Mono- or di-substituted indole derivatives as dengue viral replication inhibitors

Patent metadata

Field	Value
Publication number	US-9944598-B2
Application number	US-201515515574-A
Country	US
Kind code	B2
Filing date	Sep 30, 2015
Priority date	Oct 1, 2014
Publication date	Apr 17, 2018
Grant date	Apr 17, 2018

Abstract

The present invention concerns mono- or di-substituted indole derivatives (I) which are useful to prevent or treat dengue viral infections and also relates to said compounds for use as a medicine, more preferably for use as a medicine to treat or prevent dengue viral infections. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of dengue viral infections. The invention also relates to processes for preparation of the compounds.

First claim

The invention claimed is:

1. A compound of formula (I)

wherein:
when R 1 is H, and R 2 is F then R 3 is H, F or CH 3 ;
when R 1 is F or CH 3 , R 2 is OCH 3 then R 3 is H;
when R 1 is F, and R 2 is H then R 3 is CH 3 ;
when R 1 is H, and R 2 is OCH 3 then R 3 is H;
when R 1 is H, and R 2 is Cl then R 3 is H or CH 3 ;
when R 1 is F, and R 2 is F then R 3 is H; and
when R 1 is CH 3 , and R 2 is H then R 3 is F;
or a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.

2. A compound of claim 1 selected from the group consisting of:

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

3. A pharmaceutical composition comprising a compound of formula (I) or a stereo- isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof; according to claim 1 and one or more pharmaceutically acceptable excipients, diluents or carriers.

4. A method of treating a dengue viral infection, comprising administering to a mammal a therapeutically effective amount of at least one compound or a stereo- isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof as claimed in claim 1 .

5. A method of inhibiting the replication of dengue virus in a biological sample or patient, comprising administering to said biological sample or patient a therapeutically effective amount of at least one compound or a stereo- isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof as claimed in claim 1 .

6. The method as claimed in claim 5 further comprising co-administering an additional therapeutic agent.

7. The method as claimed in claim 6 wherein said additional therapeutic agent is at least one selected from the group consisting of an antiviral agent and a dengue vaccine.

8. A pharmaceutical composition comprising a compound or a stereo- isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof according to claim 2 and one or more pharmaceutically acceptable excipients, diluents or carriers.

9. A method of treating a dengue viral infection, comprising administering to a mammal a therapeutically effective amount of at least one compound or a stereo- isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof as claimed in claim 2 .

10. The compound of claim 2 which is

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

11. The compound of claim 10 , which is

12. The method of claim 4 wherein said compound is

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

13. The method of claim 12 , wherein said compound is

14. The method of claim 5 , wherein said compound is

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

15. The method of claim 14 , wherein said compound is

16. The pharmaceutical composition of claim 8 , wherein said compound is

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

17. The pharmaceutical composition of claim 16 , wherein said compound is

Assignees

• Janssen Pharmaceuticals Inc
• Univ Leuven Kath

Inventors

• Kesteleyn Bart Rudolf Romanie
• Bonfanti Jean-François
• Jonckers Tim Hugo Maria
• Raboisson Pierre Jean-Marie Bernard
• Bardiot Dorothée Alice Marie-Eve
• Marchand Arnaud Didier M

Classifications

• A61P43/00

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

• A61P31/12

  Antivirals · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C07D209/14 Primary

  Radicals substituted by nitrogen atoms, not forming part of a nitro radical · CPC title