Pyrrolo-pyridine derivative compound, method for preparing same, and pharmaceutical composition containing same as active ingredient for prevention or treatment of protein kinase-related diseases

Abstract

The present invention relates to a pyrrolo-pyridine derivative compound, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for the prevention or treatment of protein kinase-related diseases. A compound represented by chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, according to the present invention, has excellent inhibitory activity against various protein kinases including DYRK1A, and therefore, the pharmaceutical composition containing the same as an active ingredient can be favorably used in the treatment or prevention of protein kinase-related diseases. Particularly, the pharmaceutical composition can be effectively used in the prevention, treatment, or alleviation of Alzheimer's disease, dementia, or Alzheimer's dementia.

1 . A method of treating a subject having a disease selected from the group consisting of cancer and metabolic disease, comprising administering an effective amount of a compound to the subject, wherein the compound is represented by chemical formula 1: 
       
         
           
           
               
               
           
         
         the optical isomer thereof or a pharmaceutically acceptable salt thereof, or a composition thereof, wherein: 
         Z is cyano (—CN); or straight or branched C 1 -C 3  alkyl substituted with one or more halogens; 
         X is —NR a —, —O— or —S—, wherein R a  is hydrogen or straight or branched C 1 -C 10  alkyl, wherein, the alkyl can be substituted with one or more substituents selected from the group consisting of —OH and C 1 -C 3  alkoxy; 
         R 1  is straight or branched C 1 -C 10  alkyl, C 3 -C 8  cycloalkyl or C 6-14  aryl, wherein, the alkyl or cycloalkyl can be substituted with one or more substituents selected from the group consisting of —OH, and, straight or branched C 1 -C 3  alkyl and C 1 -C 3  alkoxy, and the aryl can be substituted with one or more substituents selected from the group consisting of straight or branched C 1 -C 3  alkyl and straight or branched C 1 -C 3  alkoxy, nonsubstituted or substituted with one or more halogens; 
         or, R a  can form nonsubstituted or substituted 5-8 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S along with R 1  and nitrogen atom to which they are attached, and the substituted heterocycloalkyl can be substituted with one or more substituents selected from the group consisting of straight or branched C 1 -C 6  alkyl and straight or branched C 1 -C 6  alkoxy; and 
       
       
         
           
           
               
               
           
         
         wherein, each R 2 , R 4 , R 6 , R 8 , R 11 , R 17 , R 23  and R 24  are independently one or more substituents selected from the group consisting of hydrogen, halogen, straight or branched C 1 -C 6  alkyl and straight or branched C 1 -C 6  alkoxy; 
         R 3 , R 5 , R 7  and R 9  are independently hydrogen; straight or branched C 1 -C 6  alkyl or alkoxy; 3-8 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N and O; or —(C═O)NR 26 R 27 , wherein R 26  and R 27  are independently hydrogen, straight or branched C 1 -C 3  alkyl or 3-8 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N and O substituted with 3-5 membered heterocycloalkyl containing one or more oxygen atoms, or, R 26  and R 27  form 3-8 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N and O along with nitrogen atom to which they are attached, wherein, the alkyl or heterocycloalkyl is substituted with one or more substituents selected from the group consisting of —CN, halogen, straight or branched C 1 -C 3  alkyl, and, 3-6 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N and O nonsubstituted or substituted with one or more straight or branched C 1 -C 3  alkyl 
         R 10  is —CR 28 R 29 —CN, wherein R 28  and R 29  are independently hydrogen or straight or branched C 1 -C 3  alkyl, 
         R 12 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  are independently hydrogen or straight or branched C 1 -C 3  alkyl, or, two of R 12 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  bonded to the same carbon can form carbonyl along with the carbon to which they are attached, and 
         R 16 , R 22  and R 25  are independently hydrogen or straight or branched C 1 -C 3  alkyl, wherein the alkyl can be substituted with one or more halogens). 
       
     
     
         2 . The method according to  claim 1 , wherein:
 Z is —CN or methyl substituted with one or more halogens;   X is —NR a — or —O—, wherein R a  is hydrogen or straight or branched C 1 -C 6  alkyl, wherein, the alkyl can be substituted with one or more substituents selected from the group consisting of —OH and C 1 -C 3  alkoxy;   R 1  is straight or branched C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl or C 6-10  aryl, wherein, the alkyl can be substituted with one or more substituents selected from the group consisting of —OH, methyl and methoxy, and the aryl can be substituted with one or more substituents selected from the group consisting of methyl and methoxy, nonsubstituted or substituted with one or more halogens;   or, R a  can form nonsubstituted or substituted 5-6 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S along with R 1  and nitrogen atom to which they are attached, and the substituted heterocycloalkyl can be substituted with one or more substituents selected from the group consisting of straight or branched C 1 -C 3  alkyl and straight or branched C 1 -C 3  alkoxy; and   
       
         
           
           
               
               
           
         
         wherein, R 2 , R 4 , R 6 , R 8 , R 11 , R 17 , R 23  and R 24  are independently one or more substituents selected from the group consisting of hydrogen, halogen, straight or branched C 1 -C 3  alkyl and straight or branched C 1 -C 3  alkoxy; 
         R 3 , R 5 , R 7  and R 9  are independently hydrogen, straight or branched C 1 -C 3  alkyl or alkoxy, morpholinyl, piperazinyl, piperidinyl or —(C═O)NR 26 R 27 , 
         wherein R 26  and R 27  are independently hydrogen, methyl, morpholinyl, piperazinyl or piperidinyl, or, R 26  and R 27  form morpholinyl, piperazinyl or piperidinyl along with nitrogen atom to which they are attached, wherein, the C 1 -C 3  alkyl, morpholinyl, piperazinyl or piperidinyl can be substituted with one or more substituents selected from the group consisting of —CN, fluoro, oxetanyl, morpholinyl, piperazinyl, and, nonsubstituted or methyl substituted piperidinyl, 
         R 10  is —CR 28 R 29 —CN, wherein R 28  and R 29  are independently hydrogen, methyl or ethyl, 
         R 12 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  are independently hydrogen, methyl or ethyl, or, two of R 2 , R 13 , R 14 , R 1 , R 18 , R 19 , R 20  and R 21  bonded to the same carbon can form carbonyl along with the carbon to which they are attached, and 
         R 16 , R 22  and R 25  are independently hydrogen, methyl nonsubstituted or substituted with one or more halogens or ethyl nonsubstituted or substituted with one or more halogens. 
       
     
     
         3 . The method according to  claim 1 , wherein:
 Z is —CN or —CF 3 ;   X is —NR a — or —O—, wherein R a  is hydrogen or methyl;   R 1  is methyl, ethyl, n-propyl, isopropyl, cyclopropyl,   
       
         
           
           
               
               
           
         
          1-methylcyclopropyl, or, phenyl substituted with one or more CF 3 ; 
         or, R a  can form morpholinyl along with R 1  and nitrogen atom to which they are attached; and 
       
       
         
           
           
               
               
           
         
         wherein, R 2 , R 4 , R 6 , R 8 , R 11 , R 17 , R 23  and R 24  are independently one or more substituents selected from the group consisting of hydrogen, chloro, fluoro, methyl and methoxy; 
         R 3  and R 7  are independently methoxy, 
       
       
         
           
           
               
               
           
         
         B 5  and R 9  are independently methyl, isopropyl 
       
       
         
           
           
               
               
           
         
         R 10  is —CR 28 R 29 —CN, wherein R 28  and R 29  are independently hydrogen or methyl, 
         R 12 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  are independently hydrogen or methyl, or, two of R 2 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  bonded to the same carbon can form carbonyl along with the carbon to which they are attached, and 
         R 16 , R 22  and R 25  are independently hydrogen, or, methyl nonsubstituted or substituted with one or more halogens. 
       
     
     
         4 . The method according to  claim 1 , wherein:
 Z is —CN or —CF 3 ;   X is —NR a — or —O—, wherein R a  is hydrogen or methyl;   R 1  is methyl, ethyl, n-propyl, isopropyl, cyclopropyl,   
       
         
           
           
               
               
           
         
          1-methylcyclopropyl, or 
       
       
         
           
           
               
               
           
         
         or, R a  can form morpholinyl along with R 1  and nitrogen atom to which they are attached; and 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         5 . The method according to  claim 1 , wherein the compound represented by chemical formula 1 is selected from the group consisting of the following compounds:
 (1) 6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (2) 4-(ethylamino)-6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (3) 6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-4-((2-methoxyethyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (4) 6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-((2-methoxyethyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (5) 4-((2-methoxyethyl)amino)-6-((3,4,5-trimethoxyphenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (6) 4-((2-methoxyethyl)amino)-6-((1-methyl-1H-pyrazol-4-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (7) 4-((2-methoxyethyl)amino)-6-((1-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (8) 4-(ethylamino)-6-((3,4,5-trimethoxyphenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (9) 6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-4-(propylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (10) 6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-(propylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (11) 4-(propylamino)-6-((3,4,5-trimethoxyphenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (12) 6-((1-methyl-1H-pyrazol-4-yl)amino)-4-(propylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (13) 6-((1-methyl-1H-pyrazol-3-yl)amino)-4-(propylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (14) 4-(ethylamino)-6-((1-methyl-1H-pyrazol-4-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (15) 4-(ethylamino)-6-((1-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (16) 6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (17) 6-((5-fluoro-2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (18) 4-(ethylamino)-6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (19) 6-((5-fluoro-2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (20) 6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-((2-methoxyethyl)(methyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (21) 6-((5-fluoro-2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-((2-methoxyethyl)(methyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (22) (R)-6-((2-methoxy-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (23) (S)-6-((2-methoxy-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (24) 6-((4-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)-2-methoxyphenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (25) 6-((4-(4,4-difluoropiperidine-1-carbonyl)-2-methoxyphenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (26) (R)-4-(ethylamino)-6-((2-methoxy-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (27) (S)-4-(ethylamino)-6-((2-methoxy-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (28) 6-((4-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)-2-methoxyphenyl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (29) 6-((4-(4,4-difluoropiperidine-1-carbonyl)-2-methoxyphenyl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (30) 6-((1,3-dimethyl-1H-pyrazol-4-yl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (31) 6-((1,5-dimethyl-1H-pyrazol-4-yl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (32) 4-(ethylamino)-6-((1-isopropyl-3-methyl-1H-pyrazol-4-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (33) 4-(ethylamino)-6-((1-isopropyl-5-methyl-1H-pyrazol-4-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (34) 6-((1,5-dimethyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (35) 6-((1,3-dimethyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (36) 6-((1-isopropyl-3-methyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (37) 6-((1-isopropyl-5-methyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (38) 6-((1-(2-cyanopropan-2-yl)-3-methyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (39) 6-((3-methoxy-5-(morpholine-4-carbonyl)pyridin-2-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (40) 4-(ethylamino)-6-((3-methoxy-5-(morpholine-4-carbonyl)pyridin-2-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (41) 6-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (42) 6-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (43) (R)-4-(ethylamino)-6-((3-methoxy-5-(2-methylmorpholine-4-carbonyl)pyridin-2-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (44) (R)-6-((3-methoxy-5-(2-methylmorpholine-4-carbonyl)pyridin-2-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (45) (5-methoxy-6-(4-(methylamino)-3-(trifluromethyl)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone;   (46) (3-methoxy-4-((4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (47) 4-methoxy-6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (48) 4-methoxy-6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (49) 4-ethoxy-6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (50) 4-ethoxy-6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (51) (R)-6-((3-methoxy-5-(2-methylmorpholine-4-carbonyl)pyridin-2-yl)amino)-4-(1-methylcyclopropoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (52) 6-((3-methoxy-5-(morpholine-4-carbonyl)pyridin-2-yl)amino)-4-(1-methylcyclopropoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (53) N 4 -ethyl-3-(trifluoromethyl)-N 6 -(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (54) N 4 -ethyl-N 6 -(1-methyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (55) N 4 -ethyl-N 6 -(1-methyl-1H-pyrazol-4-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (56) (4-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(morpholino)methanone;   (57) (4-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone;   (58) (3-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(morpholino)methanone;   (59) (3-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-morpholinopiperidin-1-yl)methanone;   (60) (2-fluoro-5-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)methanone;   (61) (3-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (62) N 6 -(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-N 4 -methyl-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (63) (3-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)methanone;   (64) (3-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-6yl)amino)phenyl)(morpholino)methanone;   (65) (3-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-morpholinopiperidin-1-yl)methanone;   (66) (3-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)-methanone;   (67) (3-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (68) N 6 -(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-N 4 -(2-methoxyethyl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (69) N 6 -(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-N 4 -ethyl-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (70) (4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (71) 4-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-fluoro-5methoxy-N-(1-(oxetanepiperidin-4-yl)benzamide;   (72) 4-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzylamide;   (73) 2-fluoro-5-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)(1-methylpiperidin-4-yl)benzamide;   (74) 4-((4-(ethylamino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-fluoro-N-(1-isopropylpiperidin-4-yl)-5-methoxybenzamide;   (75) (R)-(2,4-dimethylpiperazin-1-yl)(2-fluoro-5-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)methanone;   (76) (3-methoxy-4-((4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(morpholino)methanone;   (77) N-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-6-amine;   (78) N6-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-N4-methyl-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (79) N6-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-3-methoxyethyl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (80) 1-(6-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-7-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethan-1-one;   (81) N4-ethyl-N6-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-6-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (82) (3-methoxy-4-((4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)methanone;   (83) (3-methoxy-4-((4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (84) (3-methoxy-4-(3-(trifluoromethyl)-4-(3-(trifluoromethyl)phenylamino)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)phenyl)(morpholino)methanone;   (85) (3-methoxy-4-(3-(trifluoromethyl)-4-(3-(trifluoromethyl)phenylamino)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)phenyl)(4-morpholinopiperidin-1-yl)methanone;   (86) N6-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-3-(trifluoromethyl)-N4-(3-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (87) (3-methoxy-4-((4-methoxyethyl)(methyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(morpholino)methanone;   (88) (3-methoxy-4-((4-methoxyethyl)(methyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)((4-morpholinopiperidin-1-yl)methanone;   (89) N6-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)methoxyethyl)-N4-methyl-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (90) (4-(4-(isopropylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone;   (91) (R)-(4-((4-((1-hydroxy-3-methylbutan-2-yl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]amino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone;   (92) (R)-(4-((4-((1-hydroxy-3-methylbutan-2-yl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]amino)-3-methoxyphenyl)(morpholino)methanone;   (93) (S)-(4-((4-(2-butylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)-methanone;   (94) (4-((4-(cyclopropylamino)-3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone;   (95) (4-((4-(cyclopropylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(morpholino)methanone;   (96) 5-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-6-methoxy-2-methylisoindolin-1-one;   (97) 7-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-6-methoxy-2,2,4-trimethyl-2H-benzo[1,4]oxazin-3(4H)-1-one;   (98) 6-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-5-methoxy-2-methylisoindolin-1-one;   (99) 4-(ethylamino)-6-((6-methoxy-2-methyl-3-oxoisoindol-5-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (100) 6-((2(2-cyanopropan-2-yl)-4-methylthiazol-5-yl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (101) (6-chloro-5-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-methylisoindolin-1-one;   (102) 5-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-methylisoindolin-1-one;   (103) 4-(ethylamino)-6-((2-methyl-1-oxoisoindol-5-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (104) 6-((6-chloro-2-methyl-1-oxoisoindolin-5-yl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile; and,   (105) 4-(ethylamino)-6-((6-methoxy-2,2,4-trimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile.   
     
     
         6 . (canceled) 
     
     
         7 . A pharmaceutical composition comprising a compound represented by chemical formula 1: 
       
         
           
           
               
               
           
         
         the optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein: 
         Z is cyano (—CN): or straight or branched C 1 -C 3  alkyl substituted with one or more halogens: 
         X is —NR a —, —O— or —S—, wherein R a  is hydrogen or straight or branched C 1 -C 10  alkyl, wherein, the alkyl can be substituted with one or more substituents selected from the group consisting of —OH and C 1 -C 3  alkoxy; 
         R 1  is straight or branched C 1 -C 10  alkyl, C 3 -C 8  cycloalkyl or C 6-14  aryl, wherein, the alkyl or cycloalkyl can be substituted with one or more substituents selected from the group consisting of —OH, and, straight or branched C 1 -C 3  alkyl and C 1 -C 3  alkoxy, and the aryl can be substituted with one or more substituents selected from the group consisting of straight or branched C 1 -C 3 alkyl and straight or branched C 1 -C 3  alkoxy, nonsubstituted or substituted with one or more halogens; 
         or, R a  can form nonsubstituted or substituted 5-8 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S along with R 1  and nitrogen atom to which they are attached, and the substituted heterocycloalkyl can be substituted with one or more substituents selected from the group consisting of straight or branched C 1 -C 6  alkyl and straight or branched C 1 -C 6  alkoxy; and 
       
       
         
           
           
               
               
           
         
         wherein, each R 2 , R 4 , R 6 , R 8 , R 11 , R 17 , R 23  and R 24  are independently one or more substituents selected from the group consisting of hydrogen, halogen, straight or branched C 1 -C 6  alkyl and straight or branched C 1 -C 6  alkoxy; 
         R 3 , R 5 , R 7  and R 9  are independently hydrogen; straight or branched C 1 -C 6  alkyl or alkoxy; 3-8 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N and O; or —(C═O)NR 26 R 27 , wherein R 26  and R 27  are independently hydrogen, straight or branched C 1 -C 3  alkyl or 3-8 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N and O substituted with 3-5 membered heterocycloalkyl containing one or more oxygen atoms, or, R 26  and R 27  form 3-8 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N and O along with nitrogen atom to which they are attached, wherein, the alkyl or heterocycloalkyl is substituted with one or more substituents selected from the group consisting of —CN, halogen, straight or branched C 1 -C 3  alkyl, and, 3-6 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N and O nonsubstituted or substituted with one or more straight or branched C 1 -C 3  alkyl 
         R 10  is —CR 28 R 29 —CN, wherein R 28  and R 29  are independently hydrogen or straight or branched C 1 -C 3  alkyl, 
         R 12 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  are independently hydrogen or straight or branched C 1 -C 3  alkyl, or, two of R 12 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  bonded to the same carbon can form carbonyl along with the carbon to which they are attached, and 
         R 16 , R 22  and R 25  are independently hydrogen or straight or branched C 1 -C 3  alkyl, wherein the alkyl can be substituted with one or more halogens. 
       
     
     
         8 . The pharmaceutical composition according to  claim 7 , wherein the composition further comprises diluents or excipients. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . The method according to  claim 1 , wherein the cancer is brain cancer, brain tumor, benign astrocytoma, malignant astrocytoma, pituitary adenoma, meningioma, brain lymphoma, oligodendroglioma, intracranial carcinoma, ependymoma, brainstem tumor, polymorphic glioblastoma, malignant glioma, brain blastoma, metastatic brain tumor, head and neck tumor, larynx cancer, oropharyngeal cancer, nasal cavity/paranasal sinus cancer, nasopharyngeal cancer, salivary gland cancer, hypopharyngeal cancer, thyroid cancer, oral cancer, thoracic tumor, small cell lung cancer, non-small cell lung cancer, thymus cancer, mediastinal tumor, esophageal cancer, breast cancer, male breast cancer, abdominal tumor, stomach cancer, liver cancer, gallbladder cancer, biliary cancer, pancreatic cancer, small bowel cancer, colon cancer, rectal cancer, anal cancer, bladder cancer, kidney cancer, male genital tumor, penile cancer, prostate cancer, female genital tumor, cervical cancer, endometrial cancer, ovarian cancer, uterine sarcoma, vaginal cancer, female external genital cell cancer, female urethral cancer or skin cancer. 
     
     
         14 . The method according to  claim 1 , wherein the cancer is brain cancer, non-small cell lung cancer, breast cancer, colon cancer, rectal cancer, kidney cancer, pancreatic cancer, ovarian cancer, salivary gland cancer, or prostate cancer. 
     
     
         15 . The method according to  claim 1 , wherein the metabolic disease is diabetes, hypoglycemia, hypercholesterolemia, hyperlipidemia, hemochromatosis, amyloidosis or porphyria. 
     
     
         16 . The pharmaceutical composition according to  claim 7 , wherein:
 Z is —CN or methyl substituted with one or more halogens;   X is —NR a — or —O—, wherein R a  is hydrogen or straight or branched C 1 -C 6  alkyl, wherein, the alkyl can be substituted with one or more substituents selected from the group consisting of —OH and C 1 -C 3  alkoxy;   R 1  is straight or branched C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl or C 6-10  aryl, wherein, the alkyl can be substituted with one or more substituents selected from the group consisting of —OH, methyl and methoxy, and the aryl can be substituted with one or more substituents selected from the group consisting of methyl and methoxy, nonsubstituted or substituted with one or more halogens;   or, R a  can form nonsubstituted or substituted 5-6 membered heterocycloalkyl containing one or more heteroatoms selected from the group consisting of N, O and S along with R 1  and nitrogen atom to which they are attached, and the substituted heterocycloalkyl can be substituted with one or more substituents selected from the group consisting of straight or branched C 1 -C 3  alkyl and straight or branched C 1 -C 3  alkoxy; and   
       
         
           
           
               
               
           
         
         wherein, R 2 , R 4 , R 6 , R 8 , R 11 , R 17 , R 23  and R 24  are independently one or more substituents selected from the group consisting of hydrogen, halogen, straight or branched C 1 -C 3  alkyl and straight or branched C 1 -C 3  alkoxy; 
         R 3 , R 8 , R 7  and R 9  are independently hydrogen, straight or branched C 1 -C 3  alkyl or alkoxy, morpholinyl, piperazinyl, piperidinyl or —(C═O)NR 26 R 27 , 
         wherein R 26  and R 27  are independently hydrogen, methyl, morpholinyl, piperazinyl or piperidinyl, or, R 26  and R 27  form morpholinyl, piperazinyl or piperidinyl along with nitrogen atom to which they are attached, wherein, the C 1 -C 3  alkyl, morpholinyl, piperazinyl or piperidinyl can be substituted with one or more substituents selected from the group consisting of —CN, fluoro, oxetanyl, morpholinyl, piperazinyl, and, nonsubstituted or methyl substituted piperidinyl, 
         R 10  is —CR 28 R 29 —CN, wherein R 28  and R 29  are independently hydrogen, methyl or ethyl, 
         R 12 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  are independently hydrogen, methyl or ethyl, or, two of R 2 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  bonded to the same carbon can form carbonyl along with the carbon to which they are attached, and 
         R 16 , R 22  and R 25  are independently hydrogen, methyl nonsubstituted or substituted with one or more halogens or ethyl nonsubstituted or substituted with one or more halogens. 
       
     
     
         17 . The pharmaceutical composition according to  claim 7 , wherein:
 Z is —CN or —CF 3 ;   X is —NR a — or —O—, wherein R a  is hydrogen or methyl;   R 1  is methyl, ethyl, n-propyl, isopropyl, cyclopropyl,   
       
         
           
           
               
               
           
         
          1-methylcyclopropyl, or, phenyl substituted with one or more CF 3 ; 
         or, R a  can form morpholinyl along with R 1  and nitrogen atom to which they are attached; and 
       
       
         
           
           
               
               
           
         
         wherein, R 2 , R 4 , R 6 , R 8 , R 11 , R 17 , R 23  and R 24  are independently one or more substituents selected from the group consisting of hydrogen, chloro, fluoro, methyl and methoxy; 
         R 3  and R 7  are independently methoxy, 
       
       
         
           
           
               
               
           
         
         R 5  and R 9  are independently methyl, isopropyl, N or 
       
       
         
           
           
               
               
           
         
         R 10  is —CR 28 R 29 —CN, wherein R 28  and R 29  are independently hydrogen or methyl, 
         R 12 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  are independently hydrogen or methyl, or, two of R 2 , R 13 , R 14 , R 15 , R 18 , R 19 , R 20  and R 21  bonded to the same carbon can form carbonyl along with the carbon to which they are attached, and 
         R 16 , R 22  and R 25  are independently hydrogen, or, methyl nonsubstituted or substituted with one or more halogens. 
       
     
     
         18 . The pharmaceutical composition according to  claim 7 , wherein:
 Z is —CN or —CF 3 ;   X is —NR a — or —O—, wherein R a  is hydrogen or methyl;   R 1  is methyl, ethyl, n-propyl, isopropyl, cyclopropyl,   
       
         
           
           
               
               
           
         
          1-methylcyclopropyl, or 
       
       
         
           
           
               
               
           
         
         or, R a  can form morpholinyl along with R 1  and nitrogen atom to which they are attached; and 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         19 . The pharmaceutical composition according to  claim 7 , wherein the compound represented by chemical formula 1 is selected from the group consisting of the following compounds:
 (1) 6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (2) 4-(ethylamino)-6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (3) 6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-4-((2-methoxyethyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (4) 6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-((2-methoxyethyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (5) 4-((2-methoxyethyl)amino)-6-((3,4,5-trimethoxyphenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (6) 4-((2-methoxyethyl)amino)-6-((1-methyl-1H-pyrazol-4-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (7) 4-((2-methoxyethyl)amino)-6-((1-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (8) 4-(ethylamino)-6-((3,4,5-trimethoxyphenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (9) 6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-4-(propylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (10) 6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-(propylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (11) 4-(propylamino)-6-((3,4,5-trimethoxyphenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (12) 6-((1-methyl-1H-pyrazol-4-yl)amino)-4-(propylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (13) 6-((1-methyl-1H-pyrazol-3-yl)amino)-4-(propylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (14) 4-(ethylamino)-6-((1-methyl-1H-pyrazol-4-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (15) 4-(ethylamino)-6-((1-methyl-1H-pyrazol-3-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (16) 6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (17) 6-((5-fluoro-2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (18) 4-(ethylamino)-6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (19) 6-((5-fluoro-2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (20) 6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-((2-methoxyethyl)(methyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (21) 6-((5-fluoro-2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-4-((2-methoxyethyl)(methyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (22) (R)-6-((2-methoxy-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (23) (S)-6-((2-methoxy-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (24) 6-((4-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)-2-methoxyphenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (25) 6-((4-(4,4-difluoropiperidine-1-carbonyl)-2-methoxyphenyl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (26) (R)-4-(ethylamino)-6-((2-methoxy-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (27) (S)-4-(ethylamino)-6-((2-methoxy-4-(2-methylmorpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (28) 6-((4-((2R,6S)-2,6-dimethylmorpholine-4-carbonyl)-2-methoxyphenyl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (29) 6-((4-(4,4-difluoropiperidine-1-carbonyl)-2-methoxyphenyl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (30) 6-((1,3-dimethyl-1H-pyrazol-4-yl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (31) 6-((1,5-dimethyl-1H-pyrazol-4-yl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (32) 4-(ethylamino)-6-((1-isopropyl-3-methyl-1H-pyrazol-4-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (33) 4-(ethylamino)-6-((1-isopropyl-5-methyl-1H-pyrazol-4-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (34) 6-((1,5-dimethyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (35) 6-((1,3-dimethyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (36) 6-((1-isopropyl-3-methyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (37) 6-((1-isopropyl-5-methyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (38) 6-((1-(2-cyanopropan-2-yl)-3-methyl-1H-pyrazol-4-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (39) 6-((3-methoxy-5-(morpholine-4-carbonyl)pyridin-2-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (40) 4-(ethylamino)-6-((3-methoxy-5-(morpholine-4-carbonyl)pyridin-2-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (41) 6-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (42) 6-((5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (43) (R)-4-(ethylamino)-6-((3-methoxy-5-(2-methylmorpholine-4-carbonyl)pyridin-2-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (44) (R)-6-((3-methoxy-5-(2-methylmorpholine-4-carbonyl)pyridin-2-yl)amino)-4-(methylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (45) (5-methoxy-6-(4-(methylamino)-3-(trifluromethyl)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)pyridin-3-yl)(4-methylpiperazin-1-yl)methanone;   (46) (3-methoxy-4-((4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (47) 4-methoxy-6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (48) 4-methoxy-6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (49) 4-ethoxy-6-((2-methoxy-4-(4-morpholinopiperidine-1-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (50) 4-ethoxy-6-((2-methoxy-4-(morpholine-4-carbonyl)phenyl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (51) (R)-6-((3-methoxy-5-(2-methylmorpholine-4-carbonyl)pyridin-2-yl)amino)-4-(1-methylcyclopropoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (52) 6-((3-methoxy-5-(morpholine-4-carbonyl)pyridin-2-yl)amino)-4-(1-methylcyclopropoxy)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (53) N 4 -ethyl-3-(trifluoromethyl)-N 6 -(3,4,5-trimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (54) N 4 -ethyl-N 6 -(1-methyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (55) N 4 -ethyl-N 6 -(1-methyl-1H-pyrazol-4-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (56) (4-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(morpholino)methanone;   (57) (4-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone;   (58) (3-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(morpholino)methanone;   (59) (3-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-morpholinopiperidin-1-yl)methanone;   (60) (2-fluoro-5-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)methanone;   (61) (3-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (62) N 6 -(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-N 4 -methyl-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (63) (3-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)methanone;   (64) (3-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-6yl)amino)phenyl)(morpholino)methanone;   (65) (3-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-morpholinopiperidin-1-yl)methanone;   (66) (3-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)-methanone;   (67) (3-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (68) N 6 -(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-N 4 -(2-methoxyethyl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (69) N 6 -(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-N 4 -ethyl-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (70) (4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (71) 4-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-fluoro-5methoxy-N-(1-(oxetanepiperidin-4-yl)benzamide;   (72) 4-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzylamide;   (73) 2-fluoro-5-methoxy-4-((4-((2-methoxyethyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)(1-methylpiperidin-4-yl)benzamide;   (74) 4-((4-(ethylamino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-fluoro-N-(1-isopropylpiperidin-4-yl)-5-methoxybenzamide;   (75) (R)-(2,4-dimethylpiperazin-1-yl)(2-fluoro-5-methoxy-4-((4-(methylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)methanone;   (76) (3-methoxy-4-((4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(morpholino)methanone;   (77) N-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-6-amine;   (78) N6-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-N4-methyl-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (79) N6-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-3-methoxyethyl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (80) 1-(6-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-7-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethan-1-one;   (81) N4-ethyl-N6-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-6-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (82) (3-methoxy-4-((4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-methylpiperazin-1-yl)methanone;   (83) (3-methoxy-4-((4-morpholino-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(4-(4-methylpiperazin-1-yl)piperidin-1-yl)methanone;   (84) (3-methoxy-4-(3-(trifluoromethyl)-4-(3-(trifluoromethyl)phenylamino)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)phenyl)(morpholino)methanone;   (85) (3-methoxy-4-(3-(trifluoromethyl)-4-(3-(trifluoromethyl)phenylamino)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)phenyl)(4-morpholinopiperidin-1-yl)methanone;   (86) N6-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-3-(trifluoromethyl)-N4-(3-(trifluoromethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (87) (3-methoxy-4-((4-methoxyethyl)(methyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)(morpholino)methanone;   (88) (3-methoxy-4-((4-methoxyethyl)(methyl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)phenyl)((4-morpholinopiperidin-1-yl)methanone;   (89) N6-(5-chloro-1-((3S,4S)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)methoxyethyl)-N4-methyl-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-4,6-diamine;   (90) (4-(4-(isopropylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone;   (91) (R)-(4-((4-((1-hydroxy-3-methylbutan-2-yl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]amino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone;   (92) (R)-(4-((4-((1-hydroxy-3-methylbutan-2-yl)amino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]amino)-3-methoxyphenyl)(morpholino)methanone;   (93) (S)-(4-((4-(2-butylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)-methanone;   (94) (4-((4-(cyclopropylamino)-3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-3-methoxyphenyl)(4-morpholinopiperidin-1-yl)methanone;   (95) (4-((4-(cyclopropylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-3-methoxyphenyl)(morpholino)methanone;   (96) 5-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-6-methoxy-2-methylisoindolin-1-one;   (97) 7-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-6-methoxy-2,2,4-trimethyl-2H-benzo[1,4]oxazin-3(4H)-1-one;   (98) 6-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-5-methoxy-2-methylisoindolin-1-one;   (99) 4-(ethylamino)-6-((6-methoxy-2-methyl-3-oxoisoindol-5-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (100) 6-((2(2-cyanopropan-2-yl)-4-methylthiazol-5-yl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (101) (6-chloro-5-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-methylisoindolin-1-one;   (102) 5-((4-(ethylamino)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)amino)-2-methylisoindolin-1-one;   (103) 4-(ethylamino)-6-((2-methyl-1-oxoisoindol-5-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;   (104) 6-((6-chloro-2-methyl-1-oxoisoindolin-5-yl)amino)-4-(ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile; and,   (105) 4-(ethylamino)-6-((6-methoxy-2,2,4-trimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)amino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile.