Dihydropyranopyrimidines for the treatment of viral infections

Patent metadata

Field	Value
Publication number	US-11053256-B2
Application number	US-201716312687-A
Country	US
Kind code	B2
Filing date	Jun 30, 2017
Priority date	Jul 1, 2016
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

Abstract

This invention relates to dihydropyranopynmidine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

First claim

The invention claimed is:

1. A method of treating viral hepatitis in which the activation of TLR7 and/or TLR8 is involved in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula (I), (II) or (III) having the structure

or a pharmaceutically acceptable salt, tautomer, stereo-isomeric form, or solvate thereof, wherein
R 1 is C 1-6 alkyl substituted by one or more substituents independently selected from hydroxyl or C 1-3 alkoxy;
R 2 is selected from hydrogen, fluorine, C 1-3 alkyl, cyclopropyl, —CF 3 , C 1-3 alkoxy or nitrile.

2. A method of treating viral hepatitis in which the activation of TLR7 and/or TLR8 is involved in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound having a structure selected from the group consisting of:

or a pharmaceutically acceptable salt, tautomer, stereo-isomeric form, or solvate thereof.

3. The method of claim 1 , wherein the activation of TLR8 is involved in the subject in need thereof.

4. The method of claim 1 , wherein R 1 is C 1-6 alkyl substituted by hydroxyl.

5. The method of claim 1 , wherein R 1 is C 6 alkyl substituted by hydroxyl.

6. The method of claim 1 , wherein R 1 is:

7. The method of claim 1 , wherein R 1 is:

8. The method of claim 1 , wherein R 2 is hydrogen.

9. The method of claim 2 , wherein the activation of TLR8 is involved in the subject in need thereof.

10. A method of activating human TLR7 and/or TLR8 in a subject, comprising administering to the subject an effective amount of a compound of formula (I), (II) or (III) having the structure

or a pharmaceutically acceptable salt, tautomer, stereo-isomeric form, or solvate thereof, wherein
R 1 is C 1-6 alkyl substituted by one or more substituents independently selected from hydroxyl or C 1-3 alkoxy;
R 2 is selected from hydrogen, fluorine, C 1-3 alkyl, cyclopropyl, —CF 3 , C 1-3 alkoxy or nitrile.

11. The method of claim 10 , wherein the compound has a structure selected from the group consisting of:

or a pharmaceutically acceptable salt, tautomer, stereo-isomeric form, or solvate thereof.

Assignees

• Janssen Sciences Ireland Unlimited Co

Inventors

• Jonckers Tim Hugo Maria
• Raboisson Pierre Jean-Marie Bernard
• Guillemont Jérôme Émile Georges
• Mcgowan David Craig
• Embrechts Werner Constant Johan
• Cooymans Ludwig Paul
• Calmus Laurent

Classifications

• C07D491/052 Primary

  the oxygen-containing ring being six-membered · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P31/02

  Local antiseptics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title