A compound of the Formula or a tautomer, pharmaceutically-acceptable salt, solvate, chelate or non-covalent complex thereof, wherein, R 1 is selected from the group consisting of C 1-6 alkyl, substituted C 1-6 alkyl, halogen, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 3-6 cycloalkyl and substituted C 3-6 cycloalkyl R 2 is 6-10 membered heteroaryl or substituted 6-10 membered heteroaryl, wherein the 6-10 membered heteroaryl independently contains 1, 2 or 3 heteroatom selected from the group consisting of N, O and S; R 3 is selected from the group consisting of H, amino, cyano, halogen, hydroxy, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-8 cycloalkyl, substituted C 3-8 cycloalkyl, C 1-6 alkoxy, substituted C 1-6 alkoxy, C 3-8 cycloalkyloxy, substituted C 3-8 cycloalkyloxy and cyano substituted cyclopropyl C 1-6 alkyleneoxy; R 4 is wherein X and Y are independently C 1-2 alkylene; Z is selected from the group consisting of CH, N and O; R 4a and R 4b are independently absent or are selected from the group consisting of H, C 1-6 alkyl, substituted C 1-6 alkyl, acryloyl, C 3-6 cycloalkyl, substituted C 3-6 cycloalkyl, 3-8 membered heterocyclyl, substituted 3-8 membered heterocyclyl and -(C=O) C 1-6 alkyl, wherein the 3-8 membered heterocyclyl independently contains 1, 2 and 3 heteroatoms independently selected from the group consisting of N, O and S; wherein the substituted C 1-6 alkyl, the substituted C 2-6 alkenyl, the substituted C 3-6 cycloalkyl, the substituted 6-10 membered heteroaryl, the substituted C 1-6 alkoxy, the substituted C 3-8 cycloalkyloxy and the substituted 3-8 membered heterocyclyl are substituted by halogen, C 1-8 alkyl, C 3-12 cycloalkyl, -ORi', -SR 1 ', =O, =S, -C R 1 ', -C R 1 ', =NR 1 ', -C OR 1 ', -C OR 1 ', -NR 1 'R 2 ', -C NR 1 'R 2 ', cyano, nitro, -S 2 R 1 ', -OS(O 2)OR 1 ', -OS 2 R 1 ' or -OP (OR 1 ')(OR 2 '), wherein R 1 ' and R 2 ' are independently selected from -H, C 1-6 alkyl, and C 1-6 haloalkyl; R 5 is unsubstituted or halo substituted acryloyl; or a compound selected from the group consisting of: and R 1 is selected from the group consisting of C 1-6 alkyl, substituted C 1-6 alkyl, halogen, C 2-6 alkenyl, substituted C 2-6 alkenyl, C 3-6 cycloalkyl and substituted C 3-6 cycloalkyl R 2 is 6-10 membered heteroaryl or substituted 6-10 membered heteroaryl, wherein the 6-10 membered heteroaryl independently contains 1, 2 or 3 heteroatom selected from the group consisting of N, O and S; R 3 is selected from the group consisting of H, amino, cyano, halogen, hydroxy, C 1-6 alkyl, substituted C 1-6 alkyl, C 3-8 cycloalkyl, substituted C 3-8 cycloalkyl, C 1-6 alkoxy, substituted C 1-6 alkoxy, C 3-8 cycloalkyloxy, substituted C 3-8 cycloalkyloxy and cyano substituted cyclopropyl C 1-6 alkyleneoxy; R 4 is wherein X and Y are independently C 1-2 alkylene; Z is selected from the group consisting of CH, N and O; R 4a and R 4b are independently absent or are selected from the group consisting of H, C 1-6 alkyl, substituted C 1-6 alkyl, acryloyl, C 3-6 cycloalkyl, substituted C 3-6 cycloalkyl, 3-8 membered heterocyclyl, substituted 3-8 membered heterocyclyl and -(C=O) C 1-6 alkyl, wherein the 3-8 membered heterocyclyl independently contains 1, 2 and 3 heteroatoms independently selected from the group consisting of N, O and S; wherein the substituted C 1-6 alkyl, the substituted C 2-6 alkenyl, the substituted C 3-6 cycloalkyl, the substituted 6-10 membered heteroaryl, the substituted C 1-6 alkoxy, the substituted C 3-8 cycloalkyloxy and the substituted 3-8 membered heterocyclyl are substituted by halogen, C 1-8 alkyl, C 3-12 cycloalkyl, -ORi', -SR 1 ', =O, =S, -C R 1 ', -C R 1 ', =NR 1 ', -C OR 1 ', -C OR 1 ', -NR 1 'R 2 ', -C NR 1 'R 2 ', cyano, nitro, -S 2 R 1 ', -OS(O 2)OR 1 ', -OS 2 R 1 ' or -OP (OR 1 ')(OR 2 '), wherein R 1 ' and R 2 ' are independently selected from -H, C 1-6 alkyl, and C 1-6 haloalkyl; R 5 is unsubstituted or halo substituted acryloyl; or a compound selected from the group consisting of: and