-fluorobenzyl)-N2′-(trans-4-((2-methoxyethyl)(methyl)amino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

N2′-(trans-4-aminocyclohexyl)-5′-chloro-N6-(((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

4-((5′-chloro-5-fluoro-2′-(trans-4-(2-methoxyethylamino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((2′-(trans-4-aminocyclohexylamino)-5′-chloro-5-fluoro-2,4′-bipyridin-6-yl-mino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((5′-chloro-5-fluoro-2′-(trans-4-(propylamino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((5′-chloro-2′-(trans-4-(dipropylamino)cyclohexylamino)-5-fluoro-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((5′-chloro-5-fluoro-2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((5′-chloro-2′-(trans-4-((2-methyl-1,3-dioxolan-2-yl)methyl)aminocyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

(4-((5′-chloro-2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-yl)methanol; and

5′-chloro-5-fluoro-N6-((4-methyltetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(1,1-dioxotetrahydrothiophen-3-yl-amino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine.

9. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

10. A compound of claim 1 , wherein:

R 1 is X—R 16 ;

X is a bond, or C 1-2 alkyl;

R 16 is selected from the group consisting of C 1-2 -alkyl, cyclopentyl, cyclohexyl, piperidine, piperazine, morpholine, pyridine, pyrrolidine, cyclohexenyl, and, tetrahydro-2H-pyran;

wherein R 16 is substituted with one to three groups selected from amino, hydroxyl, NHCH 2 -phenyl, CH 2 -amino, COO-t-butyl, H, methoxy, NH—SO 2 -ethyl, CH 2 —NHSO 2 -ethyl, SO 2 -ethyl, t-butyl, methyl, CH 2 —COOH, CO—NHCH 3 , CON(CH 3 ) 2 , NHC(CH 3 )—CH 2 —SO 2 —CH 3 , NH—COO—CH 2 -phenyl, hydroxy-methyl, CH 2 —NH—CH 3 , CH 2 —NH-ethyl, NH—CH 2 —CH 2 -methoxy, CH 2 —NH—CO—CH 3 , NH—CH 2 —CH 2 OH, NH—CO—CH 2 —N(CH 3 ) 2 , NH—CO-methylpyrrolidine, NH—CH 2 —C(CH 3 )-dioxolane, NH—CO-pyridyl, NH-ethyl, pyrrolidine, CH 2 NH—CO-pyridyl, NH-tetrahydropyran, COCH 2 —N(CH 3 ) 2 , NH—CH 2 —C(CH 3 )-dimethyldioxolane, tetrahydropyran, CO-methylpyrrolidine, CH 2 -methylpiperidine, NH—CO—CH 3 , NH—SO 2 —CH 3 , NH—CH(CH 2 —OCH 3 ) 2 , NH—CH 2 -tetrahydrofuran, NH—CH 2 -oxetane, NH-tetrahydropyran, NH—CH 2 -dioxane, N(CH 3 )—CH 2 CH 2 —OCH 3 , CH(OH)—CH 2 -amino, NH—CH 2 CH 2 —OCF 3 , NHCH 2 —OCH 3 , NH—CH 2 —CH(CF 3 )—OCH 3 , NH—CH(CH 3 )—CH 2 —OH, F, NH-oxetane, CH 2 —CH 2 —OCH 3 , CH 2 —OCH 3 , CH 2 -tetrahydropyran, CH 2 -methylpiperizine, NH 2 —CH 2 —CH(OH)—CF 3 , piperidine, CH 2 -pyrrolidine, NH—CH(CH 3 )CH 2 OCH 3 , NH-tetrahydrofuran, (CH 2 ) 3 —NH 2 , hydroxyethyl, propyl, CH 2 -pyridyl, CH 2 -piperidine, morpholine, NH-chloropyrimidine, NH—CH 2 CH 2 —SO 2 -methyl, (CH 3 ) 3 —N(CH 3 ) 2 , piperizine,

and CH 2 -morpholine;

R 3 is selected from H, methyl, cyano, chloro, CONH 2 , amino, cyclopropyl, ethyl, and fluoro;

R 4 is selected from halogen, methyl, hydrogen, and halo-methyl;

R 6 is H;

R 7 is selected from H, COOH, Cl, F, CONH 2 , CN, and CF 3 ;

R 8 is Cl;

R 17 and R 18 are each, independently, selected from the group consisting of hydrogen C 1-3 alkyl, C 1-4 haloalkyl, C 3-6 branched alkyl, R 22 —OR 12 , R 22 —S(O) 2 R 12 , R 22 —NR 15 S(O) 2 R 12 , heterocycloalkyl or heteroaryl; alternatively, R 17 and R 18 along with the nitrogen atom to which they are attached to can be taken together to form a four to six membered heterocyclic ring wherein said ring carbon atoms are optionally substituted with R 20 , and the ring nitrogen atoms are optionally substituted with R 21 ;

R 19 is selected from C 1-3 -alkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl;

R 20 represents the group C 1-3 alkyl;

R 22 is selection from the group consisting of C 1-4 alkyl, and C 3-6 branched alkyl;

L is selected from C 1-4 -alkyl, and cyclopropyl;

R 2 is selected from the group consisting of C 3-7 cycloalkyl, a five to seven membered heterocycloalkyl, phenyl, and pyridyl, wherein each said R 2 group is substituted with one, two, or three substituents independently selected from hydrogen, cyano, CO—NH 2 , halogen, methoxy, dihalo-methoxy, trihalo-methoxy, trihalo alkyl, C 1-3 -alkyl, and hydroxy; and

R 9 represents methyl, hydrogen, or ethyl.

11. A compound of claim 1 , which is selected from:

3,5′-dichloro-N2′-(trans-4-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)aminocyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-(((S)-tetrahydro-2H-pyran-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-(((R)-tetrahydro-2H-pyran-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-3-fluoro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-5-fluoro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-5-fluoro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-((1,1-dioxotetrahydro-2H-thiopyran-4-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-5-fluoro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4;

3,5′-dichloro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

2-(trans-4-(3,5′-dichloro-6-((tetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)ethanol;

3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-4(((R)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-4(((S)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

3,5′-dichloro-N2′-(trans-4(2-methoxyethyl)(methyl)amino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-3-fluoro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

3-bromo-5′-chloro-N2′-(trans-4-(2-methoxyethylamino)cyclohexyl)-N6-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine;

trans-4-(3,5′-dichloro-6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexanol;

(2S)-3-(trans-4-(3,5′-dichloro-6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)-1,1,1-trifluoropropan-2-ol;

(2R)-3-(trans-4-(3,5′-dichloro-6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexylamino)-1,1,1-trifluoropropan-2-ol;

3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(2-(trifluoromethoxy)ethylamino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

4-((5′-chloro-5-fluoro-2′-(trans-4-(2-methoxyethylamino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((2′-(trans-4-aminocyclohexylamino)-5′-chloro-5-fluoro-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((5′-chloro-5-fluoro-2′-(trans-4-(propylamino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((5′-chloro-2′-(trans-4-(dipropylamino)cyclohexylamino)-5-fluoro-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

4-((5′-chloro-5-fluoro-2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; and

5′-chloro-5-fluoro-N6-((4-methyltetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(1,1-dioxotetrahydrothiophen-3-yl-amino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine.

12. A compound of claim 1 , which is selected from:

5′-chloro-N6-((tetrahydro-2H-pyran-4-yl)dideuteromethyl)-N2′-(trans -4-(((S)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

4-((5′-chloro-2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile;

5′-chloro-N6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-4(R)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

5′-chloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-4(S)-tetrahydrofuran-2-yl)methyl)aminocyclohexyl)-2,4′-bipyridine-2′,6-diamine;

4-((5′-chloro-2′-(trans-4-((2-methyl-1,3-dioxolan-2-yl)methyl)aminocyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-carbonitrile; and

(4-((5′-chloro-2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexylamino)-2,4′-bipyridin-6-yl-amino)methyl)tetrahydro-2H-pyran-4-yl)methanol.