Benzodiazepine derivatives as RSV inhibitors
The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit Respiratory Syncytial Virus (RSV). The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from RSV infection. The invention also relates to methods of treating an RSV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
1. A compound represented by Formula (VIa-1) or (VIb-1):
or a pharmaceutically acceptable salt thereof, wherein:
R 4 is selected from the group consisting of:
1) —C 3 -C 12 cycloalkyl;
2) —C 3 -C 12 cycloalkenyl;
3) 3- to 12-membered heterocyclyl;
4) aryl;
5) heteroaryl;
6) aryl-O—;
7) heteroaryl-O;
8) aryl-C 1 -C 4 -alkyl; and
9) heteroaryl-C 1 -C 4 -alkyl;
each of which is optionally substituted with one or more substituents independently selected from CH 3 , CN, fluoro, chloro, CH 3 O—, CH 3 C(O)—, CH 3 OCH 2 —, CH 3 OCH 2 CH 2 O—, —CF 3 , CF 3 O—,
each heteroaryl is monocyclic or bicyclic and has one or more ring atoms selected from N, O and S;
each heterocyclyl is monocyclic and has 1 to 3 ring atoms selected from N, O and S; and
R 6 is absent or halogen.
2. The compound of claim 1 , represented by the formula:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from the group consisting of:
each of which is optionally substituted as defined in claim 1 .
4. The compound of claim 1 selected from the compounds set forth in the table below, or a pharmaceutically acceptable salt thereof,
5. The compound of claim 4 having the formula
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 4 having the formula
or a pharmaceutically acceptable salt thereof.
7. The compound of claim 4 having the formula
or a pharmaceutically acceptable salt thereof.
8. The compound of claim 4 having the formula
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 4 having the formula
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 4 having the formula
or a pharmaceutically acceptable salt thereof.
11. A compound selected from the compounds set forth below, or a pharmaceutically acceptable salt thereof,
12. The compound of claim 11 having the formula
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 11 having the formula
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 11 having the formula
or a pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition, comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
16. A pharmaceutical composition comprising the compound according to claim 5 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
17. A pharmaceutical composition comprising the compound according to claim 6 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
18. A pharmaceutical composition comprising the compound according to claim 7 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
19. A pharmaceutical composition comprising the compound according to claim 8 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
20. A pharmaceutical composition comprising the compound according to claim 9 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
21. A pharmaceutical composition comprising the compound according to claim 10 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
22. A pharmaceutical composition comprising the compound according to claim 12 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
23. A pharmaceutical composition comprising the compound according to claim 13 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
24. A pharmaceutical composition comprising the compound according to claim 14 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.
25. A method of treating an RSV infection in an subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.
26. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 5 or a pharmaceutically acceptable salt thereof.
27. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 6 or a pharmaceutically acceptable salt thereof.
28. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 7 or a pharmaceutically acceptable salt thereof.
29. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 8 or a pharmaceutically acceptable salt thereof.
30. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 9 or a pharmaceutically acceptable salt thereof.
31. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 10 or a pharmaceutically acceptable salt thereof.
32. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 12 or a pharmaceutically acceptable salt thereof.
33. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 13 or a pharmaceutically acceptable salt thereof.
34. A method of treating an RSV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 14 or a pharmaceutically acceptable salt thereof.