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, a pharmaceutically acceptable salt or a prodrug thereof,

• wherein
• A is
• wherein U1 is N or CR1;
• U2 is N or CR2;
• U3 is N or CR3;
• U4 is N or CR4;
• 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 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;
• each of R6 and R8 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, 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 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 and (5- to 10-membered heteroaryl)-C1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;
• R7 is —ORg, methyl, 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 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′;
• or, R6 and R7, together with the carbon atoms to which they are attached, or R7 and R8, 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 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, RdReN—C1-4 alkylene, —C(═O)Ra, —C(═O)ORb, —C(═O)NRcRd, C1-6 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 C1-6 alkyl, 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;
• R9 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 C1-8 alkyl, C3-12 carbocyclyl or 3- to 12-membered heterocyclyl, and wherein each of C1-8 alkyl, C3-12 carbocyclyl and 3- to 12-membered heterocyclyl is independently unsubstituted or substituted with 1, 2, 3 or 4 Rw;
• each Rw is independently D, F, Cl, Br, CN, NO2, oxo (═O), —C(═O)Ra, —C(═O)ORb, —C(═O)NRcRh, —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—C1I2 alkylene, C1-6 alkyl, 5- to 6-membered heteroaryl or 5- to 6-membered heterocyclyl, and wherein each of C1-6 alkyl, 5- to 6-membered heteroaryl and 5- to 6-membered heterocyclyl 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 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, NO2, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy or C1-6 alkylamino;
• Rg is C1-6 haloalkyl, C2-6 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 or (5- to 10-membered heteroaryl)-C1-4 alkylene, and wherein each of C2-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 carbocyclyl, C3-6 carbocyclyl-C1-4 alkylene, 3- to 12-membered hereocyclyl, (3- to 12-membered hereocyclyl)-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 or 4 substituents independently selected from D, F, Cl, CN, OH, NH2, NO2, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy or C1-6 alkylamino;
• Rh is 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 Rh, together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocyclyl or 5- to 8-membered heteroaryl, and wherein each of 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, Cl, CN, OH, NH2, NO2, C1-6 alkyl, C1-6 alkoxy or C1-6 alkylamino.