# US 2014/0194476 A1 · Pyridone derivatives and their use in the treatment, ameloriation or prevention of a viral disease

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- Number: US 2014/0194476 A1
- Document ID: US20140194476A1
- Status: Published application
- Kind: A1
- Application number: 14/149,218
- Filed: 2014-01-07
- Published: 2014-07-10
- Earliest claimed: 2013-01-08
- Assignees: European Molecular Biology Laboratory; F. Hoffmann-La Roche AG; Savira pharmaceuticals GmbH
- Applicants: Savira pharmaceuticals GmbH; European Molecular Biology Laboratory; F. Hoffmann-La Roche AG
- Inventors: Andrea Wolkerstorfer; Oliver Szolar; Norbert Handler; Helmut Buschmann; Stephen Cusack; Mark Smith; Sung-Sau So; Ronald Charles Hawley
- Web page: https://patentgrep.com/patent/US20140194476A1

## CPC

- C07D 213/81: Amides; Imides
- A61K 31/4412: having oxo groups directly attached to the heterocyclic ring
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/12: Antivirals
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/78: Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 213/79: Acids; Esters
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to a compound having the general formula (II), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

## Claims

### Claim 1

A compound having the general formula (II),
wherein
X20 is NR25, N(R25)C(O), C(O)NR25, O, C(O), C(O)O, OC(O); N(R25)SO2, SO2N(R25), S, SO, or SO2;
R20 is —H, a —C1-6 alkyl group or a —C(O)—C1-6 alkyl group;
R21 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
R22 is —H, a —C1-6 alkyl group, or a —C1-6 alkyl group which is substituted by one or more halogen atoms;
or wherein R21 and R22 can be joined together to form a 3- to 7-membered carbo- or heterocyclic ring;
R23 is —R26, or —X20—R26;
R24 is H, or a C1-6 alkyl group;
R25 is —H, -(optionally substituted C1-6 alkyl), -(optionally substituted C3-7cycloalkyl), -(optionally substituted aryl), —C1-4 alkyl-(optionally substituted C3-7 cycloalkyl), or —C1-4 alkyl-(optionally substituted aryl);
R26 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);
R27 is —H, —C1-6 alkyl, or —(CH2CH2O)rH;
R28 is —H, or —C1-6 alkyl;
R is independently selected from —C1-6 alkyl, —C(O)—C1-6 alkyl, -Hal, —CF3, —CN,
—COOR27, —OR27, —(CH2)qNR27R28, —C(O)—NR27R28, and —NR27—C(O)—C1-6 alkyl;
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.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein R23 is —R26.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein R23 is —X20—R26 and X20 is N(R25)SO2.

### Claim 4 (depends on 1)

The compound according claim 1, wherein R21 and R22 are —H.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein R26 is selected from the group consisting of
wherein
X is absent, CH2, NH, C(O)NH, S or O;
Y is CH2;
Z is O or S; and
R is independently selected from —H, —C1-6 alkyl, —CF3, -halogen, —CN, —OH, and
—O—C1-6 alkyl.

### Claim 6 (depends on 1)

A pharmaceutical composition comprising:
a compound according to claim 1,
and one or more pharmaceutically acceptable excipient(s) and/or carrier(s).

### Claim 7 (depends on 6)

The pharmaceutical composition according to claim 6, which additionally comprises a further medicament selected from the group consisting of a polymerase inhibitor which is different from the compound having the general formula (II); a neuramidase inhibitor; a M2 channel inhibitor; an alpha glucosidase inhibitor; a ligand of another influenza target; an antibiotic, an anti-inflammatory agent, a lipoxygenase inhibitor, an EP ligand, a bradykinin ligand, a cannabinoid ligand, and combinations thereof.

### Claim 8 (depends on 1)

A compound according to claim 1,
wherein the compound is for use in the treatment, amelioration or prevention of a viral disease.

### Claim 9 (depends on 1)

A method of treating, ameliorating or preventing a viral disease, the method comprising administering to a patient in need thereof an effective amount of a compound according to claim 1.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the viral disease is caused by Herpesviridae, Retroviridae, Filoviridae, Paramyxoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, Arenaviridae, Coronaviridae, Picornaviridae, Togaviridae, or Flaviviridae.

### Claim 11 (depends on 9)

The method according to claim 9 further comprising administering an effective amount of at least one further medicament which is selected from the group consisting of a polymerase inhibitor which is different from the compound having the general formula (II); a neuramidase inhibitor; a M2 channel inhibitor; an alpha glucosidase inhibitor; a ligand of another influenza target; an antibiotic, an anti-inflammatory agent, a lipoxygenase inhibitor, an EP ligand, a bradykinin ligand, a cannabinoid ligand, and combinations thereof.

### Claim 12 (depends on 1)

The compound according to claim 1, which exhibits an IC50 of less than about 40 μM in an FRET endonuclease activity assay.

### Claim 13 (depends on 9)

The method according to claim 9, wherein the viral disease is influenza.

### Claim 14 (depends on 11)

The method according to claim 11, wherein the further medicament is administered concurrently with, sequentially with or separately from the compound having the general formula (II).