Inhibitors of influenza virus replication, application methods and uses thereof

A compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, or a pharmaceutically acceptable salt thereof,

• wherein,
• U is N or CR5;
• each of R1, R2, R3, R4 and R5 is independently H, D, F, Cl, Br, CN, NO2, —C(═O)Ra, —C(═O)ORb, —C(═O)NRcRd, ORb, —NRcRd, RbO—C1-4 alkylene, RdRcN—C1-4 alkylene, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, and wherein each of the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, ORb, —NRcRd, C1-6 alkyl, C1-6 haloalkyl, RbO—C1-4 alkylene or RdRcN—C1-4 alkylene;
• R6 is ORb, C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocyclyl, C3-12 carbocyclyl-C1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C1-4 alkylene, C6-10 aryl, C6-10 aryl-C1-4 alkylene, 5- to 16-membered heteroaryl or (5- to 16-membered heteroaryl)-C1-4 alkylene, and wherein each of the C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 carbocyclyl, C3-12 carbocyclyl-C1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C1-4 alkylene, C6-10 aryl, C6-10 aryl-C1-4 alkylene, 5- to 16-membered heteroaryl and (5- to 16-membered heteroaryl)-C1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;
• R7 is H, D, F, Cl, Br, CN, NO2, —C(═O)Ra, —C(═O)ORb, —C(═O)NRcRd, ORb, —NRcRd, RbO—C1-4 alkylene, RdRcN—C1-4 alkylene, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl, C3-12 cycloalkyl-C1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C1-4 alkylene, C6-10 aryl, C6-10 aryl-C1-4 alkylene, 5- to 10-membered heteroaryl or (5- to 10-membered heteroaryl)-C1-4 alkylene, and wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-12 cycloalkyl, C3-12 cycloalkyl-C1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C1-4 alkylene, C6-10 aryl, C6-10 aryl-C1-4 alkylene, 5- to 10-membered heteroaryl and (5- to 10-membered heteroaryl)-C1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;
• or, R6 and R7, together with the carbon atoms to which they are attached, form a C3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C6-10 aromatic ring or 5- to 10-membered heteroaromatic ring, and wherein each of the C3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C6-10 aromatic ring and 5- to 10-membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;
• each R′ is independently D, F, Cl, Br, CN, NO2, ORb, —NRcRd, RbO—C1-4 alkylene, RdRcN—C1-4 alkylene, —C(═O)Ra, —C(═O)ORb, —C(═O)NRcRd, C1-12 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-4 alkylene, 3- to 8-membered heterocyclyl, (3- to 8-membered heterocyclyl)-C1-4 alkylene, C6-10 aryl, C6-10 aryl-C1-4 alkylene, 5- to 8-membered heteroaryl or (5- to 8-membered heteroaryl)-C1-4 alkylene, and wherein each of the C1-12 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-4 alkylene, 3- to 8-membered heterocyclyl, (3- to 8-membered heterocyclyl)-C1-4 alkylene, C6-10 aryl, C6-10 aryl-C1-4 alkylene, 5- to 8-membered heteroaryl and (5- to 8-membered heteroaryl)-C1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO2, ORb, —NRcRd, C1-6 alkyl, C1-6 haloalkyl, RbO—C1-4 alkylene or RdRcN—C1-4 alkylene;
• R8 is H, D or C1-6 alkyl, and wherein C1-6 alkyl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO2 or ORb;
• W is one of the following sub-formulae:
• wherein n is 0, 1, 2, 3, or 4;
• each Rw is independently D, F, Cl, Br, CN, NO2, oxo (═O), —C(═O)Ra, —C(═O)ORb, —NReC(═O)Ra, —NReC(═O)NRcRd, —S(═O)2Rf, —S(═O)2NReC(═O)Ra, —S(═O)2NRcRd, (RbO)2P(═O)—C0-2 alkylene, ORb, RbO—C1-2 alkylene, C1-6 alkyl or 5- to 6-membered heteroaryl, and wherein each of the C1-6 alkyl and 5- to 6-membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, N3, oxo (═O), NO2, ORb, C1-6 alkyl or C1-6 haloalkyl;
• each Ra, Rb, Rc, Rd, Re and Rf is independently H, D, C1-6 haloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 carbocyclyl, C3-6 carbocyclyl-C1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C1-4 alkylene, C6-10 aryl, C6-10 aryl-C1-4 alkylene, 5- to 10-membered heteroaryl, (5- to 10-membered heteroaryl)-C1-4 alkylene;
• or, Rc and Rd, together with the nitrogen atom to which they are attached, form 3- to 8-membered heterocyclyl or 5- to 8-membered heteroaryl, and wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 carbocyclyl, C3-6 carbocyclyl-C1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C1-4 alkylene, C6-10 aryl, C6-10 aryl-C1-4 alkylene, 5- to 10-membered heteroaryl, (5- to 10-membered heteroaryl)-C1-4 alkylene, 3- to 8-membered heterocyclyl and 5- to 8-membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, CN, OH, NH2, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy or C1-6 alkylamino.