Pyrazine compounds and uses thereof

Abstract

The present disclosure novel pyrazine compounds targeting adenosine receptors (especially A1 and A2, particularly A2a). The present disclosure also relates to pharmaceutical compositions comprising one or more of the compounds as an active ingredient, and use of the compounds in the treatment of adenosine receptor (AR) associated diseases, for example cancer such as NSCLC, RCC, prostate cancer, and breast cancer.

What is claimed is: 
     
         1 . A method of treating an Adenosine receptor-associated disease, comprising administering to a subject an effective amount of one or more compounds of Formula (I), 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising one or more compounds of Formula (I) and a pharmaceutically acceptable carrier,
 wherein, 
 X is amino; 
 ring A is selected from 
 
       
       
         
           
           
               
               
           
         
         
           ring B is selected from 5-6 membered saturated or unsaturated carbocyclyl, or 5-6 membered saturated or unsaturated heterocyclyl having 1, 2, or 3 heteroatoms selected from N or O; 
           W is —C 1-12  alkylene- or —C(O)—, which can be mono or independently multi-substituted by hydroxyl, C 1-12  alkyl, C 1-12  alkoxyl, or C 1-12  alkyl-OH; 
           V is —NH—, —NH—C 1-12  alkylene-, —NH—C(O)—, or N-linked pyrrolidinyl, which can be mono or independently multi-substituted by hydroxyl, C 1-12  alkyl, C 1-12  alkoxyl, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino or C 1-12  alkyl-OH; 
           Y is halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbonyl, carbamate, sulphonyl, C 1-12  alkyl, C 1-12  alkoxyl, C 1-12  alkanoyl, C 1-12  alkyl-OH, C 1-12  alkyl-cyano, C 1-12  haloalkyl, C 1-12  haloalkoxyl, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkylsulphonyl, C 1-12  alkanoylamino, 3-12 membered saturated or unsaturated carbocyclyl, or 3-12 membered saturated or unsaturated heterocyclyl, which can be optionally mono- or independently multi-substituted by R 3 ; 
           each R 1  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkanoylamino, a 3-10 membered saturated or unsaturated carbocyclyl, or a 3-10 membered saturated or unsaturated heterocyclyl, wherein each R 1  can be optionally further mono- or independently multi-substituted by R 4 ; 
           each R 2  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkanoylamino, a 3-10 membered saturated or unsaturated carbocyclyl, or a 3-10 membered saturated or unsaturated heterocyclyl, wherein each R 2  can be optionally further mono- or independently multi-substituted by R 5 ; 
           each R 3  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, sulphonyl, phosphate, phosphoryl, phosphinyl, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 3-12  cycloalkyl)amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, (C 1-12  alkyl)sulphonyl, (C 1-12  alkyl)phosphinyl, (C 1-12  alkyl) 2 phosphinyl, (C 1-12  alkyl)phosphoryl, (C 1-12  alkyl) 2  phosphoryl, C 1-12  alkanoylamino, N—(C 1-12  alkyl-OH)amino, a 3-10 membered saturated or unsaturated carbocyclyl, or a 3-10 membered saturated or unsaturated heterocyclyl, wherein each R 3  can be optionally further mono- or independently multi-substituted by R 6 ; 
           wherein each R 4 , R 5  or R 6  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, sulphonyl, phosphinyl, urea, carbamate, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, (C 1-12  alkyl) sulphonyl, (C 1-12  alkyl)phosphinyl, (C 1-12  alkyl) 2 phosphinyl, C 1-12  alkanoylamino, C 1-12  alkylsulphonyl, C 1-12  alkyl substituted cycloalkyl; 
           m is 0, 1, 2, 3 or 4; 
           n is 0, 1, 2, 3, or 4. 
         
       
     
     
         2 . The method of  claim 1 , wherein
 X is amino; and/or   each R 1  is independently selected from hydroxyl, fluoro, chloro, bromo, amino, carbamoyl, urea, carbamate, cyano, methyl, ethyl, n-propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylamino, dimethylamino, ethylamino, hydroxymethyl, hydroxyethyl, cyclopropyl, oxacyclopentanyl, oxetanyl, or 1,1-dioxothietanyl, which can be optionally further mono- or independently multi-substituted by R 4 , wherein each R 4  is independently selected from halogen, hydroxyl, cyano, amino, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; and/or   m is 0, 1 or 2; and/or   ring B is selected from:   
       
         
           
           
               
               
           
         
         each R 2  is independently selected from halogen, hydroxyl, amino, C 1-12  alkyl, or C 1-12  haloalkyl, wherein each R 2  can be optionally further mono- or independently multi-substituted by R 5  selected from halogen, hydroxyl, cyano, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; optionally, wherein each R 2  is independently selected from cyano, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, ethoxyl, methoxyl, difluoromethoxy, trifluoromethoxy, methylamino, dimethylamino, ethylamino, isopropanylamino, hydroxymethyl, or hydroxyethyl; and/or 
         n is 0, 1 or 2. 
       
     
     
         3 . The method of  claim 1 , wherein W is methylene or —C(O)—; optionally, wherein when W is methylene, V is —NH—C(O)—; or when W is —C(O)—, V is —NH—, —NH—C 1-12  alkylene-, or N-linked pyrrolidinyl, which can be mono or independently multi-substituted by hydroxyl, C 1-12  alkyl, C 1-12  alkoxyl, or C 1-12  alkyl-OH. 
     
     
         4 . The method of  claim 1 , wherein Y is 3-12 membered saturated or unsaturated carbocyclyl, or 3-12 membered saturated or unsaturated heterocyclyl selected from: 
       
         
           
           
               
               
           
         
         which can be optionally mono- or independently multi-substituted by R 3 ; 
         optionally, wherein Y is hydroxyl, amino, cyano, carbonyl, carbamoyl, C 1-12  alkyl, C 1-12  alkyl-OH, C 1-12  alkoxyl, sulphonyl, (C 1-12  alkyl)sulphonyl, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, 3-12 membered saturated or unsaturated carbocyclyl or 3-12 membered saturated or unsaturated heterocyclyl, which can be optionally mono- or independently multi-substituted by R 3 . 
       
     
     
         5 . The method of  claim 1 , wherein each R 3  is independently selected from hydroxyl, amino, cyano, carbamoyl, sulphonyl, phosphoryl, phosphinyl, fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, methoxyl, ethoxyl, ethylamino, hydroxyethyl, hydroxymethyl, hydroxyethoxyl, sulphonylmethyl, aminomethyl, cyclopropyl, cyclopropylcarbonyl, cyclobutylamino, cyclopropyl, cyclobutanyl, cyclohexyl, pyranyl, furanyl, phenyl, pyridinyl, pyrazinyl, piperazinyl, morpholinyl, azetidinyl, pyrrolidinyl, piperidinyl, 1,4-oxanyl, bicycle[1.1.1]petanyl, 1,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 2,5-diazabicyclo[2.2.1]heptanyl, and 3,8-diazabicyclo[3.2.1]octanyl, which can be optionally further mono- or independently multi-substituted by fluoro, hydroxyl, methoxyl, ethyoxyl, amino, methylamino, dimethylamino, sulphonyl, methylsulphonyl, carbamoyl, N-methylcarbamoyl, N,N-dimethylcarbamoyl, hydroxymethyl, hydroxyethyl, cyclopropyl, cyclopropanecarbonyl. 
     
     
         6 . The method of  claim 1 , wherein each R b  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, sulphonyl, urea, carbamate, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkanoylamino, C 1-12  alkylsulphonyl or C 1-12  alkyl substituted cycloalkyl. 
     
     
         7 . The method of  claim 1 , wherein the compound has a structure of formula (Ia): 
       
         
           
           
               
               
           
         
         wherein, 
         ring A is selected from 
       
       
         
           
           
               
               
           
         
         ring B is 5-6 membered saturated or unsaturated carbocyclyl, or 5-6 membered saturated or unsaturated heterocyclyl having 1, 2, or 3 heteroatoms selected from N or O; 
         Z is —C 1-12  alkylene- or a bond; 
         Y is amino, carbamoyl, carbonyl, sulphonyl, C 1-12  alkyl, C 1-12  alkoxyl, C 1-12  alkyl-OH, C 1-12  alkyl-cyano, C 1-12  haloalkyl, C 1-12  haloalkoxyl, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkylsulphonyl, C 1-12  alkanoylamino, 3-6 membered saturated or unsaturated carbocyclyl, or 3-6 membered saturated or unsaturated heterocyclyl, which can be optionally mono- or independently multi-substituted by R 3 ; 
         each R 1  is independently selected from hydroxyl, fluoro, chloro, bromo, amino, carbamoyl, urea, carbamate, cyano, methyl, ethyl, n-propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylamino, dimethylamino, ethylamino, hydroxymethyl, hydroxyethyl, cyclopropyl, oxacyclopentanyl, oxetanyl, or 1,1-dioxothietanyl, which can be optionally further mono- or independently multi-substituted by R 4 ; 
         each R 2  is independently halogen, hydroxyl, amino, C 1-12  alkyl, or C 1-12  haloalkyl, wherein each R 2  can be optionally further mono- or independently multi-substituted by R 5 ; 
         each R 3  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, sulphonyl, phosphate, phosphoryl, phosphinyl, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 3-12  cycloalkyl)amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, (C 1-12  alkyl)sulphonyl, (C 1-12  alkyl)phosphinyl, (C 1-12  alkyl) 2 phosphinyl, (C 1-12  alkyl)phosphoryl, (C 1-12  alkyl) 2  phosphoryl, C 1-12  alkanoylamino, N—(C 1-12  alkyl-OH)amino, a 3-10 membered saturated or unsaturated carbocyclyl, or a 3-10 membered saturated or unsaturated heterocyclyl, wherein each R 3  can be optionally further mono- or independently multi-substituted by R 6 ; 
         each R 4  is independently selected from halogen, hydroxyl, cyano, amino, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; 
         each R 5  is independently selected from halogen, hydroxyl, cyano, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; 
         each R 6  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, sulphonyl, urea, carbamate, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkanoylamino, C 1-12  alkylsulphonyl or C 1-12  alkyl substituted cycloalkyl; 
         m is 0, 1, 2, 3 or 4; and 
         n is 0, 1, 2, 3 or 4. 
       
     
     
         8 . The method of  claim 7 , wherein Z is a bond, Y is cyclobutyl mono-substituted by C 1-12  alkoxyl, optionally by methoxyl; or wherein Z is ethylene, Y is methoxyl. 
     
     
         9 . The method of  claim 1 , wherein the compound has a structure of formula (Ia-i): 
       
         
           
           
               
               
           
         
         wherein, 
         ring A is selected from 
       
       
         
           
           
               
               
           
         
         ring B is 5-6 membered saturated or unsaturated carbocyclyl, or 5-6 membered saturated or unsaturated heterocyclyl having 1, 2, or 3 heteroatoms selected from N or O; 
         ring Q is 3-6 membered saturated or unsaturated carbocyclyl, or 3-6 membered saturated or unsaturated heterocyclyl; 
         R 7  is hydrogen, C 1-12  alkyl, C 1-12  alkoxyl, or C 1-12  alkyl-OH; 
         each R 1  is independently selected from hydroxyl, fluoro, chloro, bromo, amino, carbamoyl, urea, carbamate, cyano, methyl, ethyl, n-propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylamino, dimethylamino, ethylamino, hydroxymethyl, hydroxyethyl, cyclopropyl, oxacyclopentanyl, oxetanyl, or 1,1-dioxothietanyl, which can be optionally further mono- or independently multi-substituted by R 4 ; 
         each R 2  is independently halogen, hydroxyl, amino, C 1-12  alkyl, or C 1-12  haloalkyl, wherein each R 2  can be optionally further mono- or independently multi-substituted by R 5 ; 
         each R 3  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, sulphonyl, phosphate, phosphoryl, phosphinyl, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 3-12  cycloalkyl)amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, (C 1-12  alkyl)sulphonyl, (C 1-12  alkyl)phosphinyl, (C 1-12  alkyl) 2 phosphinyl, (C 1-12  alkyl)phosphoryl, (C 1-12  alkyl) 2  phosphoryl, C 1-12  alkanoylamino, N—(C 1-12  alkyl-OH)amino, a 3-10 membered saturated or unsaturated carbocyclyl, or a 3-10 membered saturated or unsaturated heterocyclyl, wherein each R 3  can be optionally further mono- or independently multi-substituted by R 6 ; 
         each R 4  is independently selected from halogen, hydroxyl, cyano, amino, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; 
         each R 5  is independently selected from halogen, hydroxyl, cyano, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; 
         each R 6  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, sulphonyl, urea, carbamate, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkanoylamino, C 1-12  alkylsulphonyl or C 1-12  alkyl substituted cycloalkyl; 
         m is 0, 1, 2, 3 or 4; 
         n is 0, 1, 2, 3 or 4; and 
         i is 0, 1, 2, 3 or 4. 
       
     
     
         10 . The method of  claim 1 , wherein the compound has a structure of formula (Ib); 
       
         
           
           
               
               
           
         
         wherein, 
         ring A is selected from 
       
       
         
           
           
               
               
           
         
         ring B is 5-6 membered saturated or unsaturated carbocyclyl, or 5-6 membered saturated or unsaturated heterocyclyl having 1, 2, or 3 heteroatoms selected from N or 0; 
         ring Q is 3-6 membered saturated or unsaturated carbocyclyl, or 3-6 membered saturated or unsaturated heterocyclyl; 
         R 7  is hydrogen, C 1-12  alkyl, C 1-12  alkoxyl, or C 1-12  alkyl-OH; 
         each R 1  is independently selected from hydroxyl, fluoro, chloro, bromo, amino, carbamoyl, urea, carbamate, cyano, methyl, ethyl, n-propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylamino, dimethylamino, ethylamino, hydroxymethyl, hydroxyethyl, cyclopropyl, oxacyclopentanyl, oxetanyl, or 1,1-dioxothietanyl, which can be optionally further mono- or independently multi-substituted by R 4 ; 
         each R 2  is independently halogen, hydroxyl, amino, C 1-12  alkyl, or C 1-12  haloalkyl, wherein each R 2  can be optionally further mono- or independently multi-substituted by R 5 ; 
         each R 3  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, sulphonyl, phosphate, phosphoryl, phosphinyl, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 3-12  cycloalkyl)amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, (C 1-12  alkyl)sulphonyl, (C 1-12  alkyl)phosphinyl, (C 1-12  alkyl) 2 phosphinyl, (C 1-12  alkyl)phosphoryl, (C 1-12  alkyl) 2  phosphoryl, C 1-12  alkanoylamino, N—(C 1-12  alkyl-OH)amino, a 3-10 membered saturated or unsaturated carbocyclyl, or a 3-10 membered saturated or unsaturated heterocyclyl, wherein each R 3  can be optionally further mono- or independently multi-substituted by R; 
         each R 4  is independently selected from halogen, hydroxyl, cyano, amino, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; 
         each R 5  is independently selected from halogen, hydroxyl, cyano, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; 
         each R 6  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, sulphonyl, urea, carbamate, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkanoylamino, C 1-12  alkylsulphonyl or C 1-12  alkyl substituted cycloalkyl; 
         m is 0, 1, 2, 3 or 4; 
         n is 0, 1, 2, 3 or 4; and 
         i is 0, 1, 2, 3 or 4. 
       
     
     
         11 . The method of  claim 10 , wherein
 each R 1  is independently selected from fluoro, chloro, amino, methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxyethyl, hydroxypropyl, methoxyethyl, 2-hydroxypropyl, cyclopropyl, or oxetanyl; and/or   wherein m is 0, 1 or 2; and/or   wherein ring B is selected from:   
       
         
           
           
               
               
           
         
          and/or 
         wherein R 2  is methyl or fluoro; and/or wherein n is 0 or 1; and/or 
         wherein ring Q is selected from: 
       
       
         
           
           
               
               
           
         
          and/or 
         wherein each R 3  is independently selected from fluoro, chloro, bromo, cyano, methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxyl, ethoxyl, difluoromethoxyl, trifluoromethoxyl, trifluoroethoxyl, hydroxymethyl, hydroxyethyl, hydroxyethyloxyl, methoxyethyloxyl, amino, methylamino, dimethylamino, ethylamino, isopropylamino, hydroxyethylamino, methylaminoethyloxyl, dimethylaminoethyloxyl, dimethylphosphinyl-methyl, carbamoyl, carbamoylmethoxyl, azetidinyl, pyrrolidyl, morpholinyl, pyrazinyl, dimethylaminoazetidinyl, 1-methyl-pyrazin-4-yl, 3-methyl-3,8-diaza-bicyclo[3.2.1]octan-8-yl, 3-Methyl-3,6-diaza-bicyclo[3.1.1]heptanyl, 8-methyl-3,8-diaza-bicyclo[3.2.1]octan-3-yl, 6-methyl-2,6-diaza-spiro[3.4]octan-2-yl, or 5-methyl-2,5-diaza-spiro[3.3]-heptan-2-yl; and/or 
         wherein i=0, 1, 2 or 3. 
       
     
     
         12 . The method of  claim 1 , wherein the compound has a structure of formula (Ia-ii): 
       
         
           
           
               
               
           
         
         wherein, 
         ring A is selected from 
       
       
         
           
           
               
               
           
         
         Z is —C 1-12  alkylene- or a bond; 
         Y is hydrogen, C 1-12  alkyl, C 1-12  alkoxyl, C 1-12  alkyl-OH, 3-6 membered saturated or unsaturated carbocyclyl, or 3-6 membered saturated or unsaturated heterocyclyl, which can be optionally mono- or independently multi-substituted by R 3 ; 
         each R 1  is independently selected from hydroxyl, fluoro, chloro, bromo, amino, carbamoyl, urea, carbamate, cyano, C 1-12  alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, methoxy, ethoxy, trifluoromethoxy, trifluoroethoxy, methylamino, dimethylamino, ethylamino, hydroxymethyl, hydroxyethyl, cyclopropyl, oxacyclopentanyl, oxetanyl, or 1,1-dioxothietanyl, which can be optionally further mono- or independently multi-substituted by R 4 ; 
         each R 3  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, urea, carbamate, sulphonyl, phosphate, phosphoryl, phosphinyl, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C 1-12  alkyl) 2 amino, N—(C 3-12  cycloalkyl)amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, (C 1-12  alkyl)sulphonyl, (C 1-12  alkyl)phosphinyl, (C 1-12  alkyl) 2 phosphinyl, (C 1-12  alkyl)phosphoryl, (C 1-12  alkyl) 2  phosphoryl, C 1-12  alkanoylamino, N—(C 1-12  alkyl-OH)amino, a 3-10 membered saturated or unsaturated carbocyclyl, or a 3-10 membered saturated or unsaturated heterocyclyl, wherein each R 3  can be optionally further mono- or independently multi-substituted by R 6 ; 
         each R 4  is independently selected from halogen, hydroxyl, cyano, amino, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, or C 1-12  haloalkoxyl; 
         each R 6  is independently selected from halogen, hydroxyl, cyano, amino, carbamoyl, sulphonyl, urea, carbamate, C 1-12  alkyl, C 1-12  haloalkyl, C 1-12  alkoxyl, C 1-12  haloalkoxyl, C 1-12  alkyl-OH, N—(C 1-12  alkyl)amino, N,N—(C1.2 alkyl) 2 amino, N—(C 1-12  alkyl)carbamoyl, N,N—(C 1-12  alkyl) 2 carbamoyl, C 1-12  alkanoylamino, C 1-12  alkylsulphonyl or C 1-12  alkyl substituted cycloalkyl; 
         m is 0, 1, 2, 3 or 4; and 
         n is 0, 1, 2, 3 or 4. 
       
     
     
         13 . The method of  claim 12 , wherein ring A is azaindolizinyl; and/or
 wherein m is 1, and R 1  is C 1-12  alkyl, preferably C 1-3  alkyl, more preferably methyl.   
     
     
         14 . The method of  claim 12 , wherein
 Z is a bond, Y is cyclobutyl mono-substituted by methoxyl; or   Z is ethylene, Y is methoxyl; or   Z is methylene, Y is phenyl, pyrrolidyl, or tetrahydrofuryl, which can be optionally mono- or independently multi-substituted by R 3 , optionally, wherein R 3  is halogen or C 1-12  alkyl; optionally, wherein R 3  is fluoro or methyl.   
     
     
         15 . The method of  claim 1 , wherein the compound is selected from the group consisting of:
 3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-N-((3-fluoropyridin-2-yl) methyl)pyrazine-2-carboxamide;   3-amino-N-(2,6-difluorobenzyl)-6-(2,6-dimethylpyridin-4-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(2,6-difluorobenzyl)-6-(2,6-dimethylmorpholino)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   N-((3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazin-2-yl)methyl)picolinamide;   3-amino-N-((6-(dimethylamino)pyridin-2-yl)methyl)-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-N-(2,6-difluorobenzyl)-6-(2-methylpyridin-4-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(dimethylamino)pyridin-2-yl)methyl)-5-(4-fluorophenyl)-6-(2-methylpyridin-4-yl)pyrazine-2-carboxamide;   3-amino-N-(2,6-difluorobenzyl)-6-(imidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   6-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-amino-N-(2,6-difluorobenzyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(2,6-difluorobenzyl)-6-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3-fluoropyridin-2-yl)methyl)-6-(imidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(imidazo[1,2-a]pyridin-6-yl)-N-((2-methylthiazol-4-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(imidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(thiazol-4-ylmethyl)pyrazine-2-carboxamide;   3-amino-6-(1H-benzo[d]imidazol-5-yl)-N-((3-fluoropyridin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-aminopyridin-2-yl)methyl)-6-(imidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3-fluoropyridin-2-yl)methyl)-6-(3-methyl-3H-benzo[d]imidazol-5-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(4-fluoro-2-methoxybenzyl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-N-(2-(trifluoromethyl)benzyl)pyrazine-2-carboxamide   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(3-fluoro-2-methoxybenzyl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-N-(2-(difluoromethyl)benzyl)-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-methoxybenzyl)-5-(1H-pyrazol-1-yl)pyrazine-2-carboxamide;   3-amino-N-((3-(difluoromethoxy)pyridin-2-yl)methyl)-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-6-(2-amino-6-methylpyridin-4-yl)-N-(2-(difluoromethoxy)phenyl)-5-(3-methyl-1H-pyrazol-1-yl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-methoxybenzyl)-5-(5-methylfuran-2-yl) pyrazine-2-carboxamide;   3-amino-N-(2,6-difluorobenzyl)-6-(2,6-dimethylpyridin-4-yl)-5-(5-methylfuran-2-yl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-methoxybenzyl)-5-(1-methyl-1H-pyrazol-4-yl)pyrazine-2-carboxamide;   3-amino-N-(2,6-difluorobenzyl)-6-(2,6-dimethylpyridin-4-yl)-5-(1-methyl-1H-pyrazol-4-yl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-N-(2-(trifluoromethoxy)benzyl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-N-((2-methoxypyridin-3-yl)methyl)pyrazine-2-carboxamide;   3-amino-6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-N-(2-methoxybenzyl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-N-((3-methoxypyridin-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-methoxybenzyl)-5-(5-methyl-1H-pyrazol-1-yl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-methoxybenzyl)-5-(3-methyl-1H-pyrazol-1-yl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-fluorobenzyl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-N-(2-chlorobenzyl)-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-N-(2-bromobenzyl)-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-N-(2-methylbenzyl)pyrazine-2-carboxamide;   3-amino-6-(2-amino-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-N-(2-methoxybenzyl) pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-ethylbenzyl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-N-(2-(difluoromethoxy)-6-fluorobenzyl)-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   N-((3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazin-2-yl)methyl)-2-methoxybenzamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)-N-(2-methoxybenzyl) pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-fluoro-6-methoxybenzyl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-N-(2-(difluoromethoxy)benzyl)-6-(2,6-dimethylpyridin-4-yl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(5-fluoro-2-methoxybenzyl)-5-(4-fluorophenyl)pyrazine-2-carboxamide;   3-amino-6-(2,6-dimethylpyridin-4-yl)-N-(2-methoxybenzyl)-5-phenylpyrazine-2-carboxamide;   3-amino-6-(imidazo[1,2-a]pyridin-6-yl)-N-((5-methylthiazol-4-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((4-aminopyrimidin-2-yl)methyl)-6-(imidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(2-(dimethylphosphoryl)-6-fluorobenzyl)-6-(imidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(imidazo[1,2-a]pyridin-6-yl)-N-((6-(methylamino)pyridin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   6-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-amino-N-((3-fluoropyridin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3-fluoropyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3-fluoropyridin-2-yl)methyl)-6-(imidazo[1,2-a]pyridin-6-yl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(3-(dimethylamino)azetidin-1-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((6-(4-methylpiperazin-1-yl)pyridin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-N-((3-(2-hydroxyethoxy)pyridin-2-yl)methyl)-6-(3-methyl-3H-benzo[d]imidazol-5-yl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-N-((3-(2-methoxyethoxy)pyridin-2-yl)methyl)-6-(3-methyl-3H-benzo[d]imidazol-5-yl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-6-(3-methyl-3H-benzo[d]imidazol-5-yl)-N-((3-(2-(methylamino)ethoxy)pyridin-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-N-((3-(2-(dimethylamino)ethoxy)pyridin-2-yl)methyl)-5-(4-fluorophenyl)-6-(3-methyl-3H-benzo[d]imidazol-5-yl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-N-((3-(2-hydroxyethylamino)pyridin-2-yl)methyl)-6-(3-methyl-3H-benzo[d]imidazol-5-yl)pyrazine-2-carboxamide;   3-amino-N-((4-(dimethylamino)pyridin-3-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3-(2-amino-2-oxoethoxy)pyridin-2-yl)methyl)-5-(4-fluorophenyl)-6-(3-methyl-3H-benzo[d]imidazol-5-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)meth yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   (R)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(pyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(pyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpiperidin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   (R)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrazine-2-carboxamide;   (R)-3-amino-6-(3-ethylpyrazolo[1,5-a]pyridin-5-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-ethylpyrazolo[1,5-a]pyridin-5-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-methyl-3H-benzo[d]imidazol-5-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-6-(3-methyl-3H-benzo[d]imidazol-5-yl)-N-((1-methylpyrrolidin-2-yl) methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-ethyl-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-isopropyl-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(oxetan-2-ylmethyl)pyrazine-2-carboxamide (isomers);   (R)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydrofuran-3-yl)methyl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydrofuran-3-yl)methyl)pyrazine-2-carboxamide;   (R)-3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   (S)-3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-meth ylpyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-N-(2-cyanoethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(3-(dimethylamino)-3-oxopropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-(1-methylpyrrolidin-3-yl)pyrazine-2-carboxamide;   (R)-3-amino-N-(2-hydroxypropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-N-(2-hydroxypropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(2-methoxyethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(2-(trifluoromethoxy)ethyl)pyrazine-2-carboxamide;   3-amino-N-(3-methoxypropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-(2-(methylsulfonyl)ethyl)pyrazine-2-carboxamide;   3-amino-N-((1r,3r)-3-methoxycyclobutyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((1s,3s)-3-methoxycyclobutyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(2-(dimethylamino)ethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((1-(dimethylamino)cyclopropyl)methyl)-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazine-2-carboxamide;   3-amino-N-(cyclopropylmethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)—N-((3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)-1-methylpyrrolidine-2-carboxamide;   (R)—N-((3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)-1-methylpyrrolidine-2-carboxamide;   N-(2-(1H-pyrazol-1-yl)ethyl)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-N-(1-methoxypropan-2-yl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-N-(1-methoxypropan-2-yl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-N-((4,4-difluoro-1-methylpyrrolidin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-N-((4,4-difluoro-1-methylpyrrolidin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(tetrahydro-2H-pyran-3-yl)pyrazine-2-carboxamide (isomers);   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydro-2H-pyran-2-yl)methyl)pyrazine-2-carboxamide (isomers);   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydro-2H-pyran-3-yl)methyl)pyrazine-2-carboxamide (isomers);   (R)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(1-methyl-1,6-diazaspiro[3.3]heptan-6-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-((1R,5S)-3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-((1R,5S)-8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(3-methyl-3,6-diazabicyclo[3.1.1]heptan-6-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(6-methyl-2,6-diazaspiro[3.4]octan-2-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((6-(1-methylpiperidin-4-yl)pyridin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(pyrrolidin-2-yl methyl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpiperidin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydrofuran-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-6-(3-ethylpyrazolo[1,5-a]pyridin-5-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methyl-3H-benzo[d]imidazol-5-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(oxetan-2-ylmethyl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydrofuran-3-yl)methyl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-(1-methylpyrrolidin-3-yl)pyrazine-2-carboxamide;   3-amino-N-(2-hydroxypropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(3-methoxycyclobutyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   N-((3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)-1-methylpyrrolidine-2-carboxamide;   3-amino-N-(1-methoxypropan-2-yl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((4,4-difluoro-1-methylpyrrolidin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(tetrahydro-2H-pyran-3-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydro-2H-pyran-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydro-2H-pyran-3-yl)methyl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-(aminomethyl)imidazo[1,2-a]pyridin-6-yl)-N-((3-fluoropyridin-2-yl) methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-N-((3-(2-(methylamino)ethoxy)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazine-2-carboxamide 2,2,2-trifluoroacetate;   (R)-3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-(1-methylpyrrolidin-3-yl)pyrazine-2-carboxamide;   (S)-3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-(1-methylpyrrolidin-3-yl)pyrazine-2-carboxamide;   (S)-3-amino-5-(3-methyl-1H-pyrazol-1-yl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   (R)-3-amino-5-(3-methyl-1H-pyrazol-1-yl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-N-((1-methylpyrrolidin-2-yl)methyl)-5-(oxazol-2-yl)-6-(3-(trifluoromethyl) imidazo[1,2-a]pyridin-6-yl)pyrazine-2-carboxamide (isomers);   (R)-(3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)(3-(dimethylamino)pyrrolidin-1-yl)methanone;   (S)-(3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)(3-(dimethylamino)pyrrolidin-1-yl)methanone;   (R)-(3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)(2-(methoxymethyl)pyrrolidin-1-yl)methanone;   (S)-(3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)(2-(methoxymethyl)pyrrolidin-1-yl)methanone;   3-amino-N-(2-(1-methyl-1H-imidazol-2-yl)ethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   rac-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((4-methylmorpholin-2-yl) methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(2-(2-oxopyrrolidin-1-yl)ethyl)pyrazine-2-carboxamide;   (R)-3-amino-6-(3-chloroimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-chloroimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((1-methyl-5-oxopyrrolidin-3-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   rac-N-((1,4-dioxan-2-yl)methyl)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   rac-3-amino-N-((1-methyl-5-oxopyrrolidin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(3-oxo-3-(piperidin-1-yl)propyl)pyrazine-2-carboxamide;   3-amino-N-((1-methyl-2-oxopyrrolidin-3-yl)methyl)-6-(3-methylimidazo[1,2-a]pyri din-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(3-oxo-3-(pyrrolidin-1-yl)propyl)pyrazine-2-carboxamide;   3-amino-N-cyclobutyl-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-N-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-N-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(bicyclo[1.1.1]pentan-1-yl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3-fluoropyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-morpholinopyrazine-2-carboxamide;   Cis-3-amino-N-((6-(3-(dimethylamino)cyclobutylamino)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   Trans-3-amino-N-((6-(3-(dimethylamino)cyclobutylamino)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(3-(methylamino)-3-oxopropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((tetrahydrofuran-2-yl)methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   rac-3-amino-N-(2-methoxypropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(2-methoxypropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((1,4,4-trimethylpyrrolidin-2-yl)methyl)pyrazine-2-carboxamide (isomers);   (R)-3-amino-5-(3-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   3-amino-N-((6-(3-(dimethylamino)pyrrolidin-1-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   rac-3-amino-N-(2-(methyl(tetrahydrofuran-3-yl)amino)ethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-N-(4-(dimethylamino)-4-oxobutan-2-yl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-N-(4-(dimethylamino)-4-oxobutan-2-yl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(2-(2-oxopyridin-1(2H)-yl)ethyl)pyrazine-2-carboxamide;   3-amino-N-(2,6-difluorobenzyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-morpholinopyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazine-2-carboxamide;   3-amino-N-(2-(methyl(pyridin-2-yl)amino)ethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((tetrahydrofuran-3-yl)methyl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(2-methoxyethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(2-(methyl(phenyl)amino)ethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-cyclopropyl-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((4-methylmorpholin-2-yl)methyl)pyrazine-2-carboxamide (isomers);   3-amino-N-((1,2-dimethylpyrrolidin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   3-amino-N-(4-methoxycyclohexyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((3-methyltetrahydrofuran-3-yl) methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   3-amino-N-(2-cyclopropyl-2-(dimethylamino)ethyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide (isomers);   3-amino-N-((1-methyl-2-oxopiperidin-3-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(tetrahydrofuran-3-yl)pyrazine-2-carboxamide;   (S)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(tetrahydrofuran-3-yl)pyrazine-2-carboxamide;   3-amino-5-(4-fluorophenyl)-N-((1-methyl-2-oxopyrrolidin-3-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazine-2-carboxamide;   (R)—N-((3-amino-5-(3,4-difluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)-1-methylpyrrolidine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-N-(1-(tetrahydrofuran-2-yl)ethyl)pyrazine-2-carboxamide;   (R)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)-5-phenylpyrazine-2-carboxamide;   3-amino-N-((4,4-dimethyloxetan-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(3-((dimethylamino)methyl)azetidin-1-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)—N-((3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)tetrahydrofuran-3-carboxamide;   (R)—N-((3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)tetrahydrofuran-3-carboxamide;   (S)—N-((3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)tetrahydrofuran-2-carboxamide;   (R)—N-((3-amino-5-(4-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)tetrahydrofuran-2-carboxamide;   cis-3-amino-N-(3-(dimethylamino)cyclobutyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   Trans-3-amino-N-(3-(dimethylamino)cyclobutyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-5-(3,4-difluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((1-methylpyrrolidin-2-yl)methyl)pyrazine-2-carboxamide;   (S)-3-amino-N-((1-(dimethylcarbamoyl)pyrrolidin-3-yl)methyl)-6-(3-methylimidazo [1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-N-((6-morpholinopyridin-2-yl)methyl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)—N-((3-amino-5-(3-fluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)-1-methylpyrrolidine-2-carboxamide;   3-amino-N-((−3-methoxytetrahydrofuran-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(3-(dimethylamino)-2,2-dimethyl-3-oxopropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-((1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyridin-2-yl) methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyridin-2-yl) methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)-3-amino-N-((6-(3,4-dimethylpiperazin-1-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-N-((6-(3,4-dimethylpiperazin-1-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)-3-amino-N-((6-(2,4-dimethylpiperazin-1-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3,3-dimethyloxetan-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)—N-((3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(2H-1,2,3-triazol-2-yl)pyrazin-2-yl)methyl)-1-methylpyrrolidine-2-carboxamide;   (R)—N-((3-amino-5-(3,5-difluorophenyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)pyrazin-2-yl)methyl)-1-methylpyrrolidine-2-carboxamide;   3-amino-N-(3-methoxycyclohexyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)—N-(1-(1H-1,2,3-triazol-1-yl)propan-2-yl)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (S)—N-(1-(2H-1,2,3-triazol-2-yl)propan-2-yl)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   (R)—N-(1-(2H-1,2,3-triazol-2-yl)propan-2-yl)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-(3-methoxypropyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(2H-1,2,3-triazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3-(2-hydroxyethoxy)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((3-(2-(methylamino)ethoxy)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(4-(dimethylamino)piperidin-1-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-N-((6-(3-(methylamino)azetidin-1-yl)pyridin-2-yl)methyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide;   3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(pyridin-2-yl)-N-((tetrahydrofuran-3-yl)methyl)pyrazine-2-carboxamide;   rac-N-(1-(1H-1,2,4-triazol-1-yl)propan-2-yl)-3-amino-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)pyrazine-2-carboxamide.   
     
     
         16 . The method of  claim 1 , further comprising administering one or more immunotherapeutics or chemotherapeutics to the subject, and/or applying radiotherapy to the subject. 
     
     
         17 . The method of  claim 16 , wherein the immunotherapeutics is selected from the group consisting of anti-PD-1/PD-L1 antibody, anti-CTLA-4 antibody, anti-CD73 antibody, anti-CD39 antibody, anti-CCR2 antibody and any combination thereof. 
     
     
         18 . The method of  claim 16 , wherein the chemotherapeutics is selected from the group consisting of Platinum based chemotherapeutics (CISPLATIN, OXALIPLATION), Docetaxel, Paclitaxel, Doxorubicin, Etoposide, Mitoxantrone and any combination thereof. 
     
     
         19 . The method of  claim 1 , wherein the Adenosine receptor-associated disease is cancer, Parkinson disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute heart failure and chronic heart failure, chronic obstructive pulmonary disease (COPD), or Asthma. 
     
     
         20 . The method of  claim 19 , wherein the cancer is NSCLC, RCC, prostate cancer, or breast cancer.