7-oxo-thiazolopyridine carbonic acid derivatives and their use in the treatment, amelioration or prevention of a viral disease

A pharmaceutical composition comprising (i) a compound having the general formula (A)

• wherein
• R* is —H, —Hal, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl), -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), —C1-4 alkyl-(optionally substituted aryl) or —X1—R1;
• X1 is O, C(O), C(O)O, OC(O);
• S, SO, SO2, NR4, N(R5)C(O), C(O)NR5;
• X2 is O, S, NR4;
• X3 is O or S;
• X4 is O or S;
• R1 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl), -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), —C1-4 alkyl-(optionally substituted aryl);
• R3 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl), -(optionally substituted aryl), or —C1-4 alkyl-(optionally substituted aryl) or if X2 is NR4, then R3 can also be —OH;
• R4 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) or if X1 is NR4, then R4 and R1 can be joined together to form a 5- to 7-membered ring, which can optionally contain O, S or further N or if X2 is NR4, then R4 and R3 can be joined together to form a 5- to 7-membered ring, which can optionally contain O, S or further N;
• and
• R5 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);
• and
• R6 is —H, or —C1-6 alkyl;
• wherein the optional substituent of the alkyl group is selected from the group consisting of halogen, —CN, —NR6R6, —OH, and —O—C1-6 alkyl;
• wherein the optional substituent of the cycloalkyl group, the aryl group or the hydrocarbon group is selected from the group consisting of —C1-6 alkyl, halogen, —CF3, —CN, —X1—R5 and —C1-4 alkyl-aryl;
• wherein R2 is selected from the group consisting of
• wherein
• X is absent, CH2, NH, C(O)NH, S or O;
• Y is CH2;
• or
• X and Y can be joined together to form an annulated, carbo- or heterocylic 3- to 8-membered ring which can be saturated or unsaturated;
• and
• R is independently selected from H, —C1-6 alkyl, halogen, —CN, —OH, and —O—C1-6 alkyl;
• or a pharmaceutically acceptable salt, solvate, polymorph, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof,
• wherein, the prodrug is a compound where X2 is O or S, and R3 is one of the following groups:
• wherein R6 is the same or different,
• wherein R9 is aryl or C3-7 cycloalkyl,
• p is 2-8;
• and (ii) a pharmaceutically acceptable excipient.

A compound having the general formula (A)

• wherein
• R* is —H, —Hal, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl), -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), —C1-4 alkyl-(optionally substituted aryl) or —X1—R1;
• X1 is O, C(O), C(O)O, OC(O);
• S, SO, SO2, NR4, N(R5)C(O), C(O)NR5;
• X2 is O, S, NR4;
• X3 is O or S;
• X4 is O or S;
• R1 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl), -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), —C1-4 alkyl-(optionally substituted aryl);
• R3 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7 cycloalkyl), -(optionally substituted aryl), or —C1-4 alkyl-(optionally substituted aryl) or if X2 is NR4, then R3 can also be —OH;
• R4 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) or if X1 is NR4, then R4 and R1 can be joined together to form a 5- to 7-membered ring, which can optionally contain O, S or further N or if X2 is NR4, then R4 and R3 can be joined together to form a 5- to 7-membered ring, which can optionally contain O, S or further N;
• and
• R5 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);
• and
• R6 is —H, or —C1-6 alkyl;
• wherein the optional substituent of the alkyl group is selected from the group consisting of halogen, —CN, —NR6R6, —OH, and —O—C1-6 alkyl;
• wherein the optional substituent of the cycloalkyl group, the aryl group or the hydrocarbon group is selected from the group consisting of —C1-6 alkyl, halogen, —CF3, —CN, —X1—R5 and —C1-4 alkyl-aryl;
• wherein R2 is selected from the group consisting of
• wherein
• X is absent, CH2, NH, C(O)NH, S or O;
• Y is CH2;
• or
• X and Y can be joined together to form an annulated, carbo- or heterocylic 3- to 8-membered ring which can be saturated or unsaturated;
• and
• R is independently selected from H, —C1-6 alkyl, halogen, —CN, —OH, and —O—C1-6 alkyl;
• or a pharmaceutically acceptable salt, solvate, polymorph, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof,
• wherein, the prodrug is a compound where X2 is O or S, and R3 is one of the following groups:
• wherein R6 is the same or different,
• wherein R9 is aryl or C3-7 cycloalkyl,
• p is 2-8;
• wherein the compound is for use in the treatment or amelioration of a viral disease, wherein the viral disease is influenza.