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