Indoles as respiratory syncytial virus antiviral agents

1. A compound of formula I, N-oxide, addition salt, quaternary amine, or a stereochemically isomeric form thereof;

wherein each X independently is C or N;

each R 1 is independently selected from the group consisting of H, halogen, C 1 -C 6 alkoxy, —CF 3 , and OCF 3 ;

R 2 is selected from the group consisting of H, halogen, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 6 alkoxy, and CO(R 7 );

R 3 is —(CR 8 R 9 ) n —R 10 ;

R 4 is selected from the group consisting of H, C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 10 alkenyl, SO 2 —R 8 , CH 2 CF 3 , SO 2 CH 3 or a 4 to 6 membered saturated ring containing an oxygen atom;

R 5 is present where X is C, and is independently selected from the group consisting of H, C 1 C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 6 alkoxy, CO(R 7 ), CF 3 and halogen;

R 5 is absent where X is N;

R 7 is selected from the group consisting of OH, O(C 1 -C 6 alkyl), NH 2 , NHSO 2 N(C 1 -C 6 alkyl) 2 , NHSO 2 NHCH 3 , NHSO 2 (C 1 -C 6 alkyl), NHSO 2 (C 3 -C 7 cycloalkyl), and N(C 1 -C 6 -alkyl) 2 , NR 8 R 9 , NR 9 R 10 ;

n is an integer from 2 to 6;

R 8 and R 9 are each independently chosen from H, C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl or R 8 and R 9 taken together form a 4 to 6 membered aliphatic ring that optionally contains one or more heteroatoms selected from the group N, S, O;

R 10 is selected from the group consisting of H, C 1 -C 6 alkyl, OH, CN, F, CF 2 H, CF 3 , C(═NOH)NH 2 , CONR 8 R 9 , COOR 8 , CONR 8 SO 2 R 9 , CON(R 8 )SO 2 N(R 8 R 9 ), NR 8 R 9 , NR 8 COOR 9 , OCOR 8 , NR 8 SO 2 R 9 , SO 2 NR 8 R 9 , SO 2 R 8 or a 4 to 6 membered saturated ring containing an oxygen atom.

2. A compound according to claim 1 ,

wherein

R 4 is selected from the group consisting of H, C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, C 2 -C 10 alkenyl, SO 2 —R 8 , or a 4 to 6 membered saturated ring containing an oxygen atom.

3. A compound according to claim 1 wherein each R 1 is independently selected from the group consisting of H, and halogen.

4. A compound according to claim 1 , wherein R 1 in the para position to N—R 3 is selected from the group consisting of H, halogen, and all other R 1 are H.

5. A compound according to claim 4 , wherein R 1 in the para position to N—R 3 is selected from the group consisting of bromo and chloro.

6. A compound according to claim 1 , wherein R 2 is selected from the group consisting of H, halogen, and CO(R 7 ).

7. A compound according to claim 1 , wherein R 2 is selected from the group consisting of H, I, and CONH 2 .

8. A compound according to claim 1 , wherein R 3 comprises a —(CR 8 R 9 ) n chain wherein R 8 and R 9 are H and n is 2-4.

9. A compound according to claim 1 , wherein R 10 is selected from the group consisting of F, CF 3 , OH, SO 2 R 8 , and CN, with R 8 being methyl.

10. A compound according to claim 1 , wherein R 4 is C 3 -C 7 cycloalkyl or CH 2 CF 3 .

11. A compound according to claim 1 , wherein R 4 is isopropyl.

12. A compound according to claim 1 , wherein R 4 is oxetan-3-yl.

13. A compound according to claim 1 , wherein the X in para position to N—R 4 is C and the R 5 on that X is F.

14. A compound according to claim 1 , wherein one X is N and the other X's are C, the N being in para position to N—R 4 .

15. A compound according to claim 1 , wherein at most one R 5 is selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 -alkoxy, and halogen, and the other R 5 are H.

16. A compound according to claim 1 , wherein all R 5 are H.

17. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and as active ingredient a therapeutically effective amount of a compound as claimed in claim 1 .

18. A process for preparing a pharmaceutical composition, said process comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 1 .

19. A compound according to claim 1 , wherein the compound is

or N-oxide, addition salt, or quaternary amine thereof.

20. A compound of the formula