Inhibitors of serine proteases
The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is an optionally substituted aryl:
R 2 and R 3 together form an oxo group;
A is —O—, or —CH 2 —;
R 4 is —NH—CHR 4x —C(O)—(CO)—N(R 4z )R 4W ;
R 4W is hydrogen, optionally substituted aliphatic, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloaliphatic, or optionally substituted cycloaliphatic;
R 4X is hydrogen, optionally substituted aliphatic, optionally substituted heteroaryl, optionally substituted phenyl, optionally substituted cycloaliphatic, or optionally substituted heterocycloaliphatic;
R 4Z is hydrogen, optionally substituted aliphatic, optionally substituted cycloaliphatic, optionally substituted heterocycloaliphatic, optionally substituted aryl, or optionally substituted heteroaryl;
R 5 is
R 13 is
T is —C(O)—, and
R is
2. The compound of claim 1 , wherein R 1 is a monocyclic or bicvclic aryl, each of which is optionally substituted.
3. The compound of claim 2 , wherein R 1 is
phenyl optionally substituted with 1-3 substituents selected from halo, hydroxy, aliphatic, aryl, heteroaryl, cycloaliphatic, and heterocycloaliphatic.
4. The compound of claim 1 , wherein R 4 is —NH—CHR 4X —C(O)—C(O)—NH-cyclopropyl.
5. The compound of claim 1 , wherein R 4 is:
wherein R 4x is
and R4W is
or hydrogen.
6. The compound of claim 1 , wherein R 4 is one selected from the group consisting of
7. The compound of claim 6 , wherin R 4 is
8. The compound of claim 1 , wherein R 5 is:
wherein
T is —C(O)—, and
R is
9. The compound of claim 8 , wherein R 5 is one selected from the group consisting of
10. A compound selected from the group of compounds:
11. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof in an amount effective to inhibit a serine protease; and an acceptable carrier, adjuvant or vehicle.