Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors

1. A compound of formula (I)

wherein

E is selected from N and CR E ;

R 1 , R 2 and R E are independently selected from H, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 1-4 hydroxyalkyl and C 3-7 cycloalkyl;

R 3 is selected from

(i) C 1-4 alkyl which is unsubstituted or substituted with 1 or more substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 alkyl, oxo, CN, —(C 0-3 alkyl)-NR 3a R 3b , C 3-7 cycloalkyl and C 3-7 heterocyclyl, and wherein the C 3-7 cycloalkyl or C 3-7 heterocyclyl is unsubstituted or substituted with 1 to 3 substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, oxo and —(C 0-3 alkyl)-NR 3a R 3b ;

(ii) C 1-4 alkoxy which is unsubstituted or substituted with 1 or more substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 haloalkyl, C 1-4 alkoxy C 1-4 alkyl, oxo, CN, —(C 0-3 alkyl)-NR 3a R 3b , C 3-7 cycloalkyl and C 3-7 heterocyclyl, and wherein the C 3-7 cycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, oxo and —(C 0-3 alkyl)-NR 3a R 3b ;

(iii) —C 3-7 cycloalkyl or —O—C 3-7 cycloalkyl wherein the C 3-7 cycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, oxo and —(C 0-3 alkyl)-NR 3a R 3b ;

(iv) —(C 0-3 alkyl)-C 3-7 cycloalkyl or —O—(C 0-3 alkyl)-C 3-7 cycloalkyl wherein the C 3-7 cycloalkyl is spiro fused to a second C 3-7 cycloalkyl or C 3-7 heterocyclyl by one single carbon atom, and wherein the C 3-7 cycloalkyl or C 3-7 heterocyclyl is unsubstituted or substituted with 1 to 3 substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, oxo and —(C 0-3 alkyl)-NR 3a R 3b ;

(v) —(C 0-3 alkyl)-C 3-7 heterocyclyl or —O—(C 0-3 alkyl)-C 3-7 heterocyclyl, and wherein said C 3-7 heterocyclyl is unsubstituted or substituted with 1 to 3 substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 alkyl C 1-4 alkoxy, C 1-4 haloalkyl, oxo and —(C 0-3 alkyl)-NR 3a R 3b ;

(vi) —(C 0-3 alkyl)-C 3-7 heterocyclyl or —(O—C 0-3 alkyl)-C 3-7 heterocyclyl, and wherein said C 3-7 heterocyclyl is spiro fused to a second C 3-7 heterocyclyl or a C 3-7 cycloalkyl by one single carbon atom, and wherein the C 3-7 heterocyclyl or C 3-7 cycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 alkyl C 1-4 alkoxy, C 1-4 haloalkyl, oxo and —(C 0-3 alkyl)-NR 3a R 3b ; and

(vii) H;

R 4 is selected from H and C 1-4 alkyl; or

R 3 and R 4 together with the nitrogen atom to which they are attached form a C 3-7 heterocyclyl, which C 3-7 heterocyclyl is optionally spiro fused to a second C 3-7 heterocyclyl or a C 3-7 cycloalkyl by one single carbon atom, and which C 3-7 heterocyclyl and C 3-7 cycloalkyl are unsubstituted or substituted with 1 to 3 substituents independently selected from hydroxy, C 1-4 hydroxyalkyl, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, oxo and —(C 0-3 alkyl)-NR 3a R 3b ;

R 3a and R 3b are independently selected from H, C 1-4 alkyl and C 1-4 haloalkyl; and

Y is selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein

R 3 is selected from

or R 3 and R 4 together with the nitrogen atom to which they are attached form a ring selected from

or a pharmaceutically acceptable salt thereof.

3. A compound of formula (I)

wherein

E is selected from N and CR E ;

R 1 , R 2 and R E are independently selected from H, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 1-4 haloalkoxy, C 1-4 hydroxyalkyl and C 3-7 cycloalkyl;

Y is selected from the group consisting of

R 4 is H and R 3 is selected from the group consisting of

or R 3 and R 4 together with the nitrogen atom to which they are attached form a C 3-7 heterocyclyl selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 selected from

3-[5-amino-6-(5-methyl-[1,3,4]oxadiazol-2-yl)-pyrazin-2-yl]-N-(4-hydroxy-cyclohexyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(3-methyl-[1,2,4]oxadiazol-5-yl)-pyrazin-2-yl]-N-(4-hydroxy-cyclohexyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(3-methyl-[1,2,4]oxadiazol-5-yl)-pyrazin-2-yl]-N-(3-hydroxy-3-methyl-butyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(3-methyl-isoxazol-5-yl)-pyrazin-2-yl]-N-(4-hydroxy-cyclohexyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(1-methyl-1H-pyrazol-4-yl)-pyrazin-2-yl]-4-methyl-N-(3-methyl-oxetan-3-ylmethyl)-benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-[5-amino-6-(2-methyl-thiazol-5-yl)-pyrazin-2-yl]-N-(3-hydroxy-2,2-dimethyl-propyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)-pyrazin-2-yl]-N-(6-hydroxy-spiro[3.3]hept-2-yl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxypropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(pyridin-4-yl)pyrazin-2-yl)-N-(4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-[5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)-pyrazin-2-yl]-N-(3-hydroxy-3-methyl-butyl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-[5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)-pyrazin-2-yl]-4-methyl-N—[(R)-1-(tetrahydrofuran-3-yl)methyl]-benzenesulfonamide;

3-[5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)-pyrazin-2-yl]-4-methyl-N-(3-methyl-oxetan-3-ylmethyl)-benzenesulfonamide;

3-[5-amino-6-(2-methyl-2H-[1,2,3]triazol-4-yl)-pyrazin-2-yl]-N-(2-hydroxy-2-methyl-propyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(2,5-dimethyl-2H-[1,2,3]triazol-4-yl)-pyrazin-2-yl]-N-(2-hydroxy-2-methyl-propyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(2-methyl-thiazol-5-yl)-pyrazin-2-yl]-N-(3-hydroxy-cyclobutylmethyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(2-cyclopropyl-thiazol-5-yl)-pyrazin-2-yl]-N-(2-hydroxy-2-methyl-propyl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-pyridin-3-yl-pyrazin-2-yl)-N-(4-hydroxy-cyclohexyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-pyrazin-2-yl]-N-(4-hydroxy-cyclohexyl)-4-methyl-benzene sulfonamide;

3-[5-amino-6-(3-cyclopropyl-[1,2,4]oxadiazol-5-yl)-pyrazin-2-yl]-N-(4-hydroxy-cyclohexyl)-4-methyl-benzene sulfonamide;

3-[5-amino-6-(3-methyl-[1,2,4]triazol-1-yl)-pyrazin-2-yl]-N-(2-hydroxy-2-methyl-propyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(3-cyclopropyl-[1,2,4]triazol-1-yl)-pyrazin-2-yl]-N-(3-hydroxy-3-methyl-butyl)-4-methyl-benzenesulfonamide;

3-[5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)-pyrazin-2-yl]-N—((R)-1-ethyl-pyrrolidin-2-ylmethyl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-[1,2,4]triazol-1-yl-pyrazin-2-yl)-N-(1-hydroxy-cyclopropylmethyl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-[1,2,4]triazol-1-yl-pyrazin-2-yl)-4-methyl-N-(3-methyl-oxetan-3-ylmethyl)-benzenesulfonamide;

3-[5-amino-6-(5-morpholin-4-ylmethyl-thiophen-3-yl)-pyrazin-2-yl]-N-(3-hydroxy-3-methyl-butyl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-[1,2,4]triazol-1-yl-pyrazin-2-yl)-N-(2-hydroxy-2-methyl-propoxy)-4-methyl-benzenesulfonamide;

3-(5-amino-6-[1,2,4]triazol-1-yl-pyrazin-2-yl)-N-(4-hydroxy-tetrahydropyran-4-ylmethyl)-4-methylbenzenesulfonamide;

N-(2-amino-ethyl)-3-(5-amino-6-[1,2,4]triazol-1-yl-pyrazin-2-yl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-[1,2,4]triazol-1-yl-pyrazin-2-yl)-N-(2,2-difluoro-ethyl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-[1,2,4]triazol-1-yl-pyrazin-2-yl)-N-(3-hydroxymethyl-oxetan-3-ylmethyl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-[1,2,4]triazol-1-yl-pyrazin-2-yl)-N-(3,3-dimethyl-2-oxo-butyl)-4-methyl-benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-chloro-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-chloro-N-(3-hydroxy-3-methylbutyl)benzenesulfonamide;

3-(5-amino-6-(furan-3-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2,5-dimethylthiazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-((1-ethylpyrrolidin-2-yl)methyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxycyclobutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-((3-(hydroxymethyl)oxetan-3-yl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(2-hydroxyethyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-(oxetan-3-ylmethyl)benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydro-2H-pyran-4-yl)benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydro-2H-pyran-2-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-(2,2,2-trifluoroethyl)benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-2-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydrofuran-3-yl)benzenesulfonamide;

(1-(3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methylphenylsulfonyl)azetidin-3-yl)methanol;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-((4-hydroxytetrahydro-2H-pyran-4-yl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-((3-hydroxyoxetan-3-yl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-((4-methylmorpholin-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1,5-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2,4-dimethylthiazol-5-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3,4-dimethyl-1H-pyrazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2,4-dimethyl-1H-imidazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-methyl-H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-(4,4,4-trifluoro-3-hydroxybutyl)benzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-(4,4,4-trifluoro-3-hydroxybutyl)benzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-(4,4,4-trifluoro-3-hydroxybutyl)benzenesulfonamide;

5-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-6-methylpyridine-3-sulfonamide;

3-(5-amino-6-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(4,4-difluorocyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(4,4-difluorocyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(4-methyl-1H-imidazol-1-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(4-methyl-1H-imidazol-1-yl)pyrazin-2-yl)-N-(3-hydroxypropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(pyrimidin-5-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-fluoropyridin-4-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-imidazol-1-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-pyrazol-1-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(4-methyl-1H-imidazol-1-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-methyl-1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-isopropyl-1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(6-hydroxyspiro[3.3]heptan-2-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydro-2H-pyran-4-yl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxy-4-methylcyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1s,4s)-4-hydroxy-4-methylcyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(6-hydroxyspiro[3.3]heptan-2-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(6-hydroxyspiro[3.3]heptan-2-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1r,3r)-3-hydroxycyclobutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1s,3s)-3-hydroxycyclobutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(((1s,3s)-3-hydroxycyclobutyl)methyl) 4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(6-hydroxyspiro[3.3]heptan-2-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-((1s,4s)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-((1s,4s)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-methyl-1H-pyrazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-cyclopropylisoxazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-cyclopropylisoxazol-5-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(4-methylthiazol-2-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-methyl-1H-1,2,3-triazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-ethyl-2H-1,2,3-triazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-ethyl-1H-1,2,3-triazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-(2,2,2-trifluoroethyl)-2H-1,2,3-triazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methyl-2H-1,2,3-triazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-((1s,4s)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-methylisoxazol-5-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-methylisoxazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-methyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(((1s,3s)-3-hydroxycyclobutyl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-methyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(((1s,3s)-3-hydroxycyclobutyl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-isopropyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(1-(hydroxymethyl)cyclopropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-cyclopropylisoxazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-2,2-dimethylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-cyclopropylisoxazol-5-yl)pyrazin-2-yl)-N-(1s,3s)-3-hydroxycyclobutyl)methyl)-4-methylbenzenesulfonamide;

2-(3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenylsulfonyl)-2-azaspiro[3.3]heptan-6-ol;

3-(1,3-dimethyl-1H-pyrazol-4-yl)-5-(5-(3-methoxy-3-methylazetidin-1-ylsulfonyl)-2-methylphenyl)pyrazin-2-amine;

3-(5-amino-6-(1H-pyrazol-1-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-(pyrrolidin-2-ylmethyl)benzenesulfonamide;

3-(5-amino-6-(2-cyclopropylthiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(thiazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methoxythiazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(4-methyl-1H-pyrazol-1-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-ethoxy-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-tert-butoxy-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-(dimethylamino)ethoxy)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-isopropoxy-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-isobutoxy-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydrofuran-3-yloxy)benzenesulfonamide;

5-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-2-fluoro-N-(3-hydroxypropyl)-4-methylbenzenesulfonamide;

5-(5-amino-6-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-2-fluoro-N-(3-hydroxypropyl)-4-methylbenzenesulfonamide;

5-(5-amino-6-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-2-fluoro-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

5-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-2-fluoro-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-((dimethylamino)methyl)-1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

5-(2-methyl-5-(3-(trifluoromethyl)piperazin-1-ylsulfonyl)phenyl)-3-(2-methylthiazol-5-yl)pyrazin-2-amine;

3-(5-amino-6-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-fluoropyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(4-methoxypyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methoxypyridin-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methoxypyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(pyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-chloropyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(5-methylpyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(5-chloro-2-fluoropyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(6-chloro-4-methylpyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-fluoropyridin-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-fluoropyridin-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-isopropoxypyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-meth t)-4-methylbenzenesulfonamide;

3-(5-amino-6-(6-ethoxypyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(furan-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-meth t)-4-methylbenzenesulfonamide;

3-(5-amino-6-(6-(pyrrolidin-1-yl)pyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(6-fluoropyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1,5-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(pyrimidin-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(6-morpholinopyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-methyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(6-(piperidin-1-yl)pyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbut)-4-methylbenzenesulfonamide;

3-(5-amino-6-(6-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-propyl-H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-isopentyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(pyridin-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-isopropyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-isobutyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-pyrazol-4-ylpyrazin-2-yl)-N-(3-hydroxy-3-meth l butyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-ethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(5-(hydroxymethyl)thiophen-2-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-(pyridin-2-ylmethyl)-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-(pyridin-3-ylmethyl)-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methyloxazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-pyrazol-3-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(4-methylthiophen-2-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(5-methylthiophen-2-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(thiophen-2-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(5-cyclopropylthiophen-2-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-((3-methyloxetan-3-yl)methyl)benzenesulfonamide;

5-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-2,4-dimethylbenzenesulfonamide;

5-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-2-fluoro-N-(2-hydroxy-2-methylpropyl) 4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide;

5-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-2-chloro-N-(2-hydroxy-2-methylpropyl) 4-methylbenzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropoxy) 4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methyloxazol-5-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(222-trifluoroethyl)benzenesulfonamide;

5-(5-(3,3-difluoropiperidin-1-ylsulfonyl)-2-methylphenyl)-3-(1H-1,2,4-triazol-1-yl)pyrazin-2-amine;

5-(5-(3-fluoropyrrolidin-1-ylsulfonyl)-2-methylphenyl)-3-(1H-1,2,4-triazol-1-yl)pyrazin-2-amine;

5-(5-(3,3-difluoropyrrolidin-1-ylsulfonyl)-2-methylphenyl)-3-(1H-1,2,4-triazol-1-yl)pyrazin 2-amine;

5-(5-(3,3-difluoroazetidin-1-ylsulfonyl)-2-methylphenyl)-3-(1H-1,2,4-triazol-1-yl)pyrazin-2-amine;

5-(5-(3-fluoroazetidin-1-ylsulfonyl)-2-methylphenyl)-3-(1H-1,2,4-triazol-1-yl)pyrazin-2-amine;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(4-(hydroxymethyl)cyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3,3-difluorocyclobutyl)-4-methylbenzenesulfonamide;

5-(2-methyl-5-(3,3,4,4-tetrafluoropyrrolidin-1-ylsulfonyl)phenyl)-3-(1H-1,2,4-triazol-1-yl)pyrazin-2-amine;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(5-hydroxypentyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-methoxypropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1-hydroxycyclohexyl)methyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1-ethylpyrrolidin-2-yl)methyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-hydroxypropyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-2-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1-hydroxycyclobutyl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydro-2H-pyran-2-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-((1-methylpyrrolidin-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydro-2H-pyran-3-yl)methyl)benzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydrofuran-3-yl)benzenesulfonamide;

(S)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydrofuran-3-yl)benzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(3,3,3-trifluoro-2-hydroxy-2-methylpropyl)benzenesulfonamide;

(S)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(3,3,3-trifluoro-2-hydroxy-2-methylpropyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(4,4,4-trifluoro-3-hydroxy-3-methylbutyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1-(hydroxymethyl)cyclopentyl)methyl)-4-methylbenzenesulfonamide;

(S)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-3-yl)methyl)benzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-fluoroethyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-fluoropropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(2-oxotetrahydrofuran-3-yl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(3,3,3-trifluoropropyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(2-methyl-2-morpholinopropyl)benzenesulfonamide;

5-(5-(4,4-difluoropiperidin-1-ylsulfonyl)-2-methylphenyl)-3-(1H-1,2,4-triazol-1-yl)pyrazin-2-amine;

5-(5-(4-fluoropiperidin-1-ylsulfonyl)-2-methylphenyl)-3-(1H-1,2,4-triazol-1-yl)pyrazin-2-amine;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1-hydroxycyclopentyl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-(1-hydroxycyclopentyl)ethyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2-(1-hydroxycyclohexyl)ethyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1-(hydroxymethyl)cyclopropyl)methyl)-4-methylbenzenesulfonamide;

(S)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((5,5-dimethyltetrahydrofuran-2-yl)methyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((5,5-dimethyltetrahydrofuran-2-yl)methyl)-4-methylbenzenesulfonamide;

(S)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(1-hydroxypropan-2-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(1-hydroxypropan-2-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(2,2-difluoropropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(3-methylbutan-2-yl)benzenesulfonamide;

(1-(3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenylsulfonyl)azetidin-3-yl)methanol;

1-(3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenylsulfonyl)-3-methylazetidin-3-ol;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((3-hydroxyoxetan-3-yl)methyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(1-cyano-2-hydroxyethyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1-(hydroxymethyl)cyclobutyl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(2-oxotetrahydrothiophen-3-yl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((1-(hydroxymethyl)cyclohexyl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-cyclopropyl-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-cyclobutyl-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-cyclopentyl-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(pyrrolidin-3-ylmethyl)benzenesulfonamide;

(S)-3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(pyrrolidin-3-ylmethyl)benzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-((3R,4R)-4-hydroxypyrrolidin-3-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-((3-(hydroxymethyl)oxetan-3-yl)methyl)-4-methylbenzenesulfonamide;

(S)-3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-((1-ethylpyrrolidin-2-yl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-((4-methylmorpholin-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-((4-methylmorpholin-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-((4-methylmorpholin-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-((2-methyltetrahydrofuran-2-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-((4-methylmorpholin-2-yl)methyl)benzenesulfonamide;

(R)-3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-(morpholin-3-ylmethyl)benzenesulfonamide;

(S)-3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-(morpholin-3-ylmethyl)benzenesulfonamide;

3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-4-methyl-N-(morpholin-2-ylmethyl)benzenesulfonamide;

(R)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(2-hydroxypropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(4-(hydroxymethyl)cyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(3,3-difluorocyclobutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(5-hydroxypentyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-((1-hydroxycyclohexyl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-((1-hydroxycyclobutyl)methyl)-4-methylbenzenesulfonamide;

(S)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(1-hydroxybutan-2-yl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(1-hydroxybutan-2-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-4-methylbenzenesulfonamide;

(S)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(2-hydroxypropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydro-2H-pyran-4-yl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(3-methoxypropyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-2-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(4,4,4-trifluoro-3-hydroxy-3-methylbutyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydro-2H-pyran-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(2-methoxy-2-methylpropyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydro-2H-pyran-2-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-2-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-3-yl)methyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(4-hydroxy-4-methylcyclohexyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(3,3,3-trifluoro-2-hydroxy-2-methylpropyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(1-isopropylpiperidin-4-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(1-methylpiperidin-4-yl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(3-(diethylamino)propyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(3-(dimethylamino)-2,2-dimethylpropyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-((1-ethylpyrrolidin-2-yl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(2-(dimethylamino)ethyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(2-(pyrrolidin-1-yl)ethyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(2-morpholinoethyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(2-methyl-2-morpholinopropyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-((1-methylpyrrolidin-3-yl)methyl)benzenesulfonamide;

4-((3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methylphenylsulfonamido)methyl)tetrahydro-2H-pyran-4-carboxamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-((3-hydroxyoxetan-3-yl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(2-(methylamino)ethyl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(2-aminoethyl)-4-methylbenzenesulfonamide;

(R)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(pyrrolidin-3-ylmethyl)benzenesulfonamide;

(S)-3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(pyrrolidin-3-ylmethyl)benzenesulfonamide;

5-(5-(2,6-diazaspiro[3.3]heptan-2-ylsulfonyl)-2-methylphenyl)-3-(2-methylpyridin-4-yl)pyrazin-2-amine;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-((1S,2S)-2-aminocyclopentyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-ylpyrazin-2-yl)-N-((1R,2R)-2-aminocyclopentyl)-4-methylbenzenesulfonamide;

(R)-5-(5-(3-aminopyrrolidin-1-ylsulfonyl)-2-methylphenyl)-3-(2-methylpyridin-4-yl)pyrazin-2-amine;

5-(5-(4-aminopiperidin-1-ylsulfonyl)-2-methylphenyl)-3-(2-methylpyridin-4-yl)pyrazin-2-amine;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-(((1S,3R)-3-(aminomethyl)cyclohexyl)methyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-((1r,4r)-4-aminocyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1-(2,22-trifluoroethyl)-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methyl-N-(oxetan-3-ylmethyl)benzenesulfonamide;

3-(5-amino-6-(1-benzyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

2-(3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenylsulfonamido)acetamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-4-methyl-N-(2-oxopiperidin-4-yl)benzenesulfonamide;

3-(5-amino-6-(2-methylpyridin-4-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-ethyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-ethyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(azetidin-3-yl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(5-ethyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-ethyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

3-(5-amino-6-(3-propyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-((1r,4r)-4-hydroxycyclohexyl)-4-methylbenzenesulfonamide;

(1-(3-(5-amino-6-(3-ethyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-4-methylphenylsulfonyl)piperidin-4-yl)methanol;

cis-3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxycyclobutyl)-4-methylbenzenesulfonamide;

trans-3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxycyclobutyl)-4-methylbenzenesulfonamide;

(R)-3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-2-yl)methyl)benzenesulfonamide;

(S)-3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-((tetrahydrofuran-2-yl)methyl)benzenesulfonamide;

(R)-3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydrofuran-3-yl)benzenesulfonamide;

(S)-3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-4-methyl-N-(tetrahydrofuran-3-yl)benzenesulfonamide;

3-(5-Amino-6-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(2-hydroxy-2-methylpropyl)-4-methylbenzenesulfonamide; and

3-(5-Amino-6-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)pyrazin-2-yl)-N-(3-hydroxy-3-methylbutyl)-4-methylbenzenesulfonamide;

or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition, comprising:

a therapeutically effective amount of the compound or salt according claim 1 and one or more pharmaceutically acceptable carriers.

6. A pharmaceutical combination, comprising:

a therapeutically effective amount of the compound or salt according to claim 1 and a second active agent.

7. A method of treating a disorder or disease mediated by the activation of PI 3-kinase gamma isoform, comprising administering to a subject having said disorder or disease a therapeutically effective amount of a compound or salt according to claim 1 .

8. The method of claim 7 , wherein the disorder or disease is selected from the group consisting of respiratory diseases, allergies, rheumatoid arthritis, osteoarthritis, rheumatic disorders, psoriasis, ulcerative colitis, Crohn's disease, septic shock, cancer, atherosclerosis, allograft rejection following transplantation, diabetes, stroke, obesity and restenosis.

9. A pharmaceutical composition, comprising a compound or salt according to claim 1 and one or more pharmaceutically acceptable carriers.

10. A pharmaceutical combination, comprising a compound or salt according to claim 1 and a second active agent.

11. A pharmaceutical composition, comprising a compound or salt according to claim 3 and one or more pharmaceutically acceptable carriers.

12. A pharmaceutical combination, comprising a compound or salt according to claim 3 and a second active agent.

13. A pharmaceutical composition, comprising a compound or salt according to claim 4 and one or more pharmaceutically acceptable carriers.

14. A pharmaceutical combination, comprising a compound or salt according to claim 4 and a second active agent.