Mono- or di-substituted indoles as dengue viral replication inhibitors
The present invention concerns mono- or di-substituted indole compounds of formula (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:
(1) R 1 is H, R 2 is F, and R 3 is H, F or CH 3 ;
(2) R 1 is F or CH 3 , R 2 is OCH 3 , and R 3 is H;
(3) R 1 is H, R 2 is Cl, and R 3 is H or CH 3 ;
(4) R 1 is F, R 2 is H, and R 3 is CH 3 ;
(5) R 1 is H, R 2 is OCH 3 , and R 3 is Cl;
(6) R 1 is F, R 2 is F, and R 3 is H;
(7) R 1 is H, R 2 is OCH 3 , and R 3 is CH 3 ; or
(8) R 1 is CH 3 , R 2 is H, and R 3 is F;
or a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.
2. A compound 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 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 to a patient in need thereof.
5. A method of inhibiting the replication of dengue virus in a biological sample or patient, comprising administering 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 to said biological sample or patient in need thereof.
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 another antiviral agent.
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 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 to a patient in need thereof.