Aminothiazole derivatives useful as antiviral agents

A compound represented by Formula (I)

• or an enantiomer, diastereomer, tautomer, N-oxide, formulation and pharmaceutically acceptable salt thereof, wherein:
• X is selected from
• R1 is selected from H, halogen, C1-6-alkyl, halo-C1-6-alkyl, C3-6-cycloakyl, halo-C3-6-cycloalkyl, —O—C1-6-alkyl, —O-halo-C1-6-alkyl and —NH—C1-6-alkyl;
• R2 is selected from H, —CN, —NO2, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C0-10-alkylene-C3-10cycloalkyl, C0-10-alkylene-C3-10-heterocycloalkyl, C0-10-alkylene-(5- to 10-membered heteroaryl), C0-10-alkylene-(6- to 10-membered aryl), C0-10-alkylene-(6-to 10-membered heteroaryl), C0-10-alkylene-OR11, C0-10-alkylene-CO2R11, C0-10-alkylene-C(═O)NR11R12, C0-10-alkylene-C(═S)NR11R12, C0-10-alkylene-C(═O)NR11SO2R13, C0-10-alkylene-C(═S)NR11SO2R11, C0-10-alkylene-C(═O)R11, C0-10-alkylene-C(═S)R11, C0-10-alkylene-SR11, C0-10-alkylene-SOxR13, C0-10-alkylene-SO3R11, C0-10-alkylene-SO2NR11R12, C0-10-alkylene-NR11C(═O)R11, C0-10-alkylene-NR11C(═S)R11, C0-10-alkylene-NR11SO2R13, C0-10-alkylene-NR11C(═O)NR11R12, C0-10-alkylene-NR11C(═S))N11R12, C0-10-alkylene-NR11SO2NR11R12, C0-10-alkylene-NR11R12, wherein alkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of oxo, —CN, —NO2, OR11, O—C2-6-alkylene-OR11, C1-6-alkyl, halo-C1-6-alkyl, halogen, CO2R11, C(═O)NR11R12, C(═O)NR11SO2R11, C(═O)R11, SR11, SOxR11, SO3R11, P(═O)(OR11)2, SO2NR11R12, NR11C(═O)R11, NR11SO2R13, NR11C(═O)NR11R12, NR11SO2NR11R12, C3-10-cycloalkyl, O—C3-10-cycloalkyl, C3-10-heterocycloalkyl, O—C3-10-heterocycloalkyl and NR11R12;
• R3 is selected from H, C1-6-alkyl, halo-C1-6-alkyl, —O—C1-6-alkyl, —O-halo-C1-6-alkyl, C3-6-cycloalkyl and C3-6-heterocycloalkyl, wherein alkyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 5 substituents independently selected from halogen, —CN, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl, SO2—C1-3-alkyl, CO2H;
• or R2 and R3 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 additional heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO2, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl, SO2—C1-3-alkyl, CO2H;
• R4 is selected from H, C1-6-alkyl, C1-6-acyl, C2-6-alkenyl, C3-8-cycloalkyl and C3-8-heterocycloalkyl, wherein alkyl, acyl, alkenyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 5 substituents independently selected from halogen, —CN, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl;
• R5 and R6 and R5′ and R6′ are independently selected from H, halogen, C1-6-alkyl, NH2, NHC1-6-alkyl, N(C1-6-alkyl)2, C0-6-alkylene-C(═O)NH2;
• or R5 and R6 and R5′ and R6′ independently when taken together with the carbon to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO2, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl, SO2—C1-3-alkyl, CO2H;
• or R5 and R5′ and R6 and R6′ independently when taken together with the two adjacent carbon to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO2, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl, SO2—C1-3-alkyl, CO2H;
• R7 is selected from a 6-membered aryl and 5- or 6-membered heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1 to 4 substituents independently selected from halogen, —CN, —NO2, OH, C1-6-alkyl, O—C1-6-alkyl, C3-6-cycloalkyl, O—C3-6-cycloalkyl, C3-6-heterocycloalkyl, O—C3-6-heterocycloalkyl, SOy—C1-6-alkyl, CO2H, C(═O)O—C1-6-alkyl, 6- to 10-membered aryl, 5- or 10-membered heteroaryl, O-(6- to 10-membered aryl) and O-(5- or 10-membered heteroaryl), wherein alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with 1 to 5 substituents independently selected from halogen, —CN, —NO2, OH, R13, OR13, CO2R11, NR11R12, C(═O)R11, C(═S)R11, C(═O)NR11R12, NR11C(═O)NR11R12, NR11C(═O)OR13, OC(═O)NR11R12, C(═S)NR11R12, NR11C(═S)NR11R12, NR11C(═S)OR13, OC(═S)NR11R12;
• SOy—C1-6-alkyl, SOy-halo-C1-6-alkyl, SR11, SOxR13, SO3R11, SO2NR11R12, NR11SO2R13, NR11SO2NR11R12;
• R8 is selected from H, —CN, —NO2, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C0-10-alkylene-C3-10-cycloalkyl, C0-10-alkylene-C3-10-heterocycloalkyl, C0-10-alkylene-(5 to 10-membered heteroaryl), C0-10-alkylene-(6 to 10-membered aryl), C0-10-alkylene-(6 to 10-membered heteroaryl), C0-10-alkylene-OR11, C0-10-alkylene-CO2R11, C0-10-alkylene-C(═O)NR11R12, C0-10-alkylene-C(═S)NR11R12, C0-10-alkylene-C(═O)NR11SO2R13, C0-10-alkylene-C(═S)NR11SO2R11, C0-10-alkylene-C(═O)R11, C0-10-alkylene-C(═S)R11, C0-10-alkylene-SR11, C0-10-alkylene-SOx—R13, C0-10-alkylene-SO3R11, C0-10-alkylene-SO2NR11R12, C0-10-alkylene-NR11C(═O)R11, C0-10-alkylene-NR11C(═S)R11, C0-10-alkylene-NR11SO2R11, C0-10-alkylene-NR11C(═O)NR11R12, C0-10-alkylene-NR11C(═S)NR11R12, C0-10-alkylene-NR11—SO2—NR11R12, C0-10-alkylene-NR11R12, wherein alkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of oxo, —CN, —NO2, OR11, O—C2-6-alkylene-OR11, C1-6-alkyl, halo-C1-6-alkyl, halogen, CO2R11, CONR11R12, CONR11SO2R11, COR11, SOxR11, SO3H, PO(OH)2, SO2NR11R12, NR11COR11, NR11SO2R11, NR11—CO—NR11R12, NR11—SO2—NR11R12, C3-10-cycloalkyl, O—C3-10-cycloalkyl, C3-10-heterocycloalkyl, O—C3-10-heterocycloalkyl and NR11R12;
• R9 is selected from C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C0-10-alkylene-C3-10-cycloalkyl, C0-10-alkylene-C3-10-heterocycloalkyl, C0-10-alkylene-(5- to 10-membered heteroaryl), C0-10-alkylene-(6- to 10-membered aryl), C0-10-alkylene-(6- to 10-membered heteroaryl), C0-10-alkylene-OR11, C0-10-alkylene-CO2R11, C0-10-alkylene-C(═O)NR11R12, C0-10-alkylene-C(═S)NR11R12, C0-10-alkylene-C(═O)NR11SO2R13, C0-10-alkylene-C(═S)NR11SO2R11, C0-10-alkylene-C(═O)R11, C0-10-alkylene-C(═S)R11, C0-10-alkylene-SR11, C0-10-alkylene-SOxR13, C0-10-alkylene-SO3R11, C0-10-alkylene-SO2NR11R12, C0-10-alkylene-NR11C(═O)R11, C0-10-alkylene-NR11C(═S)R11, C0-10-alkylene-NR11SO2R13, C0-10-alkylene-NR11C(═O)NR11R12, C0-10-alkylene-NR11C(═S)NR11R12, C0-10-alkylene-NR11SO2NR11R12, C0-10-alkylene-NR11R12, wherein alkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of oxo, —CN, —NO2, OR11, O—C2-6-alkylene-OR11, C1-6-alkyl, halo-C1-6-alkyl, halogen, CO2R11, C(═O)NR11R12, C(═O)NR11SO2R11, C(═O)R11, SR11, SOxR11, SO3R11, P(═O)(OR11)2, SO2NR11R12, NR11C(═O)R11, NR11SO2R13, NR11C(═O)NR11R12, NR11SO2NR11R12, C3-10-cycloalkyl, O—C3-10-cycloalkyl, C3-10-heterocycloalkyl, O—C3-10-heterocycloalkyl and NR11R12;
• R11 is independently selected from H, C1-6-alkyl, C0-6-alkylene-C3-10-cycloalkyl and C0-6-alkylene-C3-10-heterocycloalkyl, wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 6 substituents independently selected from the group consisting of halogen, —CN, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl, NH2, NH(C1-3-alkyl), N(C1-3-alkyl)2, C3-6-heterocycloalkyl, C3-6-cycloalkyl, SO2—NHC1-3-alkyl, SO2—N(C1-3-alkyl)2 and SO2—C1-3-alkyl, wherein cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of F, OH, oxo, CH3, CHF2 and CF3;
• R12 is independently selected from H, C1-6-alkyl, halo-C1-6-alkyl and C3-6-cycloalkyl;
• or R11 and R12 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO2, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl, SO2—C1-3-alkyl, CO2H;
• R13 is independently selected from C1-6-alkyl, C0-6-alkylene-C3-10-cycloalkyl and C0-6-alkylene-C3-10-heterocycloalkyl, wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 6 substituents independently selected from the group consisting of halogen, —CN, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl, NH2, NH(C1-3-alkyl), N(C1-3-alkyl)2, C3-6-heterocycloalkyl, C3-6-cycloalkyl, SO2—NHC1-3-alkyl, SO2—N(C1-3-alkyl)2 and SO2—C1-3-alkyl, wherein cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of F, OH, oxo, CH3, CHF2 and CF3;
• n is selected from 0 and 1;
• x is independently selected from 1 and 2;
• y is independently selected from 0, 1 and 2;
• and wherein optionally R1 is connected to one residue selected from R2, R3, R8, R9, or R12 to form a 5 to 8-membered heterocycle, which is optionally substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —ON, —NO2, OH, oxo, C1-3-alkyl, halo-C1-3-alkyl, O—C1-3-alkyl, O-halo-C1-3-alkyl, SO2—C1-3-alkyl, CO2H.