Benzimidazole respiratory syncytial virus inhibitors
View Patent ↗Benzimidazoles having inhibitory activity on RSV replication and having the formula the prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms thereof, compositions containing these compounds as active ingredient and processes for preparing these compounds and compositions.
1. A compound represented by formula I, a prodrug, N-oxide, addition salt, quaternary amine, metal complex, or a stereochemically isomeric form thereof;
wherein
each X independently is C or N;
R 1 is H;
R 2 is selected from the group consisting of Br and Cl;
R 3 is —(CR 6 R 7 ) n —R 8 ;
R 4 is selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 2 -C 10 alkenyl, —(CR 6 R 7 ) n —R 8 ; —CH 2 -p-Fluorophenyl, CH 2 CF 3 and —SO 2 CH 3 ;
R 5 is present where X is C, whereby each R 5 is selected, each independently, from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, and CN;
R 5 is absent where X is N;
R 6 and R 7 are H;
R 8 is selected from the group consisting of H, OH, CF 3 , CHF 2 , F, Cl, SO 2 CH 3 , SO 2 C 3 -C 7 cycloalkyl, NR 6 SO 2 R 6 , SO 2 NR 6 R 7 , NR 6 SO 2 C 3 -C 7 cycloalkyl, CN, NR 6 R 7 , COOH, COOR 6 , CONR 6 R 7 , OCOC 1 -C 6 alkyl, CONR 6 SO 2 R 7 , CONH—R 6 —SO 2 R 7 , CONH—R 6 —SO 2 NR 6 R 7 CONR 6 SO 2 NR 6 R 7 , phtalimido or a 5 to 6 membered aliphatic or aromatic ring that optionally contains one or more heteroatoms selected from the group N, S, O;
n is an integer having a value from 1 to 6.
2. A compound according to claim 1 wherein
R 4 is selected from the group consisting of H, C 3 -C 7 cycloalkyl, C 2 -C 10 alkenyl, and —SO 2 CH 3 ;
R 8 is selected from the group consisting of H, OH, CF 3 , CHF 2 , F, SO 2 CH 3 , SO 2 C 3 -C 7 cycloalkyl, NR 6 SO 2 R 6 , SO 2 NR 6 R 7 , NR 6 SO 2 C 3 -C 7 cycloalkyl, CN, NR 6 R 7 .
3. A compound according to claim 1 wherein R 2 is Br.
4. A compound according to claim 1 wherein R 2 is Cl.
5. A compound according to claim 1 , wherein n is 2-4.
6. A compound according to claim 1 , wherein R 8 is selected from the group consisting of F, CN, OH, CF 3 and SO 2 CH 3 .
7. A compound according to claim 1 , wherein R 8 is selected from the group consisting of F, CN, OH, and SO 2 CH 3 .
8. A compound according to claim 1 , wherein R 4 is C 3 -C 7 cycloalkyl or CH 2 CF 3 .
9. A compound according to claim 1 , wherein R 4 is cyclopropyl or CH 2 CF 3 .
10. A compound according to claim 1 , wherein one X is N and the other X's are C.
11. A compound according to claim 10 , wherein the N is in para position to N—R 4 .
12. 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, halogen, and CN.
13. A compound according to claim 1 , wherein all R 5 are H.
14. A compound according to claim 1 , wherein R 2 is Cl; one X is N and the other X's are C, wherein the N is in para position to N—R 4 ; and R 4 is cyclopropyl or CH 2 CF 3 .
15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and as active ingredient a therapeutically effective amount of a compound as claimed in claim 1 .
16. A process for preparing a pharmaceutical composition as claimed in claim 15 , said process comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of compound.