Pyrimidone derivatives and their use in the treatment, amelioration or prevention of a viral disease

A compound,

• for use in the treatment, amelioration or prevention of a viral disease caused by Herpesviridae, Filoviridae, Paramyxoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, Arenaviridae, Coronaviridae, Picornaviridae, Togaviridae, or Flaviviridae.
• wherein the compound has the general formula (I):
• wherein
• X10 is NR15, N(R15)C(O), C(O)NR15, O, C(O), C(O)O, OC(O);
• N(R15)SO2, SO2N(R15), S, SO, or SO2;
• R10 is —H, a —C1-6 alkyl group or a —C(O)—C1-6 alkyl group;
• R11 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
• R12 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
• or wherein R11 and R12 can be joined together to form a 3- to 7-membered carbo- or heterocyclic ring;
• R13 is —R16, or —X10—R16;
• R14 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl),
• -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
• R15 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl),
• -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
• R16 is -(optionally substituted hydrocarbon group which contains from 5 to 20 carbon atoms and optionally 1 to 4 heteroatoms selected from O, N and S and which contains at least one ring);
• R17 is —H, —C1-6 alkyl, or —(CH2CH2O)rH;
• R18 is —H, or —C1-6 alkyl;
• R is independently selected from —C1-6 alkyl, —C(O)—C1-6 alkyl, -Hal, —CF3, —CN,
• —COOR17, OR17, —(CH2)qNR17R18, —C(O)—NR17R18, and —NR17—C(O)—C1-6 alkyl;
• R* is independently selected from —H, —C1-6 alkyl, and —C3-7 cycloalkyl;
• q is 0 to 4;
• and
• r is 1 to 3;
• wherein the alkyl group, aryl group, hydrocarbon group and/or cycloalkyl group can be optionally substituted with one or more substituents R;
• or a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof.

A method of treating, ameliorating or preventing a viral disease caused by Herpesviridae, Filoviridae, Paramyxoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, Arenaviridae, Coronaviridae, Picornaviridae, Togaviridae, or Flaviviridae;

• the method comprising administering to a patient in need thereof an effective amount of a compound having the general formula (I):
• wherein
• X10 is NR15, N(R15)C(O), C(O)NR15, O, C(O), C(O)O, OC(O);
• N(R15)SO2, SO2N(R15), S, SO, or SO2;
• R10 is —H, a —C1-6 alkyl group or a —C(O)—C1-6 alkyl group;
• R11 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
• R12 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
• or wherein R11 and R12 can be joined together to form a 3- to 7-membered carbo- or heterocyclic ring;
• R13 is —R16, or —X10—R16;
• R14 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl),
• -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
• R15 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl),
• -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
• R16 is -(optionally substituted hydrocarbon group which contains from 5 to 20 carbon atoms and optionally 1 to 4 heteroatoms selected from O, N and S and which contains at least one ring);
• R17 is —H, —C1-6 alkyl, or —(CH2CH2O)rH;
• R18 is —H, or —C1-6 alkyl;
• R is independently selected from —C1-6 alkyl, —C(O)—C1-6 alkyl, -Hal, —CF3, —CN,
• —COOR17, —OR17, —(CH2)qNR17R18, —C(O)—NR17R18, and —NR17—C(O)—C1-6 alkyl;
• R* is independently selected from —H, —C1-6 alkyl, and —C3-7 cycloalkyl;
• q is 0 to 4;
• and
• r is 1 to 3;
• wherein the alkyl group, aryl group, hydrocarbon group and/or cycloalkyl group can be optionally substituted with one or more substituents R;
• or a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof.

A compound,

• for use in the treatment, amelioration or prevention of influenza, wherein the compound has the general formula (I):
• wherein
• X10 is NR15, N(R15)C(O), C(O)NR15, O, C(O), C(O)O, OC(O);
• N(R15)SO2, SO2N(R15), S, SO, or SO2;
• R10 is —H, a —C1-6 alkyl group or a —C(O)—C1-6 alkyl group;
• R11 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
• R12 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
• or wherein R11 and R12 can be joined together to form a 3- to 7-membered carbo- or heterocyclic ring;
• R13 is —R16, or —X10—R16;
• R14 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl),
• -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
• R15 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl),
• -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
• R16 is -(optionally substituted hydrocarbon group which contains from 5 to 20 carbon atoms and optionally 1 to 4 heteroatoms selected from O, N and S and which contains at least one ring);
• R17 is —H, —C1-6 alkyl, or —(CH2CH2O)rH;
• R18 is —H, or —C1-6 alkyl;
• R is independently selected from —C1-6 alkyl, —C(O)—C1-6 alkyl, -Hal, —CF3, —CN,
• —COOR17, —OR17, —(CH2)qNR17R18, —C(O)—NR17R18, and —NR17—C(O)—C1-6 alkyl;
• R* is independently selected from —H, —C1-6 alkyl, and —C3-7 cycloalkyl;
• q is 0 to 4;
• and
• r is 1 to 3;
• wherein the alkyl group, aryl group, hydrocarbon group and/or cycloalkyl group can be optionally substituted with one or more substituents R;
• or a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof.

A method of treating, ameliorating or preventing influenza;

• the method comprising administering to a patient in need thereof an effective amount of a compound having the general formula (I):
• wherein
• X10 is NR15, N(R15)C(O), C(O)NR15, O, C(O), C(O)O, OC(O);
• N(R15)SO2, SO2N(R15), S, SO, or SO2;
• R10 is —H, a —C1-6 alkyl group or a —C(O)—C1-6 alkyl group;
• R11 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
• R12 is —H a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
• or wherein R11 and R12 can be joined together to form a 3- to 7-membered carbo- or heterocyclic ring;
• R13 is —R16, or —X10—R16;
• R14 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl),
• -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
• R15 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl),
• -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
• R16 is -(optionally substituted hydrocarbon group which contains from 5 to 20 carbon atoms and optionally 1 to 4 heteroatoms selected from O, N and S and which contains at least one ring);
• R17 is —H, —C1-6 alkyl, or —(CH2CH2O)rH;
• R18 is —H, or —C1-6 alkyl;
• R is independently selected from —C1-6 alkyl, —C(O)—C1-6 alkyl, -Hal, —CF3, —CN,
• —COOR17, —OR17, —(CH2)qNR17R18, —C(O)—NR17R18, and —NR17—C(O)—C1-6 alkyl;
• R* is independently selected from —H, —C1-6 alkyl, and —C3-7 cycloalkyl;
• q is 0 to 4;
• and
• r is 1 to 3;
• wherein the alkyl group, aryl group, hydrocarbon group and/or cycloalkyl group can be optionally substituted with one or more substituents R;
• or a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof.